MT
VETERINARY MEDICINAL PRODUCTS REGULATIONS *
Table of Provisions (117)
Statutory Text (117 Articles)
SUBSIDIARY LEGISLATION 437.47
VETERINARY MEDICINAL PRODUCTS
REGULATIONS *
12th November, 2004
LEGAL NOTICE 469 of 2004, as amended by Legal Notices 82 of 2006,
and 23 and 360 of 2009, 179 and 470 of 2021.
TITLE I
(1) The title of these regulations is the Veterinary
Medicinal Products Regulations.
(2) The scope of these regulations is to implement the rules laid
down under European Union Council Directive 2001/82/EEC on
the European Community code relating to veterinary medicinal
products.
(3)
(a) These regulations shall apply to veterinary medicinal
products, including pre-mixes for medicated
feedingstuffs, intended to be placed on the market in
Malta and prepared industrially or by a method
involving an industrial process.
(b) In cases of doubt, where, taking into account all its
characteristics, a product may fall within the definition
of a "veterinary medicinal product" and within the
definition of a product covered by other Community
legislation, the provisions of these regulations shall
apply.
(c) Notwithstanding paragraph (a), these regulations shall
also apply to active substances used as starting
materials to the extent set out in regulations 44, 44A,
45 and 72 and additionally to certain substances that
may be used as veterinary medicinal products that
have anabolic, anti-infectious, anti-parasitic, anti-
inflammatory, hormonal or psychotropic properties to
the extent set out in regulation 61.
Substituted by
L.N. 360 of 2009.
REQUIREMENTS AND ANALYTICAL PROTOCOL, SAFETY TESTS,
PRE-CLINICAL AND CLINICAL FOR TESTS
OF VETERINARY MEDICINAL PRODUCTS
TABLE OF CONTENTS
INTRODUCTION AND GENERAL PRINCIPLES
TITLE I
REQUIREMENTS FOR VETERINARY MEDICINAL PRODUCTS OTHER
THAN IMMUNOLOGICAL VETERINARY MEDICINAL PRODUCTS
PART 1
SUMMARY OF THE DOSSIER
A.
ADMINISTRATIVE INFORMATION
B.
SUMMARY OF PRODUCT CHARACTERISTICS, LABELLING AND
PACKAGE LEAFLET
C.
DETAILED AND CRITICAL SUMMARIES
PART 2
PHARMACEUTICAL (PHYSICO-CHEMICAL, BIOLOGICAL OR
MICROBIOLOGICAL INFORMATION (QUALITY))
Basic principles and requirements
A.
QUALITATIVE AND
QUANTITATIVE
PARTICULARS
OF
THE
CONSTITUENTS
1. Qualitative particulars
2. Usual terminology
3. Quantitative particulars
4. Development pharmaceutics
B.
DESCRIPTION OF THE MANUFACTURING METHOD
C.
CONTROL OF STARTING MATERIALS
1. General requirements
1.1. Active Substances
1.1.1. Active substances listed in pharmacopoeias
1.1.2. Active substances not in a pharmacopoeia
1.1.3. Physico-chemical characteristics liable to affect bioavailability
1.2. Excipients
1.3. Container-closure systems
1.3.1. Active substance
1.3.2. Finished Product
1.4. Substances of biological origin
D.
CONTROL TESTS CARRIED OUT AT INTERMEDIATE STAGES OF
THE MANUFACTURING PROCESS
E.
TESTS ON THE FINISHED PRODUCT
VETERINARY MEDICINAL PRODUCTS
1. General characteristics of the finished product
2. Identification and assay of active substance(s)
3. Identification and assay of excipient components
4. Safety tests
F.
STABILITY TEST
1. Active substances(s)
2. Finished product
G.
OTHER INFORMATION
PART 3
SAFETY AND RESIDUES TESTS
A.
Safety tests
CHAPTER I: PERFORMANCE OF TESTS
1. Precise identification of the product and of its active substance(s)
2. Pharmacology
2.1. Pharmacodynamics
2.2. Pharmacokinetics
3. Toxicology
3.1. Single-dose toxicity
3.2. Repeat-dose toxicity
3.3. Tolerance in the target species
3.4. Reproductive toxicity including developmental toxicity
3.4.1. Study of the effects on reproduction
3.4.2. Study of developmental toxicity
3.5. Genotoxicity
3.6. Carcinogenicity
3.7. Exceptions
4. Other requirements
4.1. Special studies
4.2. Microbiological properties of residues
4.2.1. Potential effects on the human gut flora
4.2.2. Potential effects on the microorganisms used for industrial food processing
4.3. Observations in humans
4.4. Development of resistance
5. User safety
6. Environmental risk assessment
6.1. Environmental risk assessment of veterinary medicinal products not
containing or consisting of genetically modified organisms
6.2. Environmental risk assessment for veterinary medicinal products containing
or consisting of genetically modified organisms
VETERINARY MEDICINAL PRODUCTS
CHAPTER II: PRESENTATION OF PARTICULARS AND DOCUMENTS
B.
Residue tests
CHAPTER I: PERFORMANCE OF TESTS
1. Introduction
2. Metabolism and residue kinetics
2.1. Pharmacokinetics (absorption, distribution, metabolism, excretion)
2.2. Depletion of residues
3. Residue analytical method
CHAPTER II: PRESENTATION OF PARTICULARS AND DOCUMENTS
1. Identification of the product
PART 4
PRE-CLINICAL AND CLINICAL TRIAL
CHAPTER I: PRE-CLINICAL REQUIREMENTS
A.
Pharmacology
A.1. Pharmacodynamics
A.2. Development of resistance
A.3. Pharmacokinetics
B.
Tolerance in the target animal species
CHAPTER II: CLINICAL REQUIREMENTS
1. General principles
2. Conduct of clinical trials
CHAPTER III: PARTICULARS AND DOCUMENTS
1. Results of pre-clinical trials
2. Results of clinical trials
TITLE II
REQUIREMENTS FOR IMMUNOLOGICAL VETERINARY MEDICINAL
PRODUCTS
PART 1
SUMMARY OF THE DOSSIER
A.
ADMINISTRATIVE INFORMATION
B.
SUMMARY OF PRODUCT CHARACTERISTICS, LABELLING AND
PACKAGE LEAFLET
C.
DETAILED AND CRITICAL SUMMARIES
PART 2
CHEMICAL,
PHARMACEUTICAL
AND
BIOLOGICAL/
MICROBIOLOGICAL INFORMATION (QUALITY)
A.
QUALITATIVE AND
QUANTITATIVE
PARTICULARS
OF
THE
CONSTITUENTS
1. Qualitative particulars
2. "Usual terminology"
3. Quantitative particulars
4. Product development
DESCRIPTION OF MANUFACTURING METHOD
PRODUCTION AND CONTROL OF STARTING MATERIALS
1. Starting materials listed In Pharmacopoeias
2. Starting materials not listed in a pharmacopoeia
2.1. Starting materials of biological origin
2.2. Starting materials of non-biological origin
CONTROL TESTS DURING THE MANUFACTURING PROCESS
CONTROL TESTS ON THE FINISHED PRODUCT
1. General characteristics of the finished product
2. Identification of active substance(s)
3. Batch titre or potency
4. Identification and assay of adjuvants
5. Identification and assay of excipient components
6. Safety tests
7. Sterility and purity test
8. Residual humidity
9. Inactivation
BATCH TO BATCH CONSISTENCY
STABILITY TESTS
OTHER INFORMATION
PART 3
SAFETY TESTS
INTRODUCTION AND GENERAL REQUIREMENTS
LABORATORY TESTS
1. Safety of the administration of one dose
2. Safety of one administration of an overdose
3. Safety of the repeated administration of one dose
4. Examination of reproductive performance
5. Examination of immunological functions
6. Special requirements for live vaccines
6.1. Spread of the vaccine strain
6.2. Dissemination in the vaccinated animal
6.3. Reversion to virulence of attenuated vaccines
6.4. Biological properties of the vaccine strain
6.5. Recombination or genomic reassortment of strains
7. User safety
8. Study of residues
9. Interactions
FIELD STUDIES
ENVIRONMENTAL RISK ASSESSMENT
ASSESSMENT
REQUIRED
FOR
VETERINARY
MEDICINAL
PRODUCTS CONTA INING O R CO NSISTING OF G ENETICALLY
MODIFIED ORGANISMS
PART 4
EFFICACY TESTS
CHAPTER I
1. General principles
2. Performance of trials
CHAPTER II
General requirements
Laboratory trials
Field trials
PART 5
PARTICULARS AND DOCUMENTS
INTRODUCTION
LABORATORY STUDIES
FIELD STUDIES
PART 6
BIBLIOGRAPHICAL REFERENCES
TITLE III
APPLICATIONS
1. Generic veterinary medicinal products
2. Similar biological veterinary medicinal products
3. Well-established veterinary use
4. Combination veterinary medicinal products
5. Informed consent applications
6. Documentation for applications in exceptional circumstances
7. Mixed marketing authorisation applications
TITLE IV
REQUIREMENTS FOR MARKETING AUTHORISATION APPLICATIONS
FOR PARTICULAR VETERINARY MEDICINAL PRODUCTS
1. IMMUNOLOGICAL VETERINARY MEDICINAL PRODUCTS
2. HOMEOPATHIC VETERINARY MEDICINAL PRODUCTS
INTRODUCTION AND GENERAL PRINCIPLES
1. The particulars and documents accompanying an application for marketing
authorisation pursuant to regulations 12 to 13(1) shall be presented in accordance
with the requirements set out in this Schedule and shall take into account the
guidance published by the Commission in The rules governing medicinal products in
the European Union, Volume 6 B, Notice to applicants, Veterinary medicinal
VETERINARY MEDICINAL PRODUCTS
products, Presentation and Contents of the Dossier.
2. In assembling the dossier for application for marketing authorisation,
applicants shall also take into account the current state of veterinary medicinal
knowledge and the scientific guidelines relating to the quality, safety and efficacy of
veterinary medicinal products published by the European Medicines Agency
(Agency) and the other pharmaceutical Union guidelines published by the
Commission in different volumes of The rules governing medicinal products in the
European Union.
3. For veterinary medicinal products other than immunological veterinary
medicinal products, with respect to the quality (pharmaceutical) part (physico-
chemical, biological and microbiological tests) of the dossier, all relevant
monographs including general monographs and the general chapters of the European
Pharmacopoeia are applicable. For immunological veterinary medicinal products,
with respect to the quality, safety and efficacy parts of the dossier, all relevant
monographs including general monographs and the general chapters of the European
Pharmacopoeia are applicable.
4. The manufacturing process shall comply with the requirements of
Commission Directive 91/412/EEC * laying down the principles and guidelines for
veterinary medicinal products and with the principles and guidelines on Good
Manufacturing Practice (GMP), published by the Commission in The rules
governing medicinal products in the European Union, Volume 4.
5. All information which is relevant to the evaluation of the veterinary
medicinal product concerned shall be included in the application, whether
favourable or unfavourable to the product. In particular, all relevant details shall be
given of any incomplete or abandoned test or trial relating to the veterinary
medicinal product.
6. Pharmacological, toxicological, residue and safety tests shall be carried out
in conformity with the provisions related to Good Laboratory Practice (GLP) laid
down in Directive 2004/10/EC of the European Parliament and of the Council † and
Directive 2004/9/EC of the European Parliament and of the Council ‡ .
7. The Authority shall ensure that all experiments on animals are conducted in
accordance with Council Directive 86/609/EEC § .
8. In order to monitor the risk/benefit assessment, any new information not in
the original application and all pharmacovigilance information shall be submitted to
the competent authority. After marketing authorisation has been granted, any change
to the content of the dossier shall be submitted to the competent authorities in
accordance with Commission Regulations (EC) No 1084/2003 ** or (EC) No 1085/
2003 †† for veterinary medicinal products authorised as defined in Article 1 of such
regulations, respectively.
9. The environmental risk assessment connected with the release of veterinary
medicinal products containing or consisting of Genetically Modified Organisms
(GMOs) within the meaning of Article 2 of Directive 2001/18/EC of the European
Parliament and of the Council ‡‡ shall be provided in the dossier. The information
shall be presented in accordance with the provisions of Directive 2001/18/EC and
*OJ L 228, 17.8.1991, p. 70.
†OJ L 50, 20.2.2004, p. 44.
‡OJ L 50, 20.2.2004, p. 28.
§OJ L 358, 18.12.1986, p. 1.
** OJ L 159, 27.6.2003, p. 1.
††OJ L 159, 27.6.2003, p. 24.
‡‡OJ L 106, 17.4.2001, p. 1.
VETERINARY MEDICINAL PRODUCTS
Regulation (EC) No 726/2004 of the European Parliament and of the Council * ,
taking into account guidance documents published by the Commission.
10. In cases of applications for marketing authorisations for veterinary
medicinal products indicated for animal species and indications representing smaller
market sectors, a more flexible approach may be applicable. In such cases, relevant
scientific guidelines and/or scientific advice should be taken into account.
This Schedule is divided in four titles
Title I describes the standardised requirements for applications for veterinary
medicinal products other than immunological veterinary medicinal products.
Ti t l e I I d e s c r i b e s t h e s t a n d a r d i s e d r e q u i r e m e n t s f o r a p p l i c a t i o n s f o r
immunological veterinary medicinal products.
Title III describes specific types of marketing authorisation dossiers and
requirements.
Title IV describes the dossier requirements for particular types of veterinary
medicinal products.
TITLE I
REQUIREMENTS FOR VETERINARY MEDICINAL PRODUCTS OTHER
THAN IMMUNOLOGICAL VETERINARY MEDICINAL PRODUCTS
The following requirements shall apply to veterinary medicinal products other
than immunological veterinary medicinal products, except where otherwise set out in
Title III.
PART 1: SUMMARY OF THE DOSSIER
A.
ADMINISTRATIVE INFORMATION
The veterinary medicinal product, which is the subject of the application, shall be
identified by its name and by the name of the active substance(s), together with the
strength, the pharmaceutical form, the route and method of administration (vide
regulation 12) and a description of the final presentation of the product, including
packaging, labelling and package leaflet (vide regulation 12).
The name and address of the applicant shall be given, together with the name and
address of the manufacturers and the sites involved in the different stages of the
manufacture, testing and release (including the manufacturer of the finished product
and the manufacturer(s) of the active substance(s)), and where relevant the name and
address of the importer.
The applicant shall identify the number and titles of volumes of documentation
submitted in support of the application and indicate what samples, if any, are also
provided.
Annexed to the administrative information shall be a document showing that the
manufacturer is authorised to produce the veterinary medicinal products concerned,
as defined in regulation 38, together with a list of countries in which authorisation
has been granted, copies of all the summaries of product characteristics in
accordance with regulation 14 as approved by the Director and a list of countries in
which an application has been submitted or refused.
B.
SUMMARY OF PRODUCT CHARACTERISTICS, LABELLING AND
PACKAGE LEAFLET
*OJ L 136, 30.4.2004, p. 1.
VETERINARY MEDICINAL PRODUCTS
The applicant shall propose a summary of the product characteristics, in
accordance with regulation 14.
A proposed labelling text for the immediate and outer packaging shall be provided
in accordance with Title V of these regulations, together with a package leaflet
where such is required pursuant to regulation 51 of these regulations. In addition the
applicant shall provide one or more specimens or mock-ups of the final
presentation(s) of the veterinary medicinal product in at least one of the official
languages of the European Union; the mock-up may be provided in black and white
and electronically where prior agreement from the competent authority has been
obtained.
C.
DETAILED AND CRITICAL SUMMARIES
In accordance with regulation 12(3), detailed and critical summaries shall be
provided on the results of pharmaceutical (physico-chemical, biological or
microbiological) tests, of the safety tests and residue tests, of the pre-clinical and
clinical trials and of the tests assessing the potential risks posed by the veterinary
medicinal product for the environment.
Each detailed and critical summary shall be prepared in the light of the state of
scientific knowledge at the time of submission of the application. It shall contain an
e v a l u a ti o n o f t h e v a r i ou s t e s t s a n d t r i a l s , wh i c h c o ns t it u t e t h e m a r k e t i n g
authorisation dossier, and shall address all points relevant to the assessment of the
quality, safety and efficacy of the veterinary medicinal product. It shall give detailed
results of the tests and trials submitted and precise bibliographic references.
All important data shall be summarised in an appendix, whenever possible in
tabular or graphic form. The detailed and critical summaries and the appendices shall
contain precise cross references to the information contained i n the mai n
documentation.
The detailed and critical summaries shall be signed and dated, and information
about the author’s educational background, training and occupational experience
shall be attached. The professional relationship of the author with the applicant shall
be declared.
Where the active substance has been included in a medicinal product for human
use authorised in accordance with the requirements of Annex I to Directive 2001/83/
EC of the European Parliament and of the Council * the overall quality summary
provided for in Module 2, section 2.3 of that Annex may replace the summary
regarding the documentation related to the active substance or the product, as
appropriate.
Where the competent authority has publicly announced that the chemical,
pharmaceutical and biological/microbiological information for the finished product
may be included in the dossier in the Common Technical Document (CTD) format
only, the detailed and critical summary on the results of pharmaceutical tests may be
presented in the quality overall summary format.
In the case of application for an animal species or for indications representing
smaller market sectors, the quality overall summary format may be used without
prior agreement of the competent authorities.
PART 2: PHARMACEUTICAL (PHYSICO-CHEMICAL, BIOLOGICAL OR
MICROBIOLOGICAL INFORMATION (QUALITY))
Basic principles and requirements
* OJ L 311, 28.11.2001, p. 67.
VETERINARY MEDICINAL PRODUCTS
The particulars and documents which shall accompany the application for
marketing authorisation pursuant to regulation 12 of these regulations shall be
submitted in accordance with the requirements below.
The pharmaceutical (physico-chemical, biological or microbiological) data shall
include for the active substance(s) and for the finished veterinary medicinal product
information on the manufacturing process, the characterisation and properties, the
quality control procedures and requirements, the stability as well as a description of
the composition, the development and presentation of the veterinary medicinal
product.
All monographs, including general monographs and general chapters of the
European Pharmacopoeia, or failing that, of Malta are applicable.
All test procedures shall fulfil the criteria for analysis and control of the quality of
the starting materials and the finished product and should take account of established
guidance and requirements. The results of the validation studies shall be provided.
All the test procedure(s) shall be described in sufficiently precise detail so as to be
reproducible in control tests, carried out at the request of the competent authority;
any special apparatus and equipment, which may be used shall be described in
adequate detail, possibly accompanied by a diagram. The formulae of the laboratory
reagents shall be supplemented, if necessary, by the method of preparation. In the
case of test procedures included in the European Pharmacopoeia or the
pharmacopoeia of Malta, this description may be replaced by a detailed reference to
the pharmacopoeia in question.
Where relevant, chemical and biological reference material of the European
Pharmacopoeia shall be used. If other reference preparations and standards are used,
they shall be identified and described in detail.
In cases where the active substance has been included in a medicinal product for
human use authorised in accordance with the requirements of Annex I to Directive
2 00 1 /8 3 / E C t h e ch e m i c a l, p h a r m a c e u t ic a l a n d b i ol o gi c a l /m i c r ob i ol o g ic a l
information provided for in Module 3 of that Directive may replace the
documentation related to the active substance or the finished product, as appropriate.
The chemical, pharmaceutical and biological/microbiological information for the
active substance or the finished product may be included in the dossier in CTD
format only where the competent authority has publicly announced this possibility.
In the case of any application for an animal species or for indications representing
smaller market sectors the CTD format may be followed without prior agreement of
the competent authorities.
A.
QUALITATIVE
AND
QUANTITATIVE
PARTICULARS
OF
THE
CONSTITUENTS
1. Qualitative particulars
"Qualitative particulars" of all the constituents of the medicinal product shall
mean the designation or description of
- the active substance(s),
-
the constituents of the excipients, whatever their nature or the quantity
used, including colouring matter, preservatives, adjuvants, stabilisers,
thickeners, emulsifiers, flavouring and aromatic substances,
-
the constituents, intended to be ingested or otherwise administered to
animals, of the outer covering of the veterinary medicinal products,
such as capsules, gelatine capsules.
VETERINARY MEDICINAL PRODUCTS
These particulars shall be supplemented by any relevant data concerning the
immediate packaging and if relevant the secondary packaging and, where
appropriate, its manner of closure, together with details of devices with which the
medicinal product will be used or administered and which will be supplied with the
medicinal product.
2. Usual terminology
The usual terminology to be used in describing the constituents of veterinary
medicinal products means, notwithstanding the application of the other provisions of
regulation 12(3)(c)
in respect of constituents which appear in the European Pharmacopoeia
or, failing this, in the national pharmacopoeia of one of the Member
States, the main title at the head of the monograph in question, with
reference to the pharmacopoeia concerned,
in respect of other constituents, the international non-proprietary name
(INN) recommended by the World Health Organisation (WHO), which
may be accompanied by another non-proprietary name, or, failing these,
the exact scientific designation; constituents not having an international
non-proprietary name or an exact scientific designation shall be
described by a statement of how and from what they were prepared,
supplemented, where appropriate, by any other relevant details,
in respect of colouring matter, designation by the "E" code assigned to
them by Council Directive 78/25/EEC * .
3. Quantitative particulars
3.1. In order to give "quantitative particulars" of all the active substances of the
veterinary medicinal products, it is necessary, depending on the pharmaceutical form
concerned, to specify the mass, or the number of units of biological activity, either
per dosage-unit or per unit of mass or volume, of each active substance.
Units of biological activity shall be used for substances, which cannot be defined
chemically. Where an International Unit of biological activity has been defined by
the World Health Organisation, this shall be used. Where no International Unit has
been defined, the units of biological activity shall be expressed in such a way as to
provide unambiguous information on the activity of the substances by using where
applicable the European Pharmacopoeia Units.
Whenever possible, biological activity per units of mass or volume shall be
indicated. This information shall be supplemented
in respect of single-dose preparations, by the mass or units of biological
activity of each active substance in the unit container, taking into
account the usable volume of the product, after reconstitution, where
appropriate,
in respect of veterinary medicinal products to be administered by drops,
by the mass or units of biological activity of each active substance
contained per drop or contained in the number of drops corresponding
to 1 ml or 1 g of the preparation,
in respect of syrups, emulsions, granular preparations and other
pharmaceutical forms to be administered in measured quantities, by the
mass or units of biological activity of each active substance per
measured quantity.
*OJ L 11, 14.1.1978, p. 18.
3.2. Active substances present in the form of compounds or derivatives shall be
described quantitatively by their total mass, and if necessary or relevant, by the mass
of the active entity or entities of the molecule.
3.3. For veterinary medicinal products containing an active substance which is
the subject of an application for marketing authorisation in any Member State for the
first time, the quantitative statement of an active substance which is a salt or hydrate
shall be systematically expressed in terms of the mass of the active entity or entities
in the molecule. All subsequently authorised veterinary medicinal products in Malta
shall have their quantitative composition stated in the same way for the same active
4. Development pharmaceutics
An explanation shall be provided with regard to the choice of composition,
constituents, immediate packaging, possible further packaging, outer packaging if
relevant, the intended function of the excipients in the finished product and the
method of manufacture of the finished product. This explanation shall be supported
by scientific data on development pharmaceutics. The overage, with justification
thereof, shall be stated. The microbiological characteristics (microbiological purity
and antimicrobial activity) and usage instructions shall be proven to be appropriate
for the intended use of the veterinary medicinal product as specified in the marketing
authorisation application dossier.
DESCRIPTION OF THE MANUFACTURING METHOD
The name, address and responsibility of each manufacturer and each proposed
production site or facility involved in manufacturing and testing shall be indicated.
The description of the manufacturing method accompanying the application for
marketing authorisation pursuant to regulation 12(3)(d) hereof, shall be drafted in
such a way as to give an adequate synopsis of the nature of the operations employed.
For this purpose it shall include at least
mention of the various stages of manufacture, so that an assessment can
be made of whether the processes employed in producing the
pharmaceutical form might have produced an adverse change in the
constituents,
in the case of continuous manufacture, full details concerning
precautions taken to ensure the homogeneity of the finished product,
the actual manufacturing formula, with the quantitative particulars of all
the substances used, the quantities of excipients, however, being given
in approximate terms insofar as the pharmaceutical form makes this
necessary; mention shall be made of any substances that may disappear
in the course of manufacture; an overage shall be indicated and
justified,
a statement of the stages of manufacture at which sampling is carried
out for in-process control tests and the limits applied, where other data
in the documents supporting the application show such tests to be
necessary for the quality control of the finished product,
experimental studies validating the manufacturing process and where
appropriate a process validation scheme for production scale batches,
for sterile products, where non-pharmacopoeial standard sterilisation
conditions are used, details of the sterilisation processes and/or aseptic
procedures used.
VETERINARY MEDICINAL PRODUCTS
C.
CONTROL OF STARTING MATERIALS
1. General requirements
For the purposes of this paragraph, "starting materials" shall mean all the
constituents of the veterinary medicinal product and, if necessary, of its container
including its closure, as referred to in Section A, point 1, above.
The dossier shall include the specifications and information on the tests to be
conducted for quality control of all batches of starting materials.
The routine tests carried out on each batch of starting materials must be as stated
in the application for marketing authorisation. If tests other than those mentioned in
a pharmacopoeia are used, this shall be justified by providing proof that the starting
materials meet the quality requirements of that pharmacopoeia.
Where a Certificate of Suitability has been issued by the European Directorate for
the Quality of Medicines and HealthCare for a starting material, active substance or
excipient, this Certificate constitutes the reference to the relevant monograph of the
European Pharmacopoeia.
Where a Certificate of Suitability is referred to, the manufacturer shall give an
assurance in writing to the applicant that the manufacturing process has not been
modified since the granting of the certificate of suitability by the European
Directorate for the Quality of Medicines and HealthCare.
Certificates of Analysis shall be presented for the starting materials in order to
demonstrate compliance with the defined specification.
1.1. Active substances
The name, address, and responsibility of each manufacturer and each proposed
production site or facility involved in manufacturing and testing of an active
substance shall be indicated.
For a well-defined active substance, the active substance manufacturer or the
applicant may arrange for the following information to be supplied in a separate
document directly to the competent authorities by the manufacturer of the active
substance as an Active Substance Master File
(a) a detailed description of the manufacturing process;
(b) a description of the quality control during manufacture;
(c) a description of the process validation.
In this case, the manufacturer shall however provide the applicant with all the data
which may be necessary for the latter to take responsibility for the veterinary
medicinal product. The manufacturer shall confirm in writing to the applicant that he
shall ensure batch to batch consistency and not modify the manufacturing process or
specifications without informing the applicant. Documents and particulars
supporting the application for such a change shall be supplied to the competent
authorities those documents and particulars shall also be supplied to the applicant
where they concern the applicant’s part of the Active Substance Master File.
Additionally, information on the method of manufacture, on quality control and on
impurities as well as evidence of the molecular structure shall be provided where a
Certificate of Suitability for the active substance is not available
1. Information on the manufacturing process shall include a description of the
active substance manufacturing process that represents the applicant’s commitment
for the manufacture of the active substance. All materials needed in order to
manufacture the active substance(s) shall be listed, identifying where each material
VETERINARY MEDICINAL PRODUCTS
is used in the process. Information on the quality and control of those materials shall
be provided. Information demonstrating that materials meet standards which are
appropriate for their intended use shall be provided.
2. Information on quality control shall contain tests (including acceptance
criteria) carried out at every critical step, information on the quality and control of
intermediates and process validation and/or evaluation studies as appropriate. It shall
also contain validation data for the analytical methods applied to the active
substance, where appropriate.
3. Information on impurities shall indicate predictable impurities together with
the levels and nature of observed impurities. It shall also contain information on the
safety of these impurities where relevant.
4. For biotechnological veterinary medicinal products, evidence of molecular
structure shall include the schematic amino acid sequence and relative molecular
mass.
1.1.1. Active substances listed in pharmacopoeias
The general and specific monographs of the European Pharmacopoeia shall be
applicable to all active substances appearing in it.
Constituents fulfilling the requirements of the European Pharmacopoeia or the
pharmacopoeia of one of the Member States shall be deemed to comply sufficiently
with regulation 12(3). In this case the description of the analytical methods and
procedures shall be replaced in each relevant section by an appropriate reference to
the pharmacopoeia in question.
In cases where a specification contained in a monograph of the European
Pharmacopoeia or in the national pharmacopoeia of Malta is insufficient to ensure
the quality of the substance, the competent authorities may request more appropriate
specifications from the applicant, including limits for specific impurities with
validated test procedures.
The competent authorities shall inform the authorities responsible for the
pharmacopoeia in question. The marketing authorisation holder shall provide the
authorities of that pharmacopoeia with the details of the alleged insufficiency and
the additional specifications applied.
In the absence of a European Pharmacopoeia monograph for an active substance,
and where the active substance is described in the pharmacopoeia of Malta, that
monograph may be applied.
In cases where an active substance is described neither in the European
Pharmacopoeia nor in the pharmacopoeia of Malta, compliance with the monograph
of a third country pharmacopoeia may be accepted if its suitability is demonstrated;
in such cases, the applicant shall submit a copy of the monograph accompanied by a
translation where appropriate. Data to demonstrate the ability of the monograph to
adequately control the quality of the active substance shall be presented.
1.1.2. Active substances not in a pharmacopoeia
Constituents which are not given in any pharmacopoeia shall be described in the
form of a monograph under the following headings
(a) the name of the constituent, meeting the requirements of Section A
point 2, shall be supplemented by any trade or scientific synonyms;
(b) the definition of the substance, set down in a form similar to that used in
the European Pharmacopoeia, shall be accompanied by any necessary
explanatory evidence, especially concerning the molecular structure.
VETERINARY MEDICINAL PRODUCTS
Where substances can only be described by their manufacturing method,
the description shall be sufficiently detailed to characterise a substance
which is constant both on its composition and in its effects;
(c) methods of identification may be described in the form of complete
techniques as used for production of the substance, and in the form of
tests which ought to be carried out as a routine matter;
(d) purity tests shall be described in relation to each individual predictable
impurity, especially those which may have a harmful effect, and, if
necessary, those which, having regard to the combination of substances
to which the application refers, might adversely affect the stability of
the medicinal product or distort analytical results;
(e) tests and limits to control parameters relevant to the finished product,
such as particle size and sterility shall be described and methods shall
be validated where relevant;
(f)
with regard to complex substances of plant or animal origin, a
distinction must be made between the case where multiple
pharmacological effects render chemical, physical or biological control
of the principal components necessary, and the case of substances
containing one or more groups of principles having similar activity, in
respect of which an overall method of assay may be accepted.
Those data shall demonstrate that the proposed set of test procedures is sufficient
to control the quality of the active substance from the defined source.
1.1.3. Physico-chemical characteristics liable to affect bioavailability The
following items of information concerning active substances, whether or not listed in
the pharmacopoeias, shall be provided as part of the general description of the active
substances if the bioavailability of the veterinary medicinal product depends on
crystalline form and solubility coefficients,
particle size, where appropriate after pulverisation,
state of hydration,
oil/water coefficient of partition,
pK/pH values.
The first three indents are not applicable to substances used solely in solution.
1.2. Excipients
The general and specific monographs of the European Pharmacopoeia shall be
applicable to all substances appearing in it.
Excipients shall comply with the requirements of the appropriate European
Pharmacopoeia monograph. Where such a monograph does not exist reference may
be made to the pharmacopoeia of Malta. In the absence of such a monograph
reference may be made to the pharmacopoeia of a third country. In this case the
suitability of this monograph shall be demonstrated. Where appropriate, additional
tests to control parameters such as particle size, sterility, residual solvents shall
supplement the requirements of the monograph. In the absence of a pharmacopoeial
monograph a specification shall be proposed and justified. The requirements for
specifications as set out in section 1.1.2 (a to e) for the active substance shall be
followed. The proposed methods and their supporting validation data shall be
Colouring matters for inclusion in veterinary medicinal products shall satisfy the
VETERINARY MEDICINAL PRODUCTS
requirements of Directive 78/25/EEC, except for certain veterinary medicinal
products for topical use, such as insecticidal collars and ear tags, where the use of
other colouring matters is justified.
Colouring matters shall meet the purity criteria as laid down in Commission
Directive 95/45/EC * .
For novel excipients, that is to say excipient(s) used for the first time in a
veterinary medicinal product or by a new route of administration, details of
manufacture, characterisation, and controls, with cross references to supporting
safety data, both clinical and non-clinical, shall be provided.
1.3. Container-closure systems
1.3.1. Active substance
Information on the container-closure system for the active substance shall be
given.
The level of information required shall be determined by the physical state (liquid,
solid) of the active substance.
1.3.2. Finished product
Information on the container-closure system for the finished product shall be
given.
The level of information required shall be determined by the route of
administration of the veterinary medicinal product and the physical state (liquid,
solid) of the dosage form.
Packaging materials shall comply with the requirements of the appropriate
European Pharmacopoeia monograph. Where such a monograph does not exist
reference may be made to the pharmacopoeia of Malta. In the absence of such a
monograph reference may be made to the Pharmacopoeia of a third country. In this
case the suitability of this monograph shall be demonstrated.
In the absence of a pharmacopoeial monograph, a specification shall be proposed
and justified for the packaging material.
Scientific data on the choice and suitability of the packaging material shall be
presented.
For novel packaging materials in contact with the product, information on their
composition, manufacture and safety shall be presented.
Specifications and, if appropriate, performance data shall be presented for any
dosing or administration device supplied with the veterinary medicinal product.
1.4. Substances of biological origin
Where source materials such as microorganisms, tissues of either plant or animal
origin, cells or fluids (including blood) of human or animal origin or
biotechnological cell constructs are used in the manufacture of veterinary medicinal
products, the origin and history of starting materials shall be described and
documented.
The description of the starting material shall include the manufacturing strategy,
purification/inactivation procedures with their validation and all in-process control
procedures designed to ensure the quality, safety and batch to batch consistency of
the finished product.
*OJ L 226, 22.9.1995, p. 1.
