Veterinary Medicinal Products Regulations, 2004 (ln_2004_469) | MT

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Preamble — Veterinary Medicinal Products Regulations, 2004 Open official source

B

L.N. 469 of 2004

VETERINARY SERVICES ACT, 2001

(ACT NO. XXIII OF 2001)

Veterinary Medicinal Products Regulations, 2004

IN exercise of the powers conferred by articles 30 and 31 of the Veterinary Services Act,

2001, the Minister for Rural Affairs and the Environment has made the following regulations:-

TITLE I

Title and scope

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 1 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) The title to these regulations is the Veterinary Medicinal Products Regulations, 2004.

(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) The provisions of these regulations shall apply to veterinary medicinal products intended

to be placed on the market inter alia in the form of medicinal products, readymade veterinary

medicinal products or pre-mixes for medicated feeding-stuffs.

Definitions

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Schedule I — Veterinary Medicinal Products Regulations, 2004 Open official source

REQUIREMENTS AND ANALYTICAL PROTOCOL, SAFETY TESTS, PRE-CLINICAL AND CLINICAL

FOR TESTS OF VETERINARY MEDICINAL PRODUCTS

INTRODUCTION

The particulars and documents accompanying an application for marketing authorisation pursuant to regulations 12 and

13 (1) shall be presented in accordance with the requirements set out in this Schedule and taking account of the

guidance contained in the "Notice to applicants for marketing authorisations for veterinary medicinal products in the

Member States of the European Community", published by the European Commission in The rules governing

medicinal products in the European Community, volume V: Veterinary Medicinal Products.

In assembling the dossier for application for marketing authorisation, applicants shall take into account the European

Community guidelines relating to the quality, safety and efficacy of veterinary medicinal products published by the

European Commission in The rules governing medicinal products in the European Community.

All information which is relevant to the evaluation of the 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. Moreover, after marketing

authorisation, any information not in the original application, pertinent to the benefit, risk assessment, shall be

submitted forthwith to the Veterinary Services.

All experiments on animals are conducted in accordance with European Union Council Directive 86/609/EEC on the

protection of animals used for experimental and other scientific purposes.

The provisions of Title I of this Schedule shall apply to veterinary medicinal products other than immunological

veterinary medicinal products.

The provisions of Title II of this Schedule shall apply to immunological veterinary medicinal products.

TITLE I

Requirements for Veterinary Medicinal Products other than Immunological Veterinary Medicinal Products

PART 1

Summary of the dossier

A. Administrative data

The 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 strength and pharmaceutical form, the method and route of administration and a

description of the final sales presentation of the product.

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 (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 data 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 territory of Malta or Member States and a list of countries in which an application has been

submitted.

B. Summary of product characteristics

The applicant shall propose a summary of the product characteristics, in accordance with regulation 14 of these

regulations.

In addition the applicant shall provide one or more specimens or mock-ups of the sales presentation of the veterinary

medicinal product, together with a package insert where one is required.

C. Expert reports

In accordance with regulation 15 (2) and (3), expert reports must be provided on the analytical documentation, the

pharmacotoxicological documentation, the residues documentation and the clinical documentation.

Each expert report shall consist of a critical evaluation of the various tests and, or trials which have been carried out in

accordance with these regulations, and bring out all the data relevant for evaluation. The expert shall give his opinion as

to whether sufficient guarantees have been provided as to the quality, safety and efficacy of the product concerned. A

factual summary is not sufficient.

All important data shall be summarized in an appendix to the expert report, whenever possible in tabular or graphic

form. The expert report and the summaries shall contain precise cross references to the information contained in the

main documentation.

Each expert report shall be prepared by a suitably qualified and experienced person. It shall be signed and dated by the

expert, and attached to the report shall be brief information about the educational background, training and

occupational experience of the expert. The professional relationship of the expert to the applicant shall be declared.

PART 2

Analytical (physicochemical, biological or microbiological) tests of Veterinary Medicinal Products other than

Immunological Veterinary Medicinal Products

All test procedures shall correspond to the state of scientific progress at the time and shall be validated procedures;

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 Veterinary Services; 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 the territory of Malta, this description may be replaced by a detailed reference

to the pharmacopoeia in question.

A. Qualitative and quantitative particulars of the constituents

The particulars and documents which must accompany applications for marketing authorisation, pursuant to regulation

12 (3) (c), shall be submitted in accordance with the following requirements.

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 constituent (s) of the excipients, whatever their nature or the quantity used, including colouring matter,

preservatives, adjuvants, stabilisers, thickeners, emulsifiers, flavouring and aromatic substances, etc,

- the constituents, intended to be ingested or otherwise administered to animals, of the outer covering of the

medicinal products-capsules, gelatine capsules, etc.

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 medicinal product will be used or administered and

which will be delivered with the medicinal product.

2. The "usual terminology", to be used in describing the constituents of 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 national

pharmacopoeia of the territory of Malta, the main title at the head of the monograph in question, with

reference to the pharmacopoeia concerned,

- in respect of other substances, the international non-proprietary name recommended by the World Health

Organization (WHO), 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 the legislation concerning the

colouring matters authorised for use in medicinal products.

3. Quantitative particulars

3.1. In order to give "quantitative particulars" of all the active substances of the 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.

Whenever possible, biological activity per units of mass or volume shall be indicated.

This information shall be supplemented -

- in respect of injectable 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 medicinal products to be administered by drops, by the mass or units of biological

activity of each active substance contained in the number of drops corresponding to 1ml or 1g 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.

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 medicinal products containing an active substance which is the subject of an application for marketing

authorisation in the territory of Malta and 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 medicinal products in the territory of

Malta and Member States shall have their quantitative composition stated in the same way for the same active

substance.

4. Development pharmaceutics

An explanation shall be provided with regard to the choice of composition, constituents and container and the intended

function of the excipients in the finished product. This explanation shall be supported by scientific data on development

pharmaceutics. The overage, with justification thereof, shall be stated.

B. Description of the manufacturing method

The description of the manufacturing method accompanying the application for marketing authorisation pursuant to

regulation 12 (3) (d), 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 in so far as the pharmaceutical form makes this

necessary; mention shall be made of any substances that may disappear in the course of manufacture; any

overage shall be indicated and justified,

- a statement of the stages of manufacture at which sampling is carried out for in-process control tests, 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, where a non-standard method of manufacture is

used or where it is critical for the product,

- for sterile products, details of the sterilisation processes and, or aseptic procedures used.

C. Control of starting materials

1. For the purposes of this paragraph, "starting materials" shall mean all the constituents of the medicinal product and,

if necessary, of its container, as referred to in Section A, point 1, above. In the case of -

- an active substance not described in the European Pharmacopoeia or in the pharmacopoeia of the territory of

Malta or a Member State,

- an active substance described in the European Pharmacopoeia or in the pharmacopoeia of the territory of

Malta or a Member State when prepared by a method liable to leave impurities not mentioned in the

pharmacopoeial monograph and for which the monograph is inappropriate to adequately control its quality,

which is manufactured by a person different from the applicant, the latter may arrange for the detailed description of

the manufacturing method, quality control during manufacture and process validation to be supplied directly to the

Veterinary Services by the manufacturer of the active substance. 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 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 Veterinary Services.

The particulars and documents accompanying the application for marketing authorisation pursuant to regulations 12 (3)

(i) and (j) and regulation 13 (1), shall include the results of the tests, including batch analyses particularly for active

substances, relating to quality control of all the constituents used. These shall be submitted in accordance with the

following provisions -

1.1. Starting materials listed in pharmacopoeias

The monographs of the European Pharmacopoeia shall be applicable to all substances appearing in it.

In respect of other substances, the territory of Malta 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 territory of Malta or

one of the Member States shall be deemed to comply sufficiently with regulation 12 (3) (i). In this case the description

of the analytical methods may be replaced by a detailed reference to the pharmacopoeia in question.

However, where a starting material in the European Pharmacopoeia or in the pharmacopoeia of the territory of Malta or

a Member State has been prepared by a method liable to leave impurities not controlled in the pharmacopoeia

monograph, these impurities and their maximum tolerance limits must be declared and a suitable test procedure must be

described.

Colouring matter shall, in all cases, satisfy the legal requirements of the European Community concerning this matter.

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 contained in a monograph of the European Pharmacopoeia or in the national

pharmacopoeia of the territory of Malta or a Member State might be insufficient to ensure the quality of the substance,

the Veterinary Services may request more appropriate specifications from the marketing authorisation holder.

The Veterinary Services 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 cases where a starting material is described neither in the European Pharmacopoeia nor in the pharmacopoeia of the

territory of Malta or of a Member State, 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 the test procedures contained in the monograph and by a translation where appropriate.

1.2. Starting materials 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 substance, 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

where appropriate; it must be accompanied by an appropriate description of the method of synthesis. 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 the sum total of predictable impurities, 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) 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;

(f) when materials of animal origin are used, measures to ensure freedom from potentially pathogenic agents

shall be described;

(g) any special precautions that may be necessary during storage of the starting material and, if necessary, the

maximum period of storage before retesting shall be given.

1.3. Physicochemical 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 medicinal product

depends on them -

- crystalline form and solubility coefficients,

- particle size, where appropriate after pulverisation,

- state of solvation,

- oil, water coefficient of partition.

The first three indents are not applicable to substances used solely in solution.

2. Where source materials such as micro-organisms, 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.

2.1. 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.

2.2. Seed materials, cell banks, pools of serum and other material of biological origin and, whenever possible,

the source materials from which they are derived shall be tested for adventitious agents. If the presence of

potentially pathogenic adventitious agents is inevitable, the material shall be used only when further

processing ensures their elimination and/or inactivation, and this shall be validated.

D. Specific measures concerning the prevention of the transmission of animal spongiform encephalopathies

The applicant must demonstrate that the veterinary medical product is manufactured in accordance with the Note for

Guidance on minimising the risk of transmitting animal spongiform encephalopathy agents via veterinary medicinal

products and its updates, published by the European Commission in Volume 7 of its publication "The rules governing

medicinal products in the European Community".

E. Control tests carried out at intermediate stages of the manufacturing process

The particulars and documents accompanying an application for marketing authorisation, pursuant to regulation 12 (3)

(i) and (j) and also regulation 13 (1), 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 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

active substances (or of all the excipient components subject to the same 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.

F. Tests on the finished product

1. 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 particulars and documents accompanying the application for marketing authorisation pursuant to regulation 12 (3)

(i) and (j) and also regulation 13 (1), 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 general monographs of the European Pharmacopoeia, or failing that, of the territory of Malta or

of a Member State, shall be applicable to all products defined therein.

If test procedures and limits other than those mentioned in the general monographs of the European Pharmacopoeia, or

failing this, in the national pharmacopoeia of the territory of Malta or of a Member State, are used, proof shall 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.

1.1. 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, physical or microbiological tests, organoleptic characteristics, physical characteristics such as density, pH,

refractive index, etc. For each of these 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 the territory of

Malta or of a Member States, 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; these studies shall also be carried out where

administration is by another means if the competent authorities of the territory of Malta or of a Member State

concerned consider this necessary.

1.2. 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 must propose and justify maximum acceptable tolerance limits in

the active substance content of the finished product up to the end of the proposed shelf-life.

In certain exceptional 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 relaxation may not be

extended to the characterisation of the substances concerned. This simplified technique 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 physicochemical 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 possible in the manufacturing process.

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, 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.

1.3. Identification and assay of excipient components

In so far as is necessary, the excipient components shall be subject at least to identification tests.

The test procedure proposed for identifying colouring matters must enable a verification to be made that such matters

appear to be authorised in accordance with the rules found under European Union Council Directive 78/25/EEC.

An upper and lower limit test shall be obligatory in respect of preserving agents and an upper limit test for any other

excipient component liable to affect adversely physiological functions; an upper and lower limit test shall be obligatory

in respect of the excipient if it is liable to affect the bio-availability of an active substance, unless bio-availability is

guaranteed by other appropriate tests.

1.4. Safety tests

Apart from the toxico-pharmacological tests submitted with the application for marketing authorisation, particulars of

safety tests, such as sterility, bacterial endotoxin, pyrogenicity and local tolerance in animals 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.

G. Stability test

The particulars and documents accompanying the application for marketing authorisation pursuant to regulation 12 (3)

(f) and (i) shall be submitted in accordance with the following requirements.

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.

In the case of pre-mixes for medicated feedingstuffs, information shall also be given as necessary on the shelf life of the

medicated feedingstuffs manufactured from these pre-mixes in accordance with the recommended instructions for use.

Where a finished product requires reconstitution prior to administration, details of the proposed shelf life for the

reconstituted product are required, supported by relevant stability data.

In the case of multi-dose vials, stability data shall be presented to justify a shelf life for the vial after it has been

punctured for the first time.

Where a finished product is liable to give rise to degradation products, the applicant must declare these and indicate

characterisation methods and test procedures.

The conclusions shall contain the results of analyses, justifying the proposed shelf life under the recommended storage

conditions and the specifications of the finished product at the end of the shelf life of the finished product under these

recommended storage conditions.

The maximum acceptable level of 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 or aerosols for internal use are concerned.

PART 3

Safety and residues testing

The particulars and documents which shall accompany the application for marketing authorisation pursuant to

regulations 12 (3) (j) and 13 (1) shall be submitted in accordance with the requirements below.

The territory of Malta shall ensure that the tests are carried out in accordance with the provisions relating to good

laboratory practice as provided under the relevant European Community rules.

A. Safety testing

Chapter I

Performance of tests

1. Introduction

The safety documentation shall show -

1. the potential toxicity of the 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;

2. 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;

3. the potential risks which may result from the exposure of human beings to the medicinal product, for

example during its administration to the animal;

4. the potential risks for the environment resulting from the use of the medicinal product.