VETERINARY MEDICINAL PRODUCTS
When cell banks are used, the cell characteristics shall be shown to have remained
unchanged at the passage level used for the production and beyond.
Seed materials, cell banks and pools of serum and, whenever possible, the source
materials from which they are derived shall be tested for extraneous agents.
When starting materials of animal or human origin are used, the measures used to
ensure freedom from potentially pathogenic agents shall be described.
If the presence of potentially pathogenic extraneous agents is inevitable, the
material shall be used only when further processing ensures their elimination and/or
inactivation, and this shall be validated.
Documentation shall be supplied to demonstrate that the seed materials, cell seeds,
batches of serum and other material originating from animal species relevant for the
transmission of TSE comply with the Note for Guidance on minimising the risk of
transmitting animal spongiform encephalopathy agents via human and veterinary
medicinal products * , as well as with the corresponding monograph of the European
Pharmacopoeia. Certificates of Suitability issued by the European Directorate for the
Quality of Medicines and HealthCare, with reference to the relevant monograph of
the European Pharmacopoeia, may be used to demonstrate compliance.
D.
CONTROL TESTS CARRIED OUT AT INTERMEDIATE STAGES OF
THE MANUFACTURING PROCESS
The dossier shall include particulars relating to the product control tests that may
be carried out at an intermediate stage of the manufacturing process, with a view to
ensuring the consistency of the technical characteristics and the production process.
These tests are essential for checking the conformity of the veterinary medicinal
product with the formula when, exceptionally, an applicant proposes an analytical
method for testing the finished product which does not include the assay of all the
activ e sub stances (or o f all th e excipient components subject t o t he sam e
requirements as the active substances).
The same applies where the quality control of the finished product depends on in-
process control tests, particularly if the substance is essentially defined by its
manufacturing method.
Where an intermediate product may be stored prior to further processing or
primary assembly, a shelf life for the intermediate product shall be defined on the
basis of the data resulting from stability studies.
E.
TESTS ON THE FINISHED PRODUCT
For the control of the finished product, a batch of a finished product comprises all
the units of a pharmaceutical form which are made from the same initial quantity of
material and have undergone the same series of manufacturing and/or sterilisation
operations or, in the case of a continuous production process, all the units
manufactured in a given period of time.
The application for marketing authorisation shall list those tests, which are carried
out routinely on each batch of finished product. The frequency of the tests which are
not carried out routinely shall be stated. Release limits shall be indicated.
The dossier shall include particulars relating to control tests on the finished
product at release. They shall be submitted in accordance with the following
requirements.
The provisions of the relevant monographs and general chapters of the European
*OJ C 24, 28.1.2004, p. 6.
VETERINARY MEDICINAL PRODUCTS
Pharmacopoeia, or failing that, of Malta, shall be applicable to all products defined
therein.
If test procedures and limit s other than those mentioned in the relevant
monographs and general chapters of the European Pharmacopoeia, or failing this, in
the pharmacopoeia of Malta are used, this shall be justified by providing proof that
the finished product would, if tested in accordance with those monographs, meet the
quality requirements of that pharmacopoeia for the pharmaceutical form concerned.
1. General characteristics of the finished product
Certain tests of the general characteristics of a product shall always be included
among the tests on the finished product. These tests shall, wherever applicable,
relate to the control of average masses and maximum deviations, to mechanical,
p h y s i c a l o r m i c r o b i o l o g i c a l t e s t s , o rg a n o l e p t i c c h a r a c t e r i s t i c s , p h y s i c a l
c h a r a c t e r i s t i c s s u c h a s d e n s i t y, p H , r e f r a c t i v e i n d e x . F o r e a c h o f t h e s e
characteristics, standards and tolerance limits shall be specified by the applicant in
each particular case.
The conditions of the tests, where appropriate, the equipment/apparatus employed
and the standards shall be described in precise details whenever they are not given in
the European Pharmacopoeia or the pharmacopoeia of Malta; the same shall apply in
cases where the methods prescribed by such pharmacopoeias are not applicable.
Furthermore, solid pharmaceutical forms having to be administered orally shall be
subjected to in vitro studies on the liberation and dissolution rate of the active
substance or substances, unless otherwise justified. Those studies shall also be
carried out where administration is by another means if the competent Authority
concerned consider this necessary.
2. Identification and assay of active substance(s)
Identification and assay of the active substance(s) shall be carried out either in a
representative sample from the production batch or in a number of dosage units
analysed individually.
Unless there is appropriate justification, the maximum acceptable deviation in the
active substance content of the finished product shall not exceed ± 5 % at the time of
manufacture.
On the basis of the stability tests, the manufacturer shall propose and justify
maximum acceptable deviation limits in the active substance content of the finished
product up to the end of the proposed shelf life.
In certain cases of particularly complex mixtures, where assay of active
substances which are very numerous or present in very low amounts would
necessitate an intricate investigation difficult to carry out in respect of each
production batch, the assay of one or more active substances in the finished product
may be omitted, on the express condition that such assays are made at intermediate
stages in the production process. This simplified technique may not be extended to
the characterisation of the substances concerned. It shall be supplemented by a
method of quantitative evaluation, enabling the competent authority to have the
conformity of the medicinal product with its specification verified after it has been
placed on the market.
An in vivo or in vitro biological assay shall be obligatory when physico-chemical
methods cannot provide adequate information on the quality of the product. Such an
assay shall, whenever possible, include reference materials and statistical analysis
allowing calculation of confidence limits. Where these tests cannot be carried out on
the finished product, they may be performed at an intermediate stage, as late as
VETERINARY MEDICINAL PRODUCTS
possible in the manufacturing process.
Where degradation occurs during manufacture of the finished product, the
maximum acceptable levels of individual and total degradation products
immediately following manufacture shall be indicated.
Where the particulars given in Section B show that a significant overage of an
active substance is employed in the manufacture of the medicinal product or where
the stability data show that the assay of the active substance declines on storage, the
description of the control tests on the finished product shall include, where
appropriate, the chemical and, if necessary, the toxico-pharmacological investigation
of the changes that this substance has undergone, and possibly the characterisation
and/or assay of the degradation products.
3. Identification and assay of excipient components
An identification test and an upper and lower limit test shall be obligatory for each
individual antimicrobiological preservative and for any excipient that is liable to
affect the bioavailability of the active substance, unless the bioavailability is
guaranteed by other appropriate tests. An identification test and an upper limit test
shall be obligatory for any antioxidant and for any excipient liable to adversely
affect physiological functions, with a lower limit test also included for antioxidants
at time of release.
4. Safety tests
Apart from the toxico-pharmacological tests submitted with the application for
marketing authorisation, particulars of safety tests, such as sterility and bacterial
endotoxins, shall be included in the analytical particulars wherever such tests must
be undertaken as a matter of routine in order to verify the quality of the product.
F.
STABILITY TEST
1. Active substances(s)
A retest period and storage conditions for the active substance shall be specified
except in the case where the active substance is the subject of a monograph in the
European Pharmacopoeia and the manufacturer of the finished product fully retests
the active substance immediately before its use in the manufacture of the finished
product.
Stability data shall be presented to support the defined retest period and storage
conditions. The type of stability studies conducted, protocols used, the analytical
procedures used and their validation together with the detailed results shall be
presented. The stability commitment with a summary of the protocol shall be
provided.
However, where a Certificate of Suitability for the active substance from the
proposed source is available and specifies a retest period and storage conditions,
stability data for the active substance from that source are not required.
2. Finished product
A description shall be given of the investigations by which the shelf life, the
recommended storage conditions and the specifications at the end of the shelf life
proposed by the applicant have been determined.
The type of stability studies conducted, protocols used, the analytical procedures
used and their validation together with the detailed results shall be presented.
Where a finished product requires reconstitution or dilution prior to
administration, details of the proposed shelf life and specification for the
VETERINARY MEDICINAL PRODUCTS
reconstituted/diluted product are required, supported by relevant stability data.
In the case of multi-dose containers, where relevant, stability data shall be
presented to justify a shelf life for the product after it has been broached for the first
time and an in-use specification shall be defined.
Where a finished product is liable to give rise to degradation products, the
applicant shall declare these and indicate the identification methods and test
procedures.
The conclusions shall contain the results of analyses, justifying the proposed shelf
life and if appropriate, the in-use shelf life, under the recommended storage
conditions and the specifications of the finished product at the end of the shelf life,
and in-use shelf life if appropriate, of the finished product under these recommended
storage conditions.
The maximum acceptable level of individual and total degradation products at the
end of shelf life shall be indicated.
A study of the interaction between product and container shall be submitted
wherever the risk of such interaction is regarded as possible, especially where
injectable preparations are concerned.
The stability commitment with a summary of the protocol shall be provided.
G.
OTHER INFORMATION
Information relating to the quality of the veterinary medicinal product not covered
in the previous sections may be included in the dossier.
For medicated premixes (products intended for incorporation into medicated
feedingstuffs), information shall be provided on inclusion rates, instructions for
incorporation, homogeneity in-feed, compatibility/suitable feedingstuffs, stability
in- feed, and the proposed in-feed shelf life. A specification for the medicated
feedingstuffs, manufactured using these pre-m ixes in accordance with the
recommended instructions for use shall also be provided.
PART 3: SAFETY AND RESIDUES TESTS
The particulars and documents which shall accompany the application for
marketing authorisation pursuant to the second and fourth indents of regulation
12(3) shall be submitted in accordance with the requirements below.
A.
Safety tests
CHAPTER I: PERFORMANCE OF TESTS
The safety documentation shall show
(a) the potential toxicity of the veterinary medicinal product and any
dangerous or undesirable effects which may occur under the proposed
conditions of use in animals; these should be evaluated in relation to the
severity of the pathological condition concerned;
(b) the potential harmful effects to man of residues of the veterinary
medicinal product or substance in foodstuffs obtained from treated
animals and what difficulties these residues may create in the industrial
processing of foodstuffs;
(c) the potential risks which may result from the exposure of human beings
to the veterinary medicinal product, for example during its
administration to the animal;
(d) the potential risks for the environment resulting from the use of the
VETERINARY MEDICINAL PRODUCTS
veterinary medicinal product.
All resu lts shall b e reliabl e an d vali d general ly. Whenever appro priat e,
mathematical and statistical procedures shall be used in designing the experimental
methods and in evaluating the results. Additionally, information shall be provided
regarding the therapeutic potential of the product and about the hazards connected
with its use.
In some cases it may be necessary to test the metabolites of the parent compound
where these represent the residues of concern.
An excipient used in the pharmaceutical field for the first time shall be treated like
an active substance.
1. Precise identification of the product and of its active substance(s)
-
international non-proprietary name (INN),
-
International Union of Pure and Applied Chemistry Name (IUPAC),
-
Chemical Abstract Service (CAS) number,
-
therapeutic, pharmacological and chemical classification,
-
synonyms and abbreviations,
-
structural formula,
-
molecular formula,
-
molecular weight,
-
degree of impurity,
-
qualitative and quantitative composition of impurities,
-
description of physical properties,
-
melting point,
-
boiling point,
-
vapour pressure,
-
solubility in water and organic solvents expressed in g/l, with indication
of temperature,
-
density,
-
spectra of refraction, rotation, etc,
-
formulation of the product.
2. Pharmacology
Pharmacological studies are of fundamental importance in clarifying the
mechanisms by which the veterinary medicinal product produces its therapeutic
effects and therefore pharmacological studies conducted in experimental and target
species of animal shall be included in Part 4.
However, pharmacological studies may also assist in the understanding of
toxicological phenomena. Moreover, where a veterinary medicinal product produces
pharmacological effects in the absence of a toxic response, or at doses lower than
those required to elicit toxicity, these pharmacological effects shall be taken into
account during the evaluation of the safety of the veterinary medicinal product.
Therefore the safety documentation shall always be preceded by details of
pharmacological investigations undertaken in laboratory animals and all relevant
information observed during clinical studies in the target animal.
VETERINARY MEDICINAL PRODUCTS
2.1. Pharmacodynamics
Information on the mechanism of action of the active substance(s) shall be
provided, together with information on primary and secondary pharmacodynamic
effects in order to assist in the understanding of any adverse effects in the animal
studies.
2.2. Pharmacokinetics
Data on the fate of the active substance and its metabolites in the species used in
the toxicological studies shall be provided, covering absorption, distribution,
metabolism and excretion (ADME). The data shall be related to the dose/effect
findings in the pharmacological and toxicological studies, to determine adequate
exposure. Comparison with the pharmacokinetic data obtained in the studies on the
target species, Part 4, Chapter I, Section A.2, shall be included in Part 4 in order to
determine the relevance of the results obtained in the toxicology studies for the
toxicity to the target species.
3. Toxicology
The documentation on toxicology shall follow the guidance published by the
Agency on the general approach to testing and guidance on particular studies. This
guidance includes
1. basic tests required for all new veterinary medicinal products for use in
food-producing animals in order to assess the safety of any residues
present in food for human consumption;
2. additional tests that may be required depending on specific
toxicological concerns such as those associated with the structure, class,
and mode of action of the active substance(s);
3. special tests which might assist in the interpretation of data obtained in
the basic or additional tests.
The studies shall be conducted with the active substance(s), not with the
formulated product. Where studies of the formulated product are required, this is
specified in the text below.
3.1. Single-dose toxicity
Single-dose toxicity studies may be used to predict
-
the possible effects of acute overdosage in the target species,
-
the possible effects of accidental administration to humans,
-
the doses which may usefully be employed in the repeat dose studies.
Single-dose toxicity studies should reveal the acute toxic effects of the substance
and the time course for their onset and remission.
The studies to be carried out shall be selected with a view to providing
information on user safety, e.g. if substantial exposure by inhalation or dermal
contact of the user of the veterinary medicinal product is anticipated, those routes of
exposure shall be studied.
3.2. Repeat-dose toxicity
Repeat-dose toxicity tests are intended to reveal any physiological and/or
pathological changes induced by repeated administration of the active substance or
combination of active substances under examination, and to determine how these
changes are related to dosage.
In the case of pharmacologically active substances or veterinary medicinal
VETERINARY MEDICINAL PRODUCTS
products intended solely for use in non-food-producing animals, a repeat-dose
toxicity study in one species of experimental animal shall normally be sufficient.
This study may be replaced by a study conducted in the target animal. The frequency
and route of administration, and the duration of the study shall be chosen having
regard to the proposed conditions of clinical use. The investigator shall give his
reasons for the extent and duration of the trials and the dosages chosen.
In the case of substances or veterinary medicinal products intended for use in
food-producing animals, repeat-dose (90 day) toxicity testing shall be performed in a
rodent and a non-rodent species in order to identify target organs and toxicological
endpoints and identify the appropriate species and the dose levels to be used in
chronic toxicity testing, if appropriate.
The investigator shall give his reasons for the choice of species, having regard to
the available knowledge of the metabolism of the product in animals and man. The
test substance shall be administered orally. The investigator shall clearly state and
give his reasons for the method and frequency of administration and the length of the
trials.
The maximum dose should normally be selected so as to bring harmful effects to
light. The lowest dose level should not produce any evidence of toxicity.
Evaluation of the toxic effects shall be based on observation of behaviour, growth,
haematology and physiological tests, especially those relating to the excretory
organs, and also on autopsy reports and accompanying histological data. The choice
and range of each group of tests depends on the species of animal used and the state
of scientific knowledge at the time.
In t he c a s e o f n e w co m bi n a t io n s of k no w n s u b s ta nc e s w hi c h ha ve b e e n
investigated in accordance with the provisions of these regulations, the repeat-dose
tests may, except where toxicity tests have demonstrated potentiation or novel toxic
effects, be suitably modified by the investigator, who shall submit his reasons for
such modifications.
3.3. Tolerance in the target species
A summary shall be provided of any signs of intolerance which have been
observed during studies conducted, usually with the final formulation, in the target
species in accordance with the requirements of Part 4, Chapter I, Section B. The
studies concerned, the dosages at which the intolerance occurred and the species and
breeds concerned shall be identified. Details of any unexpected physiological
changes shall also be provided. The full reports of these studies shall be included in
Part 4.
3.4. Reproductive toxicity including developmental toxicity
3.4.1. Study of the effects on reproduction
The purpose of this study is to identify possible impairment of male or female
r e p r o d u c t i v e f u n c t i o n o r h a r m f u l e ff e c t s o n p r o g e n y r e s u l t i n g f r o m t h e
administration of the veterinary medicinal products or substance under investigation.
In the case of pharmacologically active substances or veterinary medicinal
products intended for use in food-producing animals, the study of the effects on
reproduction shall be performed in the form of a multi-generation reproduction
study, designed to detect any effect on mammalian reproduction. These include
effects on male and female fertility, mating, conception, implantation, ability to
maintain pregnancy to term, parturition, lactation, survival, growth and development
of the offspring from birth through to weaning, sexual maturity and the subsequent
reproductive function of the offspring as adults. At least three dose levels shall be
VETERINARY MEDICINAL PRODUCTS
used. The maximum dose should be selected so as to bring harmful effects to light.
The lowest dose level should not produce any evidence of toxicity.
3.4.2. Study of developmental toxicity
In the case of pharmacologically active substances or veterinary medicinal
products intended for use in food-producing animals, tests on developmental toxicity
shall be performed. These tests shall be designed to detect any adverse effects on the
pregnant female and development of the embryo and foetus consequent to exposure
of the female from implantation through gestation to the day before predicted birth.
Such adverse effects include enhanced toxicity relative to that observed in non-
pregnant females, embryo-foetal death, altered foetal growth, and structural changes
to the foetus. A developmental toxicity test in the rat is required. Depending on the
results, a study in a second species may have to be performed, in accordance with
established guidance.
In the case of pharmacologically active substances or veterinary medicinal
products not intended for use in food producing animals, a study of developmental
toxicity shall be performed in at least one species, which may be the target species, if
the product is intended for use in female animals which may be used for breeding.
However, where the use of the veterinary medicinal product would result in
significant exposure to users, standard developmental toxicity studies shall be
performed.
3.5. Genotoxicity
Tests for genotoxic potential shall be performed to reveal changes which a
substance may cause in the genetic material of cells. Any substance intended to be
included in a veterinary medicinal product for the first time must be assessed for
genotoxic properties.
A standard battery of in vitro and in vivo genotoxicity tests in accordance with
established guidance shall usually be carried out on the active substance(s). In some
cases, it may also be necessary to test one or more metabolites that occur as residues
in foodstuffs.
3.6. Carcinogenicity
The decision on whether carcinogenicity testing is required shall take into account
the results of genotoxicity tests, structure-activity relationships and the findings in
systemic toxicity tests that may be relevant to neoplastic lesions in longer term
studies.
Any known species specificity of the mechanism of toxicity shall be considered,
as well as any differences in metabolism between the test species, target animal
species, and human beings.
Where carcinogenicity testing is necessary, generally a two-year rat study and an
18-month mouse study are required. With appropriate scientific justification,
carcinogenicity studies may be carried out in one rodent species, preferably the rat.
3.7. Exceptions
Where a veterinary medicinal product is intended for topical use, systemic
absorption shall be investigated in the target animal species. If it is proved that
systemic absorption is negligible, the repeated dose toxicity tests, the tests for
reproductive toxicity and the carcinogenicity tests may be omitted, unless
-
under the intended conditions of use laid down, oral ingestion of the
veterinary medicinal product by the animal is to be expected, or
VETERINARY MEDICINAL PRODUCTS
-
under the intended conditions of use laid down, exposure of the user of
the veterinary medicinal product by other routes than the dermal route is
to be expected, or
-
the active substance or metabolites may enter foodstuffs obtained from
the treated animal.
4. Other requirements
4.1. Special studies
For particular groups of substances or if the effects observed during repeated dose
studies in animals include changes indicative of e.g. immunotoxicity, neurotoxicity -
or, endocrine dysfunction, further testing shall be required, e.g. sensitisation studies
or delayed neurotoxicity tests. Depending on the nature of the product, it may be
necessary to conduct additional studies to assess the underlying mechanism of the
toxic effect or the irritation potential. Such studies shall usually be conducted with
the final formulation.
The state of scientific knowledge and established guidance shall be taken into
account when designing such studies and evaluating their results.
4.2. Microbiological properties of residues
4.2.1. Potential effects on the human gut flora
The potential microbiological risk presented by residues of antimicrobial
compounds for the human intestinal flora shall be investigated in accordance with
established guidance.
4.2.2. Potential effects on the microorganisms used for industrial food processing
In certain cases, it may be necessary to carry out tests to determine whether
microbiologically active residues may interfere in technological processes in the
industrial processing of foodstuff.
4.3. Observations in humans
Information shall be provided showing whether the pharmacologically active
substances of the veterinary medicinal product are used as medicinal products in
human therapy; if this is so, a compilation shall be made of all the effects observed
(including adverse reactions) in humans and of their cause, to the extent that they
may be important for the assessment of the safety of the veterinary medicinal
product, where appropriate including results from published studies; where
constituents of the veterinary medicinal products are themselves not used or are no
longer used as medicinal products in human therapy, the reasons shall be stated.
4.4. Development of resistance
Data on the potential emergence of resistant bacteria of relevance for human
health are necessary in the case of veterinary medicinal products. The mechanism of
the development of such resistance is particularly important in this regard. Where
necessary, measures to limit resistance development from the intended use of the
veterinary medicinal product shall be proposed.
Resistance relevant for clinical use of the product shall be addressed in accordance
with Part 4. Where relevant, cross reference shall be made to the data set out in Part
4.
5. User safety
This section shall include a discussion of the effects found in the preceding
sections and relate this to the type and extent of human exposure to the product with
a view to formulating appropriate user warnings and other risk management
VETERINARY MEDICINAL PRODUCTS
measures.
6. Environmental risk assessment
6.1. Environmental risk assessment of veterinary medicinal products not
containing or consisting of genetically modified organisms
An environmental risk assessment shall be performed to assess the potential
harmful effects, which the use of the veterinary medicinal product may cause to the
environment and to identify the risk of such effects. The assessment shall also
identify any precautionary measures which may be necessary to reduce such risk.
This assessment shall normally be conducted in two phases. The first phase of the
assessment shall always be performed. The details of the assessment shall be
provided in accordance with accepted guidance. It shall indicate the potential
exposure of the environment to the product and the level of risk associated with any
such exposure taking into account in particular the following items
-
the target animal species, and the proposed pattern of use,
-
the method of administration, in particular the likely extent to which the
product will enter directly into environmental systems,
-
the possible excretion of the product, its active substances or relevant
metabolites into the environment by treated animals; persistence in such
excreta,
-
the disposal of unused veterinary medicinal product or other waste
product.
In the second phase, further specific investigation of the fate and effects of the
product on particular ecosystems shall be conducted, in accordance with established
guidance. The extent of exposure of the product to the environment, and the
available information about the physical/chemical, pharmacological and/or
toxicological properties of the substance(s) concerned, including metabolites in case
of an identified risk, which has been obtained during the conduct of the other tests
and trials required by these regulations, shall be taken into consideration.
6.2. Environmental risk assessment for veterinary medicinal products containing
or consisting of genetically modified organisms.
In the case of a veterinary medicinal product containing or consisting of
genetically modified organisms the application shall also be accompanied by the
documents required under Article 2 and Part C of Directive 2001/18/EC.
CHAPTER II: PRESENTATION OF PARTICULARS AND DOCUMENTS
The dossier of safety tests shall include the following
-
an index of all studies included in the dossier,
-
a statement confirming that all data known by the applicant at the time
of submission, whether favourable or unfavourable, are included,
-
a justification for the omission of any type of study,
-
an explanation of the inclusion of an alternative type of study,
-
a discussion of the contribution that any study that pre-dates studies
performed in line with good laboratory practice (GLP) according to
Directive 2004/10/EC can make to the overall risk assessment.
Each study report shall include
-
a copy of the study plan (protocol),
VETERINARY MEDICINAL PRODUCTS
a statement of compliance with good laboratory practice, where
applicable,
a description of the methods, apparatus and materials used,
a description and justification of the test system,
a description of the results obtained, in sufficient detail to allow the
results to be critically evaluated independently of their interpretation by
the author,
a statistical analysis of the results where appropriate,
a discussion of the results, with comment on observed and no-observed-
effect levels, and on any unusual findings,
a detailed description and a thorough discussion of the results of the
study of the safety profile of the active substance, and its relevance for
the evaluation of potential risks presented by residues to humans.
Residue tests
CHAPTER I: PERFORMANCE OF TESTS
1. Introduction
For the purposes of this Schedule, the definitions of Council Regulation (EEC) No
2377/90 * shall apply.
The purpose of studying the depletion of residues from the edible tissues or of
eggs, milk and honey derived from treated animals is to determine under what
conditions and to what extent residues may persist in foodstuffs produced from these
In addition, the studies shall enable the determination of a withdrawal period.
In the case of veterinary medicinal products intended for use in food-producing
animals, the residue documentation shall show
1. to what extent, and how long, do residues of the veterinary medicinal
product or its metabolites persist in the edible tissues of the treated
animal or in milk, eggs and/or honey obtained therefrom;
2. that in order to prevent any risk to the health of the consumer of
foodstuffs from treated animals, or difficulties in the industrial
processing of foodstuffs, it is possible to establish realistic withdrawal
periods which can be observed under practical farming conditions;
3. that the analytical method(s) used in the residues depletion study are
sufficiently validated to provide the necessary reassurance that the
residues data submitted are suitable as the basis for a withdrawal period.
2. Metabolism and residue kinetics
2.1. Pharmacokinetics (absorption, distribution, metabolism, excretion)
The following characteristics shall be described
specificity,
accuracy,
precision,
limit of detection,
*OJ C 24, 28.1.2004, p. 6.
limit of quantification,
practicability and applicability under normal laboratory conditions,
susceptibility to interference,
stability of incurred residues.
The suitability of the analytical method proposed shall be evaluated in the light of
the state of scientific and technical knowledge at the time the application is
The analytical method shall be presented in an internationally agreed format.
CHAPTER II: PRESENTATION OF PARTICULARS AND DOCUMENTS
1. Identification of the product
An identification of the veterinary medicinal product(s) used in the testing shall be
provided, including
composition,
the physical and chemical (potency and purity) test results for the
relevant batch(es),
batch identification
relationship to the final product,
specific activity and radio-purity of labelled substances,
position of labelled atoms in the molecule.
The dossier of residue tests shall include
an index of all studies included in the dossier,
a statement confirming that all data known by the applicant at the time
of submission, whether favourable or unfavourable, are included,
a justification for the omission of any type of study,
an explanation of the inclusion of an alternative type of study,
a discussion of the contribution that any study that pre-dates GLP can
make to the overall risk assessment,
a withdrawal period proposal.
Each study report shall include
a copy of the study plan (protocol),
a statement of compliance with good laboratory practice, where
applicable,
a description of the methods, apparatus and materials used,
a description of the results obtained, in sufficient detail to allow the
results to be critically evaluated independently of their interpretation by
the author,
a statistical analysis of the results where appropriate,
a discussion of the results,
an objective discussion of the results obtained, and proposals
concerning the withdrawal periods necessary to ensure that no residues
which might constitute a hazard for consumers are present in foodstuffs
obtained from treated animals.
VETERINARY MEDICINAL PRODUCTS
PART 4: PRE-CLINICAL AND CLINICAL TRIAL
The particulars and documents, which shall accompany applications for marketing
authorisations in terms of regulation 12(3)(j) shall be submitted in accordance with
the requirements below.
CHAPTER I: PRE-CLINICAL REQUIREMENTS
Pre-clinical studies are required to establish the pharmacological activity and the
tolerance of the product.
A.
Pharmacology
A.1. Pharmacodynamics
The pharmacodynamic effects of the active substance(s) included in the veterinary
medicinal product shall be characterised.
First, the mechanism of action and the pharmacological effects on which the
recommended application in practice is based shall be adequately described. The
results shall be expressed in quantitative terms (using, for example, dose-effect
curves, time-effect curves, etc.) and, wherever possible, in comparison with a
substance the activity of which is well known. Where a higher efficacy is being
claimed for an active substance, the difference shall be demonstrated and shown to
be statistically significant.
Secondly, an overall pharmacological assessment of the active substance shall be
provided, with special reference to the possibility of secondary pharmacological
effects. In general, the effects on the main body functions shall be investigated.
Any effect of the other characteristics of the products (such as the route of
administration or formulation) on the pharmacological activity of the active
substance shall be investigated.
The investigations shall be intensified where the recommended dose approaches a
dose likely to produce adverse reactions.
The experimental techniques, unless they are standard procedures, shall be
described in such detail as to allow them to be reproduced, and the investigator shall
establish their validity. The experimental results shall be set out clearly and, for
certain types of tests, their statistical significance quoted.
Unless good reasons are given to the contrary, any quantitative modification of
responses resulting from repeated administration of the substance shall also be
investigated.
Fixed combinations may be prompted either on pharmacological grounds or by
clinical indications. In the first case, the pharmacodynamic and/or pharmacokinetic
studies shall demonstrate those interactions, which might make the combination
itself of value in clinical use. In the second case, where scientific justification for the
medicinal combination is sought through clinical experimentation, the investigation
shall determine whether the effects expected from the combination can be
demonstrated in animals and, at least, the importance of any adverse reactions shall
be checked. If a combination includes a new active substance, the latter shall have
been previously studied in depth.
A.2. Development of resistance
Where relevant, data on the potential emergence of resistant organisms of clinical
relevance are necessary for veterinary medicinal products. The mechanism of the
development of such resistance is particularly important in this regard. Measures to
VETERINARY MEDICINAL PRODUCTS
limit resistance development from the intended use of the veterinary medicinal
product shall be proposed by the applicant.
Where relevant, cross reference shall be made to data set out in Part 3.
A.3. Pharmacokinetics
Basic pharmacokinetic data concerning a new active substance are required in the
context of assessment of the clinical safety and efficacy of the veterinary medicinal
product.
The objectives of pharmacokinetic studies in the target animal species can be
divided into three main areas
(i)
descriptive pharmacokinetics leading to the determination of basic
parameters.;
(ii)
use of these parameters to investigate the relationships between dosage
regimen, plasma and tissue concentration over time and
pharmacological, therapeutic or toxic effects;
(iii)
where appropriate, to compare the kinetics between different target
species and to explore possible species differences having an impact on
target animal safety and efficacy of the veterinary medicinal product.
In the target animal species, pharmacokinetic studies are, as a rule, necessary as a
complement to the pharmacodynamic studies to support the establishment of
effective dosage regimens (route and site of administration, dose, dosing interval,
number of administrations, etc.). Additional pharmacokinetic studies may be
required to establish dosage regimens according to certain population variables.
Where pharmacokinetic studies have been submitted under Part 3 cross reference
to such studies may be made.
I n t he c a s e o f ne w co m b in a t i on s o f k n ow n su b s t a n c e s w h ic h h a v e be en
investigated in accordance with the provisions of these regulations, pharmacokinetic
studies of the fixed combination are not required if it can be justified that the
administration of the active substances as a fixed combination does not change their
pharmacokinetic properties.
Appropriate bioavailability studies shall be undertaken to establish
bioequivalence
-
when comparing a reformulated veterinary medicinal product with the
existing one,
-
where necessary for the comparison of a new method or route of
administration with an established one.
B.
Tolerance in the target animal species
The local and systemic tolerance of the veterinary medicinal product shall be
investigated in the target animal species. The purpose of these studies is to
characterise signs of intolerance and to establish an adequate margin of safety using
the recommended route(s) of administration. This may be achieved by increasing the
therapeutic dose and/or the duration of treatment. The report on the trials shall
contain details of all expected pharmacological effects and all adverse reactions.
CHAPTER II: CLINICAL REQUIREMENTS
1. General principles
The purpose of clinical trials is to demonstrate or substantiate the effect of the
veterinary medicinal product after administration at the proposed dosage regimen via
VETERINARY MEDICINAL PRODUCTS
the proposed route of administration and to specify its indications and contra-
indications according to species, age, breed and sex, its directions for use as well as
any adverse reactions which it may have.
Experimental data shall be confirmed by data obtained under normal field
conditions.
Unless justified, clinical trials shall be carried out with control animals (controlled
clinical trials). The efficacy results obtained should be compared with those from the
target animal species that have received a veterinary medicinal product authorised in
the Union for the same indications for use in the same target animal species, or a
placebo or no treatment. All the results obtained, whether positive or negative, shall
be reported.
Established statistical principles shall be used in protocol design, analysis and
evaluation of clinical trials, unless justified.
In the case of a veterinary medicinal product intended primarily for use as a
performance enhancer, particular attention shall be given to
1. the yield of animal produce,
2. the quality of animal produce (organoleptic, nutritional, hygienic and
technological qualities),
3. nutritional efficiency and growth of target animal species,
4. general health status of the target animal species.
2. Conduct of clinical trials
All veterinary clinical trials shall be conducted in accordance with a detailed trial
protocol.
Clinical field trials shall be conducted in accordance with established principles of
good clinical practice, unless otherwise justified.
Before the commencement of any field trial, the informed consent of the owner of
the animals to be used in the trial shall be obtained and documented. In particular,
the animal owner shall be informed in writing of the consequences of participation in
the trial for the subsequent disposal of treated animals or for the taking of foodstuffs
from treated animals. A copy of this notification, countersigned and dated by the
animal owner, shall be included in the trial documentation.
Unless the field trial is conducted with a blind design, the provisions of
regulations 55, 56 and 57 shall apply respectively to the labelling of formulations
intended for use in veterinary field trials. In all cases, the words "for veterinary field
trial use only" shall appear prominently and indelibly upon the labelling.
CHAPTER III: PARTICULARS AND DOCUMENTS
The dossier on efficacy shall include all pre-clinical and clinical documentation
and/or results of trials, whether favourable or unfavourable to the veterinary
medicinal products, in order to enable an objective overall assessment of the risk/
benefit balance of the product.
1. Results of pre-clinical trials
Wherever possible, particulars shall be given of the results of
(a) tests demonstrating pharmacological actions;
(b) tests demonstrating the pharmacodynamic mechanisms underlying the
therapeutic effect;
(c) tests demonstrating the main pharmacokinetic profile;
(d) tests demonstrating target animal safety;
(e) tests investigating resistance.