All results shall be reliable and valid generally. Whenever appropriate, mathematical and statistical procedures shall be

used in designing the experimental methods and in evaluating the results. Additionally, clinicians shall be given

information about 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.

2. Pharmacology

Pharmacological studies are of fundamental importance in clarifying the mechanisms by which the medicinal product

produces its therapeutic effects and therefore pharmacological studies conducted in experimental and target species of

animal should be included in Part 4.

However, pharmacological studies may also assist in the understanding of toxicological phenomena. Moreover, where a

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 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.

3. Toxicology

3.1. Single dose toxicity

Single dose toxicity studies can be used to predict -

- the possible effects of acute over-dosage 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.

These studies should normally be carried out in at least two mammalian species. One mammalian species may be

replaced, if appropriate, by an animal species for which the medicinal product is intended. At least two different routes

of administration should normally be studied. One of these may be the same as, or similar to, that proposed for the

target species. If substantial exposure of the user of the medicinal product is anticipated, for example by inhalation or

dermal contact, these routes should be studied.

In order to reduce the number and suffering of the animals involved, new protocols for single dose toxicity testing are

continually being developed. Studies carried out in accordance with these new procedures when properly validated will

be accepted, as well as studies carried out in accordance with established internationally recognised guidelines.

3.2. Repeated-dose toxicity

Repeated-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 substances or medicinal products intended solely for use in non food-producing animals, a repeated dose

toxicity study in one species of experimental animal will 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 should 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 medicinal products intended for use in food producing animals, the study should be

conducted in at least two species, one of which should be a non-rodent. 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 duration of the test shall be at least 90 days. 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 the case of new combinations of known substances which have been investigated in accordance with the provisions

of these regulations, the repeated-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

Details should be provided of any signs of intolerance which have been observed during studies conducted 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 should be identified. Details of any unexpected

physiological changes should also be provided.

3.4. Reproductive toxicity including teratogenicity

3.4.1. Study of the effects on reproduction.

The purpose of this study is to identify possible impairment of male or female reproductive function

or harmful effects on progeny resulting from the administration of the medicinal products or

substance under investigation. In the case of substances or medicinal products intended for use in

food-producing animals, the study of the effects on reproduction shall be carried out in the form of a

two-generation study on at least one species, usually a rodent. The substance or product under

investigation shall be administered to males and females at an appropriate time prior to mating.

Administration should continue until the weaning of the F2 generation. At least three dose levels shall

be 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.

Evaluation of the effects on reproduction shall be based upon fertility, pregnancy and maternal

behaviour; the suckling, growth and development of the F1 offspring from conception to maturity;

the development of the F2 offspring to weaning.

3.4.2. Study of embryotoxic, fetotoxic effects including teratogenecity

In the case of substances or medicinal products intended for use in food producing animals, studies of

embryotoxic, fetotoxic effects, including teratogenicity, shall be carried out. These studies shall be

carried out in at least two mammalian species, usually a rodent and the rabbit. The details of the test

(number of animals, doses, time at which administered and criteria for the evaluation of results) shall

depend on the state of scientific knowledge at the time the application is lodged and the level of

statistical significance which the results should attain. The rodent study may be combined with the

study of effects on reproductive function.

In the case of substances or medicinal products which are not intended for use in food producing

animals, a study of embryotoxic, fetotoxic effects, including teratogenicity, shall be required in at

least one species, which may be the target species, if the product is intended for use in animals which

might be used for breeding.

3.5. Mutagenicity

Mutagenicity tests are intended to assess the potential of substances to cause transmissible changes in the genetic

material of cells.

Any new substance intended for use in veterinary medicinal products must be assessed for mutagenic properties.

The number and types of tests and the criteria for the evaluation of the results shall depend on the state of scientific

knowledge when the application is submitted.

3.6. Carcinogenicity

Long term animal carcinogenicity studies will usually be required for substances to which human beings will be

- which have a close chemical analogy with known carcinogens,

- which during mutagenicity testing produced results indicating a possibility of carcinogenic effects,

- which have given rise to suspect signs during toxicity testing.

The state of scientific knowledge at the time the application is submitted shall be taken into account when designing

carcinogenicity studies and evaluating their results.

3.7. Exceptions

Where a medicinal product is intended for topical use, systemic absorption shall be investigated in the target species of

animal. 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 conditions of use laid down, oral ingestion of the medicinal product by the animal is to be

expected, or

- the medicinal particular may enter foodstuffs obtained from the treated animal (intramammary preparations).

4. Other requirements

4.1. Immunotoxicity

Where the effects observed during repeated dose studies in animals include specific changes in lymphoid organ weights

and, or histology and changes in the cellularity of lymphoid tissues, bone marrow or peripheral leukocytes, the

investigator shall consider the need for additional studies of the effects of the product on the immune system. The state

of scientific knowledge at the time the application is submitted 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 microbiological risk presented by residues of antimicrobial compounds for the human intestinal flora shall be

investigated in accordance with the state of scientific knowledge at the time the application is submitted.

4.2.2. Potential effects on the micro-organisms used for industrial food processing. In certain cases, it

may be necessary to carry out tests to determine whether residues cause difficulties affecting

technological processes in industrial foodstuff processing.

4.3. Observations in humans

Information shall be provided showing whether the constituents of the veterinary medicinal product are used as

medicinal products in human therapy; if this is so, a report should be made on all the effects observed (including

adverse reactions) in humans and on their cause, to the extent that they may be important for the assessment of the

veterinary medicinal product, where appropriate in the light of trial results of bibliographical documents; where

constituents of the veterinary medicinal products are themselves not used or are no longer used as medicinal products in

human therapy, the reasons should be stated in writing.

5. Ecotoxicity

5.1. The purpose of the study of the ecotoxicity of a veterinary medicinal product 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.

5.2. An assessment of ecotoxicity shall be compulsory for any application for marketing authorisation for a

veterinary medicinal product other than applications submitted in accordance with regulations 12 (3) (j) and 13

(1).

5.3. This assessment shall normally be conducted in two phases. In the first phase, the investigator shall assess

the potential extent of exposure to the environment of the product, its active substances or relevant

metabolites, taking into account -

- the target species, and the proposed pattern of use (for example, mass-medication or individual

animal medication),

- 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 excretia,

- the disposal of unused or waste product.

5.4. In a second phase, having regard to 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

compound which has been obtained during the conduct of the other tests and trials required by these

regulations, the investigator shall then consider whether further specific investigation of the effects of the

product on particular ecosystems is necessary.

5.5. As appropriate, further investigation may be required of -

- fate and behaviour in soil,

- fate and behaviour in water and air,

- effects on aquatic organisms,

- effects on other non-target organisms.

These further investigations shall be carried out in accordance with the test protocols established under European Union

Council Directive 67/548/EEC on the approximation of laws, regulations and administrative dispositions relating to the

classification, packaging and labelling of dangerous substances, or where an end point is not adequately covered by

these protocols, in accordance with other internationally recognised protocols on the veterinary medicinal product and,

or the active substance (s) and, or the excreted metabolites as appropriate. The number and types of tests and the

criteria for their evaluation shall depend upon the state of scientific knowledge at the time the application is submitted.

Chapter II

Presentation of particulars and documents

As in any scientific work, the dossier of safety tests shall include the following -

(a) an introduction defining the subject, accompanied by any useful bibliographical references;

(b) the detailed identification of the substance under review, including -

- international non-proprietary name (INN),

- International Union of Pure and Applied Chemistry Name (IUPAC),

- Chemical Abstract Service (CAS) number,

- therapeutical and pharmacological 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;

(c) a detailed experimental protocol giving the reasons for any omission of certain tests listed above, a description of

the methods, apparatus and materials used, details of the species, breed or strain of animals, where they were obtained,

their number and the conditions under which they were housed and fed, stating inter alia whether they were free from

specific pathogens (SPF);

(d) all the results obtained, whether favourable or unfavourable. The original data should be described in sufficient

detail to allow the results to be critically evaluated independently of their interpretation by the author. By way of

explanation, the results may be accompanied by illustrations;

(e) a statistical analysis of the results, where such is called for by the test programme, and variance within the data;

(f) an objective discussion of the results obtained, leading to conclusions on the safety of the substance, on its safety

margin in the test animal and the target animal and its possible side-effects, on its fields of application, on its active

dose levels and any possible incompatibilities;

(g) a detailed description and a thorough discussion of the results of the study of the safety of residues in food, and its

relevance for the evaluation of potential risks presented by residues to humans. This discussion shall be followed by

proposals to ensure that any danger to man is eliminated by applying internationally recognised assessment criteria, for

example: no observed effect level in animals, proposals for a choice of safety factor and for acceptable daily intake

(ADI);

(h) a thorough discussion of any risks for persons preparing the medicinal product or administering it to animals,

followed by proposals for appropriate measures to reduce such risks;

(i) a thorough discussion of the risks which use of the veterinary medicinal product under the practical conditions

proposed may represent for the environment followed by appropriate proposals to reduce such risks;

(j) all information necessary to acquaint the clinician as fully as possible with the utility of the proposed product. The

discussion will be supplemented by suggestions as to side-effects and possible treatment for acute toxic reactions in

animals to which the product is to be administered;

(k) a concluding expert report which provides a detailed critical analysis of the information referred to above in the

light of the state of scientific knowledge at the time the application is submitted together with a detailed summary of all

the results of the relevant safety tests and precise bibliographical references.

B. Residue testing

Chapter I

Performance of tests

1. Introduction

For the purposes of these regulations, "residues" means all active substances or metabolites thereof which remain in

meat or other foodstuffs produced from the animal to which the medicinal product in question has been administered.

The purpose of studying residues is to determine whether, and if so under what conditions and to what extent, residues

persist in foodstuffs produced from treated animals and to ascertain the withdrawal periods to be adhered to in order to

obviate any hazard to human health and, or difficulties in the industrial processing of foodstuffs.

Assessment of the hazard due to residues entails establishing whether residues are present in the animals treated under

recommended conditions of use and investigating the effects of those residues.

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 tissues of the treated animal or foodstuffs obtained therefrom;

2. that in order to prevent any risk to the health of the consumer of foodstuffs of 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 practical analytical methods suitable for routine use are available to verify compliance with the

withdrawal period.

2. Metabolism and residue kinetics

2.1. Pharmacokinetics (absorption, distribution, biotransformation, excretion)

The purpose of pharmacokinetic studies with respect to residues of veterinary medicinal products is to evaluate the

absorption, distribution, biotransformation and excretion of the product in the target species.

The final product, or a formulation which is bioequivalent, shall be administered to the target species at the maximum

recommended dose.

Having regard to the method of administration, the extent of absorption of the medicinal product shall be fully

described. If it is demonstrated that systemic absorption of products for topical application is negligible, further residue

studies will not be required.

The distribution of the medicinal product in the target animal shall be described; the possibility of plasma protein

binding, or passage into milk or eggs and of the accumulation of lipophilic compounds shall be considered.

The pathways for the excretion of the product from the target animal shall be described. The major metabolites shall be

identified and characterised.

2.2. Depletion of residues

The purposes of these studies, which measure the rate at which residues deplete in the target animal after the last

administration of the medicinal product, is to permit the determination of withdrawal periods.

At varying times after the test animal has received the final dose of the medicinal product, the quantities of residues

present shall be determined by appropriate physical, chemical or biological methods; the technical procedures and the

reliability and sensitivity of the methods employed shall be specified.

3. Routine analytical method for the detection of residues.

Analytical procedures shall be proposed which can be carried out in the course of a routine examination and which

have a level of sensitivity such as to enable violations of legally permitted maximum residue limits to be detected with

certainty.

The analytical method proposed shall be described in detail. It shall be validated and shall be sufficiently rugged for use

under normal conditions of routine monitoring for residues.

The following characteristics shall be described -

- specificity,

- accuracy, including sensitivity,

- precision,

- limit of detection,

- limit of quantitation,

- practicability and applicability under normal laboratory conditions,

- susceptibility to interference.

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 submitted.

Chapter II

Presentation of particulars and documents

As in any scientific work, the dossier of residue tests shall include the following -

(a) an introduction defining the subject, accompanied by any useful bibliographical references;

(b) a detailed identification of the medicinal, including -

- composition,

- purity,

- batch identification,

- relationship to the final product,

- specific activity and radio purity of labelled substances,

- position of labelled atoms in the molecule;

(c) a detailed experimental protocol giving the reasons for any omission of certain tests listed above, a

description of the methods, apparatus and materials used, details of the species, breed or strain of animals,

where they were obtained, their number and the conditions under which they were housed and fed;

(d) all the results obtained, whether favourable or unfavourable. The original data should be described in

sufficient detail to allow the results to be critically evaluated independently of their interpretation by the

author. The results may be accompanied by illustrations;

(e) a statistical analysis of the results, where such is called for by the test programme, and variance within the

data;

(f) an objective discussion of the results obtained, followed by proposals for maximum residue limits for the

active substances contained in the product, specifying the marker residue and target tissues concerned, 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;

(g) a concluding expert report which provides a detailed critical analysis of the information referred to above

in the light of the state of scientific knowledge at the time the application is submitted together with a detailed

summary of the results of the residue tests and precise bibliographical references.

PART 4

Pre-clinical and clinical testing

The particulars and documents which shall accompany applications for marketing authorisations pursuant to regulations

12 (3) (j) and 13 (1) shall be submitted in accordance with the provisions of this Part.

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 study of pharmacodynamics shall follow two distinct lines of approach -

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, the investigator shall give an overall pharmacological assessment of the active substance, with special

reference to the possibility of side-effects. In general, the main functions shall be investigated.

The investigator shall identify the effect of the route of administration, formulation, etc, on the pharmacological activity

of the active substance.

The investigations shall be intensified where the recommended dose approaches that liable 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.

Medicinal 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 novel active substance, the latter shall have been previously studied in depth.

A.2. Pharmacokinetics

Basic pharmacokinetic information concerning a new active substance is generally useful in the clinical context.

Pharmacokinetic objectives can be divided into two main areas -

(i) descriptive pharmacokinetics leading to the evaluation of basic parameters such as body clearance,

volume(s) of distribution, mean residence time, etc;

(ii) use of these parameters to investigate the relationships between dosage regimen, plasma and tissue

concentration and pharmacologic, therapeutic or toxic effects.

In target species, pharmacokinetic studies are, as a rule, necessary in order to employ drugs with the greatest possible

efficacy and safety. Such studies are especially useful to assist the clinician in establishing dosage regimens (route and

site of administration, dose, dosing interval, number of administrations, etc.) and to adopt dosage regimens according to

certain population variables (e.g. age, disease). Such studies can be more efficient in number of animals and generally

provide more information than classical dose titration studies.

In the case of new combinations of known substances which have been 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.

A.2.1. Bioavailability, bioequivalence

Appropriate bio-availability studies shall be undertaken to establish bioequivalence -

- when comparing a reformulated medicinal product with the existing one,

- when comparing a new method or route of administration with an established one,

- in all cases referred to in regulation 13 (1).

B. Tolerance in the target species of animal

The purpose of this study, which shall be carried out with all animal species for which the medicinal product is

intended, is to carry out in all such animal species local and general tolerance trials designed to establish a tolerated

dosage wide enough to allow an adequate safety margin and the clinical symptoms of intolerance using the

recommended route or routes, in so far as this may be achieved by increasing the therapeutic dose and, or the duration

of treatment. The report on the trials shall contain as many details as possible of the expected pharmacological effects

and the adverse reactions; the latter shall be assessed with due regard to the fact that the animals used may be of very

high value.

The medicinal product shall be administered at least via the recommended route of administration.

C. Resistance

Data on the emergence of resistant organisms are necessary in the case of medicinal products used for the prevention or

treatment of infectious diseases or parasitic infestations in animals.

Chapter II

Clinical requirements

1. General principles

The purposes of clinical trials are to demonstrate or substantiate the effect of the veterinary medicinal product after

administration of the recommended dosage, to specify its indications and contraindications according to species, age,

breed and sex, its directions for use, any adverse reactions which it may have and its safety and tolerance under normal

conditions of use.

Unless justified, clinical trials shall be carried out with control animals (controlled clinical trials). The effect obtained

should be compared with a placebo or with absence of treatment and, or with the effect of an authorised medicinal

product known to be of therapeutic value. All the results obtained, whether positive or negative, shall be reported.

The methods used to make the diagnosis shall be specified. The results shall be set out by making use of quantitative or

conventional clinical criteria. Adequate statistical methods shall be used and justified.

In the case of a veterinary medicinal product intended primarily for use as a performance enhancer, particular attention

shall be given to -

- the yield of animal produce,

- the quality of animal produce (organoleptic, nutritional, hygienic and technological qualities),

- nutritional efficiency and growth of animal,

- the general status of health of the animal.

Experimental data shall be confirmed by data obtained under practical field conditions.

Where, in respect of particular therapeutic indications, the applicant can show that he is unable to provide

comprehensive data on therapeutic effect because -

(a) the indications for which the medicinal product in question is intended are encountered so rarely that the

applicant cannot reasonably be expected to provide comprehensive evidence;

(b) in the present state of scientific knowledge, comprehensive information cannot be provided;

The marketing authorisation may only be granted subject to the following conditions -

(a) the medicinal product in question is to be supplied on veterinary prescription only and may, in certain

cases, be administered only under strict veterinary supervision;

(b) the package insert and any other information must draw the attention of the veterinary practitioner to the

fact that, in certain specified respects, the particulars available concerning the medicinal product in question

are as yet incomplete.

2. Performance of trials

All veterinary clinical trials shall be conducted in accordance with a fully considered detailed trial 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 clinical trials shall be required.

Before the commencement of any 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 trial is conducted with a blind design, the provisions of regulations 51, 52 and 53 concerning the labelling of

veterinary medicinal products shall apply by analogy to the labelling of formulations intended for use in veterinary

clinical trials. In all cases, the words "for veterinary clinical trial use only" shall appear prominently and indelibly upon

the labelling.

Chapter III

Particulars and documents

As in any scientific work, the dossier on efficacy shall include an introduction defining the subject accompanied by any

useful bibliographical documentation.

All pre clinical and clinical documentation must be sufficiently detailed to enable an objective judgement to be made.

All studies and trials must be reported, whether favourable or unfavourable to the applicant.

1. Records of preclinical observations

Wherever possible, particulars shall be given of the results of -

(a) tests demonstrating pharmacological actions;

(b) tests demonstrating the pharmacological mechanisms underlying the therapeutic effect;

(c) tests demonstrating the main pharmacokinetic processes.

Should unexpected results occur during the course of the tests, these should be detailed.

Additionally the following particulars shall be provided in all preclinical 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 safety and efficacy of the

product. Total or partial omission of these data must be explained.

2.1. Records of clinical observations

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 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 rearing and feeding, stating the composition of the feed and the nature and quantity of any

additives contained in the feed;

(e) case history (as full as possible), occurrence and course of any intercurrent diseases;

(f) diagnosis and means used to make it;

(g) symptoms and severity of the disease, if possible according to conventional criteria;

(h) the precise identification of the clinical trial formulation used in the trial;

(i) dosage of the 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 medicinal products (other than that under study) 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 the interactions observed;

(l) all results of the clinical trials (including unfavourable or negative results) with a full statement of the

clinical observations and the results of the objective tests of activity (laboratory analyses, physiological tests),

required to evaluate the application; the techniques used must be specified, and the significance of any

variations in the results explained (e.g. variance in method, variance between individuals or the effects of the

medication); demonstration of the pharmacodynamic effect in animals shall not in itself suffice to justify

conclusions concerning any therapeutic effect;

(m) all particulars of any unintended effects, whether harmful or not, and of any measures taken in

consequence; the cause-and-effect relationship shall be investigated if possible;

(n) effect of animals' performance (e.g. egg-laying, milk production and reproductive function);

(o) effects on the quality of foodstuffs obtained from treated animals, particularly in the case of medicinal

products intended for use as performance enhancers;

(p) a conclusion on each individual case or, where collective treatment is concerned, on each collective case.

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.

2.2. Summary and conclusions of clinical observations

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 controls, the number of 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;

- received a placebo;

- received another authorised medicinal product of known effect;

- received the 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 performance (e.g. egg-laying, milk production, reproductive function and

food quality);

(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, when this is called for by the test programme.

Finally, the investigator shall draw general conclusions from the experimental evidence, expressing his opinion on the

harmlessness of the medicinal product under the proposed conditions of use, its therapeutic effect and any useful

information relating to indications and contraindications, dosage and average duration of treatment and where

appropriate, any interactions observed with other medicinal products or feed additives as well as any special

precautions to be taken during treatment and the clinical symptoms of over-dosage.

In the case of fixed combination products, the investigator shall also draw conclusions concerning the safety and the

efficacy of the product when compared with the separate administration of the active substances involved.

3. Concluding expert report

The concluding expert report shall provide a detailed critical analysis of all the pre-clinical and clinical documentation

in the light of the state of scientific knowledge at the time the application is submitted together with a detailed summary

of the results of the tests and trials submitted and precise bibliographic references.

TITLE II

Requirements for immunological veterinary medicinal products

Without prejudice to the specific requirements laid down by European Community legislation for the control and

eradication of animal disease, the following requirements shall apply to immunological veterinary medicinal products.

PART 5

Summary of the dossier

A. Administrative data

The immunological veterinary medicinal product which is the subject of the application shall be identified by name and

by name of the active substances, together with the strength and pharmaceutical form, the method and route of

administration, and a description of the final sales presentation of the product.

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 (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 data shall be copies of a document showing that the manufacturer is authorised to

produce immunological veterinary medicinal products, as defined in regulation 38 (with a brief description of the

production site). 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, copies of all the summaries of

product characteristics in accordance with regulation 14 as approved by the competent authorities and a list of countries

in which an application has been submitted.

B. Summary of product characteristics

The applicant shall propose a summary of the product characteristics, in accordance with regulation 14. In addition the

applicant shall provide one or more specimens or mock-ups of the sales presentation of the immunological veterinary

medicinal product, together with a package insert, where one is required.

C. Expert reports

In accordance with regulation 15 (2) and (3) expert reports must be provided on all aspects of the documentation. Each

expert report shall consist of a critical evaluation of the various tests and, or trials, which have been carried out in

accordance with these regulations, and bring out all the data relevant for evaluation. The expert shall give his opinion as

to whether sufficient guarantees have been provided as to the quality, safety and efficacy of the product concerned. A

factual summary is not sufficient.

All important data shall be summarised in an appendix to the expert report, whenever possible in tabular or graphic

form. The expert report and the summaries shall contain precise cross references to the information contained in the

main documentation.

Each expert report shall be prepared by a suitably qualified and experienced person. It shall be signed and dated by the

expert, and attached to the report shall be brief information about the educational background, training and

occupational experience of the expert. The professional relationship of the expert to the applicant shall be declared.

PART 6

Analytical (physicochemical, biological or microbiological) tests of immunological veterinary medicinal products

All test procedures used shall correspond to the state of scientific progress at the time and shall be validated procedures;

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 Veterinary Services; 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 the territory of Malta or of a

Member State, this description may be replaced by a detailed reference to the pharmacopoeia in question.

A. Qualitative and quantitative particulars of the constituents

The particulars and documents which must accompany applications for marketing authorisation, pursuant to regulation

12 (3) (c), shall be submitted in accordance with the following requirements.

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.

2. 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 national

pharmacopoeia of the territory of Malta or of one of the other 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

Organization, 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 accordance with European

Community rules and in accordance with European Union Council 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 section B.

Where an International Unit of biological activity has been defined, this shall be used.

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. Development pharmaceutics

An explanation shall be provided with regard to the composition, components and containers, supported by scientific

data on development pharmaceutics. The overage, with justification thereof, shall be stated. The efficacy of any

preservative system shall be demonstrated.

B. Description of manufacturing method of the finished product

The description of the manufacturing method accompanying the application for marketing authorisation pursuant to

regulation 12 (3) (d), 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 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,

- in the case of continuous manufacture, full details concerning precautions taken to ensure the homogeneity

and consistency of each batch of the finished product,

- mention of substances which cannot be recovered in the course of manufacture,

- the details of the blending, with the quantitative particulars of all the substances used,

- a statement of the stage of manufacture at which sampling is carried out for in-process control tests.

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 used for the production of the active substance are

considered as one single starting material.

In the case of -

- an active substance not described in the European Pharmacopoeia or in the pharmacopoeia of the territory of

Malta or of a Member State, or

- an active substance described in the European Pharmacopoeia or in the pharmacopoeia of the territory of

Malta or of a Member State when prepared by a method liable to leave impurities not mentioned in the

pharmacopoeial monograph and for which the monograph is inappropriate to adequately control its quality,

which is manufactured by a person different from the applicant, the latter may arrange for the detailed description of

the manufacturing method, quality control during manufacture and process validation to be supplied directly to the

competent authorities by the manufacturer of the active substance. 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 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 Veterinary Services.

The particulars and documents accompanying the application for marketing authorisation pursuant to regulation 12 (3)

(i) and (j) and regulation 13 (1) shall include the results of the tests relating to quality control of all the 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 substances appearing in it.

In respect of other substances, the Veterinary Services may require observance of its own national pharmacopoeia with

regard to products manufactured in its territory.

Components fulfilling the requirements of the European Pharmacopoeia or the pharmacopoeia of the territory of Malta

or one of the Member States shall be deemed to comply sufficiently with regulation 12 (3) (i). In this case the

description of the analytical methods may be replaced by a detailed reference to the pharmacopoeia in question.

Reference to pharmacopoeias of third countries may be permitted in cases where the substance is described neither in

the European Pharmacopoeia nor in the national pharmacopoeia concerned; in that case the monograph shall be

submitted, accompanied where necessary by a translation for which the applicant will be responsible.

Colouring matter shall, in all cases, satisfy the requirements of European Union Council 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

national pharmacopoeia of the territory of Malta or of a Member State might be insufficient to ensure the quality of the

substance, the Veterinary Services may request more appropriate specifications from the applicant for marketing

authorisation.

The Veterinary Services shall inform the authorities responsible for the pharmacopoeia in question. The applicant for

marketing authorisation shall provide the authorities of that pharmacopoeia with the details of the alleged insufficiency

and the additional specifications applied.

In cases where a starting material is described neither in the European Pharmacopoeia nor in the pharmacopoeia of the

territory of Malta or of a Member State, 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 the test procedures contained in the monograph and by a translation where appropriate. For active

ingredients, demonstration of the ability of the monograph adequately to control their quality shall be presented.

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 banks. 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;

defined pools of source materials shall be used.

The origin 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 co-transfection, added or deleted genes, biological properties of the final construct and the genes expressed,

copy number and genetic stability.

Seed materials, including cell banks and raw serum for antiserum production shall be tested for identity and

adventitious 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 in-process controls,

- details of any tests for contamination carried out on each batch of the substance.

If the presence of adventitious 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 adventitious agents shall be demonstrated.

When cell banks 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 characteristics of the seed has to be given.

When required, samples of the biological starting material or reagents used in the testing procedures shall be provided

to enable the Veterinary Services 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,

- purity shall be described in relation to the sum total of predictable impurities, 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, may adversely effect the stability of the medicinal product or distort analytical results. A

brief description shall be provided of the tests undertaken to establish the purity of each batch of the starting

material,

- any special precautions which may be necessary during storage of the starting material and, if necessary, its

storage life shall be given.