Should unexpected results occur during the course of the tests, these should be
Additionally, the following particulars shall be provided in all pre-clinical studies
(a) a summary;
(b) a detailed experimental protocol giving a description of the methods,
apparatus and materials used, details such as species, age, weight, sex,
number, breed or strain of animals, identification of animals, dose, route
and schedule of administration;
(c) a statistical analysis of the results, where relevant;
(d) an objective discussion of the results obtained, leading to conclusions
on the efficacy and safety of the veterinary medicinal product.
Total or partial omission of any of these data shall be justified.
2. Results of clinical trials
All the particulars shall be supplied by each of the investigators on individual
record sheets in the case of individual treatment and collective record sheets in the
case of collective treatment.
The particulars supplied shall take the following form
(a) name, address, function and qualifications of investigator in charge;
(b) place and date of treatment; name and address of owner of the animals;
(c) details of the clinical trial protocol giving a description of the methods
used, including methods of randomisation and blinding, details such as
the route of administration, schedule of administration, the dose,
identification of trial animals, species, breeds or strains, age, weight,
sex, physiological status;
(d) method of animal management and feeding, stating the composition of
the feed and the nature and quantity of any feed additives;
(e) case history (as full as possible), including occurrence and course of
any intercurrent diseases;
(f)
diagnosis and means used to make it;
(g) clinical signs, if possible according to conventional criteria;
(h) precise identification of the formulation of the veterinary medicinal
product used in the clinical trial and the physical and chemical test
results for the relevant batch(es);
(i)
dosage of the veterinary medicinal product, method, route and
frequency of administration and precautions, if any, taken during
administration (duration of injection, etc.);
(j)
duration of treatment and period of subsequent observation;
(k) all details concerning other veterinary medicinal products which have
been administered during the period of examination, either prior to or
concurrently with the test product and, in the latter case, details of any
interactions observed;
(l)
all results of the clinical trials, fully describing the results based on the
efficacy criteria and end points specified in the clinical trial protocol
VETERINARY MEDICINAL PRODUCTS
and including the results of the statistical analyses, if appropriate;
(m) all particulars of any unintended event, whether harmful or not, and of
any measures taken in consequence; the cause-and-effect relationship
shall be investigated if possible;
(n) effect on animals’ performance if appropriate;
(o) effects on the quality of foodstuffs obtained from treated animals,
particularly in the case of veterinary medicinal products intended for
use as performance enhancers;
(p) a conclusion on the safety and efficacy in each individual case or,
summarised in terms of frequencies or other appropriate variables where
specific mass treatment is concerned.
Omission of one or more items (a) to (p) shall be justified.
The marketing authorisation holder shall make all necessary arrangements to
ensure that the original documents, which formed the basis of the data supplied, are
kept for at least five years after the veterinary medicinal product is no longer
authorised.
In respect of each clinical trial, the clinical observations shall be summarised in a
synopsis of the trials and the results thereof, indicating in particular
(a) the number of control and test animals treated either individually or
collectively, with a breakdown according to species, breed or strain, age
and sex;
(b) the number of animals withdrawn prematurely from the trials and the
reasons for such withdrawal;
(c) in the case of control animals, whether they have
-
received no treatment, or
-
received a placebo, or
-
received another veterinary medicinal product authorised in the
Union for the same indication for use in the same target animal
species, or
-
received the same active substance under investigation in a
different formulation or by a different route;
(d) the frequency of observed adverse reactions;
(e) observations as to the effect on animal performance, if appropriate;
(f)
details concerning test animals which may be at increased risk owing to
their age, their mode of rearing or feeding, or the purpose for which
they are intended, or animals the physiological or pathological
condition of which requires special consideration;
(g) a statistical evaluation of the results.
Finally, the investigator shall draw general conclusions on the efficacy and safety
of the veterinary medicinal product under the proposed conditions of use, and in
particular any information relating to indications and contraindications, dosage and
average duration of treatment and where, appropriate, any interactions observed with
other veterinary medicinal products or feed additives as well as any special
precautions to be taken during treatment and the clinical symptoms of overdosage,
when observed.
In the case of fixed combination products, the investigator shall also draw
conclusions concerning the safety and the efficacy of the product when compared
VETERINARY MEDICINAL PRODUCTS
with the separate administration of the active substances involved.
TITLE II
REQUIREMENTS FOR IMMUNOLOGICAL VETERINARY MEDICINAL
PRODUCTS
Without prejudice to specific requirements laid down by Union legislation for the
control and eradication of specific infectious animal diseases, the following
requirements shall apply to immunological veterinary medicinal products, except
when the products are intended for use in some species or with specific indications
as defined in Title III and in relevant guidelines.
PART 1: SUMMARY OF THE DOSSIER
A.
ADMINISTRATIVE INFORMATION
The immunological veterinary medicinal product, which is the subject of the
application, shall be identified by name and by name of the active substance(s),
together with the biological activity, potency or titre, the pharmaceutical form, the
route and method if appropriate of administration and a description of the final
presentation of the product, including packaging, labelling and leaflet. Diluents may
be packed together with the vaccine vials or separately.
Information on diluents needed for making the final vaccine preparation shall be
included in the dossier. An immunological veterinary medicinal product is regarded
as one product even when more than one diluent is required so that different
preparations of the final product can be prepared, which may be for administration
by different routes or methods of administration.
The name and address of the applicant shall be given, together with the name and
address of the manufacturer and the sites involved in the different stages of
manufacture and control (including the manufacturer of the finished product and the
manufacturer(s) of the active substance(s)) and where relevant the name and address
of the importer.
The applicant shall identify the number and titles of volumes of documentation
submitted in support of the application and indicate what samples, if any, are also
provided.
Annexed to the administrative information shall be copies of a document showing
that the manufacturer is authorised to produce immunological veterinary medicinal
products, as defined in regulation 38 of these regulations. Moreover, the list of
organisms handled at the production site shall be given.
The applicant shall submit a list of countries in which authorisation has been
granted, and a list of countries in which an application has been submitted or
refused.
B.
SUMMARY OF PRODUCT CHARACTERISTICS, LABELLING AND
PACKAGE LEAFLET
The applicant shall propose a summary of the product characteristics, in
accordance with regulation 14.
A proposed labelling text for the immediate and outer packaging shall be provided
in accordance with Title V of these regulations, together with a package leaflet
where one is required pursuant to regulation 51. In addition the applicant shall
provide one or more specimens or mock-ups of the final presentation(s) of the
veterinary medicinal product in at least one of the official languages of the European
Union; the mock-up may be provided in black and white and electronically where
prior agreement from the competent authority has been obtained.
VETERINARY MEDICINAL PRODUCTS
C.
DETAILED AND CRITICAL SUMMARIES
Each detailed and critical summary referred to in regulation 12(3)(l) shall be
prepared in the light of the state of scientific knowledge at the time of submission of
the application. It shall contain an evaluation of the various tests and trials, which
constitute the marketing authorisation dossier and shall address all points relevant to
the assessment of the quality, safety and efficacy of the immunological veterinary
medicinal product. It shall give the detailed results of the tests and trials submitted
and precise bibliographic references.
All important data shall be summarised in an appendix to the detailed and critical
summaries, whenever possible in tabular or graphic form. The detailed and critical
summaries shall contain precise cross references to the information contained in the
main documentation.
The detailed and critical summaries shall be signed and dated, and information
about the author’s educational background, training and occupational experience
shall be attached. The professional relationship of the author with the applicant shall
be declared.
MICROBIOLOGICAL INFORMATION (QUALITY)
All test procedures shall fulfil the necessary criteria for analysis and control of the
quality of the starting materials and the finished product and shall be validated
procedures. The results of the validation studies shall be provided. Any special
apparatus and equipment which may be used shall be described in adequate detail,
possibly accompanied by a diagram. The formulae of the laboratory reagents shall be
supplemented, if necessary, by the manufacturing method.
In the case of test procedures included in the European Pharmacopoeia or the
pharmacopoeia of Malta, this description may be replaced by a detailed reference to
the pharmacopoeia in question.
Where available, chemical and biological reference material of the European
Pharmacopoeia shall be used. If other reference preparations and standards are used,
they shall be identified and described in detail.
A.
QUALITATIVE
AND
QUANTITATIVE
PARTICULARS
OF
THE
CONSTITUENTS
1. Qualitative particulars
"Qualitative particulars" of all the constituents of the immunological veterinary
medicinal product shall mean the designation or description of
-
the active substance(s),
-
the constituents of the adjuvants,
-
the constituent(s) of the excipients, whatever their nature or the quantity
used, including preservatives, stabilisers, emulsifiers, colouring matter,
flavouring, aromatic substances, markers, etc.,
-
the constituents of the pharmaceutical form administered to animals.
These particulars shall be supplemented by any relevant data concerning the
container and, where appropriate, its manner of closure, together with details of
devices with which the immunological veterinary medicinal product will be used or
administered and which will be delivered with the medicinal product. If the device is
not delivered together with the immunological veterinary medicinal product,
relevant information about the device shall be provided, where necessary for the
assessment of the product.
2. "Usual terminology"
The "usual terminology", to be used in describing the constituents of
immunological veterinary medicinal products, shall mean, notwithstanding the
application of the other provisions of regulation 12(3)(c)
in respect of substances which appear in the European Pharmacopoeia
or, failing this, in the pharmacopoeia of one of the Member States, the
main title of the monograph in question, which will be obligatory for all
such substances, with reference to the pharmacopoeia concerned,
in respect of other substances, the international non-proprietary name
recommended by the World Health Organisation, which may be
accompanied by another non-proprietary name or, failing these, the
exact scientific designation; substances not having an international non-
proprietary name or an exact scientific designation shall be described by
a statement of how and from what they were prepared, supplemented,
where appropriate, by any other relevant details,
in respect of colouring matter, designation by the "E" code assigned to
them in Directive 78/25/EEC.
3. Quantitative particulars
In order to give the "quantitative particulars" of the active substances of an
immunological veterinary medicinal product, it is necessary to specify whenever
possible the number of organisms, the specific protein content, the mass, the number
of International Units (IU) or units of biological activity, either per dosage-unit or
volume, and with regard to the adjuvant and to the constituents of the excipients, the
mass or the volume of each of them, with due allowance for the details provided in
Where an international unit of biological activity has been defined, this shall be
The units of biological activity for which no published data exist shall be
expressed in such a way as to provide unambiguous information on the activity of
the ingredients, e.g. by stating the immunological effect on which the method of
determining the dose is based.
4. Product development
An explanation shall be provided with regard to the composition, components and
containers, supported by scientific data on product development. The overage, with
justification thereof, shall be stated.
DESCRIPTION OF MANUFACTURING METHOD
The description of the manufacturing method accompanying the application for
marketing authorisation pursuant to regulation 12(3), shall be drafted in such a way
as to give an adequate description of the nature of the operations employed.
For this purpose the description shall include at least
the various stages of manufacture (including production of the antigen
and purification procedures) so that an assessment can be made of the
reproducibility of the manufacturing procedure and of the risks of
adverse effects on the finished products, such as microbiological
contamination; the validation of key stages in the production process
shall be demonstrated and the validation of the production process as a
whole shall be demonstrated with provision of results of three
consecutive batches produced using the method described,
VETERINARY MEDICINAL PRODUCTS
-
in the case of continuous manufacture, full details concerning
precautions taken to ensure the homogeneity and consistency of each
batch of the finished product,
-
listing of all the substances at the appropriate steps where they are used,
including those which cannot be recovered in the course of
manufacturing,
-
the details of the blending, with the quantitative particulars of all the
substances used,
-
a statement of the stages of manufacture at which sampling is carried
out for control tests during production.
C.
PRODUCTION AND CONTROL OF STARTING MATERIALS
For the purposes of this paragraph "starting materials" means all components used
in the production of the immunological veterinary medicinal product. Culture media
consisting of several components used for production of the active substance shall be
regarded as one starting material. Nevertheless, the qualitative and quantitative
composition of the any culture media shall be presented in so far as the authorities
consider that this information is relevant to the quality of the finished product and
any risks that might be posed. If materials of animal origin are used for preparation
of these culture media, the animal species and the tissue used have to be included.
The dossier shall include the specifications, information on the tests to be
conducted for the quality control of all batches of starting materials and results for a
batch for all components used and shall be submitted in accordance with the
following provisions.
1. Starting materials listed in pharmacopoeias
The monographs of the European Pharmacopoeia shall be applicable to all starting
materials appearing in it.
In respect of other substances, each Member State may require observance of its
own national pharmacopoeia with regard to products manufactured in its territory.
Constituents fulfilling the requirements of the European Pharmacopoeia or the
pharmacopoeia of one of the Member States shall be deemed to comply sufficiently
with regulation 12(3) hereof. In this case the description of the analytical methods
may be replaced by a detailed reference to the pharmacopoeia in question.
Colouring matter shall, in all cases, satisfy the requirements of Directive 78/25/
EEC.
The routine tests carried out on each batch of starting materials must be as stated
in the application for marketing authorisation. If tests other than those mentioned in
the pharmacopoeia are used, proof must be supplied that the starting materials meet
the quality requirements of that pharmacopoeia.
In cases where a specification or other provisions contained in a monograph of the
European Pharmacopoeia or in the pharmacopoeia of Malta might be insufficient to
ensure the quality of the substance, the competent authorities may request more
appropriate specifications from the applicant for marketing authorisation. The
alleged insufficiency shall be reported to the authorities responsible for the
pharmacopoeia in question.
I n ca se s w h e r e a st a r t i n g m a te r i a l i s d e s c r i b e d n e it h e r i n t h e E u r o p e a n
Pharmacopoeia nor in the pharmacopoeia of Malta, compliance with the monograph
of a third country pharmacopoeia can be accepted; in such cases, the applicant shall
submit a copy of the monograph accompanied where necessary by the validation of
VETERINARY MEDICINAL PRODUCTS
the test procedures contained in the monograph and by a translation where
appropriate.
When starting materials of animal origin are used, they shall comply with the
relevant monographs including general monographs and general chapters of the
European Pharmacopoeia. The tests and controls conducted shall be appropriate to
the starting material.
The applicant shall supply documentation to demonstrate that the starting
materials and the manufacturing of the veterinary medical product is in comply with
the requirements of the Note for Guidance on minimising the risk of transmitting
animal spongiform encephalopathy agents via human and veterinary medicinal
products, as well as with the requirements of the corresponding monograph of the
European Pharmacopoeia. Certificates of Suitability issued by the European
Directorate for the Quality of Medicines and HealthCare, with reference to the
relevant monograph of the European Pharmacopoeia, may be used to demonstrate
compliance.
2. Starting materials not listed in a pharmacopoeia
2.1. Starting materials of biological origin
The description shall be given in the form of a monograph.
Whenever possible, vaccine production shall be based on a seed lot system and on
established cell seeds. For the production of immunological veterinary medicinal
products consisting of serums, the origin, general health and immunological status of
the producing animals shall be indicated and defined pools of source materials shall
be used.
The origin, including geographical region, and history of starting materials shall
be described and documented. For genetically engineered starting materials this
information shall include details such as the description of the starting cells or
strains, the construction of the expression vector (name, origin, function of the
replicon, promoter enhancer and other regulator elements), control of the sequence
of DNA or RNA effectively inserted, oligonucleotidic sequences of plasmid vector
in cells, plasmid used for cotransfection, added or deleted genes, biological
properties of the final construct and the genes expressed, copy number and genetic
stability.
Seed materials, including cell seeds and raw serum for anti-serum production shall
be tested for identity and extraneous agents.
Information shall be provided on all substances of biological origin used at any
stage in the manufacturing procedure. The information shall include
-
details of the source of the materials,
-
details of any processing, purification and inactivation applied, with
data on the validation of these process and controls during production,
-
details of any tests for contamination carried out on each batch of the
substance.
If the presence of extraneous agents is detected or suspected, the corresponding
material shall be discarded or used in very exceptional circumstances only when
further processing of the product ensures their elimination and/or inactivation;
elimination and/or inactivation of such extraneous agents shall be demonstrated.
When cell seeds are used, the cell characteristics shall be shown to have remained
unchanged up to the highest passage level used for the production.
For live attenuated vaccines, proof of the stability of the attenuation
VETERINARY MEDICINAL PRODUCTS
characteristics of the seed has to be given.
Documentation shall be supplied to demonstrate that the seed materials, cell seeds,
batches of serum and other material originating from animal species relevant for the
transmission of TSE comply with the Note for Guidance on minimising the risk of
transmitting animal spongiform encephalopathy agents via human and veterinary
medicinal products, as well as with the corresponding monograph of the European
Pharmacopoeia. Certificates of Suitability issued by the European Directorate for the
Quality of Medicines and HealthCare, with reference to the relevant monograph of
the European Pharmacopoeia, can be used to demonstrate compliance.
When required, samples of the biological starting material or reagents used in the
testing procedures shall be provided to enable the competent authority to arrange for
check tests to be carried out.
2.2. Starting materials of non-biological origin
The description shall be given in the form of a monograph under the following
headings
-
the name of the starting material meeting the requirements of point 2 of
Section A shall be supplemented by any trade or scientific synonyms,
-
the description of the starting material, set down in a form similar to
that used in a descriptive item in the European Pharmacopoeia,
-
the function of the starting material,
-
methods of identification,
-
any special precautions which may be necessary during storage of the
starting material and, if necessary, its storage life shall be given.
D.
CONTROL TESTS DURING THE MANUFACTURING PROCESS
1. The dossier shall include particulars relating to the control tests, which are
carried out on intermediate products with a view to verifying the consistency of the
manufacturing process and the final product.
2. For inactivated or detoxified vaccines, inactivation or detoxification shall be
tested during each production run as soon as possible after the end of the inactivation
or detoxification process and after neutralisation if this occurs, but before the next
step of production.
E.
CONTROL TESTS ON THE FINISHED PRODUCT
For all tests, the description of the techniques for analysing the finished product
shall be set out in sufficiently precise detail for quality assessment.
The dossier shall include particulars relating to control tests on the finished
product. Where appropriate monographs exist, if test procedures and limits other
than those mentioned in the monographs of the European Pharmacopoeia, or failing
this, in the pharmacopoeia of Malta, are used, proof must be supplied that the
finished product would, if tested in accordance with those monographs, meet the
quality requirements of that pharmacopoeia for the pharmaceutical form concerned.
The application for marketing authorisation shall list those tests, which are carried
out on representative samples of each batch of finished product. The frequency of
the tests, which are not carried out on each batch, shall be stated. Release limits shall
be indicated.
Where available, chemical and biological reference material of the European
Pharmacopoeia shall be used. If other reference preparations and standards are used,
they shall be identified and described in detail.
VETERINARY MEDICINAL PRODUCTS
1. General characteristics of the finished product
The tests of general characteristics shall, wherever applicable, relate to the control
of average masses and maximum deviations, to mechanical, physical or chemical
tests, physical characteristics such as density, pH, viscosity, etc. For each of these
characteristics, specifications, with appropriate confidence limits, shall be
established by the applicant in each particular case.
2. Identification of active substance(s)
Where necessary, a specific test for identification shall be carried out.
3. Batch titre or potency
A quantification of the active substance shall be carried out on each batch to show
that each batch will contain the appropriate potency or titre to ensure its safety and
efficacy.
4. Identification and assay of adjuvants
Insofar as testing procedures are available, the quantity and nature of the adjuvant
and its components shall be verified on the finished product.
5. Identification and assay of excipient components
Insofar as is necessary, the excipient(s) shall be subject at least to identification
tests.
An upper and lower limit test shall be obligatory in respect of preserving agents.
An upper limit test for any other excipient components liable to give rise to an
adverse reaction shall be obligatory.
6. Safety tests
Apart from the results of tests submitted in accordance with Part 3 of this Title
(Safety Tests), particulars of the batch safety tests shall be submitted. These tests
shall preferably be overdosage studies carried out in at least one of the most
sensitive target species and by at least the recommended route of administration
posing the greatest risk. Routine application of the batch safety test may be waived
in the interests of animal welfare when a sufficient number of consecutive
production batches have been produced and been found to comply with the test.
7. Sterility and purity test
Appropriate tests to demonstrate the absence of contamination by extraneous
agents or other substances shall be carried out according to the nature of the
immunological veterinary medicinal product, the method and the conditions of
manufacture. If fewer tests than required by the relevant European Pharmacopoeia
are routinely employed for each batch, the tests carried out shall be critical to the
compliance with the monograph. Proof must be supplied that the immunological
veterinary medicinal product would meet the requirements, if fully tested according
to the monograph.
8. Residual humidity
Each batch of lyophilised product shall be tested for residual humidity.
9. Inactivation
For inactivated vaccines, a test to verify inactivation shall be carried out on the
product in the final container unless it has been conducted at a late stage in-process.
F.
BATCH-TO-BATCH CONSISTENCY
In order to ensure that quality of the product is consistent from batch to batch and
VETERINARY MEDICINAL PRODUCTS
to demonstrate conformity with specifications a full protocol of three consecutive
batches giving the results for all tests performed during production and on the
finished product shall be provided.
G.
STABILITY TESTS
The particulars and documents accompanying the application for marketing
authorisation pursuant to regulation 12(3) hereof shall be submitted in accordance
with the following requirements.
A description shall be given of the tests undertaken to support the shelf life
proposed by the applicant. These tests shall always be real-time studies; they shall be
carried out on a sufficient number of batches produced according to the described
production process and on products stored in the final container(s); these tests
include biological and physico-chemical stability tests.
The conclusions shall contain the results of analyses, justifying the proposed shelf
life under all proposed storage conditions.
In the case of products administered in feed, information shall also be given as
necessary on the shelf life of the product, at the different stages of mixing, when
mixed in accordance with the recommended instructions.
Where a finished product requires reconstitution prior to administration or is
administered in drinking water, details of the proposed shelf life are required for the
product reconstituted as recommended. Data in support of the proposed shelf life for
the reconstituted product shall be submitted.
Stability data obtained from combined products may be used as preliminary data
for derivative products containing one or more of the same components.
The proposed in-use shelf life shall be justified.
The efficacy of any preservative system shall be demonstrated.
Information on the efficacy of preservatives in other similar immunological
veterinary medicinal products from the same manufacturer may be sufficient.
H.
OTHER INFORMATION
Information relating to the quality of the immunological veterinary medicinal
product not covered by the previous sections may be included in the dossier.
PART 3: SAFETY TESTS
A.
INTRODUCTION AND GENERAL REQUIREMENTS
The safety tests shall show the potential risks from the immunological veterinary
medicinal product, which may occur under the proposed conditions of use in
animals: these shall be evaluated in relation to the potential benefits of the product.
Where immunological veterinary medicinal products consist of live organisms,
especially those, which could be shed by vaccinated animals, the potential risk to
unvaccinated animals of the same or of any other potentially exposed species shall
be evaluated.
The safety studies shall be carried out in the target species. The dose to be used
shall be the quantity of the product to be recommended for use and the batch used for
safety testing shall be taken from a batch or batches produced according to the
manufacturing process described in Part 2 of the application.
In the case of an immunological veterinary medicinal products containing a live
organism, the dose to be used in the laboratory tests described in Sections B.1 and
B.2 shall be the quantity of the product containing the maximum titre. If necessary
VETERINARY MEDICINAL PRODUCTS
the concentration of the antigen may be adjusted to achieve the required dose. For
inactivated vaccines the dose to be used shall be that quantity recommended for use
containing the maximum antigen content unless justified.
The safety documentation shall be used for assessment of the potential risks which
may result from the exposure of human beings to the veterinary medicinal product,
for example during its administration to the animal.
B.
LABORATORY TESTS
1. Safety of the administration of one dose
The immunological veterinary medicinal product shall be administered at the
recommended dose and by each recommended route of administration to animals of
each species and category in which it is intended for use, including animals of the
minimum age of administration. The animals shall be observed and examined for
signs of systemic and local reactions. Where appropriate, these studies shall include
detailed post-mortem macroscopic and microscopic examinations of the injection
site. Other objective criteria shall be recorded, such as rectal temperature and
performance measurements.
The animals shall be observed and examined until reactions may no longer be
expected, but in all cases, the observation and examination period shall be at least 14
days after administration.
This study may be part of the repeated dose study required under point 3 or
omitted if the results of the overdose study required under point 2 have revealed no
signs of systemic or local reactions.
2. Safety of one administration of an overdose
Only live immunological veterinary medicinal products require overdose testing.
An overdose of the immunological veterinary medicinal product shall be
administered by each recommended route(s) of administration to animals of the most
sensitive categories of the target species, unless the selection of the most sensitive of
several similar routes is justified. In the case of immunological veterinary medicinal
products administered by injection, the doses and route(s) of administration shall be
chosen to take account of the maximum volume, which can be administered at any
one single injection site. The animals shall be observed and examined for at least 14
days after administration for signs of systemic and local reactions. Other criteria
shall be recorded, such as rectal temperature and performance measurements.
Where appropriate, these studies shall include detailed post-mortem macroscopic
and microscopic examinations of the injection site if this has not been done under
point 1.
3. Safety of the repeated administration of one dose
In the case of immunological veterinary medicinal products to be administered
more than once, as part of the basic vaccination scheme, a study of the repeated
administration of one dose shall be required to reveal any adverse effects induced by
such administration. These tests shall be carried out on the most sensitive categories
of the target species (such as certain breeds, age groups), using each recommended
route of administration.
The animals shall be observed and examined for at least 14 days after the last
administration for signs of systemic and local reactions. Other objective criteria
shall be recorded, such as rectal temperature and performance measurements.
4. Examination of reproductive performance
VETERINARY MEDICINAL PRODUCTS
Examination of reproductive performance shall be considered when data suggest
that the starting material from which the product is derived may be a potential risk
factor.
Reproductive performance of males and non-pregnant and pregnant females shall
be investigated with the recommended dose and by the most sensitive route of
administration. In addition, harmful effects on the progeny, as well as teratogenic
and abortifacient effects, shall be investigated.
These studies may form part of the safety studies described in points 1, 2, 3 or of
the field studies provided for in Section C.
5. Examination of immunological functions
Where the immunological veterinary medicinal product might adversely affect the
immune response of the vaccinated animal or of its progeny, suitable tests on the
immunological functions shall be carried out.
6. Special requirements for live vaccines
6.1. Spread of the vaccine strain
Spread of the vaccine strain from vaccinated to unvaccinated target animals shall
be investigated, using the recommended route of administration most likely to result
in the spread. Moreover, it may be necessary to investigate the spread to non-target
animal species which could be highly susceptible to a live vaccine strain.
6.2. Dissemination in the vaccinated animal
Faeces, urine, milk, eggs, oral, nasal and other secretions shall be tested for the
presence of the organism as appropriate. Moreover, studies may be required of the
dissemination of the vaccine strain in the body, with particular attention being paid
to the predilection sites for replication of the organism. In the case of live vaccines
for zoonoses within the meaning of Directive 2003/99/EC of the European
Parliament and of the Council * to be used for food producing animals, these studies
must shall take particularly into account the persistence of the organism at the
injection site.
6.3. Reversion to virulence of attenuated vaccines
Reversion to virulence shall be investigated with the master seed. If the master
seed is not available in sufficient quantity the lowest passage seed used for the
production shall be examined. Use of another passage option shall be justified. The
initial vaccination shall be carried out using the route of administration most likely
to lead to reversion to virulence. Serial passages shall be made in target animals
through five groups of animals, unless there is justification to make more passages
or the organism disappears from the test animals sooner. Where the organism fails to
replicate adequately, as many passages as possible shall be carried out in the target
species.
6.4. Biological properties of the vaccine strain
Other tests may be necessary to determine as precisely as possible the intrinsic
biological properties of the vaccine strain (e.g. neurotropism).
6.5. Recombination or genomic reassortment of strains
The probability of recombination or genomic reassortment with field or other
strains shall be discussed.
7. User safety
* OJ L 325, 12.12.2003, p. 31.
VETERINARY MEDICINAL PRODUCTS
This section shall include a discussion of the effects found in the preceding
sections, which shall relate those effects to the type and extent of human exposure to
the product with a view to formulating appropriate user warnings and other risk
management measures.
8. Study of residues
For immunological veterinary medicinal products, it will normally not be
necessary to undertake a study of residues. However, where adjuvants and/or
preservatives are used in the manufacture of immunological veterinary medicinal
products, consideration shall be given to the possibility of any residue remaining in
the foodstuffs. If necessary, the effects of such residues shall be investigated.
A proposal for a withdrawal period shall be made and its adequacy shall be
discussed in relation to any residue studies which have been undertaken.
9. Interactions
If there is a compatibility statement with other veterinary immunological products
in the summary of product characteristics the safety of the association shall be
investigated. Any other known interactions with veterinary medicinal products shall
be described.
C.
FIELD STUDIES
Unless justified, results from laboratory studies shall be supplemented with data
from field studies, using batches according to the manufacturing process described
in the marketing authorisation application. Both safety and efficacy may be
investigated in the same field studies.
D.
ENVIRONMENTAL RISK ASSESSMENT
The purpose of the environmental risk assessment is to assess the potential
harmful effects, which the use of the product may cause to the environment and to
identify any precautionary measures, which may be necessary to reduce such risks.
This assessment shall normally be conducted in two phases. The first phase of the
assessment shall always be performed. The details of the assessment shall be
provided in accordance with established guidance. It shall indicate the potential
exposure of the environment to the product and the level of risk associated with any
such exposure, taking into account in particular the following items
-
the target animal species and the proposed pattern of use,
-
the method of administration, in particular the likely extent to which the
product will enter directly into the environmental system,
-
the possible excretion of the product, its active substances into the
environment by treated animals, persistence in such excreta,
-
the disposal of unused or waste product.
In the case of live vaccine strains which may be zoonotic, the risk to humans shall
be assessed.
Where the conclusions of the first phase indicate potential exposure of the
environment to the product, the applicant shall proceed to the second phase and
evaluate the potential risk(s) that the veterinary medicinal product might pose to the
environment. Where necessary, further investigations on the impact of the product
(soil, water, air, aquatic systems, non-target organisms) shall be carried out.
E.
ASSESSMENT
REQUIRED
FOR
VETERINARY
MEDICINAL
PRODUCTS CONTAINING OR CONSISTING OF GENETICALLY MODIFIED
ORGANISMS
VETERINARY MEDICINAL PRODUCTS
In the case of veterinary medicinal products containing or consisting of
genetically modified organisms the application shall also be accompanied by the
documents required under Article 2 and Part C of Directive 2001/18/EC.
PART 4: EFFICACY TESTS
CHAPTER I
1. General principles
The purpose of the trials described in this Part is to demonstrate or to confirm the
efficacy of the immunological veterinary medicinal product. All claims made by the
applicant with regard to the properties, effects and use of the product, shall be fully
supported by results of specific trials contained in the application for marketing
authorisation.
2. Performance of trials
All efficacy trials shall be conducted in accordance with a fully considered
detailed protocol, which shall be recorded in writing prior to commencement of the
trial. The welfare of the trial animals shall be subject to veterinary supervision and
shall be taken fully into consideration during the elaboration of any trial protocol
and throughout the conduct of the trial.
Pre-established systematic written procedures for the organisation, conduct, data
collection, documentation and verification of efficacy trials shall be required.
Field trials shall be conducted in accordance with established principles of good
clinical practice, unless otherwise justified.
Before the commencement of any field trial, the informed consent of the owner of
the animals to be used in the trial shall be obtained and documented. In particular,
the animal owner shall be informed in writing of the consequences of participation in
the trial for the subsequent disposal of treated animals or for the taking of foodstuffs
from treated animals. A copy of this notification, countersigned and dated by the
animal owner, shall be included in the trial documentation.
Unless the field trial is conducted with a blind design, the provisions of
regulations 55, 56 and 57 shall apply by analogy to the labelling of formulations
intended for use in veterinary field trials. In all cases, the words "for veterinary field
trial use only" shall appear prominently and indelibly upon the labelling.
CHAPTER II
A.
General requirements
1. The choice of antigens or vaccine strains shall be justified on the basis of
epizoological data.
2. Efficacy trials carried out in the laboratory shall be controlled trials,
including untreated control animals unless this is not justified for animal welfare
reasons and efficacy can be otherwise demonstrated.
In general, these laboratory trials shall be supported by trials carried out in field
conditions, including untreated control animals.
All trials shall be described in sufficiently precise details so as to be reproducible
in controlled trials, carried out at the request of the competent authorities. The
investigator shall demonstrate the validity of all the techniques involved.
All results obtained, whether favourable or unfavourable, shall be reported.
3. The efficacy of an immunological veterinary medicinal product shall be
demonstrated for each category of target animal species recommended for
VETERINARY MEDICINAL PRODUCTS
vaccination, by each recommended route of administration and using the proposed
schedule of administration. The influence of passively acquired and maternally
derived antibodies on the efficacy of a vaccine shall be adequately evaluated, if
appropriate. Unless justified, the onset and duration of immunity shall be established
and supported by data from trials.
4. The efficacy of each of the components of multivalent and combined
immunological veterinary medicinal products shall be demonstrated. If the product
is recommended for administration in combination with or at the same time as
another veterinary medicinal product, they shall be shown to be compatible.
5. Whenever a product forms part of a vaccination scheme recommended by
the applicant, the priming or booster effect or the contribution of the veterinary
i m m u n o l o g i c a l p r o d u c t t o t h e e ff i c a c y o f t h e s c h e m e a s a w h o l e s h a l l b e
demonstrated.
6. The dose to be used shall be the quantity of the product to be recommended
for use and the batch used for efficacy testing shall be taken from a batch or batches
produced according to the manufacturing process described in Part 2 of the
application.
7. If there is a compatibility statement with other immunological products in
the summary of product characteristics, the efficacy of the association shall be
investigated. Any other known interactions with any other veterinary medicinal
products shall be described. Concurrent or simultaneous use may be allowed if
supported by appropriate studies.
8. For diagnostic immunological veterinary medicinal products administered to
animals, the applicant shall indicate how reactions to the product are to be
interpreted.