D. Specific measures concerning the prevention of the transmission of animal spongiform encephalopathies

The applicant must demonstrate that the veterinary medical product is manufactured in accordance with the Note for

Guidance on minimising the risk of transmitting animal spongiform encephalopathy agents via veterinary medicinal

products and its updates, published by the European Commission in Volume 7 of its publication "The rules governing

medicinal products in the European Community".

E. Control tests during production

1. The particulars and documents accompanying an application for marketing authorisation, pursuant to regulation 12

(3) (i) and (j) and regulation 13 (1), shall include particulars relating to the control tests which are carried out on

intermediate products with a view to verifying the consistency of the production process and the final product.

2. For inactivated or detoxified vaccines, inactivation or detoxification shall be tested during each production run

immediately after the inactivation or detoxification process.

F. Control tests on the finished product

The particulars and documents accompanying the application for marketing authorisation pursuant to regulation 12 (3)

(i) and (j) and regulation 13 (1), 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 national pharmacopoeia of the territory of Malta or of a Member State,

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.

1. General characteristics of the finished product

Certain tests of the general characteristics of a product shall be included among the tests on the finished product, even if

they have been carried out in the course of the manufacturing process.

These tests shall, wherever applicable, relate to the control of average masses and maximum deviations, to mechanical,

physical, chemical or microbiological tests, physical characteristics such as density, pH, refractive index, etc. For each

of these characteristics, specifications, with appropriate confidence limits, shall be established by the applicant in each

particular case.

2. Identification and assay of active substance(s)

For all tests, the description of the techniques for analysing the finished product shall be set out in sufficiently precise

detail, so that they can be reproduced readily.

The assay of biological activity 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.

Where necessary, a specific test for identification shall also be carried out.

In certain exceptional cases 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 as late as possible in the production process. This relaxation may not be extended to the

characterisation of the substances concerned. This simplified technique shall be supplemented by a method of

quantitative evaluation, enabling the competent authority to verify that the immunological veterinary medicinal product

is in accordance with its formula after it has been placed on the market.

3. Identification and assay of adjuvants

In so far as testing procedures are available, the quantity and nature of the adjuvant and its components shall be verified

on the finished product.

4. Identification and assay of excipient components

In so far as is necessary, the excipient(s) shall be subject at least to identification tests.

The test procedure proposed for identifying colouring matters must enable a verification to be made that such matters

are permitted in accordance with the rules laid down under European Union Council Directive 78/25/EEC.

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.

5. Safety tests

Apart from the results of tests submitted in accordance with Part 7 of this Schedule, particulars of safety tests shall be

submitted. These tests shall preferably be over-dosage 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.

6. Sterility and purity test

Appropriate tests to demonstrate the absence of contamination by adventitious 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.

7. Inactivation

Where applicable, a test to verify inactivation shall be carried out on the product in the final container.

8. Residual humidity

Each batch of lyophilised product shall be tested for residual humidity.

9. Batch-to-batch consistency

In order to ensure that efficacy of the product is reproducible from batch to batch and to demonstrate conformity with

specifications, potency tests based upon in vitro or in vivo methods, including appropriate reference materials whenever

available, shall be carried out on each final bulk or each batch of finished product, with appropriate confidence limits;

in exceptional circumstances, potency testing may be carried out at an intermediate stage, as late as possible in the

production process.

G. Stability tests

The particulars and documents accompanying the application for marketing authorisation pursuant to regulation 12 (3)

(f) and (i) 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

physicochemical stability tests.

The conclusions shall contain the results of analysis, justifying the proposed shelf-life under all proposed storage

conditions.

In the case of products administered in the 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, 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.

PART 7

Safety testing

A. Introduction

1. 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.

2. The particulars and documents which shall accompany the application for marketing authorisation pursuant to

regulations 12 (3) (j) and 13 (1) shall be submitted in accordance with the requirements of section B.

3. The Veterinary Services shall ensure that the laboratory tests are carried out in conformity with the principles of

good laboratory practice in accordance with the relevant European Community rules.

B. General requirements

1. The safety tests shall be carried out in the target species.

2. The dose to be used shall be that quantity of the product to be recommended for use and containing the maximum

titre or potency for which the application is submitted.

3. The sample used for safety testing shall be taken from a batch or batches produced according to the manufacturing

process described in the application for marketing authorisation.

C. 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.

2. Safety of one administration of an overdose

An overdose of the immunological veterinary medicinal product shall be administered by each recommended route of

administration to animals of the most sensitive categories of the target species. The animals shall be observed and

examined for signs of systemic and local reactions. Other objective criteria shall be recorded, such as rectal temperature

and performance measurements.

The animals shall be observed and examined for at least 14 days after administration.

3. Safety of the repeated administration of one dose

Repeated administration of one dose may 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, using the 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

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 each of the recommended routes 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 paragraph 1.

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 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.

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

well established zoonotic diseases for food producing animals, these studies must be undertaken.

6.3. Reversion to virulence of attenuated vaccines

Reversion to virulence shall be investigated with material from the passage level which is least attenuated

between the master seed and the final product. The initial vaccination shall be carried out using the

recommended route of administration most likely to lead to reversion to virulence. At least five serial passages

through animals of the target species shall be undertaken. Where this is not technically possible due to failure

of the organism to replicate adequately, as many passages as possible shall be carried out in the target species.

If necessary, in vitro propagation of the organism may be carried out between passages in vivo. The passages

shall be undertaken by the route of administration most likely to lead to reversion to virulence.

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 re-assortment of strains

The probability of recombination or genomic re-assortment with field or other strains shall be discussed.

7. 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. Moreover, in the case of live vaccines for zoonotic diseases, the

determination of residues at the injection site may be required in addition to the studies described in paragraph 6.2.

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.

8. Interactions

Any known interactions with other products shall be indicated.

D. Field studies

Unless justified, results from laboratory studies shall be supplemented with supportive data from field studies.

E. Ecotoxicity

The purpose of the study of the ecotoxicity of an immunological veterinary medicinal product 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.

An assessment of ecotoxicity shall be compulsory for any application for marketing authorisation for an immunological

veterinary medicinal product other than applications submitted in accordance with regulations 12 (3) (j) and 13 (1).

This assessment shall normally be conducted in two phases.

The first phase of the assessment shall always be carried out: the investigator shall assess the potential extent of

exposure of the environment to the product, its active substances, or relevant metabolites, taking into account -

- the target species and the proposed pattern of use (e.g. mass medication or individual animal medication),

- the method of administration, in particular the likely extent to which the product will enter directly into

environmental system,

- 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 or waste product.

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 ecotoxicity of the product. For this purpose, he shall

consider the extent and duration of exposure of the environment to the product, and the information about the

physical/chemical, pharmacological and, or toxicological properties of the compound obtained during the conduct of

the other tests and trials required by these regulations. Where necessary, further investigations on the impact of the

product (soil, water, air, aquatic systems, non-target organisms) shall be carried out.

These further investigations shall be carried out in accordance with the test protocols laid down in European Union

Council Directive 67/548/EEC legislation or where an end point is not adequately covered by these protocols, in

accordance with other internationally recognised protocols on the immunological veterinary medicinal product and, or

the active substances and, or the excreted metabolites as appropriate. The number and types of tests and the criteria for

their evaluation shall depend upon the state of scientific knowledge at the time the application is submitted.

PART 8

Efficacy trials

A. Introduction

1. 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. The particulars and documents which shall accompany applications for marketing authorisations pursuant to

regulations 12 (3) (j) and 13 (1) shall be submitted in accordance with the provisions below.

3. All veterinary clinical trials shall be conducted in accordance with a fully considered detailed trial 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 clinical trials shall be required.

4. Before the commencement of any 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.

5. Unless the trial is conducted with a blind design, the provisions of regulations 51, 52 and 53 shall apply by analogy

to the labelling of formulations intended for use in veterinary clinical trials. In all cases, the words "for veterinary

clinical trial use only" shall appear prominently and indelibly upon the labelling.

B. General requirements

1. The choice of 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.

In general, these trails 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 control trials, carried out at the

request of the Veterinary Services. The investigator shall demonstrate the validity of all the techniques involved.

All results shall be presented as precisely as possible. 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 each

species recommended for 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. Any claims regarding the onset and duration of protection shall be 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 product to the efficacy of the scheme as a whole shall be demonstrated.

6. The dose to be used shall be that quantity of the product to be recommended for use and containing the minimum

titre or potency for which the application is submitted.

7. The samples used for efficacy trials shall be taken from a batch or batches produced according to the manufacturing

process described in the application for marketing authorisation.

8. For diagnostic immunological veterinary medicinal products administered to animals, the applicant shall indicate

how reactions to the product are to be interpreted.

C. Laboratory trials

1. In principle, demonstration of efficacy shall be undertaken under well controlled laboratory conditions by challenge

after administration of the immunological veterinary medicinal product to the target animal under the recommended

conditions of use. In so far as possible, the conditions under which the challenge is carried out shall mimic the natural

conditions for infection, for example with regard to the amount of challenge organism and the route of administration

of the challenge.

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.

D. Field trials

1. Unless justified, results from laboratory trials shall be supplemented with data from field trials.

2. Where laboratory trials cannot be supportive of efficacy, the performance of field trials alone may be acceptable.

PART 9

Particulars and documents concerning safety testing and efficacy trials of immunological veterinary medicinal

products

A. Introduction

As in any scientific work, the dossier of safety and efficacy studies shall include an introduction defining the subject

and indicating the tests which have been carried out in compliance with Parts 7 and 8, as well as a summary, with

references to the published literature. Omission of any tests or trials listed in Parts 7 and 8 shall be indicated and

discussed.

B. 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, breed or strain 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 of the

statistical methods used;

4. in the case of control animals, whether they received a placebo or no treatment;

5. 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.;

6. the nature, frequency and duration of observed side-effects;

7. the number of animals withdrawn prematurely from the studies and reasons for such withdrawal;

8. a statistical analysis of the results, where such is called for by the test programme, and variance within the

data;

9. occurrence and course of any inter-current disease;

10. all details concerning medicinal products (other than the product under study), the administration of which

was necessary during the course of the study;

11. an objective discussion of the results obtained, leading to conclusions on the safety and efficacy of the

product.

C. 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, 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. effect on the animals' performances (e.g. egg laying, milk production, reproductive 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 inter-current disease;

14. all details concerning 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.

D. General conclusions

General conclusions on all results of tests and trials carried out in compliance with Parts 7 and 8 shall be given. They

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.

E. Bibliographical references

The bibliographical references cited in the summary mentioned under Section A shall be listed in detail.

Mitbug] fl-Istamperija tal-Gvern - Printed at the Government Printing Press

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 2 — Veterinary Medicinal Products Regulations, 2004 Open official source

For the purposes of these regulations, the following terms shall have the following

meanings -

(1) “Proprietary medicinal product” means any ready-prepared medicinal product placed on

the market under a special name and in a special pack.

(2) “Veterinary medicinal product” means any substance or combination of substances

presented for treating or preventing disease in animals.

Any substance or combination of substances which may be administered to animals with a view to

making a medical diagnosis or to restoring, correcting or modifying physiological functions in

animals is likewise considered a veterinary medicinal product.

(3) “Readymade veterinary medicinal product” means any veterinary medicinal product

prepared in advance which does not comply with the definition of proprietary medicinal products

and which is marketed in a pharmaceutical form which may be used without further processing.

(4) “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.

(5) “Premix for medicated feeding stuffs” means any veterinary medicinal product prepared

in advance with a view to the subsequent manufacture of medicated feedingstuffs.

(6) “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.

(7) “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.

(8) “Homeopathic veterinary medicinal product” means any veterinary medicinal product

prepared from products, substances or compositions 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 the Member States. A

homeopathic veterinary medicinal product may also contain a number of principles.

(9) “Withdrawal period” means the period necessary between the last administration of the

veterinary medicinal product to animals under normal conditions of use and the production of

foodstuffs from such animals, in order to ensure that such foodstuffs do not contain residues in

quantities in excess of the maximum limits laid down in application of Regulation (EEC) No .

2377/90.

(10) “Adverse reaction” means a reaction which is harmful and unintended and which

occurs at doses normally used in animals for the prophylaxis, diagnosis or treatment of disease or

the modification of physiological function.

(11) “Human adverse reaction” means a reaction which is noxious and unintended and

which occurs in a human being following exposure to a veterinary medicine.

(12) “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.

(13) “Unexpected adverse reaction” means an adverse reaction, the nature, severity or

outcome of which is not consistent with the summary of the product characteristics.

(14) “Periodic safety update reports” means the periodical reports containing the records

referred to in regulation 68.

(15) “Post-marketing surveillance studies” means the pharmacoepidemiological study or a

clinical trial carried out in accordance with the terms of the marketing authorisation, conducted

with the aim of identifying and investigating a safety hazard relating to an authorised veterinary

medicinal product.

(16) “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.

(17) “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.

(18) “Agency” means European Agency for the Evaluation of Medicinal Products

established by EU Commission Regulation (EC) No. 2309/93.

(19) “Risk to human or animal health or the environment” means any risk relating to the

quality, safety and efficacy of the veterinary medicinal product.

(20) “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.

(21) “Veterinary Services” means the competent authority within the territory of Malta as

established under article 2 of the Veterinary Services Act.

(22) “the Commission” means the European Commission.

(23) “the Community” means the European Community as established under the Treaty

establishing the European Community.

(24) “Member State” means a State which is a Member of the European Community.

(25) “Third Country” means a State which is not a Member within the European

Community.

(26) “Pharmacist” means a licensed professional as provided under the Health Care

Professions Act.

TITLE II

Applicability

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 3 — Veterinary Medicinal Products Regulations, 2004 Open official source

These regulations shall not apply to -

(1) Medicated feeding stuffs 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

feeding stuffs in the European Community.

However, medicated feeding stuffs may be prepared only from pre-mixes which have been

authorised under these regulations.

(2) 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;

(3) Any medicinal product prepared in a pharmacy in accordance with a prescription for an

individual animal (commonly known as “the magistral formula”);

(4) Any medicinal product prepared in a pharmacy in accordance with the prescriptions of a

pharmacopoeia and is intended to be supplied directly to the end-user (commonly known as “the

officinal formula”);

(5) Veterinary medicinal products based on radioactive isotopes;

(6) 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 Council Directive.

Nevertheless, the territory of Malta may, when implementing regulation 10(1)(c) and (2)

take account of the medicinal products referred to in sub-regulations (3) and (4).

Non-inactivated immunological veterinary medicinal products

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 4 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) The territory of Malta 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) The territory of Malta may permit exemptions on its territory in respect of veterinary

medicinal products intended solely for aquarium fish, cage birds, homing pigeons, terrarium

animals and small rodents, from the provisions in regulations 5, 7 and 8

Provided that such products do not contain substances the use of which requires veterinary

control and that all possible measures have been taken to prevent unauthorised use of the products

for other animals.

TITLE III

MARKETING

CHAPTER 1

Marketing authorisation

Marketing authorisation issued by the Veterinary Services

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 5 — Veterinary Medicinal Products Regulations, 2004 Open official source

No veterinary medicinal product may be placed on the market of the territory of Malta

unless a marketing authorisation has been issued by the Veterinary Services in accordance with

these regulations or a marketing authorisation has been granted in accordance with Regulation

(EEC) No. 2309/93.

Active substances in veterinary medicinal product

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 6 — Veterinary Medicinal Products Regulations, 2004 Open official source

In order that a veterinary medicinal product may be the subject of a marketing

authorisation for the purpose of administering it to food-producing animals, the active substances

which it contains must be shown in Annexes I, II or III of Regulation (EEC) No. 2377/90.

Authorisation of the marketing or administration to animals of veterinary medicinal products

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 7 — Veterinary Medicinal Products Regulations, 2004 Open official source

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 another Member State in accordance with European Union Council Directive

2001/82/EC.

Serious disease epidemic

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 8 — Veterinary Medicinal Products Regulations, 2004 Open official source

In the event of a serious disease epidemic, the territory of Malta may provisionally allow

the use of immunological veterinary medicinal products without an authorisation for placing on the

market, in the absence of a suitable medicinal product and after informing the European

Commission of the detailed conditions of use.

Administration of veterinary medicinal product to animals

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 9 — Veterinary Medicinal Products Regulations, 2004 Open official source

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.

Exception granted by the Veterinary Services

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 10 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) Where there is no authorised medicinal product for a condition, the Veterinary

Services may exceptionally, in particular in order to avoid causing unacceptable suffering to the

animals concerned, permit the administration by a veterinarian or under his direct personal

responsibility to an animal or to a small number of animals on a particular holding -

(a) of a veterinary medicinal product authorised in the territory of Malta under these

regulations or under Regulation (EEC) No. 2309/93 for use in another animal species, or for

another condition in the same species; or

(b) if there is no product as referred to in paragraph (a), of a medicinal product authorised

for use in the territory of Malta in human beings in accordance with European Union

Council Directive 2001/83/EC on the European Community code relating to medicinal

products for human use or under Regulation (EEC) No. 2309/93/EEC; or

(c) if there is no product as referred to in paragraph (b) and within the limits of the law of

the territory of Malta, of a veterinary medicinal product prepared extemporaneously by a

person legally authorised to do so in accordance with the terms of a veterinary prescription.

For the purposes of this sub-regulation, the phrase "to an animal or to a small number of animals on

a particular holding" also covers pets, and shall be interpreted more flexibly for minor or exotic

animal species which do not produce food.

(2) The provisions of sub-regulation (1) shall apply provided that the medicinal product,

administered to food-producing animals, contains only substances to be found in a veterinary

medicinal product authorised for such animals in the territory of Malta and that in the case of food-

producing animals, the veterinarian responsible 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

eggs,

7 days

milk,

28 days

meat from poultry and mammals including fat and offal,

500 degree days

meat from fish.

With regard to homeopathic veterinary medicinal products in which the level of active principles is

equal to or less than one part per million, the withdrawal period referred to in this regulation is

reduced to zero.

Records and further details to be kept by veterinarian

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 11 — Veterinary Medicinal Products Regulations, 2004 Open official source

When a veterinarian has recourse to the provisions of regulation 10, 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 dosages administered, the

duration of treatment and the withdrawal periods recommended, and make these records available

for inspection by the Veterinary Services for a period of at least three years. This requirement may

be extended by the Veterinary Services to non food-producing animals.

Marketing authorisation for veterinary medicinal product

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 12 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) For the purposes of obtaining a marketing authorisation in respect of a veterinary

medicinal product, other than under the procedure established by Regulation (EEC) No. 2309/93,

an application shall be lodged with the Veterinary Services.

(2) A marketing authorisation may only be granted to an applicant established in the

European Community.

(3) The following particulars and documents shall accompany an application in accordance

with Schedule I :-

(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 the veterinary medicinal product (brand name, non-proprietary name, with or

without a trademark, or name of the manufacturer or scientific name or formula, with or

without a trademark, or the name of the manufacturer);

(c) qualitative and quantitative particulars of all the constituents of the veterinary medicinal

product, using the usual terminology, but not empirical chemical formulae and giving the

international non-proprietary name recommended by the World Health Organisation, where

such a name exists;

(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) if applicable, explanations of the precautionary and safety measures to be taken when

the product is stored, when it is administered to animals and when waste therefrom is

disposed of, together with an indication of any potential risks the medicinal product might

pose to the environment and the health of humans, animals or plants;

(h) indication of the withdrawal period. Where necessary, the applicant shall propose and

justify a tolerance level for residues which may be accepted in foodstuffs without risk for

the consumer, together with routine analysis methods which could be used by the

Veterinary Services to trace residues;

(i) description of the control testing methods employed by the manufacturer (qualitative and

quantitative analysis of the constituents and the finished product, specific tests e.g. sterility

tests, test for the presence of pyrogens, for the presence of heavy metals, stability tests,

biological and toxicity tests, tests on intermediate products);

(j) results of -

- physicochemical, biological or microbiological tests,

- toxicological and pharmacological tests,

- clinical trials.

(k) a summary in accordance with regulation 14 of the product characteristics, one or more

specimens or mock-ups of the sales presentation of the veterinary medicinal product

together with the package insert;

(l) a document showing that the manufacturer is authorised in his own country to produce

veterinary medicinal products;

(m) copies of any marketing authorisation obtained in a 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 an equivalent

legislation to 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

Community or a third country and the reasons for that decision.

This information shall be updated on a regular basis;

(n) in the case of medicinal products containing new active substances which are not

mentioned in Annex I, II or III to Regulation (EEC) No. 2377/90, a copy of the documents

submitted to the European Commission in accordance with Annex V to Regulation (EEC)

No. 2377/90.

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 13 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) By way of derogation from point (j) of regulation 12 (3), and without prejudice to

the law relating to the protection of industrial and commercial property -

(a) the applicant shall not be required to provide the results of toxicological and

pharmacological tests and clinical trials if he can demonstrate -

(i) either that the veterinary medicinal product is essentially similar to a medicinal

product authorised in the territory of Malta by the application and that the marketing

authorisation holder has agreed that the toxicological, pharmacological and, or

clinical references contained in the file on the original veterinary medicinal product

may be used for the purpose of examining the application in question;

(ii) or that the constituent or constituents of the veterinary medicinal product have a

well-established medicinal use, with recognised efficacy and an acceptable level of

safety, by means of detailed references to scientific literature;

(iii) or that the veterinary medicinal product is essentially similar to a medicinal

product which has been authorised within the European Community, in accordance

with European Community provisions in force, for not less than six years and is

marketed in the Member State for which the application is made; this period shall be

extended to 10 years in the case of high-technology medicinal products having been

authorised previously. Furthermore, the Veterinary Services may also extend this

period to 10 years by new regulations covering all the medicinal products marketed

in the territory where it considers this necessary in the interest of public health. The

territory of Malta is at liberty not to apply the six-year period beyond the date of

expiry of a patent protecting the original medicinal product;

(b) in the case of new veterinary medicinal products containing known constituents not

hitherto used in combination for therapeutic purposes, the results of toxicological and

pharmacological tests and of clinical trials relating to that combination must be provided,

but it shall not be necessary to provide the relevant documentation for each individual

constituent.

(2) Schedule I shall apply in like manner where, pursuant to point (a) (ii) of sub-regulation

(1), references to published data are submitted.

Summary of product characteristics

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 14 — Veterinary Medicinal Products Regulations, 2004 Open official source

The summary of the product characteristics shall contain the following information -

(1) Name of the veterinary medicinal products;

(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 international non-proprietary names recommended by the World Health

Organisation shall be used, where such names exist, or failing this, the usual non-proprietary name

or chemical description;

(3) Pharmaceutical form;

(4) Pharmacological properties and, in so far as this information is useful for the therapeutic

purposes, pharmacokinetic particulars;

(5) Clinical particulars;

(i) target species,

(ii) indications for use, specifying the target species,

(iii) contra-indications,

(iv) undesirable effects (frequency and seriousness),

(v) special precautions for use,

(vi) use during pregnancy and lactation,

(vii) interaction with other medicaments and other forms of interaction,

(viii) posology and method of administration,

(ix) overdose (symptoms, emergency procedures, antidotes if necessary),

(x) special warnings for each target species,

(xi) withdrawal periods,

(xii) special precautions to be taken by the person administering the medicinal

product to animals;

(6) Pharmaceutical particulars -

(i) major incompatibilities,

(ii) shelf life, when necessary after reconstitution of the medicinal product or when

the container is opened for the first time,

(iii) special precautions for storage,

(iv) nature and contents of container,

(v) special precautions for the disposal of unused medicinal product or waste

materials, if any;

(7) Name or corporate name and address or registered place of business of the authorisation

Necessary arrangements for documents to be drafted by experts

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 15 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) The territory of Malta shall make all necessary arrangements to ensure that the

documents and particulars listed in regulation 12 (3) (h), (i), (j) and regulation 13 (1) are drafted by

experts with the requisite technical or professional qualifications before being submitted to the

Veterinary Services. These documents and particulars shall be signed by the experts in question.

(2) According to their particular qualifications, the role of the experts shall be -

(a) to carry out such work as falls within their particular discipline (analysis,

pharmacology and similar experimental sciences, clinical trials) and to describe

objectively the results obtained in both quantitative and qualitative terms;

(b) to describe their findings in accordance with Schedule I and in particular to state

(i) in the case of analysts, whether the medicinal product conforms with the

stated composition, providing any reasons for the control testing methods

which the manufacturer is to use;

(ii) in the case of pharmacologists and appropriately qualified specialists -

- the toxicity of the medicinal

product

and

the

pharmacological properties observed,

- whether, after administration of the veterinary medicinal

product under normal conditions of use and observance of the

recommended withdrawal period, foodstuffs obtained from

the treated animals contain residues which might constitute a

health hazard to the consumer;

(iii) in the case of clinicians, whether they have found in animals treated with

the medicinal product effects corresponding to the information furnished by

the manufacturer pursuant to regulations 12 and 13(1), whether the medicinal

product is well tolerated, what dosage they recommend and what are the

contraindications and adverse reactions, if any;

(c) to give reasons for the use of the references to published data referred to in point

(a) (ii) of regulation 13 (1).

(3) The experts' detailed reports shall form part of the documentation which the applicant

shall lodge with the Veterinary Services. A brief curriculum vitae of the expert shall be appended to

each report.

CHAPTER 2

Particular provisions applicable to homeopathic veterinary medicinal products

Registration or authorisation of homeopathic veterinary medicinal products

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 16 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) The Veterinary Services shall ensure that homeopathic veterinary medicinal products

manufactured and marketed within the European Community are registered or authorised in

accordance with the provisions of regulations 17 (1) and (2), 18 and 19. The Veterinary Services

shall take due account of registrations and authorisations previously granted by another Member

(2) The Veterinary Services may refrain from establishing a special, simplified registration

procedure for the homeopathic veterinary medicinal products referred to in regulation 17 (1) and

(2). When applying this provision the Veterinary Services shall inform the European Commission

accordingly. The Veterinary Services shall allow use in the territory of Malta of homeopathic

veterinary medicinal products registered by other Member States in accordance with similar

provisions to regulation 17 (1) and (2) and regulation 18.

Homeopathic veterinary medicinal products which may be authorised

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 17 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) Only homeopathic veterinary medicinal products which satisfy all of the following

conditions may be subject to authorisation by means of a special, simplified registration procedure

(a) they are intended for administration to pet animals or exotic species which are non food-

producing,

(b) they are administered by a route described in the European Pharmacopoeia or, in

absence thereof, by the pharmacopoeias currently used officially in the territory of Malta or

in the Member States,

(c) no specific therapeutic indication appears on the labelling of the veterinary medicinal

product or in any information relating thereto,

(d) there is a sufficient degree of dilution to guarantee the safety of the medicinal product;

in particular, the medicinal product may not contain either more than one part per 10 000 of

the mother tincture or more than 1/100th of the smallest dose used in allopathy with regard

to active principles whose presence in an allopathic medicinal product results in the

obligation to submit a veterinary prescription.

At the time of registration, the Veterinary Services shall determine the classification for the

dispensing of the medicinal product.

(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 registration procedure for

homeopathic veterinary medicinal products referred to in sub-regulation (1), with the exception of

the proof of therapeutic effect.