9. For vaccines intended to allow a distinction between vaccinated and infected
animals (marker vaccines), where the efficacy claim is reliant on in vitro diagnostic
tests, sufficient data on the diagnostic tests shall be provided to allow adequate
assessment of the claims related to the marker properties.
B.
Laboratory trials
1. In principle, demonstration of efficacy shall be undertaken under well-
c o n t r o l l e d l a b o r a t o r y c o n d i t i o n s b y c h a l l e n g e a f t e r ad m i n i s t r a ti o n o f t h e
immunological veterinary medicinal product to the target animal under the
recommended conditions of use. Insofar as possible, the conditions under which the
challenge is carried out shall mimic the natural conditions for infection. Details of
the challenge strain and its relevance shall be provided.
For live vaccines, batches containing the minimum titre or potency shall be used
unless justified. For other products, batches containing the minimum active content
shall be used unless otherwise justified.
2. If possible, the immune mechanism (cell-mediated/humoral, local/general
classes of immunoglobulin) which is initiated after the administration of the
immunological veterinary medicinal product to target animals by the recommended
route of administration shall be specified and documented.
C.
Field trials
1. Unless justified, results from laboratory trials shall be supplemented with
data from field trials, using batches representative of the manufacturing process
described in the marketing authorisation application. Both safety and efficacy may
be investigated in the same field study.
VETERINARY MEDICINAL PRODUCTS
2. Where laboratory trials cannot be supportive of efficacy, the performance of
field trials alone may be acceptable.
PART 5: PARTICULARS AND DOCUMENTS
INTRODUCTION
The dossier of the safety and efficacy studies shall include an introduction
defining the subject and indicating the tests which have been carried out in
compliance with Parts 3 and 4 as well as a summary, with detailed references to the
published literature. This summary shall contain an objective discussion of all the
results obtained and lead to a conclusion on the safety and efficacy of the
immunological veterinary medicinal product. Omission of any tests or trials listed
shall be indicated and discussed.
LABORATORY STUDIES
The following shall be provided for all studies
1. a summary;
2. the name of the body having carried out the studies;
3. a detailed experimental protocol giving a description of the methods,
apparatus and materials used, details such as species or breed of
animals, categories of animals, where they were obtained, their
identification and number, the conditions under which they were housed
and fed (stating, inter alia, whether they were free from any specified
pathogens and/or specified antibodies, the nature and quantity of any
additives contained in the feed), dose, route, schedule and dates of
administration, a description and a justification of the statistical
methods used;
4. in the case of control animals, whether they received a placebo or no
treatment;
5. in the case of treated animals and where appropriate, whether they
received the test product or another product authorised in the Union;
6. all general and individual observations and results obtained (with
averages and standard deviations), whether favourable or unfavourable.
The data shall be described in sufficient detail to allow the results to be
critically evaluated independently of their interpretation by the author.
The raw data shall be presented in tabular form. By way of explanation
and illustration, the results may be accompanied by reproductions of
recordings, photomicrographs, etc;
7. the nature, frequency and duration of observed adverse reactions;
8. the number of animals withdrawn prematurely from the studies and
reasons for such withdrawal;
9. a statistical analysis of the results, where such is called for by the test
programme, and variance within the data;
10. occurrence and course of any intercurrent disease;
11. all details concerning veterinary medicinal products (other than the
product under study), the administration of which was necessary during
the course of the study;
12. an objective discussion of the results obtained, leading to conclusions
on the safety and efficacy of the product.
FIELD STUDIES
Particulars concerning field studies shall be sufficiently detailed to enable an
objective judgement to be made. They shall include the following
1. a summary;
2. name, address, function and qualifications of the investigator in charge;
3. place and date of administration, identity code that can be linked to the
name and address of the owner of the animal(s);
4. details of the trial protocol, giving a description of the methods,
apparatus and materials used, details such as the route of administration,
the schedule of administration, the dose, the categories of animals, the
duration of observation, the serological response and other
investigations carried out on the animals after administration;
5. in the case of control animals, whether they received a placebo or no
treatment;
6. identification of the treated and control animals (collective or
individual, as appropriate), such as species, breeds or strains, age,
weight, sex, physiological status;
7. a brief description of the method of rearing and feeding, stating the
nature and quantity of any additives contained in the feed;
8. all the particulars on observations, performances and results (with
averages and standard deviation); individual data shall be indicated
when tests and measurements on individuals have been carried out;
9. all observations and results of the studies, whether favourable or
unfavourable, with a full statement of the observations and the results of
the objective tests of activity required to evaluate the product; the
techniques used must be specified and the significance of any variations
in the results explained;
10. effects on the animals’ performance;
11. the number of animals withdrawn prematurely from the studies and
reasons for such withdrawal;
12. the nature, frequency and duration of observed adverse reactions;
13. occurrence and course of any intercurrent disease;
14. all details concerning veterinary medicinal products (other than the
product under study) which have been administered either prior to or
concurrently with the test product or during the observation period;
details of any interactions observed;
15. an objective discussion of the results obtained, leading to conclusions
on the safety and efficacy of the product.
PART 6: BIBLIOGRAPHICAL REFERENCES
The bibliographical references cited in the summary mentioned under Part 1 shall
be listed in detail and copies shall be provided.
TITLE III
APPLICATIONS
1. Generic veterinary medicinal products
VETERINARY MEDICINAL PRODUCTS
Applications based on regulation 13 hereof (generic veterinary medicinal
products) shall contain the data referred to in Parts 1 and 2 of Title I of this Schedule
together with an environmental risk assessment and data demonstrating that the
product has the same qualitative and quantitative composition in active substances
and the same pharmaceutical form as the reference medicinal product and data
showing bio-equivalence with the reference medicinal product. If the reference
veterinary medicinal product is a biological medicinal product, the documentation
requirements in Section 2 for similar biological veterinary medicinal products shall
be fulfilled.
For generic veterinary medicinal products the detailed and critical summaries on
safety and efficacy shall particularly focus on the following elements
the grounds for claiming essential similarity,
a summary of impurities present in batches of the active substance(s) as
well as those of the finished medicinal product (and where relevant
decomposition products arising during storage) as proposed for use in
the product to be marketed together with an evaluation of these
impurities,
an evaluation of the bio-equivalence studies or a justification as to why
studies were not performed with reference to established guidance,
if applicable, additional data in order to demonstrate the equivalence of
safety and efficacy properties of different salts, esters or derivatives of
an authorised active substance shall be provided by the applicant; those
data shall include evidence that there is no change in the
pharmacokinetic or pharmacodynamic properties of the therapeutic
moiety and/or in toxicity, which could influence the safety/efficacy
profile.
Every claim in the summary of product characteristics not known from or inferred
from the properties of the medicinal product and/or its therapeutic group should be
discussed in the non-clinical/clinical overviews/summaries and substantiated by
published literature and/or additional studies.
For generic veterinary medicinal products intended to be administered by
intramuscular, subcutaneous or transdermal routes, the following additional data
shall be provided
evidence to demonstrate equivalent or differing depletion of residues
from the administration site, which may be substantiated by appropriate
residue depletion studies,
evidence to demonstrate target animal tolerance at the administration
site, which may be substantiated by appropriate target animal tolerance
studies.
2. Similar biological veterinary medicinal products
In accordance with regulation 13(4), where a biological veterinary medicinal
product which is similar to a reference biological veterinary medicinal product does
not meet the conditions in the definition of generic medicinal product, information to
be supplied shall not be limited to Parts 1 and 2 (pharmaceutical, chemical and
biological data), supplemented with bio-equivalence and bioavailability data. In
such cases, additional data shall be provided, in particular on the safety and efficacy
of the product.
The type and amount of additional data (i.e. toxicological and other
safety studies and appropriate clinical studies) shall be determined on a
VETERINARY MEDICINAL PRODUCTS
case-by-case basis in accordance with relevant scientific guidelines.
-
Due to the diversity of biological veterinary medicinal products, the
competent authority shall determine the necessary studies foreseen in
Parts 3 and 4, taking into account the specific characteristic of each
individual biological veterinary medicinal product.
The general principles to be applied shall be addressed in guideline which shall be
adopted by the Agency, taking into account the characteristics of the concerned
biological veterinary medicinal product. If the reference biological veterinary
medicinal product has more than one indication, the efficacy and safety of the
biological veterinary medicinal product claimed to be similar shall be justified or, if
necessary, demonstrated separately for each of the claimed indications.
3. Well-established veterinary use
For veterinary medicinal products the active substance(s) of which has/have been
in "well-established veterinary use" as referred to in regulation 13A(1), with
recognised efficacy and an acceptable level of safety, the following specific rules
shall apply.
The applicant shall submit Parts 1 and 2 as described in Title I of this Schedule.
For Parts 3 and 4, a detailed scientific bibliography shall address all aspects of the
safety and efficacy.
The following specific rules shall apply in order to demonstrate the well-
established veterinary use
3.1. The following factors shall be taken into account in order to establish a well-
established veterinary medicinal use of constituents of veterinary medicinal
products
(a) the time over which an active substance has been used;
(b) quantitative aspects of the use of the active substance;
(c) the degree of scientific interest in the use of the active substance
(reflected in the published scientific literature);
(d) the coherence of scientific assessments.
Different periods of time may be necessary for establishing well-established use
of different substances. In any case, however, the period of time required for
establishing a well-established veterinary use of a constituent of a medicinal product
shall not be less than ten years from the first systematic and documented use of that
substance as a veterinary medicinal product in the Union.
3.2. The documentation submitted by the applicant shall cover all aspects of the
safety and/or efficacy assessment of the product for the proposed indication in the
target species using the proposed route of administration and dosage regimen. It
must include or refer to a review of the relevant literature, taking into account pre-
and post-marketing studies and published scientific literature concerning experience
in the form of epidemiological studies and in particular of comparative
epidemiological studies. All documentation, both favourable and unfavourable, shall
be communicated. With respect to the provisions on well-established veterinary use,
it is in particular necessary to clarify that bibliographic reference to other sources of
evidence (post-marketing studies, epidemiological studies etc.) and not just data
related to tests and trials may serve as a valid proof of safety and efficacy of a
product if an application explains and justifies the use of these sources of
information satisfactorily.
3.3. Particular attention must be paid to any missing information and
VETERINARY MEDICINAL PRODUCTS
justification must be given as to why demonstration of an acceptable level of safety
and/or efficacy can be supported although some studies are lacking.
3.4. The detailed and critical summaries regarding safety and efficacy must
explain the relevance of any data submitted which concern a product different from
the product intended for marketing. A judgement must be made whether or not the
product studied can be considered as similar to the product, for which application for
a marketing authorisation has been made in spite of the existing differences.
3.5. Post-marketing experience with other products containing the same
constituents is of particular importance and applicants shall put a special emphasis
on this issue.
4. Combination veterinary medicinal products
For applications based on regulation 13B of these regulations, a dossier containing
Parts 1, 2, 3 and 4 shall be provided for the combination veterinary medicinal
product. It shall not be necessary to provide studies on the safety and efficacy of
each active substance. It shall nevertheless be possible to include information on the
individual substances in the application for a fixed combination. The submission of
data on each individual active substance, in conjunction with the required user safety
studies, residues depletion studies and clinical studies on the fixed combination
product, may be considered a suitable justification for omitting data on the
combination product, based on animal welfare grounds and unnecessary testing on
animals, unless there is suspected interaction leading to added toxicity. Where
applicable, information regarding the manufacturing sites and the safety evaluation
of adventitious agents shall be provided.
5. Informed consent applications
Applications based on regulation 13C hereof shall contain the data described in
Part 1 of Title 1 of this Schedule, provided that the marketing authorisation holder
for the original veterinary medicinal product has given the applicant his consent to
refer to the content of Parts 2, 3 and 4 of the dossier of that product. In this case,
there is no need to submit quality, safety and efficacy detailed and critical
summaries.
6. Documentation for applications in exceptional circumstances
A marketing authorisation may be granted subject to certain specific obligations
requiring the applicant to introduce specific procedures, in particular concerning the
safety and efficacy of the veterinary medicinal product, when, as provided for in
regulation 26(2) of these regulations, the applicant can show that he is unable to
provide comprehensive data on the efficacy and safety under normal conditions of
use.
The identification of essential requirements for all applications mentioned in this
section should be subject to guidelines which shall be adopted by the Agency.
7. Mixed marketing authorisation applications
Mixed marketing authorisation applications are applications where Part(s) 3 and/
or 4 of the dossier consist of safety and efficacy studies carried out by the applicant
as well as bibliographical references. All other part(s) are in accordance with the
structure described in Part I of Title I of this Schedule. The competent authority shall
accept the proposed format presented by the applicant on a case-by-case basis.
TITLE IV
REQUIREMENTS FOR MARKETING AUTHORISATION APPLICATIONS
FOR PARTICULAR VETERINARY MEDICINAL PRODUCTS
VETERINARY MEDICINAL PRODUCTS
This part lays down specific requirements for identified veterinary medicinal
products related to the nature of the active substances contained therein.
1. IMMUNOLOGICAL VETERINARY MEDICINAL PRODUCTS
A.
VACCINE ANTIGEN MASTER FILE
For particular immunological veterinary medicinal products and by derogation
from the provisions of Title II, Part 2 Section C on active substances, the concept of
a Vaccine Antigen Master File is introduced.
For the purpose of this Schedule, a Vaccine Antigen Master File means a stand-
alone part of the marketing authorisation application dossier for a vaccine, which
contains all relevant information on quality concerning each of the active
substances, which are part of this veterinary medicinal product. The stand-alone part
may be common to one or more monovalent and/or combined vaccines presented by
the same applicant or marketing authorisation holder.
Scientific guidelines for the submission and evaluation of a vaccine antigen
master file shall be adopted by the Agency. The procedure for the submission and
evaluation of a vaccine antigen master file shall follow the guidance published by
the Commission in The rules governing medicinal products in the European Union,
Volume 6B, Notice to Applicants.
B.
MULTI-STRAIN DOSSIER
For certain immunological veterinary medicinal products (foot-and-mouth
disease, avian influenza and bluetongue) and by derogation from the provisions of
Title II, Part 2 Section C on active substances the concept of the use of a multi-strain
dossier is introduced.
A multi-strain dossier means a single dossier containing the relevant data for a
unique and thorough scientific assessment of the different options of strains/
combinations of strains permitting the authorisation of vaccines against antigenically
variable viruses.
Scientific guidelines for the submission and evaluation of multi-strain dossiers
shall be adopted by the Agency. The procedure for the submission and evaluation of
multi-strain dossiers shall follow the guidance published by the Commission in The
rules governing medicinal products in the European Union, Volume 6B, Notice to
Applicants.
2. HOMEOPATHIC VETERINARY MEDICINAL PRODUCTS
This section sets out specific provisions on the application of Title I, Parts 2 and 3
to homeopathic veterinary medicinal products as defined in regulation 2(8).
Part 2
The provisions of Part 2 shall apply to the documents submitted in accordance
with regulation 18 in the simplified registration of homeopathic veterinary medicinal
products referred to in regulation 17(1) as well as to the documents for authorisation
of other homeopathic veterinary medicinal products referred to in regulation 19(1)
with the following modifications.
(a)
Terminology
The Latin name of the homeopathic stock described in the marketing authorisation
application dossier shall be in accordance with the Latin title of the European
Pharmacopoeia or, in absence thereof, of an official pharmacopoeia of Malta. Where
relevant the traditional name(s) used in each Member State shall be provided.
(b)
Control of starting materials
VETERINARY MEDICINAL PRODUCTS
The particulars and documents on the starting materials, i.e. all of the materials
used including raw materials and intermediates up to the final dilution to be
incorporated i nto the finish ed homeopathic veteri na ry med ic inal pro duct,
accompanying the application shall be supplemented by additional data on the
homeopathic stock.
The general quality requirements shall apply to all of the starting and raw
materials as well as intermediate steps of the manufacturing process up to the final
dilution to be incorporated into the finished homeopathic product. Where a toxic
component is present, this should be controlled if possible in the final dilution.
However, if this is not possible because of the high dilution, the toxic component
shall normally be controlled at an earlier stage. Every step of the manufacturing
process from the starting materials up to the final dilution to be incorporated into the
finished product must be fully described.
In case dilutions are involved, these dilution steps shall be done in accordance
with the homeopathic manufacturing methods laid down in the relevant monograph
of the European Pharmacopoeia or, in absence thereof, in an official pharmacopoeia
of Malta.
(c)
Control tests on the finished medicinal product
The general quality requirements shall apply to the homeopathic finished
veterinary medicinal products. Any exception shall be duly justified by the
applicant.
Identification and assay of all the toxicologically relevant constituents shall be
carried out. If it can be justified that identification and/or an assay on all the
toxicologically relevant constituents is not possible e.g. due to their dilution in the
finished medicinal product the quality shall be demonstrated by complete validation
of the manufacturing and dilution process.
(d)
Stability tests
The stability of the finished product shall be demonstrated. Stability data from the
homeopathic stocks are generally transferable to dilutions/potentisations obtained
thereof. If no identification or assay of the active substance is possible due to the
degree of dilution, stability data of the pharmaceutical form may be considered.
Part 3
The provisions of Part 3 shall apply to the simplified registration of homeopathic
veterinary medicinal products referred to in regulation 17(1) with the following
specification, without prejudice to the provisions of Regulation (EEC) No 2377/90
for substances included in the homeopathic stocks intended for administration to
food-producing animal species.
Any missing information must be justified, e.g. justification must be given why
demonstration of an acceptable level of safety can be supported although some
studies are lacking.
For the purposes of these regulations, the following terms
shall have the following meanings -
"active substance" means any substance or mixture of substances
intended to be used in the manufacture of a veterinary medicinal
product and that product, when used in its production, becomes an
active ingredient of that product;
"advertising of veterinary medicinal products" means the making
of a representation in any form in connection with veterinary
medicinal products in order to promote the supply, distribution,
sale, prescription or use of veterinary medicinal products and
comprising also the supply of samples and sponsorships;
*These regulations have been repealed by Legal Notice 335 of 2024.
"Agency" means the European Medicines Agency established by
Regulation (EC) No 726/2004;
"Adverse reaction" means a reaction to a veterinary medicinal
product which is harmful and unintended and which occurs at doses
norm ally used in animals for the prophylaxis, diagnosis or
treatment of disease or to restore, correct or modify a physiological
function;
"the Commission" means the Commission in accordance with
Council Decision 1999/468/EC of 28th June, 1999;
"Director for Veterinary Services" means the Director for
Veterinary Services as defined in the Veterinary Services Act, and
includes, to the extent of the authority given, to any officer
authorised by him, in writing, to act on his behalf for any of the
purposes mentioned in the Veterinary Services Act. Whenever in
the text the words "Veterinary Services" are used these should be
construed as referring to the "Director for Veterinary Services";";
and immediately thereafter there shall be added the following new
definitions
"dispensing" means the sale or supply of veterinary medicinal
products. The products are sold or supplied from a veterinary
pharmacy or by a veterinary surgeon in licensed veterinary
establishments or during out calls;
"European Union" means the European Union as referred to in the
Treaty;
"Committee for Veterinary Medicinal Products" hereinafter
referred to as "the Committee" means part of the Agency set up to
facilitate the adoption of common decisions on the authorisation of
veterinary medicinal products on the basis of the scientific criteria
of quality, safety and efficacy. This Committee shall be appointed
in accordance with article 31 of European Union Council Directive
2001/82/EC;
"Common name" means the international non-proprietary name
recommended by the World Health Organisation, or, if one does not
exist, the usual common name;
"the Community" means the European Community as established
under the Treaty establishing the European Community;
"food" shall have the same meaning as assigned to it in the Food
Safety Act;
"Homeopathic veterinary medicinal product" means any
veterinary medicinal product prepared from substances called
homeopathic stocks in accordance with a homeopathic
manufacturing procedure described by the European
Pharmacopoeia or, in the absence thereof, by the Pharmacopoeias
currently used officially in Member States. A homeopathic
veterinary medicinal product may contain a number of principles;
"Human adverse reaction" means a reaction which is noxious and
unintended and which occurs in a human being following exposure
to a veterinary medicine;
"Immediate packaging" means the container or any other form of
packaging that is in direct contact with the medicinal product;
"Immunological veterinary medicinal product" means a
veterinary medicinal product administered to animals in order to
produce active or passive immunity or to diagnose the state of
immunity;
"imported veterinary medicinal products" means veterinary
medicinal products obtained from a source outside the EU;
"licensed veterinary establishment" has the same meaning as
assigned to it in the Private Veterinary Establishments (Licensing)
Regulations;
"Labelling" means information on the immediate or outer
packaging;
"Medicated feeding stuffs" means any mixture of a veterinary
medicinal product or products and feed or feeds which is ready
prepared for marketing and intended to be fed to animals without
further processing, because of its curative or preventive properties
or other properties as a veterinary medicinal product;
Medicinal products" shall have the same meaning as is assigned
to in the Medicines Act;
"Member State" me ans a State w hich is a member o f the
European Union;
""Metaphylactic" means the administration of a veterinary
medicinal product or a medicinal product to a group of animals after a
diagnosis of clinical disease in part of the group has been established,
with the aim of treating the clinically sick and controlling the spread of
the disease to animals in close contact and at risk and which may
already be sub clinically infected;
"Name of veterinary medicinal product" means the name, which
may be either an invented name not liable to confusion with the
common name, or a common or scientific name accompanied by a
trademark or the name of the marketing authorisation holder;
"Narcotic drugs" means the substances present on the Yellow List
prepared by the International Narcotics Control Board in accordance
with the Single Convention on Narcotic Drugs, 1961, Protocol of 25
March 1972 amending the Single Convention on Narcotic Drugs,
1961;
"Off-label use" means the use of a veterinary medicinal product
when such use is not in accordance with the summary of the
product characteristics, including the misuse and serious abuse of
the product;
"Outer packaging" means the packaging into which is placed the
immediate packaging;
"Package leaflet" means the leaflet containing information for
the user that accompanies the medicinal product;
"Periodic safety update reports" means the periodical reports
containing the records referred to in regulation 68.
"Pharmacist" means a person who is enlisted in the Register of
Pharmacists kept by the Pharmacy Council in terms of article 17 of the
Health Care Professions Act;
"placing under official control" means the detaining of any article
by the Director for Veterinary Services in order to permit the
accomplishment of any of its functions;
"Post-marketing surveillance studies" means the
pharmacoepidemiological study or a clinical trial carried out in
a c c o r d a n c e w i t h t h e t e r m s o f t h e m a r k e t i n g a u t h o r i sa t i o n ,
conducted with the aim of identifying and investigating a safety
hazard relating to an authorised veterinary medicinal product;
"Premix for medicated feeding stuffs" means any veterinary
medicinal product prepared in advance with a view to the
subsequent manufacture of medicated feeding stuffs;
"prescribing" means the act of preparing a veterinary prescription by
a veterinary surgeon being it on paper or electronic media;
"preventive use of an antimicrobial agents" means the
administration of antimicrobial agents to healthy animals to prevent
infections to compensate for inadequate good farming practice;
"procurement" means the act of acquiring, for profit or not, a
veterinary medicinal product, or part thereof, from a Member State of
the European Union;
"prophylactic administration of antimicrobials" means the
administration of a veterinary medicinal product or a medicinal
product to an animal or group of animal before clinical signs of a
disease, in order to prevent the occurrence of disease or infection
"psychotropic drugs" means the substances listed in the Third
schedule to the Medical and Kindred Professions Ordinance and
those substances listed on the Green List prepared by International
Narcotics Control Board in accordance with the Convention on
Psychotropic Substances of 1971;
"Representative of the marketing authorisation holder" means the
person, commonly known as local representative, designated by the
marketing authorisation holder to represent him in Malta;
"Risk/benefit balance" means an evaluation of the positive
therapeutic effects of the veterinary medicinal product in relation to
the risks as defined above;
"Risks relating to use of the product" means
-
any risk relating to the quality, safety and efficacy of
the veterinary medicinal products as regards animal or
human health;
-
any risk of undesirable effects on the environment;
"Serious adverse reaction" means an adverse reaction which
results in death, is life-threatening, results in significant disability
or incapacity, is a congenital anomaly and, or birth defect, or which
results in permanent or prolonged signs in the animals treated;
"source country" means a Member State of the EU or a country in
the European Economical Area from where the veterinary medicinal
products referred to in regulation 7 can be procured;
"Strength" means the content of active substances, expressed
quantitatively per dosage unit, per unit of volume or weight
according to the dosage form;
"Substance" means any matter irrespective of origin which may
be -
(a) human, e.g. human blood and human blood products;
(b) animal, e.g. micro organisms, whole animals, parts of
organs, animal secretions, toxins, extracts, blood
products;
(c) vegetable, e.g. micro organisms, plants, parts of plants,
vegetable secretions, extracts;
(d) chemical, e.g. elements, naturally occurring chemical
materials and chemical products obtained by chemical
change or synthesis;
"Suitably Qualified Persons" means that person who has a
qualification in a veterinary science and included in one of the
para-veterinary professions mentioned in the Act;
"Third Country" means a State which is not a Member within the
European Community;
"Unexpected adverse reaction" means an adverse reaction, the
nature, severity or outcome of which is not consistent with the
summary of the product characteristics;
"Veterinary medicinal product" means
(a) any substance or combination of substances presented
as having properties for treating or preventing disease
in animals; or
(b) any substance or combination of substances which
may be used in or administered to animals with a view
either to restoring, correcting or modifying
physiological functions by exerting a pharmacological,
immunological or metabolic action, or to making a
medical diagnosis;
"veterinary surgeon" means a person as described and regulated
by article 43 of the Act and whose name is entered in the Register
of Veterinary Surgeons’ Register, or that person, coming from any
other Member State of the European Union, whose name is entered
in the relevant register kept by the relevant body of that Member
State which regulates the profession of Veterinary surgeons. In the
latter case the provisions of the Mutual Recognition of
Qualifications Act and the Services (Internal Market) Act shall
apply;
"Veterinary prescription" means any prescription for a veterinary
medicinal product issued by a professional person qualified to do
so in accordance with applicable national law.
"Veterinary Services" means the competent authority within the
territory of Malta as established under article 2 of the Veterinary
Services Act;
"veterinary wholesale dealer" means that person authorised to carry
out wholesale distribution of veterinary medicinal products;
"Withdrawal period" means the period necessary between the last
administration of the veterinary medicinal product to animals,
under normal conditions of use and in accordance with the
provisions of these regulations, and the production of foodstuffs
from such animals, in order to protect public health by ensuring
that such foodstuffs do not contain residues in quantities in excess
of the maximum residue limits for active substances laid down
pursuant to European Union Regulation (EEC) No 2377/90;
"Wholesale dealing in veterinary medicinal products" means any
activity which includes the purchase, sale, import, export, or any
other commercial transaction in veterinary medicinal products,
whether or not for profit, except for -
(a) the supply by a manufacturer of veterinary medicinal
products manufactured by himself, or,
(b) retail supplies of veterinary medicinal products by
persons entitled to carry out such supplies in
accordance with regulation 59.
TITLE II
(1)
These regulations shall not apply to
(a) medicated feedingstuffs as defined in European Union
Council Directive 90/167/EEC laying down the
conditions governing the preparation, placing on the
market and use of medicated feedingstuffs in the
European Union;
(b) inactivated immunological veterinary medicinal
products which are manufactured from pathogens and
antigens obtained from an animal or animals from a
holding and used for the treatment of that animal or the
animals of that holding in the same locality;
(c) veterinary medicinal products based on radio-active
isotopes;
(d) any additives covered by European Union Council
Directive 70/524/EEC concerning additives in
feedingstuffs where they are incorporated in animal
feedingstuffs and supplementary animal feedingstuffs
in accordance with that Directive; and
However, medicated feedingstuffs referred to in paragraph
(a) may be prepared only from pre-mixes that have been authorised
under these regulations.
(2) Except for the provisions on the possession, prescription,
dispensing and administration of veterinary medicinal products,
these regulations shall not apply to
(a) any medicinal product prepared in a pharmacy in
accordance with a veterinary prescription for an
individual animal or a small group of animals,
commonly known as the magistral formula; and
(b) any medicinal product prepared in a pharmacy in
accordance with the prescriptions of a Pharmacopoeia
and intended to be supplied directly to the end-user,
commonly known as the officinal formula.
(1) The Director may provide that these regulations shall
not apply to non-inactivated immunological veterinary medicinal
products which are manufactured from pathogens and antigens
obtained from an animal or animals from a holding and used for the
treatment of that animal or the animals of that holding in the same
locality.
(2) In the case of veterinary medicinal products intended solely
for aquarium fish, cage birds, homing pigeons, terrarium animals,
small rodents, and ferrets and rabbits kept exclusively as pets,
Malta may permit exemptions from the provisions in regulations 5
to 8, provided that such products do not contain substances the use
of which requires veterinary control and that all possible measures
are taken to prevent unauthorised use of the products for other
animals.
(3) In order to be granted the exemption for the veterinary
medicinal product referred to in this sub-regulation applicants shall
submit an application with the Veterinary Services.
(4) In order to qualify under the exemption described in this
sub-regulation (2) the product must be manufactured by
(a) the holder of a manufacturing authorisation if
manufactured in Malta or in another Member State of
the European Union;
(b) the holder of a relevant licence conferring
authorisation to manufacture veterinary medicinal
products if the product is manufactured in a Third
country.
(5) The product must not be classified as requiring a veterinary
prescription.
(6) The manufacturer, importer, wholesale dealer or retailer of
a veterinary medicinal product shall declare that he will notify the
Veterinary Services within fifteen (15) days of learning of any
serious adverse reactions in accordance with sub-regulations (2)
and (3) of regulation 68. A record of each adverse reaction and
serious adverse reaction must be maintained on becoming aware of
it. The records shall be kept for five (5) years.
(7) The Veterinary Services shall prepare and publish a list of
active substances that can be used in veterinary medicinal products
authorised under sub-regulation (2), specifying the species of non-
food producing animals for which it is approved and may specify
how the active substance or a product containing the active
substances to be administered.
(8) The Veterinary Services may decide not to apply the
provisions of this Regulation to a previously exempted product if
any one or more of the following occur
(a) serious adverse reactions are reported;
(b) it is demonstrated, at any time after authorisation, that
the substance is carcinogenic, genotoxic or that it
shows
developmental
toxicity
(including
teratogenicity);
(c) the product contain active substances that are re-
classified as narcotic or psychotropic substances;
(d) any one of the ingredient/s in the product is/are not
included anymore in the list mentioned in paragraph
(d) of sub-regulation (3);
(e) it is reported and is verified by the Veterinary Services
that the product is not being used on the animals
mentioned in sub-regulation (2);
(9) The product authorised under sub-regulation (2) shall be
c l e a r l y l a b e l l e d a s b e i n g e x e m p t f r om t h e r e q u i r e m en t s o f
regulations 5, 6, 7 and 8 in relation to a Marketing Authorisation.
The information obtainable from the whole pack must at least show
the following details
(a) the name of the veterinary medicinal product;
(b) the pharmaceutical dosage form;
(c) the name and strength of each active substance;
(d) the route of administration;
(e) the batch number;
(f)
the expiry date;
(g) a sentence to the effect of "For administration on non-
food producing animals only" authorised in
accordance to regulation 4(2) of these regulations;
(h) the target species;
(i)
storage instructions;
(j)
the shelf-life after the immediate packaging has been
opened for the first time;
(k) therapeutic indications;
(l)
contra-indications;
(m) interaction with other medicines and other forms of
interaction;
(n) dosage instructions.
(10) If there is sufficient room on the label, the information may
be present only on it without the need of a package leaflet. The
information must be conveyed in a clear and legible manner.
(11) The provisions of sub-regulation 5 shall come into force on
the 1st November 2021.
(1)A veterinary medicinal product may be obtained from
any country and administered to animals for research purposes in
accordance with article 53(3) of the Veterinary Services Act.
(2) The veterinary medicinal products authorised according
this regulation may be exempt from the provisions of regulations 5,
6, 7 and 8.
(3) The veterinary medicinal products shall only be used in
authorised research facilities which are in conformity with the
Animal Welfare Act and the Protection of Animals for Scientific
Purposes Regulations.
(4) (a) In order to be allowed to carry out the activity
mentioned in sub-regulation (1) a person, herein referred to as the
"applicant for a veterinary medicinal product to be used for
research purposes", shall submit an application with the Veterinary
Services.
(b)
If the application is positively completed a licence for
Research Purposes shall be issued. The Veterinary
Services shall make, modify, add or remove any terms
and conditions pertaining to the licence that it may
deem fit in light of scientific advancements or new
information that may emerge on particular substances
or ingredients contained in the veterinary medicinal
products used for research purposes.
(c) The holder of the licence for a veterinary medicinal
product to be used for research purposes shall utilise a
product or administer it to a test animal only under the
terms and conditions set out under the Animal Welfare
Act.
(d) The holder of the licence for a veterinary medicinal
product to be used for research purposes who becomes
aware of any serious adverse reactions on the animal
or on the person administering it shall report the
reaction to the Veterinary Services within fifteen (15)
days from the day the serious adverse reaction was
discovered.
(e) Food for human consumption can be taken from test
animals only in accordance with regulation 86 and
with the prior approval of the Veterinary Services. (f)
The application submitted by the applicant shall be
granted without prejudice to any licence or permit that
the applicant may need to obtain from other
departments and directorates in order to engage in the
indicated research activity.
(g) The applicant for a veterinary medicinal product or
holder of the licence is subject to official inspections
by the Veterinary Services on the premises and the
activities undertaken within the premises.
(h) The Veterinary Services shall set out the criteria for
veterinary medicinal product which are obtained in
accordance with sub-regulation (1) and make them
public.
(1)Veterinary medicinal products may be exempted from
the provisions in regulations 5 to 8 if it can be demonstrated that
the products are veterinary samples or demonstration packs
distributed to veterinary surgeons or pharmacists by veterinary
wholesale distributors.