(3) The proof of therapeutic effect shall not be required for homeopathic veterinary

medicinal products registered in accordance with sub-regulation (1) of this regulation or, where

appropriate, admitted in accordance with regulation 16(2).

Simplified application for registration

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 18 — Veterinary Medicinal Products Regulations, 2004 Open official source

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 the application in order to demonstrate, in particular, the 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 potentiation,

(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 specimens or 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.

Other homeopathic veterinary medicinal products

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 19 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) Homeopathic veterinary medicinal products other than those referred to in regulation

17 (1) shall be authorised in accordance with the provisions of regulations 12 to 15 and of Chapter

3. (2) The territory of Malta may introduce or retain in its territory specific rules for the

pharmacological and toxicological tests and for clinical trials of homeopathic veterinary medicinal

products intended for pet animals and exotic species which are non food-producing other than those

referred to in regulation 17(1), in accordance with the principles and characteristics of homeopathy

as practised in the territory of Malta.

In this case, the Veterinary Services shall notify the European Commission of the specific

rules in force.

Immunological homeopathic veterinary medicinal products

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 20 — Veterinary Medicinal Products Regulations, 2004 Open official source

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

Procedure for authorisation to place a veterinary medicinal product on the market

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 21 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) The territory of Malta shall take all appropriate measures to ensure that the

procedure for granting an authorisation to place a veterinary medicinal product on the market is

completed within 210 days of the submission of a valid application.

(2) Where the territory of Malta notes that an application for authorisation submitted is

already under active examination in another Member State in respect of that veterinary medicinal

product, the territory of Malta may decide to suspend the detailed examination of the application in

order to await the assessment report prepared by the other Member State in accordance with

regulation 25(4).

The territory of Malta shall inform the other Member State and the applicant of its decision to

suspend detailed examination of the application in question. As soon as it has completed the

examination of the application and reached a decision, the other Member State shall forward a copy

of its assessment report to the territory of Malta.

Authorisation to forward the assessment report

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 22 — Veterinary Medicinal Products Regulations, 2004 Open official source

Where the territory of Malta is informed in accordance with regulation 12 (3) (m), that

another Member State has authorised a veterinary medicinal product which is the subject of an

application for authorisation in the territory of Malta, it shall forthwith request the authorities of the

Member State which has granted the authorisation to forward to it the assessment report referred to

in regulation 25 (4).

Within 90 days of receipt of the assessment report, the territory of Malta shall either recognise the

decision of the first Member State and the summary of the product characteristics as approved by it

or, if it considers that there are grounds for supposing that the authorisation of the veterinary

medicinal product concerned may present a risk to human or animal health or the environment, it

shall apply the procedures set out in accordance with articles 33 to 38 of European Union Council

Directive 2001/82/EEC.

Examination of application found under regulations 12 and 13

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 23 — Veterinary Medicinal Products Regulations, 2004 Open official source

In order to examine the application submitted pursuant to regulations 12 and 13 (1), the

Veterinary Services -

(1) shall check that the documentation submitted in support of the application complies with

regulations 12 and 13 (1) and, on the basis of the reports drawn up by the experts pursuant to

regulation 15 (2) and (3), ascertain whether the conditions for the issue of the marketing

authorisation have been fulfilled;

(2) may submit the medicinal product, its raw materials and if necessary intermediate

products or other constituent materials for testing by a State laboratory or by a laboratory

designated for that purpose, 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, where appropriate, require the applicant to provide further information as regards

the items listed in regulations 12 and 13 (1). Where the Veterinary Services takes 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;

(4) may require the applicant to submit substances in the quantities necessary to verify the

analytical detection method proposed by the applicant in accordance with regulation 12 (3) (h) and

to put it into effect as part of routine checks to reveal the presence of residues of the veterinary

medicinal products concerned.

Duties to be taken up by the Veterinary Services

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 24 — Veterinary Medicinal Products Regulations, 2004 Open official source

In the territory of Malta 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.

Summary of the product characteristics

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 25 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) When the marketing authorisation is issued, the holder shall be informed by the

Veterinary Services, of the summary of the product characteristics as approved by it.

(2) The Veterinary Services shall take all necessary measures to ensure that the information

given in the summary is in conformity with that accepted when the marketing authorisation is

issued or subsequently.

(3) The Veterinary Services shall forward to the Agency a copy of the authorisation together

with the summary of the product characteristics.

(4) The Veterinary Services shall draw up an assessment report and comments on the

dossier as regards the results of the analytical and pharmacotoxicological tests and the 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.

Other particulars essential for safety or health protection

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 26 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) The marketing authorisation may require the holder to indicate on the container and,

or the outer wrapping and the package insert, where the latter is required, other particulars essential

for safety or health protection, including any special precautions relating to use and any other

warnings resulting from the clinical and pharmacological trials prescribed in regulation 12 (3) (j)

and 13 (1) or from experience gained during the use of the veterinary medicinal product once it has

been marketed.

(2) The authorisation may also require the inclusion of a tracer substance in the veterinary

medicinal product.

(3) In exceptional circumstances, and following consultation with the applicant, an

authorisation may be granted subject to certain specific obligations, and subject to annual review,

including -

(a) the carrying out of further studies following the granting of authorisation,

(b) the notification of adverse reactions to the veterinary medicinal product.

These exceptional decisions may only be adopted for objective and verifiable reasons.

Holder to take account of scientific and technical progress

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 27 — Veterinary Medicinal Products Regulations, 2004 Open official source

(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 generally

accepted scientific methods.

These changes shall be subject to the approval of the Veterinary Services.

(2) Upon request from the Veterinary Services, the marketing authorisation holder shall also

review the analytical detection methods provided for in regulation 12 (3) (h) and propose any

changes which may be necessary to take account of scientific and technical progress.

(3) The marketing authorisation holder shall forthwith inform the Veterinary Services of

any new information which might entail the amendment of the particulars and documents referred

to in regulations 12 and 13 (1) or of the approved summary of the product characteristics. In

particular, he shall forthwith inform the Veterinary Services of any prohibition or restriction

imposed by the competent authority of any country in which the veterinary medicinal product is

marketed and of any serious unexpected adverse effect occurring in the animals concerned or

human beings.

(4) The marketing authorisation holder shall be required to maintain records of all adverse

reactions observed in animals or human beings. The records so established shall be kept at least five

years and shall be made available to the Veterinary Services upon request.

(5) The marketing authorisation holder shall immediately inform the Veterinary Services,

with a view to authorisation, of any alteration he proposes to make to the particulars and documents

referred to in regulations 12 and 13 (1).

Validity and renewal of authorisation

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 28 — Veterinary Medicinal Products Regulations, 2004 Open official source

Authorisation shall be valid for five years and shall be renewable for five-year periods,

on application by the holder at least three months before the expiry date and after consideration of a

dossier updating the information previously submitted.

General legal liability of manufacturer

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 29 — Veterinary Medicinal Products Regulations, 2004 Open official source

The granting of authorisation shall not diminish the general legal liability of the

manufacturer and, where appropriate, of the authorisation holder.

Instances when the marketing authorisation shall be withheld

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 30 — Veterinary Medicinal Products Regulations, 2004 Open official source

The marketing authorisation shall be withheld if examination of the documents and

particulars listed in regulations 12 and 13 (1) establishes that -

(a) the veterinary medical product is harmful under the conditions of use stated at the time

of application for authorisation; or

(b) such 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) the qualitative or quantitative composition of the product 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 veterinary medicinal product is offered for sale for a use prohibited under other

European Community provisions.

However, pending adoption of new European Community rules, the Veterinary Services may refuse

to grant authorisation for a veterinary medicinal product where such action is necessary for the

protection of public health, consumer or animal health.

Authorisation shall also be withheld if the application documents submitted to the Veterinary

Services does not comply with regulations 12, 13 (1) and 15.

CHAPTER 4

Mutual recognition of authorisations

Procedure before submitting an application for mutual recognition of marketing practices

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 31 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) Before submitting an application for mutual recognition of marketing authorisations,

the holder of the authorisation shall inform the Member State which granted the authorisation on

which the application is based (hereinafter: the reference Member State) that an application is to be

made in accordance with these regulations and shall notify it of any additions to the original dossier

that Member State may require the applicant to provide it with all the particulars and documents

necessary to enable it to check that the dossiers filed are identical.

In addition, the holder of the authorisation shall request the reference Member State which granted

the initial authorisation to prepare an assessment report in respect of the veterinary medicinal

product concerned, or, if necessary, to update it. The Member State shall prepare it within 90 days

of receipt of the request.

At the same time as the application is submitted in accordance with sub-regulation (2) the reference

Member State which granted the initial authorisation shall forward the assessment report to any

Member State concerned by the application.

(2) In order to obtain the recognition according to the procedure laid down in this Chapter in

one or more of the Member States of a marketing authorisation issued by a Member State, the

holder of the authorisation shall submit an application to the Veterinary Services or the competent

authority of any Member State concerned, together with the information and particulars referred to

in regulations 12, 13 (1), 14 and 25. He shall testify that the dossier is identical to that accepted by

the reference Member State, or shall identify any additions or amendments it may contain. In the

latter case, he shall certify that the summary of the product characteristics proposed by him in

accordance with regulation 14 is identical to that accepted by the reference Member State in

accordance with regulation 25. Moreover, he shall certify that all the dossiers filed as part of this

procedure are identical.

(3) The holder of the marketing authorisation shall transmit the application to the Agency,

inform it of the territory of Malta and of the dates of submission of the application and send it a

copy of the authorisation granted by the reference Member State. He shall also send the Agency

copies of any such authorisation which may have been granted by the other Member States in

respect of the veterinary medicinal product concerned, and shall indicate whether any application

for authorisation is currently under consideration in any Member State.

(4) Save in the exceptional case provided for in regulation 32 (1), the territory of Malta shall

recognise the marketing authorisation granted by another reference Member State within 90 days of

receipt of the application and the assessment report. They shall inform the reference Member State,

the other Member States concerned by the application, the Agency, and the holder of the

authorisation for placing the product on the market.

Procedure by the Veterinary Services upon grounds for supposing that the marketing

authorisation of the veterinary medicinal product concerned may present a risk to human

health or animal health

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 32 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) Where the territory of Malta considers that there are grounds for supposing that the

marketing authorisation of the veterinary medicinal product concerned may present a risk to human

or animal health or the environment, it shall forthwith inform the applicant, the reference Member

State, any other Member States concerned by the application and the Agency. The territory of

Malta shall state its reason in detail and shall indicate what action may be necessary to correct any

defect in the application.

(2) All the Member States concerned shall use their best endeavours to reach agreement on

the action to be taken in respect of the application. It shall provide the applicant with the

opportunity to make his point of view known orally or in writing. However, if the Member States

have not reached agreement within the time-limit referred to in regulation 31 (4) it shall forthwith

refer the matter to the Agency, for referral to the Committee for the application of the procedure

laid down in article 36 of European Union Council Directive 2001/82/EEC.

(3) Within the time-limit referred to in regulation 31 (4), the Member States concerned shall

provide the Committee with a detailed statement of the matters on which it has been unable to reach

agreement and the reasons for their disagreement. The applicant shall be provided with a copy of

this information.

(4) As soon as he is informed that the matter has been referred to the Committee, the

applicant shall forthwith forward to the Committee a copy of the information and particulars

referred to in regulation 31 (2).

Several applications for marketing authorisation for a particular veterinary medicinal

product

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 33 — Veterinary Medicinal Products Regulations, 2004 Open official source

If several applications submitted in accordance with regulations 12, 13 (1) and 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 withdrawal of that authorisation, the territory of Malta, or the European

Commission, or the marketing authorisation holder may refer the matter to the Committee for

application of the procedure laid down in article 36 of European Union Council Directive

2001/82/EC

The territory of Malta, the marketing authorisation holder or the European Commission shall

clearly identify the question which is referred to the Committee for consideration and, if

appropriate, shall inform the aforementioned holder thereof.

The territory of Malta and the marketing authorisation holder shall forward to the Committee all

available information relating to the matter in question.

Situation when the matter has to be referred to the Committee before reaching a decision

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 34 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) The territory of Malta or the European Commission or the applicant or holder of the

marketing authorisation may, 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 article

36 of European Union Council Directive 2001/82/EC before reaching a decision on a request for a

marketing authorisation or on the suspension or withdrawal of an authorisation, or on any other

variations to the terms of a marketing authorisation which appears necessary, in particular to take

account of the information collected in accordance with Title VII.

The territory of Malta or the European Commission shall clearly identify the question which is

referred to the Committee for consideration and shall inform the marketing authorisation holder.

The territory of Malta and the holder of the marketing authorisation shall forward to the Committee

all available information relating to the matter in question.

Variation of marketing authorisation

(2)

(a) Any application by the marketing authorisation holder to vary a marketing

authorisation which has been granted in accordance with the provisions of this Chapter

shall be submitted to the Veterinary Services who shall examine the matter in question

and to all the other Member States which have previously authorised the veterinary

medicinal product concerned.

(b) The Veterinary Services shall forward any comments or observations in which it

might be in contrast with what the variation proposed by the marketing authorisation

holder to the European Commission.

Necessity for variation of the terms of a marketing authorisation

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 35 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) Where the territory of Malta 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 territory of Malta 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.

Application of articles 39 and 40 of European Union Council Directive 2001/82/EC

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 36 — Veterinary Medicinal Products Regulations, 2004 Open official source

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.

Non-application to homeopathic veterinary medicinal products

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 37 — Veterinary Medicinal Products Regulations, 2004 Open official source

The provisions concerning this Chapter shall not apply to homeopathic veterinary

medicinal products referred to in regulation 19 (2).