(2) The products referred to in sub-regulation (1) may be used
under the following conditions
(a) they are distributed for free to persons authorised to
receive them or are exhibited during conferences or
similar activities which are held for intended for
veterinary surgeons and/or pharmacists;
(b) they bear a label printed "Free sample/Demonstration
pack – Not for sale";
(c) the unit pack should not contain more than
(i)
50 units for capsules/tablets;
(ii)
10 units for injections and spot-ons
(iii)
300g for powders
(iv)
3L for liquids
(v)
5 units for intra-mammary tubes
(vi)
any other measurement as established by the
Veterinary Services for all other Pharmaceutical
forms
(d) the information provided with the samples shall not
be promotional in nature;
(e) the maximum period of time the authorised
veterinary wholesale dealer can procure a
product from a Member State of the European
Union as a free sample is one (1) year from the
first consignment thereof;
(f)
if any product authorised in accordance with the
provisions of sub-regulation (1) is administered
to a food producing animals, that animal is
excluded permanently from the food chain.
Any authorisation issued under regulations 4(2), 4A and
4B, shall be deemed to be a Marketing Authorisation for the
purposes of articles 38, 53 and 57 of the Veterinary Services Act.
(1)Veterinary medicinal products may be exempted from
the provisions in regulations 5 to 8 when the products are procured
from a Member State of the European Union or imported from a
Third country under the terms and conditions mentioned in sub-
regulation (2).
(2)
The following terms and conditions shall apply
(a) the products shall not be re-sold for monetary gain;
(b) the products shall not be transferred to other third
parties unless such transfer is authorised by the
Veterinary Services;
(c) this provision is not applicable to psychotropic drugs,
narcotic drugs for all animals and in the case of food
producing animals also the substances listed in Group
A in Schedule I of Measures to monitor certain
Substances and Residues thereof in Live Animals and
Animal Products Rules and Table II of Regulation
(EU) 37/2010;
(d) the quantity of products obtained shall be proportional
to the dosage regime of the condition it will be used
for;
(e) the quantity of products which is allowed entry in
Maltese territory shall cover the period indicated as
the duration of treatment in the product’s
specifications or on the veterinary surgeons ‘s
veterinary prescription. However, products intended to
be used for recurrent or chronic conditions can be
allowed entry in Malta several times a year, provided
that cogent evidence that demonstrate the benefits
obtained by the regular use of the products can be
provided;
(f)
the individuals shall be required to provide a
veterinary prescription for products classified as
requiring such a prescription in the country from
where they are obtained or for similar veterinary
medicinal products in Malta
Provided that the Veterinary Services may still ask for
such a veterinary prescription even if the products are
classified as not requiring a veterinary prescription in
the country from where they are obtained;
(g) only products that do not contain animal by-products
which are derived from high risk areas where certain
diseases may be, or suspected to be, present or
prevalent, can be obtained;
(h) only products that do not contain ingredients that are
classified as illegal in Malta and do not have banned
indications in Malta can be obtained;
(i)
only appropriately labelled products which give clear
indication of the nature of the ingredient/s within can
be obtained;
(j)
food producing animals administered with the
veterinary
medicinal
products
authorised
in
accordance with this regulation can only be consumed
by the person getting the veterinary medicinal
products, or by consenting members of the same
household. The appropriate withdrawal period shall
apply;
(k) before a decision on antimicrobial veterinary
medicinal products and products that have a hormonal
activity is taken, a risk assessment shall be prepared by
the Veterinary Services in a timely manner;
(l)
the decision by the Veterinary Service is without
prejudice to any license or permit that the person
getting the veterinary medicinal products may need to
obtain under other regulations of the same or of
different department.
(3) The veterinary services shall decide on the release, placing
under official control or destruction of veterinary medicinal
products, or the products presumed to be veterinary medicinal
products, if and when these are intercepted at the various entry
control points throughout the territory of Malta.
(4) Pursuant to sub-regulation (3), the Veterinary Services shall
keep a record of all the opinions or decisions taken. These records
shall be kept by the Veterinary Services for a period of not less than
ten (10) years.
(5) The Veterinary Services shall set out the criteria for
veterinary medicinal product which can be obtained in accordance
with sub-regulation (1) and make them public
Provided that the provisions of this regulations shall also apply
to veterinary medicinal products that are brought in the territory of
Malta as a bona fide donation for use on animals kept in the approved
sanctuary subject to the donation on condition that the veterinary
services is pre-notified of such a request with the name, quantity and
nature of the products, and the names and addresses of the donator, the
recipient and the animal sanctuary involved.
TITLE III
MARKETING
CHAPTER 1
Marketing authorisation
(1) No veterinary medicinal product may be placed on the
market of Malta unless a marketing authorisation has been granted
by the Veterinary Services in accordance with these regulations or a
marketing authorisation has been granted in accordance with
European Union Regulation (EC) No 726/2004.
When a veterinary medicinal product has been granted an
initial authorisation in accordance with the first paragraph, any
additional species, strengths, pharmaceutical forms, administration
routes, presentations, as well as any variations and extensions, shall
also be granted an authorisation in accordance with the first
paragraph or be included in the initial marketing authorisation. All
these marketing authorisations shall be considered as belonging to
the same global marketing authorisation, in particular for the
purpose of the application of regulation 13(1).
(2)
The marketing authorisation holder shall be responsible for
the marketing of the medicinal product. The designation of a
representative shall not relieve the marketing authorisation holder
of his legal responsibility.
(1) A veterinary medicinal product may not be the subject
of a marketing authorisation for the purpose of administering it to
one or more food-producing species unless the pharmacologically
active substances which it contains appear in Annexes I, II or III to
European Regulation (EEC) No 2377/90.
(2) If an amendment to the Annexes to Regulation (EEC) No
2377/90 so warrants, the marketing authorisation holder or, where
appropriate, the Veterinary Services shall take all necessary
measures to amend or revoke the marketing authorisation within
sixty days of the date on which the amendment to the Annexes to
that Regulation was published in the Official Journal of the
European Union.
(3) By way of derogation from subregulation (1), a veterinary
medicinal product containing pharmacologically active substances
not included in Annexes I, II or III to European Regulation (EEC)
No 2377/90 may be authorised for particular animals of the equidae
family that have been declared, in accordance with European
Commission Decision 93/623/EEC establishing the identification
doc ument (pa ssport) accompanying r egiste red equidae and
European Commission Decision 2000/68/EC amending Decision
93/623/EEC and establishing the identification of equidae for
breeding and production, as not being intended for slaughter for
human consumption. Such veterinary medicinal products shall
neither include active substances that appear in Annex IV to
European Regulation (EEC) No 2377/90 nor be intended for use in
the treatment of conditions, as detailed in the authorised Summary
of Product Characteristics, for which a veterinary medicinal
product is authorized for animals of the equidae family.
Where the health situation so requires, the Veterinary
Services may authorise the marketing or administration to animals
of veterinary medicinal products which have been authorised by
a n o t h e r M e m b e r St a t e referred to as the "source country i n
accordance with European Union Council Directive 2001/82/EC.
(1) In order to be allowed to market the products under
regulation 7, a person, herein referred to as the "applicant for the
registration of veterinary medicinal product" under regulation 7,
shall submit an application to the Veterinary Services.
(2) Upon a reasoned request the Veterinary Services may
decide that regulations 60(10) and 60(11) on the legal category of
Veterinary medicinal products and regulation 51(4) do not apply to
registrations granted under regulation 7.
(3)
Before granting such a registration the Veterinary Services
may
VETERINARY MEDICINAL PRODUCTS
(a) request the competent authority in the source country
to furnish a copy of the Marketing Authorisation in
force;
(b) ensure that the entity applying for a registration in
accordance with regulation 7 is a legally established
company in the European Union or European
Economic Area;
(c) notify the Marketing Authorisation Holder of its
intention to grant a registration according to regulation
7 when the Registration Holder is not the same entity
as the Marketing Authorisation Holder in the country
of source;
(d) request the applicant for a registration in accordance
with regulation 7 to furnish an authenticated copy of
the Marketing Authorisation in force
Provided that it is not possible for the applicant to
provide an authenticated copy of the Marketing
Authorisation he shall be requested to provide other
proof of an existing Marketing Authorisation in the
country of source.
(e) request from the applicant data on the impact of the
product on the environment in Malta.
(4)
The holder of the registration granted in accordance with
regulation 7 shall ensure that
(a) the veterinary medicinal product is in accordance with
the current Marketing Authorisation issued in the
source country;
(b) notify the veterinary services of any variations to the
terms of the Marketing Authorisation approved in the
country of source;
(c) there are implemented without any delay actions
relating to issues concerning the veterinary medicinal
product which have resulted in adverse drug reaction
and/or a product or batch recall;
(d)
a person is appointed or be himself responsible for the
requirements in paragraph (c);
(e) when the applicant is not the Market Authorisation
Holder of the product in the source country he shall
furnish to the Veterinary Services a letter of access
issued by the Market Authorisation Holder granting
him the use of the Marketing Authorisation for the
purpose of regulation 7
Provided that it is not possible for the applicant to
receive a ‘letter of access’ from the Market
Authorisation Holder in the country of source the
applicant shall be requested to provide proof of the
agreement between himself and a duly authorised
veterinary wholesale distributor in the country of
source;
(f)
have a system in place for recording and investigation
adverse drug reactions and batch or product defects.
(1) In the event of serious epizootic diseases, the
Ve t e r i n a r y S e r v i c e s m a y p r o v i s i o n a l l y a l l o w t h e u s e o f
immunological veterinary medicinal products without a marketing
authorisation, in the absence of a suitable medicinal product and
after informing the European Commission of the detailed
conditions of use.
(2) If an animal is being imported from, or exported to, a third
country and is thereby subject to specific binding health rules, the
Veterinary Services may permit the use, for the animal in question,
of an immunological veterinary medicinal product that is not
covered by a marketing authorisation in Malta but is authorized
under the legislation of the third country. The Veterinary Services
shall take all appropriate measures concerning the supervision of
the importation and the use of such immunological products.
No veterinary medicinal product may be administered to
animals unless the marketing authorisation has been issued, except
for the tests of veterinary medicinal products referred to in
regulation 12(3)(j) which have been accepted by the competent
national authorities, following notification or authorisation, in
accordance with the rules in force.
(1) The Veterinary Services shall take the necessary
measures to ensure that, if there is no authorised veterinary
medicinal product in Malta for a condition affecting a non food-
producing species, by way of exception, the veterinary surgeon
responsible may, under his/her direct personal responsibility and in
particular to avoid causing unacceptable suffering, treat the animal
concerned with
(a) a veterinary medicinal product authorised in Malta
under these regulations or under European Regulation
(EC) No 726/2004 for use with another animal species,
or for another condition in the same species; or
(b) if there is no product as referred to in paragraph (a) -
(i)
either a medicinal product authorised for human
use in Malta in accordance with European
Directive 2001/83/EC of the European
Parliament and of the European Council or
under European Regulation (EC) No 726/2004,
(ii) or, in accordance with specific national
measures, a veterinary medicinal product
authorised in another Member State in
accordance with these regulations for use in the
same species or in another species for the
condition in question or for another condition; or
(c) if there is no product as referred to in paragraph (b),
and within the limits of the law of Malta, a veterinary
medicinal product prepared extemporaneously by a
pharmacist or a veterinary surgeon in accordance with
the terms of a veterinary prescription.The veterinary
surgeon may administer the medicinal product
personally or allow another person to do so under the
veterinary surgeon’s responsibility.
(2) By way of derogation from regulation 11, the provisions of
subregulation (1) hereof shall also apply to the treatment by a
veterinary surgeon of an animal belonging to the equidae family
provided that it has been declared, in accordance with European
Commission Decisions 93/623/EEC and 2000/68/EC, as not being
intended for slaughter for human consumption.
(3) In the case of a veterinary medicinal product authorised in
a no t h e r m e m b e r St a t e , v e t e r i nar y su rg e o ns s ha ll o bt a in an
authorisation from the Veterinary Services before getting the
product for the administration to the animal.
(4) In case the veterinary medicinal products contain restricted
substances resulting from the implementation of the relevant
United Nations conventions on narcotic and psychotropic
substances, consideration should be given to any special
requirement that need to be satisfied before the products could be
used.
(5) A veterinary medicinal product or a medicinal product
supplied for administration under paragraphs (a), (b) and (c) of sub-
regulation (1) may only be supplied in accordance with a veterinary
prescription from a veterinary surgeon, irrespective of the legal
category assigned to the veterinary medicinal product during the
Marketing Authorisation procedure.
(6) The veterinary prescription issued under the condition
referred to in sub-regulation (5) shall be marked as such. A
statement similar to, or stating the equivalent meaning of, the
following statement: "T h is P r o du ct h as b een pr esc r ib ed i n
accordance with the Cascade Principle", shall be included on the
veterinary prescription.
(7) Unless the veterinary surgeon who prescribed the
veterinary medicinal product or medicinal product both supplies
the product and administers it to the animal in person, the person
supplying it must label it (or ensure that it is labelled) with at least
the following information
(a) the name of the veterinary surgeon who has prescribed
the product;
(b) the identification (including the species) of the animal
or group of animals;
(c) dosage and administration instructions.
(8) When a veterinary surgeon has recourse to the provisions
of regulation 10, the veterinary surgeon shall keep adequate records
of the treatment given. The records shall at least contain the
particulars mentioned in sub-regulation (7) and shall be available
for inspection by the Veterinary Services for a period of not less
than three (3) years.
(9) When a veterinary surgeon has recourse to the provisions
in paragraphs (a), (b) and (c) of sub-regulation (1), the activity
undertaken by the veterinary surgeon is excluded from the scope of
the definition of wholesale distribution under a decision to be laid
down by the Veterinary Services.
(1) By way of derogation from regulation 10(1), where
there is no suitable veterinary medicinal product available either as
an authorised product in Malta or under the provisions of regulation
10(1), veterinary surgeons may, under their direct and only
personal responsibility, build up a case and expound it to the
Veterinary Services. Veterinary surgeon shall provide detailed
justifications to their request. The Veterinary Services may where
the disease or condition is such that the veterinary medicinal
product is likely to be needed as a matter of urgency for the
treatment of an animal, allow the importation of a veterinary
medicinal product authorised for any non-food producing species
from any third country under any conditions it may deem fit. The
Veterinary Services shall base its decision on purely scientific
grounds and shall take all precautions, in particular for the safety
and environmental risks which may be associated with the use of
the veterinary medicinal product, before granting the approval for
the importation, which importation shall be considered as a once
only grant with the possibility for repeated requests, with each
request considered as sui generis.
(2)
The provisions in regulations 10 (3), (4), (5), (7), and (8) shall
apply.
(1) The Veterinary Services shall take the necessary
measures to ensure that, if there is no authorised veterinary
medicinal product in Malta for a condition affecting a food-
producing species, by way of exception, the veterinary surgeon
responsible may, under his direct personal responsibility and in
particular to avoid causing unacceptable suffering, treat the animals
concerned on a particular holding with
(a) a veterinary medicinal product authorised in Malta
under these regulations or under European Regulation
(EC) No 726/2004 for use with another animal species,
or for another condition in the same species; or
(b) if there is no product as referred to in paragraph (a),
either -
(i)
a medicinal product for human use authorised in
Malta in accordance with European Directive
2001/83/EC or under European Regulation (EC)
No 726/2004, or
(ii) a veterinary medicinal product authorised in
another Member State in accordance with these
regulations for use in the same species or in
another food-producing species for the condition
in question or for another condition; or
(c) if there is no product as referred to in paragraph (b),
and within the limits of the law of Malta, a veterinary
medicinal product prepared extemporaneously by a
pharmacist or a veterinary surgeon in accordance with
the terms of a veterinary prescription.
The veterinary surgeon may administer the medicinal
product personally or allow another person to do so
under the veterinary surgeon’s responsibility.
(2) Subregulation
(1)
shall
apply
provided
that
pharmacologically active substances included in the medicinal
product are listed in Annex I, II or III to European Regulation
(EEC) No 2377/90, and that the veterinary surgeon specifies an
appropriate withdrawal period.
Unless the medicinal product used indicates a withdrawal
period for the species concerned, the specified withdrawal period
shall not be less than
-
7 days for eggs,
-
7 days for milk,
-
28 days for meat from poultry and mammals including
fat and offal,
-
500 degree-days for fish meat.
(3) With regard to homeopathic veterinary medicinal products
i n w h i c h a c t i v e p r i n c i p l e s fi g u r e i n A n n e x I I t o E u r o p e a n
Regulation (EEC) No 2377/90, the withdrawal period referred to in
the second paragraph of subregulation (2) shall be reduced to zero.
(4) When a veterinary surgeon has recourse to the provisions of
subregulations (1) and (2), he shall keep adequate records of the
date of examination of the animals, details of the owner, the
number of animals treated, the diagnosis, the medicinal products
prescribed, the doses administered, the duration of treatment and
the withdrawal periods recommended, and shall make these records
available for inspection by the Veterinary Services for a period of at
least five years.
(5) Without prejudice to the other provisions of these
regulations, Malta shall take all necessary measures concerning the
i m p o r t , d i s t r i b u t i o n , d is p e n s i n g o f an d i n f o r m a ti o n o n t he
medicinal products which they permit for administration to food-
producing animals in accordance with subregulation (1)(b)(ii).
(6) In the case of a veterinary medicinal product authorised in
another member State, the veterinary surgeons shall obtain an
authorisation from the Veterinary Services before procuring the
product for the administration to the food producing animal.
(7) In case the veterinary medicinal products contain restricted
substances resulting from the implementation of the relevant
United Nations conventions on narcotic and psychotropic
substances, consideration shall be given to any special requirement
that need to be satisfied before the products could be used.
(8) A veterinary medicinal product or a medicinal product
supplied for administration under paragraphs (a), (b) and (c) of sub-
r e g u l a t i o n ( 1 ) , m a y o n l y b e su p p l i e d i n a c c o r d a nc e w i t h a
prescription from a veterinary surgeon, irrespective of the legal
category assigned to the veterinary medicinal product in
accordance with regulation 60.
(9) The prescription issued under the condition referred to in
sub-regulation (8) shall be marked as such. A statement similar to,
or stating the equivalent meaning of, the following statement: "This
Product has been prescribed in accordance with Cascade Principle",
shall be included on the veterinary prescription.
(10) Unless the veterinary surgeon who prescribed the
veterinary medicinal product or the medicinal product both
supplies the product and administers it to the animal in person, the
person supplying it must label it (or ensure that it is labelled) with
at least the following information
(a) the name of the veterinary surgeon who has prescribed
the product;
(b) the name and address of the animal owner;
(c) the identification (including the species) of the animal
or group of animals;
(d) the date of supply;
(e) dosage and administration instructions;
(f)
the withdrawal period, if relevant.
(11) When a veterinary surgeon has recourse to the provisions in
sub-regulation (1) the activity undertaken by the veterinary surgeon is
excluded from the scope of the definition of wholesale distribution.
(1)By way of derogation from regulation 11 (1) and from
Article 16(1) of Regulation (EC) No 470/2009, where there is no
suitable veterinary medicinal product available either as an
authorised product i n the Malt a o r und er th e p ro visi ons of
regulation 11(1), veterinary surgeon may, under their direct and
only personal responsibility, build up a case and expound it to the
Veterinary Services. Veterinary surgeons shall provide detailed
justifications to their request. The Veterinary Services shall and
where the disease or condition is such that the veterinary medicinal
product is likely to be needed as a matter of urgency for the
treatment of an animal, allow the importation of a veterinary
medicinal product authorised for any food producing species from
any Third country under any conditions it may deem fit, including
the assignment of an appropriate withdrawal period, if applicable.
The Veterinary Services shall base its decision on purely scientific
grounds and shall take all precautions, in particular for the safety
and environmental risks which may be associated with the use of
the veterinary medicinal product, before granting the approval for
the importation, which importation shall be considered as a once
only grant with the possibility for repeated requests, with each
request considered as sui generis.
(2) The provisions of sub-regulations (6), (7), (8) and (10)of
regulations 11 shall apply.
(1) For the purposes of obtaining a marketing
authorisation in respect o f a vet erinary med icinal p rodu ct ,
otherwise than under the procedure established by European
Regulation (EC) No 726/2004, an application shall be lodged with
the Veterinary Services.
In the case of veterinary medicinal products which are
intended for one or more food-producing species but whose
pharmacologically active substances have not yet been included,
for the species in question, in Annexes I, II or III to European
Regulation (EEC) No 2377/90, a marketing authorisation may not
be applied for until after a valid application has been made for the
establishment of maximum residue limits in accordance with that
Regulation. At least six months shall elapse between a valid
application for the establishment of maximum residue limits and an
application for a marketing authorisation.
However, in the case of veterinary medicinal products
referred to in regulation 6(3), a marketing authorisation may be
a pp li e d f o r wi t ho ut a v a l id a pp li c a t io n i n a c c or d a nc e w it h
European Reg ulatio n (EEC) No 2 377/9 0. All the scient ific
documentation necessary for the demonstration of the quality,
safety and efficacy of the veterinary medicinal product, as provided
for in subregulation (3), shall be submitted.
(2) A marketing authorisation may only be granted to an
applicant established in the European Union.
(3) The application for marketing authorisation shall include
all the administrative information and scientific documentation
necessary for demonstrating the quality, safety and efficacy of the
veterinary m edicinal product in question. T he file shall be
submitted in accordance with the Schedule and shall contain, in
particular, the following information
(a) name or business name and permanent address or
registered place of business of the person responsible
for placing the product on the market and, if different,
of the manufacturer or manufacturers involved and of
the sites of manufacture;
(b) name of veterinary medicinal product;
(c) qualitative and quantitative particulars of all the
constituents of the veterinary medicinal product,
including its international non-proprietary name (INN)
recommended by the WHO, where an INN exists, or its
chemical name;
(d) description of the method of manufacture;
(e) therapeutic indications, contra-indications and adverse
reactions;
(f)
dosage for the various species of animal for which the
veterinary medicinal product is intended, its
pharmaceutical form, method and route of
administration and proposed shelf life;
(g) reasons for any precautionary and safety measures to
be taken when storing the veterinary medicinal
product, administering it to animals and disposing of
waste, together with an indication of potential risks
that the veterinary medicinal product might pose to the
environment, to human and animal health and to
plants;
(h) indication of the withdrawal period in the case of
medicinal products intended for food-producing
species;
(i)
description of the testing methods employed by the
manufacturer;
(j)
results of
-
pharmaceutical (physico-chemical, biological or
microbiological) tests,
-
safety tests and residue tests,
-
pre-clinical and clinical trials;
-
tests assessing the potential risks posed by the
medicinal product for the environment. This
impact shall be studied and consideration shall
be given on a case-by-case basis to specific
provisions seeking to limit it;
(k) a detailed description of the pharmacovigilance system
and, where appropriate, the risk management system
that the applicant will put in place;
(l)
a summary in accordance with regulation 14 of the
product characteristics, a mock-up of the immediate
packaging and the outer packaging of the veterinary
medicinal product, together with the package leaflet,
in accordance with regulations 53 to 55;
(m) a document showing that the manufacturer is
authorized in his own country to produce veterinary
medicinal products;
(n) copies of any marketing authorisation obtained in
another Member State or in a third country for the
relevant veterinary medicinal product, together with a
list of those Member States in which an application for
authorisation submitted in accordance with these
regulations is under examination. Copies of the
summary of the product characteristics proposed by
the applicant in accordance with regulation 14 or
approved by the Veterinary Services in accordance
with regulation 25 and copies of the package insert
proposed, details of any decision to refuse
authorisation, whether in the European Union or a
third country and the reasons for that decision. All this
information shall be updated on a regular basis;
(o) proof that the applicant has the services of a qualified
person responsible for pharmacovigilance and has the
necessary means for the notification of any adverse
reaction suspected of occurring either in the European
Union or in a third country;
(p) in the case of veterinary medicinal products intended
for one or more food-producing species and containing
one or more pharmacologically active substances not
yet included, for the species in question, in Annexes I,
II or III to European Regulation (EEC) No 2377/90, a
document certifying that a valid application for the
establishment of maximum residue limits has been
submitted to the Agency in accordance with the
aforementioned Regulation.
The documents and particulars relating to the results of the
tests referred to in paragraph (j) shall be accompanied by detailed
and critical summaries, drawn up as specified in regulation 15.
(1) By way of derogation from regulation 12(3)(j), and
without prejudice to the law relating to the protection of industrial
and commercial property, the applicant shall not be required to
provide the results of the safety and residue tests or of the pre-
clinical and clinical trials if he can demonstrate that the medicinal
product is a generic of a reference medicinal product which is or
has been authorised under regulation 5 for not less than eight years
in a Member State or the European Union.
A generic veterinary medicinal product authorized pursuant
to this provision shall not be placed on the market until ten years
have elapsed from the initial authorisation of the reference product.
The first subregulation shall also apply when the reference
medicinal product was not authorised in the Member State in which
the application for the generic medicinal product is submitted. In
this case, the applicant shall indicate in the application the Member
State in which the reference medicinal product is or has been
authorised. At the request of the Veterinary Services, the competent
authority of the other Member State shall transmit, within a period
of one month, confirmation that the reference medicinal product is
or has been authorized together with the full composition of the
reference product and if necessary other relevant documentation.
However, the ten-year period provided for in the second paragraph
shall be extended to thirteen years in the case of veterinary
medicinal products for fish or bees or other species designated in
accordance with the procedure referred to in Article 89(2) of
European Union Council Directive 2004/28 EC.
(2)
For the purposes of this regulation
(a) "reference medicinal product" shall mean a product
authorised within the meaning of regulation 5 in
accordance with the provisions of regulation 12;
(b) "generic medicinal product" shall mean a medicinal
product which has the same qualitative and
quantitative composition in active substances and the
same pharmaceutical form as the reference medicinal
product, and whose bioequivalence with the reference
medicinal product has been demonstrated by
appropriate bioavailability studies. The different salts,
esters, ethers, isomers, mixtures of isomers, complexes
or derivatives of an active substance shall be
considered to be the same active substance, unless they
differ significantly in properties with regard to safety
and, or efficacy. In such cases, additional information
intended to provide proof of the safety and, or efficacy
of the various salts, esters or derivatives of an
authorised active substance must be supplied by the
applicant. The various immediate-release oral
pharmaceutical forms shall be considered to be one
and the same pharmaceutical form. Bioavailability
studies neednot be required of the applicant if he can
demonstrate that the generic medicinal product meets
the relevant criteria as defined in the appropriate
detailed guidelines.
(3) In cases where the veterinary medicinal product does not
fall under the definition of a generic medicinal product set out in
subregulation (2)( b ) or where bio-equivalence cannot be
demonstrated through bioavailability studies or in the case of
changes to the active substance(s), therapeutic indications,
strength, pharmaceutical form or route of administration vis-à-vis
the reference medicinal product, the results of the appropriate
safety and residue tests and pre-clinical tests or clinical trials shall
be provided.
(4) Where a biological veterinary medicinal product which is
similar to a reference biological veterinary medicinal product does
not meet the conditions in the definition of generic medicinal
products, owing to, in particular, differences relating to raw
materials or in manufacturing processes of the biological veterinary
medicinal product and the reference biological veterinary
medicinal product, the results of appropriate pre-clinical tests or
clinical trials relating to these conditions must be provided. The
type and quantity of supplementary data to be provided must
comply with the relevant criteria stated in the Schedule and the
related detailed guidelines. The results of other tests and trials from
the reference medicinal product’s dossier shall not be provided.
(5) In the case of veterinary medicinal products intended for
one or more food-producing species and containing a new active
substance that has not been authorised in the European Union by 30
April 2004 the ten-year period provided for in the second paragraph
of subregulation (1) shall be extended by one year for each
extension of the marketing authorisation to another food-producing
species, if it is authorised within the five years following the
granting of the initial marketing authorisation.
This period shall not, however, exceed a total of thirteen
years, for a marketing authorisation for four or more food-
producing species.
The extension of the ten-year period to eleven, twelve, or
thirteen years for a veterinary medicinal product intended for food-
producing species shall be granted only if the marketing
authorisation holder also originally applied for determination of the
maximum residue limits established for the species covered by the
authorisation.
(6) Conducting the necessary studies, tests and trials with a
view to the application of subregulations (1) to (5) and the
consequential practical requirements shall not be regarded as
contrary to patent-related rights or to supplementary-protection
certificates for medicinal products.
(1) By way of derogation from regulation 12(3)(j), and
without prejudice to the law on the protection of industrial and
commercial property, the applicant shall not be required to provide
the results of safety and residue tests or of pre-clinical tests or
clinical trials if he can demonstrate that the active substances of the
veterinary medicinal product have been in well-established
veterinary use within the European Union for at least ten years,
with recognised efficacy and an acceptable level of safety in terms
of the conditions set out in the Schedule. In that event, the
applicant shall provide appropriate scientific literature.
(2) The assessment report published by the Agency following
the evaluation of an application for the establishment of maximum
residue limits in accordance with European Regulation (EEC) No
2377/90 may be used in an appropriate manner as literature,
particularly for the safety tests.
(3) If an applicant makes use of scientific literature to obtain
authorisation for a food-producing species, and submits, in respect
of the same medicinal product and with a view to obtaining
authorisation for another food-producing species, new residue
studies in acco rdance w ith European Regulation (EEC) No
2377\90, together with further clinical trials, it shall not be
permissible for a third party to use such studies or such trials
pursuant to regulation 13, for a period of three years from the grant
of the authorization for which they were carried out.
In the case of veterinary medicinal products containing
active substances used in the composition of authorized veterinary
medicinal products but not hitherto used in combination for
therapeutic purposes, the results of safety and residue tests, if
necessary, and new pre-clinical tests or new clinical trials relating
to that combination shall be provided in accordance with regulation
12 (3)( j), but it sh all not b e n ecessary to provide scien tific
references relating to each individual active substance.
After the marketing authorisation has been granted, the
marketing authorisation holder may allow use to be made of the
pharmaceutical, safety and residues, pre-clinical and clinical
documentation contained in the file for the veterinary medicinal
product with a view to examining a subsequent application for a
veterinary medicinal product having the same qualitative and
quantitative composition in active substances and the same
pharmaceutical form.
By way of derogation from regulation 12(3)(j), and in
exceptional circumstances with respect to immunological
veterinary medicinal products, the applicant shall not be required to
provide the results of certain field trials on the target species if
these trials cannot be carried out for duly substantiated reasons, in
particular on account of other European Union provisions.
The summary of the product characteristics shall contain,
in the order indicated below, the following information
(1) name of the veterinary medicinal product followed by
the strength and the pharmaceutical form;
(2) qualitative and quantitative composition in terms of
the active substances and constituents of the excipient,
knowledge of which is essential for proper
administration of the medicinal product. The usual
common name or chemical description shall be used;
(3) pharmaceutical form;
(4) clinical particulars
(i)
target species,
(ii)
indications for use, specifying the target species,
(iii)
contra-indications,
(iv)
special warnings for each target species,
(v)
special precautions for use, including special
precautions to be taken by the person
administering the medicinal product to the
animals,
(vi)
adverse reactions (frequency and seriousness),
(vii) use during pregnancy, lactation or lay,
(viii) interaction with other medicinal products and
other forms of interaction,
(ix) amounts to be administered and administration
route,
(x)
overdose (symptoms, emergency procedures,
antidotes), if necessary,
(xi)
withdrawal periods for the various foodstuffs,
including those for which the withdrawal period
is zero;
(5) pharmacological properties
(i) pharmacodynamic properties,
(ii) pharmacokinetic particulars;
(6) pharmaceutical particulars
(i) list of excipients,
(ii) major incompatibilities,
(iii) shelf life, when necessary after reconstitution of
the medicinal product or when the immediate
packaging is opened for the first time,
(iv) special precautions for storage,
(v) nature and composition of immediate packaging,
(vi) special precautions for the disposal of unused
veterinary medicinal products or waste materials
derived from the use of such products, if
appropriate;
(7) marketing authorisation holder;
(8) marketing authorisation number(s);
(9) date of the first authorisation or date of renewal of the
authorisation;
(10) date of revision of the text.
For authorisation under regulation 13, those parts of the
summary of product characteristics of the reference medicinal
product referring to indications or dosage forms which were still
covered by patent law at the time when a generic medicine was
marketed need not be included.
(1) Applicants shall ensure that the detailed and critical
summaries referred to in the second paragraph of regulation 12(3)
are drafted and signed by persons with the requisite technical or
professional qualifications, set out in a brief curriculum vitae,
before being submitted to the Veterinary Services.
(2) Persons with the technical or professional qualifications
referred to in subregulation (1) shall justify any use made of the
scientific literature referred to in regulation 13A(1) in accordance
with the conditions set out in the Schedule.
(3) A brief curriculum vitae of the persons referred to in
subregulation (1) shall be appended to the detailed critical
summaries.
CHAPTER 2
Particular provisions applicable to homeopathic
veterinary medicinal products
(1) The Veterinary Services shall ensure that homeopathic
veterinary medicinal products manufactured and placed on the
market within the European Union are registered or authorised in
accordance with regulations 17, 18 and 19, except where such
veterinary medicinal products are covered by a registration or
authorisation granted in accordance with national legislation on or
before 31 December 1993. In the case of homeopathic medicinal
products registered in accordance with regulation 17, regulation 32
and regulation 33(1) to (3) shall apply.
(2) The Veterinary Services shall establish a simplified
registration procedure for the homeopathic veterinary medicinal
products referred to in regulation 17.
(3) By way of derogation from regulation 10, homeopathic
veterinary medicinal products may be administered to non-food
producing animals under the responsibility of a veterinary surgeon.
(4) By way of derogation from regulation 11(1) and (2), Malta
s h a l l p e r m i t t h e a d m i n i st r a t i o n o f h o m e o p at h i c v e t e r i n a r y
medicinal products intended for food-producing species the active
constituents of which appear in Annex II to European Regulation
(EEC) No 2377/90 under the responsibility of a veterinary surgeon.
The Veterinary Services shall take appropriate measures to control
the use of veterinary homeopathic medicinal products registered or
authorised in another Member State in accordance with these
regulations for use in the same species.
(1) Without prejudice to the provisions of European
Regulation (EEC) No 2377/90 on the establishment of maximum
residue limits of pharmacologically active substances intended for
food-producing animals, only homeopathic veterinary medicinal
products which satisfy all of the following conditions may be
subject to a special, simplified registration procedure
(a) they are administered by a route described in the
European Pharmacopoeia or, in the absence thereof, by
the Pharmacopoeias currently used officially in Malta;
(b) no specific therapeutic indication appears on the
labelling of the veterinary medicinal product or in any
information relating thereto;
(c) there is a sufficient degree of dilution to guarantee the
safety of the medicinal product. In particular, the
medicinal product shall not contain more than one part
per 10 000 of the mother tincture.
(2) The criteria and rules of procedure provided for in Chapter
3, with the exception of regulation 25, shall apply by analogy to the
special, simplified r egistration proce dure for homeopathic
veterinary medicinal products referred to in subregulation (1), with
the exception of the proof of therapeutic effect.
A special, simplified application for registration may cover
a series of medicinal products derived from the same homeopathic
stock or stocks. The following documents shall be included with
t h e a p p l i c a t i o n i n o r d e r t o d e m o n s t r a t e , i n p a r t i c u l a r, t h e
pharmaceutical quality and the batch-to-batch homogeneity of the
products concerned
(a) scientific name or other name given in a
pharmacopoeia of the homeopathic stock or stocks,
together with a statement of the various routes of
administration, pharmaceutical forms and degree of
dilution to be registered,
(b) dossier describing how any homeopathic stock has
been obtained and is controlled, and justifying its
homeopathic nature, on the basis of an adequate
bibliography; in the case of homeopathic veterinary
medicinal products containing biological substances, a
description of the measures taken to ensure the
absence of pathogens,
(c) manufacturing and control file for each pharmaceutical
form and a description of the method of dilution and
potentisation,
(d) manufacturing authorisation
for
the
medicinal
products concerned,
(e) copies of any registrations or authorisations obtained
for the same medicinal products in Member States,
(f)
one or more mock-ups of the outer packaging and
immediate packaging of the medicinal products to be
registered,
(g) data concerning the stability of the medicinal product,
(h) proposed withdrawal period together with all requisite
justification.
(1) Homeopathic veterinary medicinal products other than
those referred to in regulation 17(1) shall be authorized in
accordance with regulations 12, 13A, 13B, 13C, 13D and 14.
(2) Malta may introduce or retain on its territory specific rules
for the safety tests and pre-clinical and clinical trials of
homeopathic veterinary medicinal products intended for pet species
and non-food-producing exotic species other than those referred to
i n r e g u l a t i o n 1 7 ( 1 ) , i n a c c o r d a n c e w i t h t h e p r i n c i p l es a n d
characteristics of homeopathy as practised in Malta. In this case,
the Veterinary Services shall notify the European Commission of
the specific rules in force.
This Chapter shall not apply to immunological
homeopathic veterinary medicinal products. The provisions of
Titles VI and VII shall apply to homeopathic veterinary medicinal
products.
CHAPTER 3
Procedure for marketing authorisation
(1) The Veterinary Services shall take all appropriate
measures to ensure that the procedure for granting a marketing
authorisation for a veterinary medicinal product is completed
within a maximum of two hundred and ten days days after the
submission of a valid application.
Applications for marketing authorisations for the same
veterinary medicinal product in two or more Member States, shall
be submitted in accordance with regulations 31 to 43.
(2) Where Malta notes that another marketing authorisation
application for the same medicinal product is being examined in
another Member State, Malta shall decline to assess the application
and shall advise the applicant that regulations 31 to 43 apply.
Where the Veterinary Services is informed, in accordance
with regulation 12(3)(n), that another Member State has authorised
a veterinary medicinal product which is the subject of an
application for authorisation in Malta, the Veterinary Services shall
reject the application unless it was submitted in compliance with
regulations 31 to 43.
In order to examine the application submitted pursuant to
regulations 12 to 13D, the Veterinary Services -
(1) shall check that the documentation submitted in
support of the application complies with regulations
12 to 13D and ascertain whether the conditions for the
issue of the marketing authorisation have been
fulfilled;
(2) may submit the medicinal product, its starting
materials and if necessary intermediate products or
other constituent materials for testing by an Official
Medicines Control Laboratory or a laboratory that has
designated for that purpose by the Veterinary Services,
in order to ensure that the testing methods employed
by the manufacturer and described in the application
documents, in accordance with regulation 12(3)(i), are
satisfactory;
(3) may similarly check, in particular through consultation
of a national or European Union reference laboratory,
that the analytical method used for detecting residues
presented by the applicant for the purposes of
regulation 12(3)(j), second indent is satisfactory;
(4) may, where appropriate, require the applicant to
provide further information as regards the items listed
in regulations 12, 13A, 13B, 13C and 13D. Where the
Veterinary Services take this course of action, the
time-limits specified in regulation 21 shall be
suspended until the further data required have been
provided. Similarly, these time-limits shall be
suspended for any period which the applicant may be
given to provide oral or written explanations.
The Director shall take all appropriate measures to ensure
that -
(a) the Veterinary Services ascertains that the
manufacturers and importers of veterinary medicinal
products from third countries are able to manufacture
them in compliance with the details supplied pursuant
to regulation 12(3)(d), and, or to carry out control tests
in accordance with the methods described in the
application documents under regulation 12(3)(i);
(b) the Veterinary Services may authorise manufacturers
and importers of veterinary medicinal products from
third countries, where circumstances so justify, to have
certain stages of manufacture and, or certain of the
control tests referred to in paragraph (a) carried out by
third parties; in such cases, checks by the Veterinary
Services shall also be carried out in the establishments
concerned.
(1) When granting a marketing authorisation, the
Veterinary Services shall inform the holder of the summary of
product characteristics that it has approved.
(2) The Veterinary Services shall take all necessary measures to
ensure that information concerning the veterinary medicinal
product, and in particular the labelling and package leaflet, is in
conformity with the summary of product characteristics approved
when the marketing authorisation was granted or subsequently.
(3) The Veterinary Services shall make the marketing
authorisation publicly available without delay, together with the
summary of product characteristics for each veterinary medicinal
product that it has authorised.
(4) The Veterinary Services shall draw up an assessment report
and comments on the file as regards the results of the
pharmaceutical, safety and residue tests and the pre-clinical and
clinical trials of the veterinary medicinal product concerned. The
assessment report shall be updated whenever new information
becomes available which is of importance for the evaluation of the
quality, safety or efficacy of the veterinary medicinal product
concerned.
The Veterinary Services shall make the assessment report
and its reasons for the opinion publicly available without delay,
after deleting any information of a commercially confidential
nature.
(1) The marketing authorisation may require the holder to
indicate on the immediate packaging and, or the outer wrapping
and the package leaflet, w here the latter is r equired, other
particulars essential for safety or health protection, including any
special precautions relating to use and any other warnings resulting
f r o m t h e c l i n i c a l a n d p h a r m a c ol o g i c a l t r i a l s p r e s c r i b ed i n
regulation 12(3)(j) and in regulations 13 to 13D or from experience
gained during the use of the veterinary medicinal product once it
has been marketed.
(2) In exceptional circumstances, and following consultation
with the applicant, the authorization may be granted subject to a
requirement for the applicant to introduce specific procedures, in
particular concerning the safety of the veterinary medicinal
product, notification to the competent authorities of any incident
relating to its use, and action to be taken. Such authorisations may
be granted only for objective, verifiable reasons. Continuation of
the authorization shall be linked to the annual reassessment of such
conditions.
(1) After a marketing authorisation has been issued, the
holder must, in respect of the manufacturing methods and control
methods provided for in regulation 12(3)(d) and (i), take account of
scientific and technical progress and introduce any changes that
may be required to enable that veterinary medicinal product to be
manufactured and checked by means of gen er al ly accepted
scientific methods.
These changes shall be subject to the approval of the
Veterinary Services.
(2) The Veterinary Services may require the applicant or the
marketing authorisation holder to provide sufficient quantities of
the substances to enable controls to be made on the identification of
the presence of residues of the veterinary medicinal products in
question.
At the Veterinary Services’ request, the marketing
authorisation holder shall provide his technical expertise to
facilitate the implementation of the analytical method for detecting
residues of the veterinary medicinal products in the national
reference laboratory designated under European Union Council
Directive 96/23/EC on measures to monitor certain substances and
residues thereof in live animals and animal products.
(3) The authorisation holder shall immediately supply the
Veterinary Services with any new information that might entail the
amendment of the particulars or documents referred to in
regulations 12(3), 13, 13A, 13B and 14 or in the Schedule.
In particular, he shall immediately inform the Veterinary
Services of any prohibition or restriction imposed by the competent
authorities of any country in which the veterinary medicinal
product is placed on the market and of any other new information
which might influence the assessment of the benefits and risks of
the veterinary medicinal product concerned.
In order to permit continuous assessment of the risk-benefit
balance, the Veterinary Services may at any time ask the marketing
authorisation holder to forward data demonstrating that the risk-
benefit balance remains favourable.
(4)
(Deleted by L.N. 82 of 2006).
(5) The marketing authorisation holder shall immediately
inform the Veterinary Services, with a view to authorisation, of any
a l t e r a t i o n w hi c h h e p r o p o s e s to m a k e t o t h e p a r t i c ul a r s o r
documents referred to in regulations 12 to 13D.
After a marketing authorisation has been granted, the
holder of the authorisation shall inform the Veterinary Services of
the date of the actual placing on the market of the veterinary
medicinal product in Malta, taking into account the various
presentations authorised.
The holder shall also notify the Veterinary Services if the
product ceases to be placed on the market o f M alta, either
temporarily or permanently. Such notification shall, otherwise than
in exceptional circumstances, be made no less than two months
before the interruption in the placing on the market of the product.
Upon request by the Veterinary Services, particularly in the
context of pharmacovigilance, the marketing authorization holder
shall provide the Veterinary Services with all data relating to the
volume of sales of the veterinary medicinal product, and any data
in his possession relating to the volume of prescriptions.
(1) Without prejudice to subregulations (4) and (5), a
marketing authorisation shall be valid for five years.
(2) The authorisation may be renewed after five years on the
basis of a re-evaluation of the risk-benefit balance.
To this end, the marketing authorisation holder shall submit
a consolidated list of all documents submitted in respect of quality,
safety and efficacy, including all variations introduced since the
marketing authorization was granted, at least six months before the
marketing authorisation ceases to be valid in accordance with
subregulatioon (1). The Veterinary Services may require the
applicant to submit the listed documents at any time.
(3) Once renewed, the marketing authorisation shall be valid
for an unlimited period, unless the Veterinary Services decides, on
justified grounds relating to pharmacovigilance, to proceed with
one additional five-year renewal in accordance with subregulation
(2).
(4) Any authorisation that is not followed within three years of
its granting by the actual placing on the market of the authorised
veterinary medicinal product in Malta, shall cease to be valid.
(5) When an authorised veterinary medicinal product
previously placed on the market in Malta is no longer actually
present on Malta for a period of three consecutive years, the
authorisation granted for that veterinary medicinal product shall
cease to be valid.
(6) The Veterinary Services may, in exceptional circumstances,
and on human or animal health grounds, grant exemptions from
subregulations (4) and (5). Such exemptions shall be duly justified.
The granting of authorisation shall not diminish the general
legal liability of the manufacturer and, where appropriate, of the
authorisation holder.
The marketing authorisation shall be refused if the file
submitted to the Veterinary Services does not comply with
regulations 12 to 13D and regulation 15.
The authorisation shall also be refused if, after examination
of the documents and particulars listed in regulations 12 and 13(1),
it is clear that -
(a) the risk-benefit balance of the veterinary medicinal
product is, under the authorised conditions of use,
unfavourable; when the application concerns a
veterinary medicinal product for zootechnical use,
particular regard shall be had to the benefits for animal
health and welfare and to consumer safety; or
(b) the product has no therapeutic effect or the applicant
has not provided sufficient proof of such effect as
regards the species of animal which is to be treated; or
(c) its qualitative or quantitative composition is not as
stated; or
(d) the withdrawal period recommended by the applicant
is not long enough to ensure that foodstuffs obtained
from the treated animal do not contain residues which
might constitute a health hazard to the consumer, or is
insufficiently substantiated; or
(e) the labelling or the package leaflet proposed by the
applicant does not comply with these regulations; or
(f)
the veterinary medicinal product is offered for sale for
a use prohibited under other European Union
provisions.
However, when a European Union legislative framework is
in the course of being adopted, the Veterinary Services may refuse
authorisation for a veterinary medicinal product where such action
is necessary for the protection of public health, consumer or animal
health.
The applicant or marketing authorisation holder shall be
responsible for the accuracy of documents and data submitted.
CHAPTER 4
Mutual recognition procedure and decentralized procedure
(1) With a view to the granting of a marketing
authorization for a veterinary medicinal product in more than one
Member State, the applicant shall submit an application based on
an identical dossier in those Member States. The dossier shall
contain all the administrative information and scientific and
technical documentation described in regulations 12 to 14. The
docu ments subm itted shall i nclu de a list of Mem ber States
concerned by the application.
The applicant shall request one Member State to act as
reference Member State and to prepare an assessment report in
respect of the veterinary medicinal product in accordance with
subregulation (2) or (3).
Where appropriate, the assessment report shall contain an
evaluation for the purposes of regulation 13(5) or regulation
13A(3).
(2) If the veterinary medicinal product has already received a
marketing authorisation at the time of application, the concerned
Member States shall recognize the marketing authorisation granted
by t he reference Mem ber State. To thi s end, t he m ark et ing
authorization holder shall request the reference Member State
either to prepare an assessment report in respect of the veterinary
m e d i c i n a l p r o d u c t o r, i f n e c e s s a r y, t o u p d a t e a n y e x i s t i n g
assessment report. The reference Member State shall prepare or
update the assessment report within ninety days of receipt of a
valid application. The assessment report together with the approved
summary of product characteristics, labelling and package leaflet
shall be forwarded to the concerned Member States and the
applicant.
(3) If the veterinary medicinal product has not received
authorisation by the time of application, the applicant shall request
the reference Member State to prepare a draft assessment report and
drafts of the summary of product characteristics, labelling and
package leaflet. The reference Member State shall prepare these
drafts within one hundred and twenty days of the receipt of a valid
application and shall send them to the concerned Member States
and the applicant.
(4) Within ninety days after receipt of the documents referred
to in subregulations (2) and (3), the Member States concerned shall
approve the assessment report, the summary of product
characteristics, the labelling and the package leaflet and inform the
reference Member State accordingly. The reference Member State
shall record the agreement of all parties, close the procedure and
inform the applicant accordingly.
(5)
Each Member State in which an application following
paragraph 1 has been submitted shall adopt a decision in
conformity with the approved assessment report, summary of
product characteristics, labelling and package leaflet within thirty
days after acknowledgement of the agreement.
(1) If Malta cannot, within the period allowed in
regulation 31(4), agree with the assessment report, summary of
product characteristics, labelling and package leaflet on grounds of
a potential serious risk to human or animal health or to the
environment, a detailed statement of the reasons shall be provided
to the reference Member State, the other Member States concerned
and the applicant. The points of disagreement shall be referred
without delay to the coordination group.
If a Member State to which an application has been
submitted invokes the reasons referred to in regulation 64(1), it
shall no longer be regarded as a Member State concerned by this
Chapter.
(2) Within the co-ordination group, all Member States referred
to in subregulation (1) shall use their best endeavours to reach
agreement on the action to be taken. They shall provide the
applicant with the opportunity to make his point of view known
orally or in writing. If, within sixty days of the communication of
the reasons for disagreement to the coordination group the Member
States reach an agreement, the reference Member State shall record
the agreement, close the procedure and inform the applicant
accordingly. Regulation 31(5) shall apply in such cases.
(3) If within the period of sixty days the Member States fail to
reach an agreement, the Agency shall be immediately informed
with a view to application of the procedure laid down in Articles
36, 37 and 38 of European Union Council Directive 2004/28/EC.
The Agency shall be provided with a detailed description of the
matters on which agreement could not be reached and the reasons
for the disagreement. The applicant shall be provided with a copy
of such information.
(4) As soon as the applicant has been informed that the matter
has been referred to the Agency, he shall forthwith forward to the
Agency a copy of the information and documents referred to in the
first subparagraph of regulation 31(1).
(5) In the case referred to in subregulation (3), the Member
States that have approved the assessment report, summary of
product characteristics, labelling and package leaflet of the
reference Member State may, on request by the applicant, grant a
marketing authorisation for the veterinary medicinal product
without waiting for the outcome of the procedure laid down in
Article 36 of European Union Council Directive 2004/28/EC. In
that case, the authorisation granted shall be without prejudice to the
outcome of that procedure.
If two or more applications submitted in accordance with
regulations 12 to 14 have been made for marketing authorisation
for a particular veterinary medicinal product and Member States
have adopted divergent decisions concerning the authorisation of
that veterinary medicinal product, or suspension or revocation of
authorisation, a Member State, or the European Commission, or the
marketing-autho risation holder m ay refer the matter to the
Committee for Medicinal Products for Veterinary Use, hereinafter
referred to as "the Committee", for the application of the procedure
laid down in Articles 36, 37 and 38 of European Union Council
Directive 2004/28/EC.
Malta or the European Commission or the applicant or
marketing authorisation holder shall, in specific cases where the
interests of the European Community are involved, refer the matter
to the Committee for the application of the procedure laid down in
Articles 36, 37 and 38 of European Union Council Directive 2004/
28/EC before a decision is reached on a request for a marketing
authorization or on the suspension or withdrawal of an
authorisation, or on any other variations to the terms of a marketing
authorisation which appear necessary, so as to take account in
particular of the information collected in accordance with Title VII.
Malta or the European Commission shall clearly identify
the question which is referred to the Committee for consideration
and shall inform the applicant or the marketing authorisation
holder.
Malta and the applicant or the marketing authorisation
holder shall forward to the Committee all available information
relating to the matter in question.
(1) Where the Director considers that the variation of the
terms of a marketing authorisation which has been granted in
accordance with the provisions of this Chapter or its suspension or
withdrawal is necessary for the protection of human or animal
health or the environment, it shall forthwith refer the matter to the
Agency for the application of the procedure laid down in articles
36, 37 and 38 of European Union Council Directive 2001/82.
(2) Without prejudice to the provisions of regulation 34(1), in
exceptional cases, where urgent action is essential to protect human
or animal health or the environment, until a definitive decision is
adopted, the Director may suspend the marketing and the use of the
veterinary medicinal product concerned on its territory. It shall
inform the European Commission and the other Member States no
later than the following working day of the reasons for its action.
Articles 39 and 40 of European Union Council Directive
2001/82/EC shall apply by analogy to veterinary medicinal
products authorised by Member States following an opinion of the
Committee given in accordance with previous regulations.
Regulations 32(3), (4) and (5) and 33 to 34 shall not apply
to the homeopathic veterinary medicinal products referred to in
regulation 17.
Regulations 31 to 34 shall not apply to the homeopathic
veterinary medicinal products referred to in regulation 19(2).
TITLE IV
MANUFACTURE AND IMPORTS
(1)
The provisions of this Title shall not apply to
(a)
magistral formula;
(b)
officinal formula;
(c)
veterinary medicinal products intended for research
and development trials;
(d)
intermediate products intended for further processing
by an authorised manufacturer;
(e)
any radionuclides in the form of sealed sources;
(f)
whole blood, plasma or blood cells of animal origin,
except for plasma which is prepared by a method
involving an industrial process;
(g)
veterinary medicinal products supplied in response to
a bona fide unsolicited order, formulated in
accordance with the specifications of a
veterinary surgeon and for use by an individual
animal under his direct personal responsibility.
(2) The provisions of these regulations shall apply also to the
manufacture and assembly of homeopathic veterinary medicinal
products, veterinary medicinal products derived from animal blood or
plasma, radiopharmaceuticals, immunological veterinary medicinal
products and herbal veterinary medicinal products..
(1) (a)No veterinary medicinal product, biological active
substance, or active substance to be used directly as an
investigational veterinary medicinal product, may be manufactured
in Malta unless there is, in respect of such product or substance, a
Manufacturing Authorisation.
This Manufacturing Authorisation shall also be required for the
processes of sterilisation of active substances.
(b) The Manufacturing Authorisation shall also be
required for the manufacture of veterinary medicinal
products intended for export.
2. (a)The Manufacturing Authorisation, which shall remain in
force for a period to be determined by the Veterinary Services, shall
be required for both total and partial manufacture, and for the
various processes of dividing up, packaging or presentation.
(b) A Manufacturing Authorisation shall not be required
for preparation, dividing up, changes in packaging or
presentation where such processes are carried out
solely for retail supply by pharmacists in veterinary
pharmacies, or by other persons legally authorised to
carry out such processes.
(3) The authorisation referred to in sub-regulation (1) shall also
be required for imports from third countries into the territory of
Malta;
The Director shall take all appropriate measures to ensure that
veterinary medicinal products brought into the territory from a
third country and destined for Member States are accompanied by a
copy of the authorisation referred to in sub-regulation (1).
(4) Any application for the grant of a licence to manufacture,
assemble or modify a veterinary medicinal product shall be made to
the Veterinary Services and shall contain such information,
d oc u m e n ts , sa m p l e s a nd o t h e r m a t e r i a l a s p r o v i d e d b y t h e
provisions of these regulations.
(5) A Manufacturing Authorisation shall include a licence to
distribute by wholesale the veterinary medicinal products in respect
of which the Manufacturing Authorisation has been issued.
(6) The Veterinary Services shall forward to the Agency a copy
of the Authorisation referred to in sub-regulation (1).
(7) The Veterinary Services shall enter the information relating to
the Authorisation referred to in sub-regulation (1) in the European
Union database referred to in regulation 72(6).
The Veterinary Services, shall only grant or renew an
Authorisation, if the applicant
(a) specifies the veterinary medicinal products and
pharmaceutical forms which are to be manufactured or
imported and the place where they are to be
manufactured and, or controlled;
(b) has at his disposal, for the manufacture or import of
veterinary medicinal products, suitable and sufficient
premises, technical equipment and control facilities
complying with requirements set by the Veterinary
Services;
(c) has at his disposal the services of at least one qualified
person within the meaning of regulation 46; and
(d) provides all necessary documentation in support of his
application.
(1)(a)The Veterinary Services shall issue the Authorisation
after verifying the contents of the application but in any case not
later than ninety (90) days from receipt of the application.
(b)
This time period shall be suspended when the
Veterinary
Services
requests
additional
information from the applicant.
(c)
The Veterinary Services shall, before determining an
application, inspect the premises indicated in the
application and shall not issue an Authorisation
until it is satisfied that such premises conform
with the requirements established by the
provisions of these regulations;
(d)
The Veterinary Services may grant a conditional
licence subject to the carrying out of certain
obligations imposed on the applicant.
(2) The Authorisation shall apply only to the premises,
veterinary medicinal products and pharmaceutical forms specified
in the application.
(3) Where the Veterinary Services considers that circumstances
may exist which would render necessary the consideration of
whether the Authorisation should be varied, suspended or revoked,
the Veterinary Services may serve on the holder of a manufacturer's
Authorisation a notice requiring him, within such time as may be
specified in the notice, to furnish it with any information specified
in the notice.
(1)When the holder of the Authorisation requests a change
in the particulars specified in regulation 4(a) and 4(b), he shall
apply in writing to the Veterinary Services.
The process of verification of such information shall not exceed
thirty (30) days. However, in exceptional cases, this period of time
may be extended to ninety (90) days.
(2) The veterinary services may upon such an application made
by the holder of Authorisation in request thereof, vary the condition
of the licence if it is satisfied that such variation will not adversely
a ffec t st and ard o f g oo d p ra ct ice i n manufac ture as m a y be
prescribed.
(3) Where the Veterinary Services considers that circumstances
may exist which would render necessary the consideration of whether
the Authorisation should be varied, suspended or revoked, the
Veterinary Services may serve on the holder of a manufacturing
Authorisation a notice requiring him, within such time as may be
specified in the notice, to furnish it with any information specified in
the notice.
(1)The Veterinary Services may suspend a manufacturing
Authorisation for such period as it may determine, or may refuse,
revoke, or vary the provisions of, any such Authorisation.
(2) The powers vested in sub-regulation (1) shall only be
exercisable in any of the following circumstances, where
(a) the matters stated in the application on which the
Authorisation was granted were false or incomplete in
an essential manner;
(b) a material change of circumstances has occurred in
relation to any of those matters;
(c) any of the conditions of the Authorisation has been
contravened;
(d) the requirements in relation to the licences as
established by these regulations have not been
complied with;
(e) the processes of manufacture or assembly of a
veterinary medicinal product are carried out in a
manner that is not in compliance with the provisions of
the marketing authorisation of that veterinary
medicinal product;
(f)
the conditions for good manufacturing practice are not
being complied with;
(g) there is sale and processing of active substance and
veterinary medicinal products under unsanitary
conditions or leading to adulteration; and
(h) in any other circumstance as is established under these
regulations.
(3) The Veterinary Services shall carry out regular inspections
to ensure that the requirements established by these regulations in
relation to the m anufacture, assem bly o r m odifi cati on of a
veterinary medicinal product or active substance are complied
(4) With respect to the manufacture of veterinary medicinal
products or active substance the Veterinary Services or any
authorised person carrying out an inspection shall
(a) inspect the manufacturing establishment and any other
location and at any reasonable time the Director may
deem necessary;
(b) examine any relevant documents;
(c) take any samples the Director may deem necessary and
if necessary submit them to designated laboratories for
testing;
(d) open or/and examine or/and seize any article believed
to be in violation of these regulations or for obtaining
evidence;
(e) draw up a report of the findings and communicate the
contents of such report to the Manufacturing
Authorisation holder or the applicant for a
Manufacturing Authorisation and to the qualified
person in relation to such inspection;
(f)
carry out any other activity the Director may deem
appropriate for the proper execution of his duties and
responsibilities as provided by these regulations;
(g) produce, upon request by the inspected part, the
designated document containing information on the
legal basis and scope of the inspection and the
identification of the inspector/s;
VETERINARY MEDICINAL PRODUCTS
(h) at the time of the inspection draw up a list of
deficiencies that may have been identified and shall
sign this list, and such list shall be countersigned by
the holder of the Authorisation or his legal
representative;
(i)
shall draw up a report of the inspection within thirty
(30) working days of the inspection and shall forward
a copy of such report to the holder of the
Authorisation.
(5) Except in urgent cases an inspection shall be carried out in
the presence of a qualified person or his representative.
(6) Subject to the provisions of these regulations, every licence
shall, unless previously renewed or revoked, continue to be valid
until such time as it is r enewed by the Veterinary S ervices
following an inspection.
(7) The Veterinary Services shall establish the period of
validity of any licence.
(8) Following the inspection mentioned in sub-regulation (1),
the Veterinary Services
(a) may renew the licence, with or without modifications,
for such a further period as specified; or
(b) if, having regard to the provisions of these regulations, it
considers it necessary or expedient to do so, may refuse
to renew the licence.
(1)The holder of the Authorisation or the manufacturer of
active substance shall
(a) comply with the EU principles and guidelines of good
manufacturing practice and any annexes thereof for
veterinary medicinal products and use only active
substances which have been manufactured in
accordance with the EU guidelines on good
manufacturing practice for active substances and
distributed in accordance with good distribution
practices for active substances. To this end, the holder
of the manufacturing authorisation shall verify
compliance by the manufacturer and distributors of
active substances with good manufacturing practice
and good distribution practices by conducting audits at
the manufacturing and distribution sites of the
manufacturer and distributors of active substances.
The holder of the manufacturing authorisation shall
verify such compliance either by himself or, without
prejudice to his responsibility as provided for in these
regulations and in the Act, through an entity acting on
his behalf under a contract;
(b) inform the competent authority and the marketing
authorisation holder immediately if he obtains
information that veterinary medicinal products which
come under the scope of his manufacturing
authorisation or the active substance are, or are
suspected of being, falsified irrespective of whether
those veterinary medicinal products were distributed
within the legal supply chain or by illegal means,
including illegal sale at a distance by means of
information society services;
(c) verify that the manufacturers, importers or distributors
from whom he obtains active substances are registered
with the competent authority of the Member State in
which they are established;
(d) verify the authenticity and quality of the active
substances and the excipients.
(e) have at his disposal the services of staff complying
with the legal requirements set by the Veterinary
Services as regards both manufacture and controls
(f)
dispose of the veterinary medicinal products only in
accordance with the legislation of the territory of
Malta;
(g) give prior notice to the Veterinary Services of any
changes which he may wish to make to any of the
particulars supplied pursuant to regulation 40 or other
significant changes or of conditions which may affect
the quality, safety or efficacy of the veterinary
medicinal product.
The Veterinary Services shall, in any event, be immediately
informed if the qualified person referred to in regulation 46(1) is
replaced;
(h) enable the qualified person referred to in regulation
46(1) to carry out his duties, particularly by placing at
his disposal all the necessary facilities;
(i)
keep detailed records of all veterinary medicinal
products supplied by him, including samples, in
accordance with the laws of the countries of
destination
(i)
date;
(ii)
name of the veterinary medicinal product;
(iii)
quantity supplied ;
(iv)
name and address of the recipient;
(v)
batch number;
These records shall be available for inspection by the Veterinary
Services for a period of at least three (3) years.
(j)
the following information at least shall be recorded in
respect of each transaction, whether or not it is made
for payment;
(k) record all suspected serious adverse reactions and
human adverse reactions relating to the use of
veterinary medicinal products that are brought to his
attention and report them promptly to the Veterinary
Services in no later than fifteen days following receipt
of the information;
(l)
implement a system for recording and reviewing
complaints together with an effective system for
recalling promptly and at any time the veterinary
medicinal products or the active substance in the
distribution network;
(m) record and investigate any complaint concerning
quality defects;
(n) other responsibilities as may be established by the
Veterinary Services from time to time;
(2)
For the purposes of this regulation, manufacture of active
substances used as starting materials shall include both total and
partial manufacture or import of an active substance used as a starting
material as defined in the Schedule Part 2. Section C of these
regulations, and the various processes of dividing up, packaging or
presentation prior to its incorporation into a veterinary medicinal
product, including repackaging or re-labelling, such as are carried out
by a distributor of starting materials.
(3)
Manufacturing Authorisation holders shall be regarded
as producers and therefore held liable for damages in the cases and
under the conditions set forth in the Consumer Affairs Act.
(4)
It shall be the duty of the importer to ensure that
(a) in the case of veterinary medicinal products and
investigational veterinary medicinal products imported
from third countries, these have been manufactured in
accordance with standards which are at least
equivalent to the good manufacturing practice
standards laid down in the Good Manufacturing
Practice for Veterinary Medicinal Products Rules;
(b) in the case of veterinary medicinal products, such
products have been manufactured by manufacturers
duly authorised for the purpose; and
(c) in the case of investigational veterinary medicinal
products, such products have been manufactured by a
manufacturer notified to the competent authorities and
accepted by them for that purpose.
For the purposes of these regulations, manufacturing
active substances for use as starting materials shall include the
com plet e or part ial m anufacture or the im po rt o f an active
substance used as a starting material, as defined in Part 2, Section C
of t h e S c hed ul e, an d th e var i ou s pr oc esses of di vi d in g up ,
packaging or presentation prior to its incorporation in a veterinary
medicinal product, including repackaging or re-labelling, such as
carried out by a starting material distributor.
The Veterinary Services may require from the applicant further
information concerning both the particulars supplied pursuant to
regulation 40 and the qualified person referred to in regulation 46(1).
Where the Veterinary Services exercise this right, application of the
time limits referred to in regulations 41 and 42(1) shall be suspended
until the additional data required have been supplied.
(1)The holder of the Authorisation shall have permanently
and continuously at his disposal the services of at least one
qualified person, in accordance with the conditions laid down in
regulation 47, responsible in particular for carrying out the duties
specified in regulation 49
Provided that when more than one qualified person is
nominated, the application will clearly delineate the specific
responsibilities of each person
Provided further that the qualified persons may nominate
another person similarly qualified to act as his representative.
(2)
When the qualified person has nominated a
representative as aforesaid he shall immediately inform the Veterinary
Services of such nomination.
(3) If the manufacturing Authorisation holder personally has the
qualifications laid down in regulation 47, then he may himself assume
the responsibility of a qualified person.
(1)For a person to be designated as qualified person, he
must possess the following qualifications
(a) a diploma;
(b) certificate or other evidence of formal qualifications
awarded on completion of a university course of study;
or
(c) a course recognised as equivalent by the territory of
Malta, extending over a period of at least four (4)
years of theoretical and practical study in one of the
following scientific disciplines - pharmacy, medicine,
veterinary
science,
chemistry,
pharmaceutical
chemistry and technology, biology.
(2) However, the minimum duration of the university course
may be three and a half (3.5) years where the course is followed by
a period of theoretical and practical training of at least one (1) year
and includes a training period of at least six (6) months in a
pharmacy open to the public, corroborated by an examination at
university level.
(3) The course shall include theoretical and practical tuition
bearing upon at least the following basic subjects
(a) experimental physics;
(b) general and inorganic chemistry;
(c) organic chemistry;
(d) analytical chemistry;
(e) pharmaceutical chemistry,
including
analysis
of
medicinal products;
(f)
general and applied biochemistry (medical);
(g) physiology;
(h) microbiology;
(i)
pharmacology,
(j)
pharmaceutical technology;
(k) toxicology;
(l)
pharmacognosy (study of the composition and effects
of the active principles of natural substances of plant
and animal origin).
(4) Tuition in these subjects should be so balanced as to enable
the person concerned to fulfil the obligations specified in
regulation 49.
(5) Where certain diplomas, certificates or other evidence of
formal qualifications mentioned in this sub-regulation do not fulfil
the criteria laid down above, the Veterinary Services shall ensure
that the person concerned provides evidence that he has, in the
subjects involved, the knowledge required for the manufacture and
control of veterinary medicinal products.
(6) The qualified person shall have acquired practical
experience over at least two (2) years, in one or more undertakings
which are authorised manufacturers, in the activities of qualitative
analysis of medicinal products, of quantitative analysis of active
substances and of the testing and checking necessary to ensure the
quality of veterinary medicinal products.