TITLE IV

MANUFACTURE AND IMPORTS

Authorisation of manufacturer of veterinary medicinal product

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 38 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) The territory of Malta shall take all appropriate measures to ensure that the

manufacture of veterinary medicinal products is subject to the holding of an authorisation. This

manufacturing authorisation shall likewise be required for veterinary medicinal products intended

for export.

(2) The authorisation referred to in sub-regulation (1) shall be required both for total and

partial manufacture and for the various processes of dividing up, packaging or presentation.

However, such authorisation shall not be required for preparation, dividing up, changes in

packaging or presentation where these processes are carried out solely for retail supply by

pharmacists in dispensing pharmacies or by persons legally authorised in the territory of Malta 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; this Title and regulation 75 shall apply to such

imports in the same way as to manufacture.

The territory of Malta 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).

Requirements for manufacturing authorisation

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 39 — Veterinary Medicinal Products Regulations, 2004 Open official source

In order to obtain the manufacturing authorisation, the applicant shall meet at least the

following requirements -

(a) he shall specify the veterinary medicinal products and pharmaceutical forms which are

to be manufactured or imported and also the place where they are to be manufactured and,

or controlled;

(b) he shall have at his disposal, for the manufacture or import of the above, suitable and

sufficient premises, technical equipment and control facilities complying with the legal

requirements which the territory of Malta lays down as regards both manufacture and

control and the storage of products, in accordance with regulation 24;

(c) he shall have at his disposal the services of at least one qualified person within the

meaning of regulation 45.

The applicant shall provide particulars in his application to establish his compliance with the above

requirements.

Accuracy of particulars

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 40 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) The Veterinary Services shall not issue the manufacturing authorisation until it has

established the accuracy of the particulars supplied pursuant to regulation 39 by means of an

inquiry carried out by its representatives.

(2) In order to ensure that the requirements referred to in regulation 39 are complied with,

authorisation may be made conditional on the fulfilment of certain obligations imposed either when

authorisation is granted or at a later date.

(3) The authorisation shall apply only to the premises specified in the application and to the

veterinary medicinal products and pharmaceutical forms specified in that application.

Time taken for the procedure to grant the authorisation

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 41 — Veterinary Medicinal Products Regulations, 2004 Open official source

The territory of Malta shall take all appropriate measures to ensure that the time taken

for the procedure for granting the manufacturing authorisation does not exceed 90 days from the

day on which the Veterinary Services receives the application.

Change in particulars

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 42 — Veterinary Medicinal Products Regulations, 2004 Open official source

If the holder of the manufacturing authorisation requests a change in any of the

particulars referred to in regulation 39, (a) and (b), the time taken for the procedure relating to this

request shall not exceed 30 days. In exceptional cases, this period of time may be extended to 90

Further information of applicant

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 43 — Veterinary Medicinal Products Regulations, 2004 Open official source

The Veterinary Services may require from the applicant further information concerning

both the particulars supplied pursuant to regulation 39 and the qualified person referred to in

regulation 45. Where the Veterinary Services exercise this right, application of the time limits

referred to in regulations 41 and 42 shall be suspended until the additional data required have been

supplied.

Obligations of holder

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 44 — Veterinary Medicinal Products Regulations, 2004 Open official source

The holder of a manufacturing authorisation shall at least be obliged to -

(a) have at his disposal the services of staff complying with the legal requirements existing

in the territory of Malta as regards both manufacture and controls;

(b) dispose of the authorised veterinary medicinal products only in accordance with the

legislation of the territory of Malta;

(c) 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 39; the Veterinary Services shall, in

any event, be immediately informed if the qualified person referred to in regulation 45 is

replaced unexpectedly;

(d) allow the representatives of the Veterinary Services access to his premises at any time;

(e) enable the qualified person referred to in regulation 45 to carry out his duties,

particularly by placing at his disposal all the necessary facilities;

(f) comply with the principles and the guidelines of good manufacturing practice for

medicinal products laid down by European Community law;

(g) keep detailed records of all veterinary medicinal products supplied by him, including

samples, in accordance with the laws of the countries of destination. The following

information at least shall be recorded in respect of each transaction, whether or not it is

made for payment -

(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 years.

Services of a qualified person to be ensured by the holder of the manufacturing authorisation

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 45 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) The territory of Malta shall take all appropriate measures to ensure that the holder of

the manufacturing authorisation has permanently and continuously at his disposal the services of at

least one qualified person who fulfils the conditions laid down in regulation 46 and is responsible,

in particular, for carrying out the duties specified in regulation 48.

(2) If such qualified person fulfils the conditions laid down in regulation 46, the holder of

the authorisation may himself assume the responsibility referred to in sub-regulation (1).

Minimum conditions of qualification

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 46 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) The territory of Malta shall ensure that the qualified person referred to in regulation

45 fulfils the minimum conditions of qualification set out in sub-regulations (2) and (3).

(2) The qualified person shall be in possession of a diploma, certificate or other evidence of

formal qualifications awarded on completion of a university course of study, or a course recognised

as equivalent by the territory of Malta, extending over a period of at least four years of theoretical

and practical study in one of the following scientific disciplines - pharmacy, medicine, veterinary

science, chemistry, pharmaceutical chemistry and technology, biology.

However, the minimum duration of the university course may be three and a half years where the

course is followed by a period of theoretical and practical training of at least one year and includes

a training period of at least six months in a pharmacy open to the public, corroborated by an

examination at university level.

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).

Tuition in these subjects should be so balanced as to enable the person concerned to fulfil the

obligations specified in regulation 48.

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.

(3) The qualified person shall have acquired practical experience over at least two 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.

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 years.

Person eligible to engage in the activities mentioned in regulation 45

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 47 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) A person engaging, in the territory of Malta, in the activities of the person referred to

in regulation 45 at the date on which these regulations became applicable, without complying with

the provisions of regulation 46, shall be eligible to continue to engage in those activities in the

territory of Malta.

(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 45 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 45, provided that he

has previously engaged in the following activities for at least two 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 45 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.

Responsibility of qualified person

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 48 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) In the territory of Malta the qualified person referred to in regulation 45 is, without

prejudice to his relationship with the holder of the manufacturing authorisation, responsible, in the

context of the procedures referred to in regulation 49, for ensuring that -

(a) in the case of veterinary medicinal products manufactured within the territory of Malta,

each batch of veterinary medicinal products has been manufactured and checked in

compliance with the laws in force in the territory of Malta and in accordance with the

requirements of the marketing authorisation;

(b) in the case of veterinary medicinal products coming from third countries, each

production batch imported has undergone in the territory of Malta (importing 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 veterinary medicinal

products in accordance with the requirements of the marketing authorisation.

Batches of veterinary medicinal products which have undergone such controls in a Member State

shall be exempt from the above controls if they are placed on the market in the territory of Malta,

accompanied by the control reports signed by the qualified person.

(2) In the case of veterinary medicinal products imported from a third country, where

appropriate arrangements have been made by the European Community with the exporting country

to ensure that the manufacturer of the veterinary medicinal product applies standards of good

manufacturing practice at least equivalent to those laid down by the European Community and to

ensure that the controls referred to under paragraph (b) of sub-regulation (1) have been carried out

in the exporting country, the qualified person may be relieved of responsibility for carrying out

those controls.

(3) In all cases, and particularly where the veterinary medicinal products are released for

sale, the qualified person shall certify, in a register or equivalent document provided for the

purpose, that each production batch satisfies the provisions of this regulation; the said register or

equivalent document shall be kept up to date as operations are carried out and shall remain at the

disposal of the representatives of the Veterinary Services for at least five years.

Obligations of qualified persons to be fulfilled by appropriate administrative measures or

following a professional code of conduct

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 49 — Veterinary Medicinal Products Regulations, 2004 Open official source

The territory of Malta the obligations of qualified persons referred to in regulation 45

are fulfilled, either by means of appropriate administrative measures or by making such persons

subject to a professional code of conduct.

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.

Applicability to homeopathic veterinary medicinal products

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 50 — Veterinary Medicinal Products Regulations, 2004 Open official source

The provisions of this Title shall apply to homeopathic veterinary medicinal products.

TITLE V

LABELLING AND PACKAGE INSERT

Information regarding labelling and packages

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 51 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) The following information shall conform to the particulars and documents provided

pursuant to regulations 12 and 13 (1) and be approved by the Veterinary Services, moreover it shall

appear in legible characters on containers and outer packages of medicinal products -

(a) Name of the veterinary medicinal product, which may be a brand name or a non-

proprietary name accompanied by a trade mark or the name of the manufacturer, or a

scientific name or formula, with or without a trade mark, or the name of the

manufacturer.

Where the special name of a medicinal product containing only one active substance

is a brand name, this name must be accompanied in legible characters by the

international non-propriety name recommended by the World Health Organisation,

where such name exists or, where no such name exists, by the usual non-proprietary

name;

(b) A statement of the active substances expressed qualitatively and quantitatively

per dosage unit or according to the form of administration for a particular volume or

weight, using the international non-proprietary names recommended by the World

Health Organisation, where such names exist or, where no such names exist, the

usual non-proprietary 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 of the manufacturer, if different;

(f) The species of animal for which the veterinary medicinal product is intended;

the method and route of administration;

(g) The withdrawal period, even if nil, in the case of veterinary medicinal products

administered to food-producing animals;

(h) Expiry date, in plain language;

(i) Special storage precautions, if any;

(j) Special precautions for disposal of unused medicinal products or waste material

from medicinal products, if any;

(k) Particulars required to be indicated pursuant to regulation 26 (1), if any;

(l) The words "For animal treatment only".

(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 Schedule I, 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 sub-regulation (1)(b).

(4) The particulars mentioned in sub-regulation (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

Information regarding ampoules

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 52 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) As regards ampoules, the particulars listed in regulation 51 (1)(a) shall be given on

the outer package. On the containers, however, only the following 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 single dose containers, other than ampoules, on which it is impossible

to give the particulars mentioned in sub-regulation (1), the requirements of regulation 51(1), (2) and

(3), shall apply only to the outer package.

(3) The particulars mentioned in the third and sixth indents of sub-regulation (1)(c) and (f)

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 products are placed on the market

Provided that the language for the territory of Malta may be either Maltese or English or

No outer package

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 53 — Veterinary Medicinal Products Regulations, 2004 Open official source

Where there is no outer package, all the particulars which should feature on such a

package pursuant to the regulations 51 and 52 shall be shown on the container.

Inclusion of a package insert

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 54 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) The inclusion of a package insert in the packaging of veterinary medicinal products

shall be obligatory unless all the information required by this regulation can be conveyed on the

container and the external packaging. The territory of Malta shall take all appropriate measures to

ensure that the insert relates solely to the veterinary medicinal product with which it is included.

The insert shall be in the official language of the territory of Malta in which the medicinal product

is marketed

Provided that the language for the territory of Malta may be either Maltese or English or

(2) The package insert shall contain at least the following information, which shall conform

to the particulars and documents provided pursuant to regulations 12 and 13 (1) and be approved by

the Veterinary Services -

(a) name or corporate name and permanent address or registered place of business of the

marketing authorisation holder and of the manufacturer, if different;

(b) name of the veterinary medicinal product and a statement of its active substances

expressed qualitatively and quantitatively;

The international non-proprietary names recommended by the World Health Organisation

shall be used wherever they exist;

(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 regulations 26 (1), if any;

(i) special precautions for the disposal of unused medicinal products or waste materials from

medicinal products, if any.

(3) The particulars referred to in sub-regulation (2) shall appear in the language of the

territory of Malta in which the product is marketed. The other information shall be clearly separate

from such particulars

Provided that the language for the territory of Malta may be either Maltese or English or

both.

Suspension or withdrawal of marketing authorisation

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 55 — Veterinary Medicinal Products Regulations, 2004 Open official source

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 withdraw the

marketing authorisation.

Non-applicability of this Title

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 56 — Veterinary Medicinal Products Regulations, 2004 Open official source

The requirements of the territory of Malta 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.

Labelling of homeopathic veterinary medicinal product

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 57 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) Without prejudice to sub-regulation (2), homeopathic veterinary medicinal products

shall be labelled in accordance with the provisions of this title and identified by the inclusion on

their labels, in clearly legible form, of the words "homeopathic 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 insert 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),

(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, WHOLESALE DISTRIBUTION AND DISPENSING OF VETERINARY

MEDICINAL PRODUCTS

Wholesale distribution of veterinary medicinal product

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 58 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) In the territory of Malta, 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 90 days from the date on which it receives the application.

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 territory of Malta 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 required to keep detailed records.

The following minimum 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.

(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.

Persons who may conduct the retail supply of veterinary medicinal products

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 59 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) In the territory of Malta, the retail supply of veterinary medicinal products is

conducted only by persons who are licensed to carry out such operations by the legislation of the

territory of Malta.

(2) Any person permitted under sub-regulation (1) to sell veterinary medicinal products

shall be required to keep detailed records. The following 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;

(d) quantity received or supplied;

(e) name and address of the supplier or recipient;

(f) where relevant, name and address of the prescribing veterinarian and a copy of the

prescription.

At least once a year a detailed audit shall be carried out, and incoming and outgoing veterinary

medicinal products 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 three

years.

(3) The Veterinary Services may limit the number of detailed documenting requirements

referred to in sub-regulation (2). However, these requirements shall always be applied in case of

veterinary medicinal products which are intended for administration to food-producing animals and

which are available only on veterinary prescription or in respect of which a withdrawal period must

be observed.

(4) The Veterinary Services shall communicate to the European Commission a list of the

veterinary medicinal products which are available without prescription.