(7) The duration of practical experience may be reduced by one
year where a university course lasts for at least five years and by a year
and a half where the course lasts for at least six (6) years.
(1) A person engaging, in Malta, in the activities of the
person referred to in regulation 46(1) on the date on which these
regulations become applicable, without complying with the
provisions of regulation 47, shall be eligible to continue to engage
in those activities within the EU.
(2) The holder of a diploma, certificate or other evidence of
formal qualifications awarded on completion of a university course
or a course recognised as equivalent by the territory of Malta in a
scientific discipline allowing him to engage in the activities of the
person referred to in regulation 46(1) in accordance with the laws
of the territory of Malta, may, if he began his course prior to the
date on which these regulations became applicable, be considered
as qualified to carry out in the territory of Malta the duties of the
person referred to in regulation 46(1), provided that he has
previously engaged in the following activities for at least two (2)
years before the date on which these regulations became applicable
in one or more undertakings with a manufacturing authorisation,
production supervision and, or qualitative and quantitative analysis
of active substances, and the necessary testing and checking under
the direct authority of a person as referred to in regulation 46(1) to
ensure the quality of veterinary medicinal products.
If the person concerned has acquired the practical experience
referred to in sub-regulation (1) before the date on which these
regulations became applicable, a further one year ’s practical
experience in accordance with the conditions referred to in sub-
regulation (1) shall be completed by him immediately before he
engages in such activities.
(1)The qualified person, without prejudice to his
r e l a t i o n s h i p wi t h t he h o ld e r of t h e A u t h or is a t i o n , sh a l l b e
responsible to ensure that
(a) each batch of veterinary medicinal products
manufactured in Malta has been manufactured and
checked in terms of the laws in force and is in
accordance with the requirements of the marketing
authorisation;
(b) in the case of veterinary medicinal products coming
from third countries, irrespective of whether the
product has been manufactured in the EU, each
production batch has undergone in a Member State a
full qualitative analysis, a quantitative analysis of at
least all the active substances and all the other tests or
checks necessary to ensure the quality of the
veterinary medicinal product in accordance with the
requirements of the marketing authorisation
Provided that when the batches of medicinal products
have already undergone the controls above mentioned in a Member
State, they shall be exempt from further controls if they are
accompanied by the control reports signed by the qualified person, and
are marketed within the EU;
(c) standards of good practice in manufacturing are
complied with at all times.
(2) The qualified person need not carry out the controls above
mentioned in the case of imported veterinary medicinal products,
where arrangements have been made by the EU with the exporting
country to ensure that the manufacturer of the veterinary medicinal
products applies standards of good manufacturing practice at least
equivalent to those laid down by the EU, and to ensure that the
controls referred to above have been carried out in the exporting
country.
(3) The Veterinary Services, may if it has reasonable suspicion
to believe that any qualified person is acting in contravention of
any of the provisions of these regulations, suspend the activity of
such qualified person by notice in writing specifying the reasons
for such suspension until such person has complied with any
requirement of the Veterinar y Servi ces to reme dy the no n-
compliance.
(1)It shall be the duty of the qualified person to keep a
register to document and certify that each production batch satisfies
provisions of these regulations.
(2) The said register shall be kept up to date as operations are
carried out and must be made available for inspection by the
Veterinary Services for at least five (5) years.
(1) The obligations of qualified persons referred to in
regulation 46(1) shall be fulfilled either by means of appropriate
administrative measures or by making such persons subject to a
professional code of conduct.
(2) The Veterinary Services may provide for the temporary
suspension of such a person upon the commencement of
administrative or disciplinary proceedings against him for failure to
fulfil his obligations.
(1)Importers, exporters, distributors and manufacturers of
active substances who are established in Malta shall register their
activity with the Veterinary Services.
(2)
The registration form shall include, at least, the
following information
(a)
name or corporate name and permanent address;
(b)
the active substances which are to be imported,
exported, distributed or manufactured;
(c)
particulars regarding the premises and the
technical equipment for their activity
Provided that the persons referred to in sub-regulation
(1) shall submit the registration form to the Veterinary Services at least
sixty (60) days prior to the intended commencement of their activity.
(3) The Veterinary Services may, based on a risk assessment,
decide to carry out an inspection. If the Veterinary Services notifies
the applicant within sixty (60) days of the receipt of the registration
form that an inspection will be carried out, the activity shall not
begin before the Veterinary Services has notified the applicant that
he may commence the activity. If within sixty (60) days of the
receipt of the registration form the Licensing Authority has not
notified the applicant that an inspection will be carried out, the
applicant may commence the activity.
(4) The persons referred to in sub-regulation (1) shall
communicate annually to the Veterinary Services an inventory of
the changes which have taken place as regards the information
provided in the registration form. Any changes that may have an
impact on the quality or safety of the active substances that are
manufactured, exported, distributed or imported shall be notified
immediately.
(5) The Veterinary Services, shall only grant or renew an
Authorisation, if the applicant
(a) specifies the veterinary medicinal products and
pharmaceutical forms which are to be manufactured or
imported and the place where they are to be
manufactured and, or controlled;
(b) has at his disposal, for the manufacture or import of
veterinary medicinal products, suitable and sufficient
premises, technical equipment and control facilities
complying with requirements set by the Veterinary
Services;
(c) has at his disposal the services of at least one qualified
person within the meaning of regulation 46(1); and
(d) provides all necessary documentation in support of his
application.
(6) The Veterinary Services shall issue the Authorisation after
verifying the contents of the application but in any case not later
than ninety (90) days from receipt of the application.
(7) The time period mentioned in sub-regulation 6 shall be
suspended when the Veterinary Services requests additional
information from the applicant.
(1) When veterinary medicinal products are brought from a
third country into Malta for the sole purpose of re-export, and
without placing them on the market in Malta, the provisions of
regulation 38 still apply even though the product remains intact and
no manufacturing activities are carried out.
(2) The only exclusion in respect of the requirement in
regulation 38, is when the operations of import for the sole purpose
of re-export are effected within a freeport, free trade zone or
customs warehouse. However, in such instances a veterinary
wholesale dealer ’s licence is still required by the company
engaging in the process.
(3) In those cases involving a manufacturing activity in relation
to imported products that are destined for re-export only, a
manufacturing authorisation is required, even if the operations are
effected within the freeport, free trade zone or customs (e.g.
bonded warehouse). Operations of re-labelling and/or affixing of
labels to the outer pack also fall within this category.
(4) The Veterinary Services shall establish procedures to ensure
that the requirements of sub-regulations (2) and (3) are complied
with.
(5) The Veterinary medicinal products imported for the sole
purpose of re-export may be exempted from obtaining a Marketing
Authorisation from the Veterinary Services.
(6) The authorisation to engage in such an activity is only
given to persons in possession of a veterinary wholesale dealer
licence and without prejudice to other authorisations that the
persons may have to obtain, particularly with respect to the
requirements of the Importation Control Regulations.
A manufacturing authorisation granted under these regulations
shall not relieve any person from the need to obtain any permit, license
or authorisation as may be required by any other law.
TITLE V
LABELLING AND PACKAGE INSERT
(1) Except in the case of the medicinal products referred
to in regulation 17(1), the Veterinary Services shall approve the
immediate packaging and outer packaging of veterinary medicinal
products. Packaging shall bear the following information, which
shall conform with the particulars and documents provided
pursuant to regulations 12 to 13D and the summary of product
characteristics, and shall appear in legible characters
(a) the name of the medicinal product, followed by its
strength and pharmaceutical form. The common name
shall appear if the medicinal product contains only one
active substance and its name is an invented name;
(b) a statement of the active substances expressed
qualitatively and quantitatively per unit or according
to the form of administration for a particular volume or
weight, using the common names;
(c) manufacturer’s batch number;
(d) marketing authorisation number;
(e) name or corporate name and permanent address or
registered place of business of the marketing
authorisation holder and, where appropriate, of the
representative
designated
by
the
marketing
authorization holder;
(f)
the species of animal for which the veterinary
medicinal product is intended; the method and, if
necessary, the route of administration. Space shall be
provided for the prescribed dose to be indicated;
(g) the withdrawal period for veterinary medicinal
products to be administered to food-producing species,
for all the species concerned and for the various
foodstuffs concerned (meat and offal, eggs, milk,
honey), including those for which the withdrawal
period is zero;
(h) expiry date, in plain language;
(i)
special storage precautions, if any;
(j)
specific precautions relating to the disposal of unused
medicinal products or waste derived from veterinary
medicinal products, where appropriate, as well as a
reference to any appropriate collection system in
place;
(k) particulars required to be indicated pursuant to
regulation 26(1), if any’
(l)
the words "For animal treatment only" or, in the case
of the medicinal products referred to in regulation 60,
the words "For animal treatment only - to be supplied
only on veterinary prescription".
(2) The pharmaceutical form and the contents by weight,
volume or number of dose-units need only be shown on the outer
package.
(3) The provisions of Part 1, A of the Schedule, in so far as
they concern the qualitative and quantitative composition of
veterinary medicinal products in respect of active substances, shall
apply to the particulars provided for in subregulation (1)(b).
(4) The particulars mentioned in subregulation (1)(f) to (l) shall
appear on the outer package and on the container of the medicinal
products in the language of the territory of Malta being the country
in which the product is placed on the market
Provided that the language for the territory of Malta may be
either Maltese or English or both.
(5) In the case of medicinal products that have been granted a
marketing authorisation under European Regulation (EC) No 726/
2004, Malta may permit or require that the outer packaging bear
additional information concerning distribution, possession, sale or
any necessary precautions, provided that such information is not in
infringement of Union law or the terms of the marketing
authorisation, and is not promotional.
This additional information shall appear in a box with a
blue border to separate it clearly from the information referred to in
subregulation (1).
(1) As regards ampoules, the particulars listed in the first
paragraph of regulation 51(1) shall be given on the outer package.
O n t h e i m m e di a t e p a c k a g i n g , h o w e v e r, o n l y t he f o l l o w in g
particulars shall be necessary
(a) name of veterinary medicinal product,
(b) quantity of the active substances,
(c) route of administration,
(d) manufacturer’s batch number,
(e) date of expiry,
(f)
the words "For animal treatment only".
(2) As regards small immediate packaging containing a single
dose, other than ampoules, on which it is impossible to give the
particulars mentioned in subregulation (1), the requirements of
regulation 51(1), (2) and (3) shall apply only to the outer package.
(3) The particulars mentioned in subregulation (1)(c) and (f)
shall appear on the outer package and on the immediate packaging
of the medicinal products in the language or languages of the
country in which they are placed on the market.
Where there is no outer package, all the particulars which
should feature on such a package pursuant to regulations 51 and 52
shall be shown on the immediate packaging.
(1) The inclusion of a package leaflet in the packaging of
veterinary medicinal products shall be obligatory unless all the
information required by this regulation can be conveyed on the
immediate packaging and the outer packaging. Malta shall take all
appropriate measures to ensure that the package leaflet relates
solely to the veterinary medicinal product with which it is included.
The package leaflet shall be written in terms that are
comprehensible to the general public and in the official language or
languages of Malta.
Subregulation (1) shall not prevent the package leaflet from
being written in several languages, provided that the information
given is identical in all the languages.
The Veterinary Services may exempt labels and package
leaflets for specific veterinary medicinal products from the
obligation for certain particulars to appear and for the leaflet to be
in the official language or languages of Malta, when the product is
intended to be administered only by a veterinary surgeon.
(2) The Veterinary Services shall approve package leaflets.
Leaflets shall contain at least the following information, in the
order indicated, which shall conform to the particulars and
documents provided pursuant to regulations 12 to 13D and the
approved summary of product characteristics
(a) name or corporate name and permanent address or
registered place of business of the marketing
authorisation holder and of the manufacturer and,
where appropriate, of the representative of the
marketing authorization holder;
(b) name of the veterinary medicinal product followed by
its strength and pharmaceutical form. The common
name shall appear if the product contains only one
active substance and its name is an invented name.
Where the medicinal product is authorised according
to the procedure provided for in regulations Articles
31 to 43 of European Union Council Directive 2004/
28/EC under different names in Malta, a list of the
names authorised in Malta;
(c) the therapeutic indications;
(d) contra-indications and adverse reactions in so far as
these particulars are necessary for the use of the
veterinary medicinal product;
(e) the species of animal for which the veterinary
medicinal product is intended, the dosage for each
species, the method and route of administration and
advice on correct administration, if necessary;
(f)
the withdrawal period, even if this is nil, in the case of
veterinary medicinal products administered to food-
producing animals;
(g) special storage precautions, if any;
(h) particulars required to be indicated pursuant to
regulation 26 (1), if any;
(i)
special precautions for the disposal of unused
medicinal products or waste materials from medicinal
products, if any.
Where the provisions of this Title are not observed and a
formal notice addressed to the person concerned has been
ineffectual, the Veterinary Services may suspend or revoke the
marketing authorisation.
The requirements of the Director concerning conditions of
supply to the public, the marking of prices on medicinal products
for veterinary use and industrial property rights shall not be
affected by the provisions of this Title.
(1) Without prejudice to subregulation (2), homeopathic
veterinary medicinal products shall be labelled in accordance with
the provisions of this title and identified by the inclusion on their
la be ls , i n c le a r l y l e g ib l e fo r m , of t he w o rd s " h o m e o pa th i c
medicinal product for veterinary use".
(2) In addition to the clear mention of the words "homeopathic
veterinary medicinal product without approved therapeutic
indications", the labelling and, where appropriate, package leaflet
for the homeopathic veterinary medicinal products referred to in
regulation 17(1) shall bear the following information and no other
information
(a) the scientific name of the stock or stocks followed by
the degree of dilution, using the symbols of the
Pharmacopoeia used in accordance with regulation
2(8). If the homeopathic veterinary medicinal product
is composed of more than one stock, the labelling may
mention an invented name in addition to the scientific
names of the stocks,
(b) name and address of the marketing authorisation
holder and, where appropriate, of the manufacturer,
(c) method of administration and, if necessary, route,
(d) expiry date, in clear terms (month, year),
(e) pharmaceutical form,
(f)
contents of the sales presentation,
(g) special storage precautions, if any,
(h) target species,
(i)
a special warning if necessary for the medicinal
product,
(j)
manufacturer’s batch number,
(k) registration number.
TITLE VI
POSSESSION, DISTRIBUTION AND DISPENSING OF
VETERINARY MEDICINAL PRODUCTS
(1) In the Director, the wholesale distribution of
veterinary medicinal products is subject to the holding of an
authorisation. The Veterinary Services shall take all appropriate
measures to ensure that the time taken for the procedure for
granting this authorisation does not exceed ninety days from the
date on which it receives the application.
When the market situation in Malta is such that it gives rise
to a temporary supply issues for an authorised veterinary medicinal
product, the procurement of small quantities of the same authorised
veterinary medicinal product, or an essentially similar veterinary
medicinal product, by a veterinary surgeon is permitted and is
excluded from the scope of the definition of wholesale distribution
Provided that when a veterinary surgeon has recourse to this
regulation he has the appropriate means to be kept informed by this
supplier of any batch or product recall and adverse drug reactions.
Supplies of small quantities of veterinary medicinal
products from one retailer to another may be excluded from the
scope of the definition of wholesale distribution under a decision to
be laid down by the Veterinary Services.
(2) In order to obtain the authorisation for distribution, the
applicant shall have at his disposal technically competent staff and
suitable and sufficient premises complying with the requirements
laid down in the Director as regards the storage and handling of
veterinary medicinal products
Provided that for the purposes of this sub-regulation
"technically competent staff" means responsible or qualified
persons who shall be professionally responsible for the activity in
question. Such person(s) must be in possession of qualifications as
required by the Veterinary Services
Provided further that, where more than one responsible or
qualified person is nominated, the application will clearly specify
the responsibilities of each respective person.
(3) The holder of the authorisation for distribution shall be
requi red t o keep detailed records. T he foll owin g m inim um
information shall be recorded in respect of each incoming or
outgoing transaction
(a) date;
(b) precise identity of the veterinary medicinal product;
(c) manufacturer’s batch number, expiry date;
(d) quantity received or supplied;
(e) name and address of the supplier or recipient.
At least once a year a detailed audit shall be carried out to
compare incoming and outgoing medicinal supplies with supplies
currently held in stock, any discrepancies being recorded.
These records shall be available for inspection by the
Veterinary Services for a period of at least three years.
(3A) The holder of a distribution authorisation shall have an
emergency plan guaranteeing the effective implementation of any
recall operation ordered by the competent authorities or undertaken
in cooperation with the manufacturer of the medicinal product in
question or the holder of the marketing authorisation.
(4) The Veterinary Services shall take all appropriate measures
to ensure that wholesalers supply veterinary medicinal products
only to persons permitted to carry out retail activities in accordance
with regulation 59, or to other persons who are lawfully permitted
to receive veterinary medicinal products from wholesalers.
(5) Any distributor, not being the marketing authorization
holder, who imports a product from another Member State shall
notify the marketing authorization holder and the Veterinary
Services to which the product will be imported of his intention to
import it. In the case of products which have not been granted an
authorisation pursuant to European Regulation (EC) No 726/2004,
the notification to the Veterinary Services shall be without
prejudice to additional procedures provided for in the legislation of
Malta.
TITLE VII
RETAIL SUPPLY OF VETERINARY MEDICINAL
PRODUCTS
In the territory of Malta, the retail supply of veterinary
medicinal products shall be conducted only from veterinary
pharmacies, licensed veterinary establishments, other establishments
mentioned in regulation 60(4)(d) and by veterinary surgeons during
out call visits.
TITLE VIII
DISPENSING REGULATIONS
(1) In the territory of Malta the dispensing of veterinary
medicinal products shall only be conducted in accordance with the
provisions of this regulation.
(2) Veterinary surgeons may dispense veterinary medicinal
products during an in-call by the animal owner/carer/keeper in the
licensed veterinary establishments and during out-call visits to the
animals under their care.
(3) Veterinary surgeons shall dispense a veterinary medicinal
product in such quantities as would be required for the treatment of
the condition, where delay in the administration of the product may
adversely affect the health of the animal
Provided that the veterinary surgeon shall supply the
quantities of veterinary medicinal product for treatments or
conditions only to animals under his care. If the type of the
packaging is such that the veterinary surgeon cannot supply lesser
quantities thereof, the veterinary surgeon may supply the animal
owner/keeper/carer with the quantities needed for the full treatment
of the condition.
Provided further that the above may not apply for
veterinary medicinal product that are regulated by specific
instruments
(4) Veterinary medicinal products can only be dispensed from
the premises referred to in regulation 60.
(5) The dispensers shall be required to keep detailed records
for veterinary medicinal products or treatments that may be
supplied only on prescription, the following information being
recorded in respect of each incoming or outgoing transaction
(a) date of the transaction;
(b) name of the veterinary medicinal product including, as
appropriate, pharmaceutical form and strength;
(c) batch number;
(d) quantity received or supplied;
(e) name or company name and permanent address or
registered place of business of the supplier in the event
of purchase, or of the recipient in the event of sale;
(f)
name and contact details of the prescribing veterinary
surgeon and, where appropriate, a copy of the
veterinary prescription;
(g) marketing authorisation number.
At least once a year a detailed audit shall be carried out, and
incoming and outgoing veterinary medicinal products and other
products issued on a veterinary prescription shall be reconciled
with products currently held in stock, any discrepancies being
recorded in an appropriate register. These records shall be available
for inspection by the Veterinary Services for a period of not less
than five (5) years.
(6) When dispensing a veterinary medicinal product the
dispenser must be satisfied that the person who will use the product
is competent to do so safely, and intends to use it for a purpose for
which it is authorised or indicated by the veterinary surgeon.
(7) When dispensing veterinary medicinal product, the
dispenser shall advise the receiver of the product on the dosing,
safe administration of the product and on any warnings or contra-
indications on the label or package leaflet, including information
on any applicable withdrawal period/s.
(8) If the dispenser dispenses an amount of veterinary
medicinal product that is less than the unit dose of a package, the
veterinary surgeons may break open any package containing a
product for the purposes of supply, other than the immediate
packaging of an injectable product.
(9) When dispensing an antimicrobial agent the dispenser must
be satisfied that all necessary precautions have been taken to
minimise the risks of antimicrobial resistance and that the prudent
use of the antimicrobial agent have been taken in consideration, in
particular to the use of critically important antimicrobials.
(10) If the dispenser has concerns about the content of a
veterinary prescription he shall resolve them with the prescribing
veterinary surgeon before dispensing the product.
(11) If a veterinary medicinal product is supplied in a container
other than that specified in the marketing authorisation, the
veterinary surgeon dispensing the product must ensure that the
container is suitably labelled and shall supply sufficient written
information to enable the product to be used safely.
(12) The veterinary surgeon referred to in regulation 79(2) shall
be responsible for the cabinet where veterinary medicinal products
are kept. In particular, storage conditions, traceability issues and
record keeping requirements shall be strictly adhered to.
(13) A veterinary surgeon dispensing a veterinary medicinal
product must be present when the product is handed over unless the
veterinary surgeon
(a) authorises each transaction individually before the
product is supplied;
(b) is satisfied that the person handing it over is competent
to do so.
(14) Only veterinary medicinal product that have not passed
their expiry date shall be dispensed.
(15) The provisions of paragraph (e) of sub-regulation (5) shall
come into force on the 1st November 2021.
TITLE IX
PRESCRIBING REGULATIONS
(1) In the territory of Malta veterinary surgeons can only
prescribe veterinary medicinal products in accordance with the
provisions of this regulation.
(2) In the territory of Malta, the prescribing of veterinary
medicinal product or medicinal product to animals shall be
conducted only by Veterinary surgeons.
(3) The prescribing of veterinary medicinal product or
medicinal product for animals shall be made only on the veterinary
prescriptions.
(4) Veterinary surgeons may only prescribe a veterinary
medicinal product or medicinal product for animals which they
have examined themselves and shall accept clinical responsibility
for the treatment of the animal under their care.
(5) Veterinary medicinal product or medicinal product may not
be used for more than one treatment under the same prescription.
(6) Before prescribing a veterinary medicinal product or
medicinal product which requires a prescription, veterinary
surgeons shall carry out a clinical assessment of the animal under
their care.
(7) The clinical assessment by the veterinary surgeons shall be
carried out recently enough for the veterinary surgeons to have
personal knowledge of the condition of the animal or current health
status of the herd or flock to make a reliable diagnosis or start
empirical treatment.
(8) Before prescribing a veterinary medicinal product or
medicinal product the veterinary surgeons must first satisfy
themselves that
(a)
the use of the veterinary medicinal product or
medicinal product is justified for the species concerned on
veterinary grounds;
(b)
the administration of the veterinary medicinal
product or medicinal product is not incompatible with a
previous treatment or use and that there is no contra-indication
or interaction where several pre-mixes are used;
(c)
the veterinary medicinal product or medicinal
product are prescribed only in such quantities as are necessary
for the purpose of the treatment;
(d)
all necessary precautions have been taken to
minimise the risks of antimicrobial resistance and that the
prudent use of the antimicrobial agent have been taken in
consideration, in particular to the use of critically important
antimicrobials.
(9) When prescribing a veterinary medicinal product or
medicinal product veterinary surgeons must be satisfied that the
person who will use the product is competent to do so safely and
intends to use it for a purpose for which it is authorised.
(10) When prescribing antimicrobial agents veterinary surgeons
shall consider the latest guidelines issued by the Veterinary
Services, and other relevant national, European and International
organisations with regard to critically important antimicrobials.
(11) When preparing a veterinary prescription the prescribing
veterinary surgeon shall advise the receiver of the prescription on
the safe administration of the product and on any warnings or
contra-indications associated with the product.
(12) A veterinary medicinal product classified as subject to
veterinary prescription may be administered without a veterinary
prescription by a veterinary surgeon personally. This does not
preclude veterinary surgeons from the record keeping obligations
referred to in regulation 59(5).
(13) The veterinary prescriptions shall be in line with the
guidelines that may be issued by the veterinary Services.
(1) Without prejudice to stricter European Union or
national rules relating to dispensing veterinary medicinal products
and serving to protect human and animal health, a veterinary
prescription shall be required for dispensing to the public the
following veterinary medicinal products
(a) those products subject to official restrictions on supply
or use, such as -
(i)
the
restrictions
resulting
from
the
implementation of the relevant United Nations
conventions on narcotic and psychotropic
substances,
(ii) the restrictions on the use of veterinary
medicinal products resulting from European
Union legislation;
(iii) veterinary medicinal products that do not fall
within the classification of regulation 6 (1)(a)(i),
(b) and (c) but nonetheless are deemed to require a
veterinary prescription for a temporary period.
(aa) veterinary medicinal products for foodproducing
animals.
However, Malta may grant exemptions from this
requirement according to criteria established in
VETERINARY MEDICINAL PRODUCTS
accordance with the procedure referred to in Article
89(2) of European Union Council Directive 2004/28/
EC;
(b) those products in respect of which special precautions
must be taken by the veterinary surgeon in order to
avoid any unnecessary risk to -
(i) the target species,
(ii) the person administering the products to the
animal,
(iii) the environment;
(c) those products intended for treatments or pathological
processes which require a precise prior diagnosis or
the use of which may cause effects which impede or
interfere with subsequent diagnostic or therapeutic
measures;
(d) official formula, within the meaning of Article 3(2)(b)
of European Union Council Directive 2004/28/EC,
intended for food-producing animals.
Malta shall take all necessary measures to ensure that, in
the case of medicinal products supplied only on prescription, the
quantity prescribed and supplied shall be restricted to the minimum
amount required for the treatment or therapy concerned.
In addition, a prescription shall be required for new
veterinary medicinal products containing an active substance that
has been authorised for use in a veterinary medicinal product for
fewer than five years.
(2) Veterinary medicinal products for food-producing animals
may be exempted from the requirement to be dispensed only
against veterinary prescription, if all of the following criteria are
satisfied
(a) the administration of veterinary medicinal products is
restricted to formulations requiring no particular
knowledge or skill in using the products;
(b) the veterinary medicinal product does not present a
direct or indirect risk, even if administered incorrectly,
to the animal or animals treated, to the person
administering the product or to the environment;
(c) the summary of product characteristics of the
veterinary medicinal product does not contain any
warnings of potential serious side effects deriving
from its correct use;
(d) neither the veterinary medicinal product nor any other
product containing the same active substance has
previously been the subject of frequent serious adverse
reaction reporting;
(e) the summary of product characteristics does not refer
to contra-indications related to other veterinary
medicinal
products
commonly
used
without
prescription;
(f)
the veterinary medicinal product is not subject to
special storage conditions;
(g) there is no risk for consumer safety as regards residues
in food obtained from treated animals even where the
veterinary medicinal products are used incorrectly;
(h) there is no risk to human or animal health as regards
the development of resistance to antimicrobials or
anthelmintic substances even where the veterinary
medicinal products containing those substances are
used incorrectly.
(i)
veterinary medicinal product classified as prescription
only medicines may be exempted from being prescribed
and dispensed by a prescription if entirely administered
by the veterinary surgeon responsible for the non-food
producing animal, who himself provides the veterinary
medicinal product, and if the animal owner does not
explicitly request a prescription.
(3) Pursuant to sub-regulation (1) there shall be the following
four (4) distribution categories of veterinary medicinal product
(a) Prescription-Only-Medicine, Veterinary surgeon and
Pharmacist- abbreviated to POM-VP.
(b) Prescription-Only-Medicine,
Veterinary
surgeon-
abbreviated to POM-V.
(c) Over- the- Counter –Medicine, abbreviated to OTC
(d) General Sales, abbreviated to GS
(4) The supply of veterinary medicinal products for each
distribution category shall be made as follows
(a) POM-VP, shall only be prescribed and/or dispensed by
a veterinary surgeon or dispensed by a pharmacist
according the terms of a veterinary prescription.
Premises from where the products can be supplied are
veterinary
pharmacies,
licensed
veterinary
establishments, and by the veterinary surgeon during
an outcall.
(b) POM-V shall only be prescribed, dispensed and
administered by a veterinary surgeon. Premises from
where the products can be supplied are licensed
veterinary establishments, and by the veterinary
surgeon during an outcall.
(c) OTC, may be dispensed without a veterinary
prescription. The persons who can dispense this
category of veterinary medicinal products are
veterinary surgeons, pharmacists and suitably
qualified persons under the direction of a pharmacist
or a veterinary surgeon. Premises from where the
products can be supplied are veterinary pharmacies,
licensed veterinary establishments, and by the
veterinary surgeon during an outcall.
(d) GS, may be dispensed without a veterinary
prescription. The persons who can dispense this
category of veterinary medicinal products are
veterinary surgeons, pharmacists and suitably
qualified persons. Products that fall under this
category can be supplied from veterinary pharmacies,
veterinary establishments, registered pet shops,
registered aquarium fish product retailers and
approved feed traders where animal medicated feeds
are produced, sold or traded
Provided that the veterinary services may make
requirements to allow products classified in this category to be
supplied from premises other those listed above to alleviate supply
shortages and facilitate accessibility to treatment that otherwise
could be detrimental to animal welfare. Such premises shall not be
general retail outlets and must be under the responsibility of a
person with an experience of not less than two (2) years in the
handling of this category of veterinary medicinal products.
(5) The Veterinary Services shall categorise the distribution
category of the veterinary medicinal product when authorising
veterinary medicinal products.
(6) When deciding the distribution category of a veterinary
medicinal product the Veterinary Services may seek the advice
from suitable expert committees and may take in consideration the
guidelines of other National, European and International relevant
bodies, as may be decided by the Veterinary Services.
(7) Notwithstanding what had been decided during the initial
Marketing Authorisation procedure, the Veterinary Services may
change the distribution category of a veterinary medicinal product
either at the request of the Marketing Authorisation Holder or due
to a compulsory variation.
(8) The Veterinary Services shall set out the criteria for the
categorisation of a Veterinary Medicinal product and make them
public.
(9) Different pack sizes of the same Marketing Authorisation
may be assigned a different distribution category.
(10) When the distribution category of the veterinary medicinal
product is POM-V or POM-VP this shall be indicated on the
immediate and/or outer packaging of the product in legible,
undeletable characters.
(11) The legible, undeletable characters citing the distribution
category of the veterinary medicinal product may be printed on the
immediate and/or outer packaging or made noticeable through an
appropriate label.
(12) Both the abbreviated form and the full description of the
distribution category of the veterinary medicinal product present on
the immediate and/or outer packaging shall be acceptable.
(13) The holders of a wholesale distribution authorisation shall
distribute veterinary medicinal products only to the premises
authorised to retailed veterinary medical according to these
regulations.
(14) The holders of a wholesale distribution authorisation shall
distribute to the premises authorised to retailed veterinary medical
only the category/categories of veterinary medicinal products that
are authorised to be retailed from each type of premises in
accordance with these regulations.
(1) In the Director, all necessary measures shall be taken
to ensure that veterinary surgeons, qualified or responsible persons
a n d p h a r m a c i s t s o n l y, p o s s e s s o r h a v e u n d e r t h e i r c o n t r o l
veterinary medicinal products or substances which may be used as
veterinary medicinal products that have anabolic, anti-infectious,
anti-parasitic, anti-inflammatory, hormonal or psychotropic
properties.
(2) The Director shall maintain a register of manufacturers and
dealers permitted to be in possession of active substances which
may be used in the manufacture of veterinary medicinal products
having the properties referred to in sub-regulation (1). Such
persons must maintain detailed records of all dealings in substances
which may be used in the manufacture of veterinary medicinal
products and keep these records available for inspection by the
Veterinary Services for a period of at least three years.
(3) Any amendments to be made to the list of substances
referred to in subregulation (1) shall be adopted in accordance with
the procedure referred to in article 89 (2) of European Union
Council Directive 2001/82/EC.
Malta shall ensure that the owners or keepers of food-
producing animals or keeper of animals that are confined within
enclosures, displayed to the public, or kept for breeding can provide
proof of purchase, possession and administration of veterinary
medicinal products or medicinal products to such animals for five (5)
years after their administration, including when the animal is
slaughtered or culled during the five (5) year period.
The Director may extend the scope of this obligation to
other veterinary medicinal products.
The records shall be kept electronically or printed hard copies.
Hard copies shall be kept as hard bound records or in paper binders.
Official hard copies or electronic templates may be provided by the
Veterinary Services. The records shall be kept in a suitable place in
the farm and available immediately for inspection by the Veterinary
Services.
Proof of purchase refers in particular to the invoices and/or to the
receipts or any document existing as hard copy or in electronic format
that provides documentary evidence of how, when and from whom the
veterinary medicinal product or medicinal product were acquired.
In particular, the Director may require the maintenance of a
record giving at least the following information
(a) date;
(b) name of the veterinary medicinal product;
(c) quantity;
VETERINARY MEDICINAL PRODUCTS
(d) name and address of the supplier of the medicinal
product;
(e) identification of the animals treated.
(f)
scenario under which the veterinary medicinal product
or medicinal products were prescribed, which could be
one or more of the following scenario: treatment,
prophylactic or metaphylactic use.
(g) scientific justification as to why antimicrobial veterinary
medicinal products or medicinal products were
prescribed by the veterinary surgeon in the case of
metaphylactic and/or prophylactic use.
By way of derogation from regulation 9 and without
prejudice to regulation 60, Malta shall ensure that veterinarian
surgeons providing services in another Member State can take with
them and administer to animals small quantities of veterinary
medicinal products not exceeding daily requirements other than
immunological veterinary medicinal products which are not
authorised for use in the Member State in which the services are
provided, provided that the following conditions are satisfied
(a) the authorisation to place the product on the market
provided for in regulations 5, 7 and 8 has been issued
by the competent authority of the Member State in
which the veterinary surgeon is established;
(b) the veterinary medicinal products are transported by
the veterinary surgeon in the original manufacturer’s
packaging;
(c) the veterinary medicinal products intended for
administration to food-producing animals have the
same qualitative and quantitative composition in terms
of active substances as the medicinal products
authorised in accordance with regulations 5, 7 and 8 in
the host Member State;
(d) the veterinary surgeon providing services in another
Member State acquaints himself with the good
veterinary practices applied in that State and ensures
that the withdrawal period specified on the labelling of
the veterinary medicinal product concerned is
complied with, unless he could reasonably be expected
to know that a longer withdrawal period should be
specified to comply with these good veterinary
practices;
(e) the veterinary surgeon shall not furnish any veterinary
medicinal product to the owner or keeper of the
animals treated in the host Member State unless this is
permissible on the basis of the rules of the host
Member State; in this case he shall, however, supply
only in relation to animals under his care and only the
minimum quantities of veterinary medicinal product
necessary to complete the treatment of animals
concerned on that occasion;
(f)
the veterinary surgeon shall be required to keep
detailed records of the animals treated, the diagnosis,
the veterinary medicinal products administered, the
dosage administered, the duration of treatment and the
withdrawal period applied. These records shall be
available for inspection by the competent authority of
the host Member State for a period of at least three
years;
(g) the overall range and quantity of veterinary medicinal
products carried by the veterinary surgeon shall not
exceed that generally required for the daily needs of
good veterinary practice.
(1) In the absence of specific European Union legislation
concerning the use of immunological veterinary medicinal products
for the eradication or control of animal disease, the Director may,
prohibit the manufacture, import, possession, sale, supply and, or
use of immunological veterinary medicinal products on the whole
or part of the territory if it is established that -
(a) the administration of the product to animals will
interfere with the implementation of a national
programme for the diagnosis, control or eradication of
animal disease, or will cause difficulties in certifying
the absence of contamination in live animals or in
foodstuffs or other products obtained from treated
animals;
(b) the disease to which the product is intended to confer
immunity is largely absent from the territory
concerned.
Malta may also invoke the provisions of the first paragraph
in order to withhold marketing authorisation in accordance with a
decentralised procedure as provided for in Articles 31 to 43 of
European Union Council Directive 2004/28/EC.
(2) The Veterinary Services shall inform the European
Commission of all instances in which the provisions of sub-
regulation (1) are applied.
Title X
PHARMACOVIGILANCE
(1) The Director shall take the appropriate measures to
encourage the reporting to the Veterinary Services of suspected
adverse reactions to veterinary medicinal products.
(2) Malta may impose specific requirements on veterinary
practitioners and other health-care professionals in respect of the
reporting of suspected serious or unexpected adverse reactions and
human adverse reactions.
In order to ensure the adoption of appropriate and
harm onised regulatory decisions concerning the veterinary
medicinal products authorised within the European Union, having
regard to information obtained about suspected adverse reactions to
veterinary medicinal products under normal conditions of use,
Malta shall administer a veterinary pharmacovigilance system. This
system shall be used to collect information useful in the
surveillance of veterinary medicinal products, with particular
reference to adverse reactions in animals and in human beings
relating to the use of veterinary medicinal products, and to evaluate
such information scientifically.
Such information shall be collated with available data on
the sale and prescription of veterinary medicinal products.
Malta shall ensure that suitable information collected
within this system is communicated to other Member States and the
Agency. This information shall be recorded in the database referred
to in point (k) of the second subparagraph of Article 57(1) of
European Regulation (EC) No 726/2004 and shall be permanently
accessible to all Member States and without delay to the public.
This system also takes into account any available
information related to the lack of expected efficacy, off-label use,
investigations of the validity of the withdrawal period and on
potential environmental problems, arising from the use of the
product, interpreted in accordance with European Commission
guidelines referred to in regulation 70(1), which may have an
impact on the evaluation of their benefits and risks.
The management of funds intended for activities connected
with pharmacovigilance, the operation of communication networks
and market surveillance shall be under the permanent control of the
Veterinary Services in order to guarantee their independence.
The marketing authorisation holder shall have permanently
and continuously at his disposal an appropriately qualified person
responsible for pharmacovigilance.
That qualified person shall reside in the European Union
and shall be responsible for the following
(a) the establishment and maintenance of a system which
ensures that information about all suspected adverse
reactions which are reported to the personnel of the
company, including its representatives, is collected
and collated in order to be accessible at least at one
point within the European Union;
(b) the preparation for the Veterinary Services of the
reports referred to in regulation 68, in such form as
may be laid down by that authority, in accordance with
the guidance referred to in regulation 70(1);
(c) ensuring that any request from the Veterinary Services
for the provision of additional information necessary
for the evaluation of the benefits and risks afforded by
a veterinary medicinal product is answered fully and
promptly, including the provision of information about
the volume of sales or prescriptions of the veterinary
medicinal product concerned;
(d) the provision to the Veterinary Services, of any other
information relevant to the evaluation of the benefits
and risks afforded by a veterinary medicinal product,
including appropriate information on post-marketing
surveillance studies.
(1) The marketing authorisation holder shall maintain
detailed records of all suspected adverse reactions occurring within
the European Union or in a third country.
Save in exceptional circumstances, these reactions shall be
communicated electronically in the form of a report in accordance
with the guidelines referred to in regulation 70(1).
(2) The marketing authorisation holder shall record all
suspected serious adverse reactions and human adverse reactions
relating to the use of veterinary medicinal products that are brought
to his attention, and report them promptly to the Veterinary
Services, and no later than fifteen days following receipt of the
information.
The marketing authorisation holder shall also record all
suspected serious adverse reactions and human adverse reactions
related to the use of veterinary medicinal products of which he can
reasonably be expected to have knowledge, and report them
promptly to the Veterinary Services, and no later than fifteen days
following receipt of the information.
(3) The marketing authorisation holder shall ensure that all
suspected serious unexpected adverse reactions, human adverse
reactions and any suspected transmission via a veterinary medicinal
product of any infectious agent occurring on the territory of a third
country are reported promptly in accordance with the guidelines
referred to in regulation 70(1), so that they are available to the
Agency and the competent authorities of the Member States in
which the veterinary medicinal product is authorised, and no later
than fifteen days following the receipt of the information.
(4) By way of derogation from subregulations (2) and (3), in
the case of veterinary medicinal products which are covered by
European Directive 87/22/EEC, have benefited from the
authorisation procedures under Articles 31 and 32 of European
Union Council Directive 2004/28/EC or have been the subject of
the procedures provided for in Articles 36, 37 and 38 of European
Union Council Directive 2004/28/EC, the marketing authorisation
holder shall additionally ensure that all suspected serious adverse
reactions and human adverse reactions occurring in the Union are
reported in such a way so as to be accessible to the reference
Member State or a competent authority designated as reference
M e m b e r St a t e . T h e r e f e r e n c e M e m b e r St a t e s h a l l a s s u m e
responsibility for the analysis and follow-up of any such adverse
reactions.
(5) Unless other requirements have been laid down as a
condition for the granting of the marketing authorisation or
subsequently as indicated in the guidelines referred to in regulation
70(1), reports of all adverse reactions shall be submitted to the
Veterinary Services in the form of a periodic safety update report,
immediately upon request or at least every six months after
authorisation until the placing on the market. Periodic safety update
reports shall also be submitted immediately upon request or at least
every six months during the first two years following the initial
placing on the market, and once a year for the following two years.
Thereafter, the reports shall be submitted at three-yearly intervals,
or immediately upon request.
The periodic safety update reports shall include a scientific
evaluation of the risk-benefit balance of the veterinary medicinal
product.
(6) Following the granting of a marketing authorisation, the
holder of such authorisation may request the amendment of the
periods referred to in subregulation (5) in accordance with the
procedure laid down by European Commission Regulation (EC) No
1084/2003.
(7) The holder of a marketing authorisation may not
communicate information relating to pharmacovigilance concerns
to the general public in relation to its authorized veterinary
medicinal product without giving prior or simultaneous notification
to the Veterinary Services.
In any case, the marketing authorisation holder shall ensure
that such information is presented objectively and is not
misleading.
Malta shall take the necessary measures to ensure that a
marketing authorisation holder who fails to discharge these
obligations is subject to effective, proportionate and dissuasive
penalties.
(1) Making use of the data-processing network set up by
the Agency, in collaboration with the European Commission, the
Veterinary Services shall ensure that reports of suspected serious
adverse reactions and human adverse reactions, in accordance with
the guidance referred to in regulation 70(1) and that have taken
place on the territory are immediately made available to the
Agency and the other Member States, and in any case within fifteen
calendar days of their notification, at the latest.
(2) The Veterinary Services shall ensure that reports of
suspected serious adverse reactions and human adverse reactions,
that have taken place on the territory are immediately made
available to the marketing authorisation holder, and in any case
within fifteen calendar days of their notification at the latest.
(1) In order to facilitate the exchange of information about
pharmacovigilance within the Director and the Member States, the
Veterinary Services, shall take due account of guidance on the
collection, verification and presentation of adverse reaction reports,
including technical requirements for electronic exchange of
veterinary pharmacovigilance information in accordance with
internationally agreed terminology drawn up by the European
Commission in consultation with the Agency, Member States and
the interested parties.
(2) For the interpretation of the definitions referred to in
regulation 2(10) to (16) and principles outlined in this title, the
marketing authorisation holder and the Veterinary Services shall
refer to the detailed guidance referred to in subregulation (1).
(1) Where, as a result of the evaluation of veterinary
pharmacovigilance data, the Veterinary Services considers that a
marketing authorisation should be suspended, withdrawn or varied
to restrict the indications or availability, amend the posology, add a
contra-indication or add a new precautionary measure, it shall
forthwith inform the Agency, the Member States and the marketing
authorisation holder.
(2) If urgent action is necessary for protecting human or animal
health, Malta may suspend the marketing authorisation of a
veterinary medicinal product, provided that the Agency, the
Commission and the other Member States are informed on the
following working day at the latest.
TITLE XI
SUPERVISION AND SANCTIONS
(1) The Veterinary Services shall ensure, by means of
repeated inspections and, if necessary, unannounced inspections,
and where appropriate, by asking an Official Medicines Control
Laboratory or a laboratory designated for that purpose to conduct
tests on samples, that the legal requirements relating to veterinary
medicinal products in any place where active substances and
veterinary medicinal products are manufactured, distributed, imported,
exported or used are complied with.
The Veterinary Services may also carry out at any
reasonable time unannounced inspections at the premises of
manufacturers of active substances used as starting materials for
veterinary medicinal products, and of the premises of the marketing
authorisation holder whenever it considers that there are grounds
for suspecting non-compliance with the provisions of regulation
Article 51 of European Union Council Directive 2004/28/EC or any
provisions of these regulations. Such inspections may also be carried
out at the request of another Member State, the Commission or the
Agency.
In order to verify whether the data submitted in order to
obtain a conformity certificate comply with the monographs of the
European Pharmacopoeia, the standardization body for
nomenclatures and quality norms within the meaning of the
Convention relating to the elaboration of a European
Pharmacopoeia (European Directorate for the Quality of
Medicines) may ask the Commission or the Agency to request such
an inspection when the starting material concerned is the subject of
a European Pharmacopoeia monograph.
The Veterinary Services may carry out inspections of
starting material manufacturers at the manufacturer’s own request.
Such inspections shall be carried out by authorized
representatives of the Veterinary Services who shall be empowered
to -
(a) inspect manufacturing or trading establishments and
any laboratories entrusted by the holder of the
manufacturing authorisation with the task of carrying
out control tests pursuant to regulation 24;
(b) take samples including with a view to an independent
analysis by an Official Medicines Control Laboratory
or by a laboratory designated for that purpose by
Malta;
(c) examine any documents relating to the object of the
inspection, subject to the provisions in force in Malta
placing restrictions on these powers with regard to the
description of the manufacturing method;
(d) inspect the premises, records and documents of
marketing authorisation holders or any firms
performing the activities described in Title VII, and in
particular regulations 67 and 68 thereof, on behalf of a
marketing authorisation holder.
(2) The Veterinary Services shall take all appropriate measures
to ensure that in the Director, the manufacturing processes used in
the manufacture of immunological veterinary medicinal products
are completely validated and batch-to-batch consistency is ensured.
(3) The authorised representatives of the Veterinary Services
shall report after each of the inspections mentioned in
subregulation (1) on whether the principles and guidelines on good
manufacturing practice referred to in Article 51 of European Union
C o u n c i l D i r e c t i v e 2 0 0 4 / 2 8 / E C o r, w h e r e a p p r o p r i a t e , t h e
requirements set out in Title VII, are being complied with. The
inspected manufacturer or market authorization holder shall be
informed of the content of such reports.
(4) Without prejudice to any arrangements which may have
been concluded between the European Union and a third country,
Malta, the European Commission or the Agency may require a
m a n u f a c t u r e r e s t a b l i s h e d i n a t h i r d c o u n t r y t o u n d e rg o a n
inspection as referred to in subregulation (1).
(5) Within ninety days after an inspection as referred to in
subregulation (1), a certificate of good manufacturing practice shall
be issued to the manufacturer if the inspection established that the
manufacturer in question is complying with the principles and
guidelines on good manufacturing practice as provided for by
Union law.
In the event of an inspection carried out at the request of the
European Pharmacopoeia, a certificate of compliance with the
monograph shall be issued, if appropriate.
(6) Malta shall enter the certificates of good manufacturing
practice which they issue in a Union database managed by the
Agency on behalf of the Union.
(7) If the outcome of the inspection as referred to in
subregulation (1) is that the manufacturer does not comply with the
principles and guidelines of good manufacturing practice as
provided for by Union legislation, the information shall be entered
in the Union database as referred to in subregulation (6).
(8) the persons responsible for the premises mentioned in this
regulation shall allow entry to the authorised representatives of the
veterinary services to carry out their duties.
(1) The Veterinary Services shall take all appropriate
measures to ensure that the marketing authorisation holder and,
where appropriate, the holder of the manufacturing authorisation
furnish proof of the control tests carried out on the veterinary
medical product and, or on the constituents and intermediate
products of the manufacturing process, in accordance with the
methods laid down for the purposes of marketing authorisation.
(2) For the purposes of implementing subregulation (1), the
Veterinary Services may require the marketing authorisation holder
for immunological veterinary medicinal products to submit to them
copies of all the control reports signed by the qualified person in
accordance with regulation 48.
The marketing authorisation holder for immunological
veterinary medicinal products shall ensure that an adequate number
of representative samples of each batch of veterinary medical
products is held in stock at least up to the expiry date, and provide
samples promptly to the Veterinary Services on request.
(1) Where it considers it necessary for reasons of human
or animal health, the Veterinary Services may require the marketing
authorisation holder for an immunological veterinary medicinal
product to submit samples of batches of the bulk product and, or
veterinary medicinal product, for control by an Official Medicines
Control Laboratory before the product is put into circulation.
(2) On request by the Veterinary Services, the marketing
authorisation holder shall promptly supply the samples referred to
in subregulation (1), together with the reports of the control
referred to in regulation 73(2).
The Veterinary Services shall inform all the other Member
States in which the veterinary medicinal product is authorised as
well as the European Directorate for the Quality of Medicines of its
intention to control batches or the batch in question.
(3) After studying the control reports referred to in regulation
73(2), the laboratory responsible for the control shall repeat, on the
samples provided, all the tests carried out by the manufacturer on
the finished product, in accordance with the relevant provisions
shown in the dossier for marketing authorisation.
The list of tests to be repeated by the laboratory responsible
for the control shall be restricted to justified tests, provided that all
Member States concerned, and if appropriate the European
Directorate for the Quality of Medicines, agree to this.
For immunological veterinary medicinal products
authorized under European Regulation (EC) No 726/2004, the list
of tests to be repeated by the control laboratory may be reduced
only after agreement by the Agency.
(4)
Malta shall recognise the results of the tests.
(5) Unless the European Commission is informed that a longer
period is necessary to conduct the tests, the Veterinary Services
shall ensure that this control is completed within sixty days of
receipt of the samples.
The Veterinary Services shall notify the other Member
States concerned, the European Directorate for the Quality of
Medicines, the marketing authorisation holder and, if appropriate,
the manufacturer, of the results of the tests within the same period
of time.
If the Veterinary Services concludes that a batch of a
veterinary medicinal product is not in conformity with the control
report of the manufacturer or the specifications provided for in the
marketing authorisation, it shall take all the necessary measures
vis-a-vis the marketing authorisation holder and the manufacturer,
where appropriate, and shall inform accordingly the other Member
States in which the veterinary medicinal product is authorised.
(1) The Veterinary Services shall suspend, revoke,
withdraw or vary marketing authorisations when it is clear that
(a) the risk-benefit assessment of the veterinary medicinal
product is, under the authorized conditions of use,
unfavourable, particular regard being had to the
benefits for animal health and welfare and to consumer
safety, when the authorisation concerns a veterinary
medicinal product for zootechnical use;
(b) the veterinary medicinal product does not have any
therapeutic effect on the species of animal for which
the treatment is intended;
(c) its qualitative and quantitative composition is not as
stated;
(d) the recommended withdrawal period is inadequate to
ensure that foodstuffs obtained from the treated animal
do not contain residues which might constitute a health
hazard to the consumer;
(e) the veterinary medicinal product is offered for sale for
a use which is prohibited by other provisions of the
European Union;
(f)
information given in the application documents
pursuant to regulations 12 to 13D and 27 is incorrect;
(g) the control tests referred to in regulation 73(1) have
not been carried out.
However, when a Union legislative framework is in the
course of being adopted, the Veterinary Services may refuse
authorisation for a veterinary medicinal product where such action
is necessary for the protection of public health, consumer and
animal health.
(2) Marketing authorisations may be suspended, revoked,
withdrawn or varied when it is established that -
(a) the particulars supporting the application, as provided
for in regulations 12 to 13D, have not been amended in
accordance with regulations 27(1) and (5);
(b) any new information as referred to in regulation 27(3)
has not been communicated to the Veterinary Services.
(1) Without prejudice to regulation 75, in the Director,
shall take the necessary measures to ensure that the supply of a
veterinary medicinal product is prohibited and the medicinal
product concerned is withdrawn from the market where -
(a) it is clear that the risk-benefit assessment of the
veterinary medicinal product is, under the authorized
conditions of use, unfavourable, particular regard
being had to the benefits for animal health and welfare
and to the safety and health benefits for the consumer,
when the authorisation concerns a veterinary
medicinal product for zootechnical use;
(b) the veterinary medicinal product has no therapeutic
effect on the species of animal for which the treatment
was intended;
(c) the qualitative and quantitative composition of the
veterinary medicinal product is not as stated;
(d) the recommended withdrawal period is inadequate to
ensure that foodstuffs obtained from the treated animal
do not contain residues which might constitute a health
hazard to the consumer;
(e) the control tests referred to in regulation 73(1) have
not been carried out, or any other requirement or
obligation relating to the grant of the manufacturing
authorisation referred to in regulation 38(1) has not
been complied with.
(2) The Veterinary Services may confine the prohibition on
supply and withdrawal from the market solely to the contested
production batches.
(1) The Veterinary Services shall suspend or withdraw the
manufacturing authorisation for a category of preparations or for
all preparations if any of the requirements laid down in regulation
39 are no longer met.
(2) The Veterinary Services may, in addition to the measures
provided for in regulation 76, either suspend manufacture or
imports of veterinary medicinal products from third countries or
suspend or withdraw the manufacturing authorisation for a category
of preparations or for all preparations in the event of non-
compliance with the provisions regarding manufacture or imports
from third countries.
(3) The Veterinary Services shall prohibit the advertising to the
general public of veterinary medicinal products that -
(a) in accordance with regulation 60, are available on
veterinary prescription only; or
(b) contain psychotropic drugs or narcotics, such as those
covered by the United Nations Conventions of 1961
and 1971.
(1)The Veterinary Services shall permit the advertising of
veterinary medicinal products that in accordance with regulation
60, are available on veterinary prescription to
(a) veterinary surgeons and pharmacists;
(b) professional keepers of animals, provided that the
veterinary medicinal products are preventive
immunological products or anti-helmintic therapies.
(2) The Veterinary Services shall permit the advertising of
veterinary medicinal products to the general public which, by
virtue of their composition and purpose, are intended and designed
for use with the advice of the pharmacist, if necessary, but without
the intervention of a veterinary surgeon for diagnostic purposes or
for the prescription or monitoring of treatment.
(3) No person may advertise medicinal product for
administration to animals. Scientific informative material can be
sent on request to the veterinary surgeon when the provisions of
regulation 10 and 11 are to be applied. The information must not be
promotional in nature and must not include a price list.
(4)
(a)
It shall not be permissible for persons allowed to
supply veterinary medicinal products to veterinary surgeons or
pharmacy owners to induce them to prescribe or supply veterinary
medicinal products by the gift, offer or promise of any benefit or
bonus, whether in money or in kind.
(b) It shall not be permissible for persons allowed to
supply veterinary medicinal products to make any
form of contractual agreement with animal keepers
that benefits the sale of their products.
(c) It shall not be permissible for persons allowed to
supply veterinary medicinal products to solicit or
accept any inducement prohibited under sub-
regulations 4(a) and 4(b). Provided that existing
measures or trade practices relating to prices, profit
margins and discounts shall not be affected.
(5)
The advertising of a veterinary medicinal product shall
(a) encourage the rational use of the veterinary medicinal
product, by presenting it objectively and without
exaggerating its properties;
(b) comply with the particulars listed in the summary of
product characteristics;
(c) not be misleading;
(d) be set out in such a way that it is clear that the message
is an advertisement and that the product is clearly
identified as a veterinary medicinal product;
(e) not give the impression that a veterinary surgeon is
unnecessary, in particular by offering a diagnosis or by
suggesting treatment by mail, internet or any other
means;
(f)
not suggests that the effects of administering the
veterinary medicinal product are guaranteed, are not
accompanied by adverse reactions or are better than, or
equivalent to, those of another treatment or veterinary
medicinal product;
(g) not suggests that the health of the animal can be
enhanced by taking the veterinary medicinal product;
(h) not suggests that the health of the animal could be
affected by not taking the veterinary medicinal product
provided that this shall not apply to the vaccination
campaigns;
(i)
not suggests that the veterinary medicinal product is a
foodstuff, cosmetic or other consumer product;
(j)
not suggests that the safety or efficacy of the
veterinary medicinal product is due to the fact that it is
natural.
(6) (a)Any advertising of a veterinary medicinal product to
persons qualified to prescribe or supply such products shall
include
(i)
the trade name;
(ii)
a list of active ingredients;
(iii)
the pharmaceutical form;
(iv)
major indications for use;
(v)
the dosage and method of use;
(vi) side
effects,
warnings,
precautions
and
contraindications;
(vii) the name
and
address
of
the
marketing
authorisation holder;
(viii) any research and/or publications on the use of the
active substance.
(b) All the information contained in the documentation
referred to in sub-regulation (6)(a) shall be accurate,
up-to-date, verifiable and sufficiently complete to
enable the recipient to form his or her own opinion of
VETERINARY MEDICINAL PRODUCTS
the therapeutic value of the veterinary medicinal
product concerned.
(c) Quotations as well as tables and other illustrative
matter taken from scientific works for use in the
documentation referred to in sub-regulation (9)(a)
shall be faithfully reproduced.
(7) (a)Free samples shall be provided on an exceptional basis
only to persons qualified to prescribe them and on the following
conditions
(i)
each sample shall be no larger than the smallest
presentation on the market;
(ii)
each sample shall be marked "free sample - not for
sale";
(iii) each sample shall be accompanied by a copy of
the summary of product characteristics;
(iv) veterinary
medicinal
products
containing
psychotropic or narcotic substances as defined under the First
Schedule to the Dangerous Drugs Ordinance and the Third
Schedule to the Medical and Kindred Professions Ordinance
cannot be distributed as samples;
(b) Starter packs shall not be regarded as samples and
shall not be labelled as such.
(c) During visits by sales representatives the persons
visited should be given information about the use of
the veterinary medicinal products, with particular
reference to any adverse reactions.
(8) The person who advertises the veterinary medicinal
products shall
(a) keep available for, or communicate to, the Veterinary
Services, a sample of all advertisements emanating
from his undertaking together with a statement
indicating the persons to whom it is addressed, the
method of dissemination and the date of first
dissemination;
(b) supply the Veterinary Services with the information
and assistance it requires to carry out its
responsibilities;
(c) ensure that the decisions taken and conditions imposed
by the Veterinary Services are immediately and fully
complied with.
(9) It is not permissible to advertise veterinary medicinal
products which are not registered with the Veterinary Services.
The provisions of this Title shall apply to homeopathic
veterinary medicinal products.
(1) The Veterinary Services shall take appropriate
measures to encourage veterinarian surgeons and other
professionals concerned to report to it any adverse reaction of
veterinary medicinal products.
(2) For the purposes of these regulations every registered or
licensed establishment where food producing animals are kept and
are not excluded from the provisions of the Official Controls
Regulation (EU) 2017/625 by the veterinary services , and the
establishments where animals are kept for display to the public or
for breeding purposes in the territory of Malta shall have an
appropriate animal health control programme designed and
implemented under the responsibility of a professional registered
with the Veterinary Surgeons Council
Provided that a register of the professionals responsible for
each animal health control programme shall be kept by the
Veterinary Services
Provided further that the Veterinary Services may from time to
time publish requirements related to animal health control programmes
in the Gazette.
(3) The provisions of sub-regulation (2) shall come into force two
(2) years from the date of coming into force of these regulations
TITLE XII
ADMINISTRATION OF VETERINARY MEDICINAL PRODUCTS
AND MEDICINAL PRODUCT TO ANIMALS
(1)In extreme and/or urgent situation to alleviate suffering
of the animal or impending spread of disease any person can
administer a veterinary medicinal product or medicinal product
which requires a veterinary prescription without the veterinary
prescription or the instructions to administer the product by the
veterinary surgeon.
(2) No person can administer, or supply for administration, a
veterinary medicinal product to animals unless the product obtains
an authorisation from the Veterinary Services.
(3) Products whose therapeutic effectiveness is merely
a n e c d o t a l s h o u l d b e u s e d w i t h c a u t i o n i n a l l a n i m a l s . Th e
administration of these products to food producing species is
subject to the approval of the veterinary services. The veterinary
services may ask the animal keeper to provide chemical data,
clinical documentation and studies about the possible
environmental impact before granting its approval.
(4) The keeper/owner/carer of animals must keep proof of
purchase of all products administered or intended to be
administered to the animals for the treatment or prevention of
disease or, if he did not buy them, documentary evidence of how he
acquired them.
(5) Metaphylactic or prophylactic antimicrobial treatment may
be allowed with conditions. Preventive use of antimicrobials
veterinary medicinal products or medicinal products is not allowed.
(6) Except in emergency situations, before prescribing a
veterinary medicinal product or a medicinal product that contains
an antimicrobial agent classified as critically important to human
health or that is reserved for treating infections in animals for
which no effective alternative treatments exist, the prescribing
veterinary surgeon shall take into account the results of the
diagnostic laboratory information (pathogen isolation,
identification and antibiogram).
(7) No person shall administer a veterinary medicinal product
or a medicinal product to a food producing species and place the
animal for slaughter to be consumed unless the relevant withdrawal
period has been observed.
(8) Stockpiling of antimicrobial veterinary medicinal products
or medicinal products in a farm to be administered at a later stage is
not permitted.
(9) Use of combination
of
antimicrobials
should
be
scientifically supported.
Title XIII
STANDING COMMITTEE
Any changes which are necessary in order to adapt the
Schedule to take account of technical progress shall be adopted in
accordance with the procedure referred to in article 89(2) of
European Union Council Directive 2001/82/EC.
TITLE XIV
GENERAL PROVISIONS
The Veterinary Services shall communicate the appropriate
information to competent authorities in other Member States,
particularly regarding compliance with the requirements adopted
for the authorisations referred to in regulation 38, for the
certificates referred to in regulation 72(5) or for authorization to
place products on the market.
Upon reasoned request, the Veterinary Services shall
forthwith communicate the reports referred to in regulation 72(3) to
the competent authorities of another Member State.
The conclusions reached following an inspection as
referred to in regulation 72(1) carried out by the inspectors of the
Veterinary Services shall be valid for the European Union.
However, by way of exception, if Malta has not been able,
for serious reasons of human or animal health, to accept the
conclusions of an inspection as referred to in regulation 72(1), the
Veterinary Services shall forthwith inform the Commission and the
Agency.
When the European Commission is informed of such
serious reasons, it may, after consulting the Veterinary Services,
ask the inspector of the Veterinary Services to carry out a new
inspection; the inspector may be accompanied by two other
i n s p e c t o r s f r o m M e m b e r St a t e s t h a t a r e n o t p a r t i e s t o t h e
disagreement.
(1) The Veterinary Services shall take all appropriate
measures to ensure that the Agency is informed immediately of
decisions granting marketing authorisation and of all decisions
refusing or withdrawing marketing authorisation, cancelling a
dec is i o n r e f us in g o r w it hd r a w in g m a r k e t in g a u t ho r isa ti on ,
prohibiting supply or withdrawing a product from the market,
together with the reasons on which such decisions are based.
(2) (a) The marketing authorisation holder shall be obliged to
notify the Veterinary Services forthwith of any action taken by him
to suspend the marketing of a veterinary medicinal product or to
withdraw a product from the market, together with the reasons for
such action if it concerns the effectiveness of the veterinary
medicinal product or the protection of public health. The Veterinary
Services shall ensure that this information is brought to the
attention of the Agency.
(b) The marketing authorisation holder shall implement a
system for recording and reviewing complaints
together with an effective system for recalling
promptly and at any time the veterinary medicinal
products in the distribution network.
(c) record and investigate any complaint concerning a
quality defect.
(d) The Veterinary Services shall be informed by the
Marketing Authorisation holder of any quality defect
that could result in a recall or abnormal restriction on
the supply. In so far as possible, the countries where
the products are marketed shall also be indicated.
(3) The Veterinary Services shall ensure that appropriate
information about actions taken pursuant to subregulations (1) and
(2) which may affect the protection of health in third countries is
forthwith brought to the attention of the relevant international
organisations, with a copy to the Agency.
The Veterinary Services shall communicate to the
c o m p e t e n t a u t h o r i t i e s o f t h e o t h e r M e m b e r St a t e s a l l t h e
information necessary to guarantee the quality and safety of
homeopathic veterinary medicinal products manufactured and
marketed within the Director, and in particular the information
referred to in regulation 81 and 82.
(1) At the request of the manufacturer or exporter of
veterinary medicinal products, or the authorities of an importing
third country, the Director shall certify that such manufacturer is in
possession of the manufacturing authorisation. When issuing such
certificates, the Ve terinary Servi ces sha ll c om pl y w it h th e
following conditions
(a) they shall have regard to the prevailing administrative
arrangements of the World Health Organisation;
(b) for veterinary medicinal products intended for export
which are already authorised in the territory, they shall
supply the summary of the product characteristics as
approved in accordance with regulation 25 or, in the
absence thereof, an equivalent document.
(2) Where the manufacturer is not in possession of an
authorisation to place the product on the market, he shall provide
the authorities responsible for establishing the certificate referred
to in subregulation (1) with a declaration explaining why such
authorisation is not available.
Any decision referred to in these regulations, taken by the
Veterinary Services, may only be taken on the grounds set out in
these regulations and shall state in detail the reasons on which it is
based.
Such a decision shall be notified to the party concerned who
shall at the same time be informed of the remedies available to him
under current legislation and the time allowed for seeking such
remedies.
Decisions to grant or revoke a marketing authorization shall
be made publicly available.
The Veterinary Services shall not permit foodstuffs for
human consumption to be taken from test animals unless an
appropriate withdrawal period has been established. The
withdrawal period shall either -
(a) be at least as laid down in regulation 11(2) including,
where appropriate, a safety factor reflecting the nature
of the substance being tested; or
(b) if maximum residue limits have been established by
the Union in accordance with Regulation (EEC) No
2377/90, ensure that this maximum limit will not be
exceeded in foodstuffs.
(1)Any person who in the course of his activity generates
veterinary medicinal products waste, shall inform himself of the
current procedures regarding the safe disposal of unused,
unsuitable or expired medicinal products from the entity
responsible for waste management in Malta and shall follow the
guidelines issued by the veterinary services.
(2)
Companies, large establishments and professional bodies
shall describe the procedure they follow for the safe disposal of
unused, unsuitable or expired veterinary medicinal products in writing,
and keep it updated according to the requirements that may change
over-time.
(3) The Veterinary Services shall ensure that veterinary
medicinal product waste producers have appropriate procedures set in
place for the disposal of unused, unsuitable or expired veterinary
medicinal products in accordance with the law of Malta and any
particular instructions described in the summary of product
characteristics of the product.
Any person who contravenes regulations 5(1),
39(1)(a)(b), 39(2)(a), 58(1) and 58A shall be guilty of an offence
against article 38 and shall be liable, on conviction, to a fine (multa) of
not less than five thousand euro (€5,000) and not more than ten
thousand euro (€10,000).
Any person who contravenes regulations 39(3), 59A(2)
and 59A(3), shall be guilty of an offence against article 38 of the Act
and shall be liable, on conviction, to a fine (multa) of not less than
three thousand euro (€3,000) and not more than seven thousand euro
(€7,000).
Any person who contravenes regulation 72(8) shall be
guilty of an offence against article 35 of the Act and shall be liable, on
conviction, to a fine (multa) of not less than three thousand euro
(€3,000) and not more than seven thousand euro (€7,000).
Any person who contravenes regulations 27A, 46(1),
50B, 50C, 59(1), 60(13), 60(14), 62 and 77A(4) shall be guilty of an
offence against article 38 of the Act and shall be liable, on conviction,
to a fine (multa) of not less than five hundred euro (€500) and not
more than one thousand euro (€1,000).
Any person who contravenes any regulation other than
those mentioned in regulations 88,89, 90 and 91 shall be guilty of an
offence and shall be liable, on conviction, to a fine (multa) of not less
than two hundred euro (€200) and not more than four hundred euro
(€400).
Where the Director has reasonable cause to believe that
an offence against these regulations has been committed and that it
would be appropriate to impose an administrative penalty under article
61 of the Act, the Director shall proceed in accordance with the
provisions of the said article 61 of the Act.
VETERINARY MEDICINAL PRODUCTS