Prescription for dispensing products to the public

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 60 — Veterinary Medicinal Products Regulations, 2004 Open official source

Without prejudice to stricter European Community rules or Maltese rules relating to

dispensing veterinary medicinal products and to protect human and animal health, a 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 Community legislation;

(b) those products in respect of which special precautions must be taken by the veterinarian

in order to avoid any unnecessary risk to -

(i) the target species,

(ii) the person administering the products to the animal,

(iii) the consumer of foodstuffs obtained from the treated animal,

(iv) 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) magistral formulae intended for animals.

In addition, a prescription shall be required for new veterinary medicinal products containing an

active substance which has been authorised for use in a veterinary medicinal product for less than

five years unless, having regard to the information and particulars provided by the applicant, or

experience acquired in the practical use of the veterinary medicinal product, the Veterinary

Services is satisfied that none of the criteria referred to in paragraphs (a) to (d) of sub-regulation (1)

apply.

Veterinary medicinal products that have anabolic, anti-infectious, anti-parasitic, anti-

inflammatory, hormonal or psychotropic properties

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 61 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) In the territory of Malta, all necessary measures shall be taken to ensure that

veterinary surgeons, qualified or responsible persons and pharmacists only, possess or have under

their control 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 territory of Malta 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 sub-regulation (1)

shall be adopted in accordance with the procedure referred to in article 89 (2) of European Union

Council Directive 2001/82/EC.

Obligations of owners or keepers of food-producing

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 62 — Veterinary Medicinal Products Regulations, 2004 Open official source

In the territory of Malta, the owners or keepers of food-producing animals can provide

proof of purchase, possession and administration of veterinary medicinal products containing the

substances set out in regulation 61.

The territory of Malta may extend the scope of this obligation to other veterinary medicinal

products.

In particular, the territory of Malta may require the maintenance of a record giving at least the

following information -

(a) date;

(b) name of the veterinary medicinal product;

(c) quantity;

(d) name and address of the supplier of the medicinal product;

(e) identification of the animals treated.

Administration of small quantities of readymade veterinary medicinal products

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 63 — Veterinary Medicinal Products Regulations, 2004 Open official source

Notwithstanding regulations 9 and 60, in the territory of Malta shall ensure that

veterinarians providing services in another Member State can take with them and administer to

animals small quantities of readymade veterinary medicinal products not exceeding daily

requirements other than immunological veterinary medicinal products which are not authorised for

use in the Member States in which the services are provided (the host Member State), providing

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 veterinarian

is established;

(b) the veterinary medicinal products are transported by the veterinarian 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 veterinarian 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 veterinarian 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 veterinarian 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

veterinarian shall not exceed that generally required for the daily needs of good veterinary

practice.

Use of immunological veterinary medicinal products for the eradication or control of animal

disease

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 64 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) In the absence of specific European Community legislation concerning the use of

immunological veterinary medicinal products for the eradication or control of animal disease, the

territory of Malta may, in accordance with its national legislation, 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.

(2) The Veterinary Services shall inform the European Commission of all instances in

which the provisions of sub-regulation (1) are applied.

TITLE VII

PHARMACOVIGILANCE

Suspected adverse reactions to veterinary medicinal products

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 65 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) The territory of Malta shall take the appropriate measures to encourage the reporting

to the Veterinary Services of suspected adverse reactions to veterinary medicinal products.

(2) The territory of 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 particular where such reporting is a condition of

the marketing authorisation.

Participation in the veterinary pharmacovigilance system

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 66 — Veterinary Medicinal Products Regulations, 2004 Open official source

In order to ensure the adoption of appropriate regulatory decisions concerning the

veterinary medicinal products authorised within the European Community, having regard to

information obtained about suspected adverse reactions to veterinary medicinal products under

normal conditions of use, the territory of Malta shall participate to the veterinary

pharmacovigilance system established by the Member States. 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 related 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.

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.

Qualified person responsible for pharmacovigilance

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 67 — Veterinary Medicinal Products Regulations, 2004 Open official source

The marketing authorisation holder shall have permanently and continuously at his

disposal an appropriately qualified person responsible for pharmacovigilance.

That qualified person 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 Community;

(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.

Detailed records of suspected adverse reactions

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 68 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) The marketing authorisation holder shall be required to maintain detailed records of

all suspected adverse reactions occurring either in the territory of Malta, Member States or in a

third country.

(2) The marketing authorisation holder shall be required to record and to report 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, or which are

brought to his attention, immediately to the competent authority of the Member State in whose

territory the incident occurred, and in no case later than 15 calendar days following the receipt of

the information.

(3) The marketing authorisation holder shall ensure that the suspected serious and

unexpected adverse reactions and human adverse reactions, occurring in the territory of a third

country, are reported immediately in accordance with the guidance referred to in regulation 70 (1),

so that they are available to the Agency and to the competent authorities of any Member State

where the veterinary medicinal product is authorised, and in no case later than 15 calendar days

following the receipt of the information.

(4) In the case of veterinary medicinal products which have been considered within the

scope of European Union Council Directive 87/22/EEC, or which have benefited from the

procedures of mutual recognition under regulations 21, 22 and 31(4) and veterinary medicinal

products for which there has been a referral to some procedures under articles 36, 37 and 38 of

European Union Council Directive 2001/82/EC, the marketing authorisation holder shall

additionally ensure that all suspected serious adverse reactions and human adverse reactions,

occurring in the territory of Malta or in other Member States, are reported in the format and at

intervals to be agreed with the reference Member State or a competent authority designated as

reference Member State, in such a way so as to be accessible to the reference Member State.

(5) Unless other requirements have been laid down as condition of the granting of

authorisation, records of all adverse reactions shall be submitted to the Veterinary Services in the

form of a periodic safety update report, either immediately upon request or periodically as follows

–

(i) six monthly for the first two years after authorisation;

(ii) annually for the subsequent two years, and at the same time of the first renewal.

Thereafter, the periodic safety update reports shall be submitted at five-yearly intervals together

with the application for renewal of the authorisation. The periodic safety update report shall include

a scientific evaluation of the benefits and risks afforded by the veterinary medicinal product.

(6) Following the granting of a marketing authorisation, the marketing authorisation holder

may request the amendment of the periods referred to in this regulation.

Reports of suspected serious adverse reactions and human adverse reactions to be made

available to the Agency and the Member States

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 69 — Veterinary Medicinal Products Regulations, 2004 Open official source

(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 15 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 15 calendar days of their notification

at the latest.

Facilitation of exchange of information regarding pharmacovigilance

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 70 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) In order to facilitate the exchange of information about pharmacovigilance within

the territory of Malta 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 sub-regulation (1).

Procedure upon the result of the evaluation

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 71 — Veterinary Medicinal Products Regulations, 2004 Open official source

(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) In case of urgency, the Veterinary Services may suspend the marketing authorisation of

a veterinary medicinal product, provided the Agency and the European Commission and the other

Member States are informed at the latest on the following working day.

TITLE VIII

SUPERVISION AND SANCTIONS

Repeated inspections

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 72 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) The Veterinary Services shall ensure by means of repeated inspections that the legal

requirements relating to veterinary medicinal products are complied with.

Such inspections shall be carried out by authorised 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;

(c) examine any documents relating to the object of the inspection,.

(2) The Veterinary Services shall take all appropriate measures to ensure that in the territory

of Malta, the manufacturing processes used in the manufacture of immunological veterinary

medicinal products are completely validated and batch-to-batch consistency is ensured.

(3) The officials representing the Veterinary Services shall report after each of the

inspections mentioned in sub-regulation (1) on whether the manufacturer complies with the

principles and guidelines of good manufacturing practice referred to in article 51 of European

Union Council Directive 2001/82/EC. The inspected manufacturer shall be informed of the content

of such reports.

Proof of the control tests which were carried out

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 73 — Veterinary Medicinal Products Regulations, 2004 Open official source

(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 sub-regulation (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.

Samples to be submitted

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 74 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) Where it considers it necessary, the Veterinary Services may require the marketing

authorisation holder for immunological products to submit samples from the batches of the bulk

and, or medical product for examination by a State laboratory or an approved laboratory before

entry into circulation.

In the case of a batch manufactured in another Member State, examined by the competent authority

of another Member State and declared to be in conformity with national specifications, such a

control may be carried out only after the control reports of the batch in question have been

examined, after the European Commission has been informed, and where the difference in

veterinary conditions between the territory of Malta and the other Member State who made the

examination justify it.

(2) Except where the European Commission has been informed that a longer period is

necessary to complete the analyses, the territory of Malta shall ensure that any such examination is

completed within 60 days of receipt of the samples. The marketing authorisation holder shall be

notified of the results of the examination within the same time-limit.

Suspension or withdrawal of marketing authorisation

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 75 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) The Veterinary Services shall suspend or withdraw marketing authorisation when it

is clear that -

(a) the veterinary medicinal product proves to be harmful under the conditions of use

stated at the time of application for authorisation or subsequently;

(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 Community.

However, pending European Community rules, the Veterinary Services may refuse

to grant authorisation for a veterinary medicinal product where such action is

necessary for the protection of public, consumer or animal health;

(f) the information given in the application documents pursuant to regulations 12, 13

(1) and 27 is incorrect;

(g) the control tests referred to in regulation 73 (1) have not been carried out;

(h) the obligation referred to in regulation 26 (2) has not been fulfilled.

(2) Authorisation may be suspended, or withdrawn where it is established that -

(a) the particulars supporting the application, as provided for in regulations 12 and

13 (1), have not been amended in accordance with regulation 27 (1) and (5);

(b) any new information as referred to in regulation 27 (3) has not been

communicated to the Veterinary Services.

Regulations dealing with the prohibition or withdrawal of the supply of a veterinary

medicinal product

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 76 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) Without prejudice to regulation 75, in the territory of Malta, 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 veterinary medicinal product is harmful under the conditions of use

stated at the time of the application for authorisation or subsequently, pursuant to regulation

27 (5);

(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.

Suspension or withdrawal of the manufacturing authorisation

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 77 — Veterinary Medicinal Products Regulations, 2004 Open official source

(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.

Applicability of this Title

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 78 — Veterinary Medicinal Products Regulations, 2004 Open official source

The provisions of this Title shall apply to homeopathic veterinary medicinal products.

Measures to be taken by the Veterinary Services

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 79 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) The Veterinary Services shall take appropriate measures to encourage veterinarians

and other professionals concerned to report to it any adverse reaction of veterinary medicinal

products.

(2) For the purposes of these regulations every licensed, registered farm in the territory of

Malta shall nominate a veterinary surgeon responsible for animal health and animal welfare on the

Provided that a register of the veterinary surgeons nominated by the licensed, registered

farms shall be kept by the Veterinary Services.

(3) The person responsible for the farm may change veterinary surgeon upon informing the

Veterinary Services within 4 days of such change.

Provided that in case of emergency the person responsible for the farm can ask for

assistance from another veterinary surgeon.

TITLE IX

STANDING COMMITTEE

Changes to be made to the Schedule

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 80 — Veterinary Medicinal Products Regulations, 2004 Open official source

Any changes which are necessary in order to adapt Schedule I 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 X

GENERAL PROVISIONS

Communication between competent authorities

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 81 — Veterinary Medicinal Products Regulations, 2004 Open official source

The Veterinary Services shall communicate the appropriate information to the

competent authorities in other Member States, in particular regarding compliance with the

requirements adopted for manufacturing authorisation, or for authorisation 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.

If, after considering the report, the Member State receiving it considers that it cannot accept the

conclusions reached by the Veterinary Services, which in turn had established the report, it shall

inform the Veterinary Services of its reasons and may request further information. The Veterinary

Services shall attempt to reach agreement with the competent authorities of the other Member State.

If necessary, in the event of serious differences of opinion, one of the Member States concerned

shall inform the European Commission.

Veterinary Services to inform Agency on decisions which grant or refuse marketing

authorisation

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 82 — Veterinary Medicinal Products Regulations, 2004 Open official source

(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 decision refusing or withdrawing

marketing authorisation, prohibiting supply or withdrawing a product from the market, together

with the reasons on which such decisions are based.

(2) 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.

(3) The Veterinary Services shall ensure that appropriate information about actions taken

pursuant to sub-regulation (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.

Communication of information necessary to guarantee the quality and safety of homeopathic

veterinary medicinal products

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 83 — Veterinary Medicinal Products Regulations, 2004 Open official source

The Veterinary Services shall communicate to the competent authorities of the other

Member States all the information necessary to guarantee the quality and safety of homeopathic

veterinary medicinal products manufactured and marketed within the territory of Malta, and in

particular the information referred to in regulation 81 and 82.

Certification on the possession of a manufacturing authorisation

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 84 — Veterinary Medicinal Products Regulations, 2004 Open official source

(1) At the request of the manufacturer or exporter of veterinary medicinal products, or

the authorities of an importing third country, the territory of Malta shall certify that such

manufacturer is in possession of the manufacturing authorisation. When issuing such certificates,

the Veterinary Services shall comply with the 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

sub-regulation (1) with a declaration explaining why such authorisation is not available.

Decision taken by the Veterinary Services

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 85 — Veterinary Medicinal Products Regulations, 2004 Open official source

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.

Marketing authorisations and revocations of such authorisations shall be published by the

Veterinary Services in the Government Gazette.

Foodstuffs taken from test animals

Malta Government Gazette — Legal Notice 2004 469 — Veterinary Medicinal Products Regulations, 2004

Reg. 86 — Veterinary Medicinal Products Regulations, 2004 Open official source

The Veterinary Services shall not permit foodstuffs for human consumption to be taken

from test animals unless maximum residue limits have been established in accordance with the

provisions of Regulation No. (EEC) 2377/90/EC and an appropriate withdrawal period has been

established to ensure that this maximum limit will not be exceeded in the foodstuffs.

Veterinary Medicinal Products Regulations, 2004

Table of Provisions (88)

Statutory Text (88 Articles)

Need to analyze how this provision applies to your matter?