Medicines (Marketing Authorisation) Regulations, 2007

L.N. 324 of 2007

MEDICINES ACT

(CAP. 458)

Medicines (Marketing Authorisation) Regulations, 2007

IN exercise of the powers conferred by article 106 of the Medicines

Act, the Minister of Health, the Elderly and Community Care, has made

the following regulations>-

The title of these regulations is the Medicines (Marketing

Authorisation) Regulations, 2007.

(1) For the purposes of these regulations –

“abuse of medicinal products” means persistent or sporadic,

intentional excessive use of medicinal products which is

accompanied by harmful physical or psychological effects<

“Annex I” means Annex I of Directive 2003#63#EC and its

subsequent amendments<

“the Act” means the Medicines Act<

“the Agency” means the European Medicines Agency

established by Regulation (EC) No 726#2004<

“the Authority” means the Medicines Authority established

under article 4 of the Act<

“the Commission” means the Commission in accordance with

Council Decision 1999#468#EC of 28 June, 1999<

“the Community” means the European Union, previously

referred to as the European Community and the European

Economic Community<

“common name” is the international non-proprietary name

recommended by the World Health Organisation, or if it does not

exist, the usual common name<

“co-ordination group” means the co-ordination group set up

in accordance with Article 27 of Directive 2001#83#EC as amended

by Directive 2004#27#EC<

“global marketing authorisation” means the marketing

authorisations containing the initial marketing authorisation and

all variations and extensions thereof, as well as any additional

strengths, pharmaceutical forms, administration routes or

presentations authorised through separate procedures and under a

different name, granted to the marketing authorisation holder of

the initial authorisation<

“homeopathic medicinal product” means any medicinal

product prepared from substances called homeopathic stocks in

accordance with a homeopathic manufacturing procedure described

by the European Pharmacopoeia or, in the absence thereof, by the

pharmacopoeias currently used officially in the Member States.

A homeopathic medicinal product may contain a number of

principles<

“Licensing Authority” means the Licensing Authority referred

to in article 3 of the Act<

“medicinal product” shall have the same meaning as defined

by the Medicines Act<

“Member State” means a State, which is a member of the

European Union, and shall also include Iceland, Norway and

Liechtenstein<

“provisional marketing authorisation” means a marketing

authorisation issued by the Licensing Authority for products present

on the market in Malta up till the 30 th November, 2002 and for

which a valid application for a marketing authorisation has been

received by the Medicines Authority<

“reference Member State” means the Member State which,

for a given medicinal product, has produced the assessment report,

which serves as the basis for the mutual recognition procedure

and the decentralised procedure<

“representative of the marketing authorisation holder” means

the person commonly known as local representative, designated

by the marketing authorisation holder to represent him in the

Member State concerned<

“risk-benefit balance” means an evaluation of the positive

therapeutic effects of the medicinal product”in relation to the risks

relating to the quality, safety and efficacy of the medicinal product

as regards patients’ health or public health<

“risks related to use of the medicinal product” means any

risk relating to the quality, safety or efficacy of the medicinal

product as regards patients’ health or public health or any risk of

undesirable effects on the environment<

“strength of the medicinal product” means the content of the

active substances expressed quantitatively per dosage unit, per unit

of volume or weight according to the dosage form<

“the Superintendent” means the Superintendent of Public

Health.

(2) The provisions of these regulations shall not apply to>

(a) any medicinal product prepared in a pharmacy in

accordance with a medical prescription for an individual patient

(commonly known as the magistral formula)<

(b) any medicinal product which is prepared in a pharmacy

in accordance with the prescriptions of a pharmacopoeia and is

intended to be supplied directly to the patients served by the

pharmacy in question, (commonly known as the officinal formula)<

(c) medicinal products intended for research and

development trials but without prejudice to the provisions of the

Clinical Trials Regulations 2004 or of Directive 2001#20#EC of

the European Parliament and of the Council of the 4 th April 2001

on the approximation of the laws, regulations and administrative

provisions of the Member States relating to the implementation of

good clinical practice in the conduct of clinical trials on medicinal

products for human use<

(d) intermediate products intended for further processing

by an authorised manufacturer<

(e)

any radionuclides in the form of sealed sources<

(f) whole blood, plasma or blood cells of human origin,

except for plasma which is prepared by a method involving an

industrial process<

(g) medicinal products supplied in response to a bona fide

unsolicited order, formulated in accordance with the specifications

of an authorised health-care professional and for use by an

individual patient under his direct personal responsibility.

(1) The provisions of these regulations shall apply to

medicinal products for human use intended to be placed on the market

in Malta and either prepared industrially or manufactured by a method

involving an industrial process.

(2) In cases of doubt, where, taking into account all its

characteristics, a product may fall within the definition of a “medicinal

product” and within the definition of a product covered by other

community legislation, the provisions of these regulations shall apply.

(1) (a) Subject to the following provisions of this Authorisation for

regulation, no medicinal product may be placed on the market in Malta placing

market.

unless there is in respect of that product a valid marketing authorisation

issued by the Licensing Authority in accordance with these regulations

or in accordance with procedures laid down in Regulation (EC) No

726#2004 of the European Parliament and of the Council of 31 March

2004 laying down Community procedures for the authorisation and

supervision of medicinal products for human and veterinary use and

establishing a European Medicines Agency), read in conjunction with

Regulation (EC) No 1901#2006 of the European Parliament and of the

Council of 12 December 2006 on medicinal products for paediatric use,

and such placing on the market is in accordance with the terms and

conditions of such marketing authorisation.

(b) When a medicinal product has been granted an

initial marketing authorisation in accordance with the preceding

paragraph, any additional strengths, pharmaceutical forms,

administration routes, presentations, as well as any variations and

extensions shall only be granted an authorisation in accordance with

the preceding subparagraph or be included in the initial marketing

authorisation. All these marketing authorisations shall be considered as

belonging to the same global marketing authorisation, in particular for

the purpose of the application of regulation 7(1).

(c) The provisions of subregulations 1(a), and (b) shall

also apply to radionuclide generators, kits, radionuclide precursor

radiopharmaceuticals and industrially prepared radiopharmaceuticals.

(d) A marketing authorisation shall not be required in

the case of a radiopharmaceutical prepared at the time of its use by a

person or by an establishment duly authorised to use such medicinal

products in an approved health care establishment exclusively from

authorised radionuclide generators, kits or radionuclide precursors in

accordance with the manufacturer’s instructions.

(e) The Licensing Authority may, in exceptional cases,

subject to any condition it deems fit, allow the use of a medicinal product

which does not have a marketing authorisation.

(f) The Licensing Authority may temporarily authorise

the distribution of an unauthorised medicinal product in response to the

suspected or confirmed spread of pathogenic agents, toxins, chemical

agents or nuclear radiation any of which could cause harm.

(g) Products having a provisional marketing

authorisation shall be allowed to remain on the market until such time

as the Licensing Authority may establish.

(h) The marketing authorisation holder shall be

responsible for marketing the medicinal product and the designation of

a representative shall not relieve the marketing authorisation holder of

his legal responsibility.

(2) (a) In the absence of a marketing authorisation or of a

pending application for a medicinal product which is authorised in

another Member State in accordance with Directive 2001#83#EC of the

European Parliament and of the Council of 6 November 2001 on the

community code relating to medicinal products for human use, and any

amendments thereto, the Licensing Authority may for justified public

health reasons authorise the placing of the said medicinal product on

the market in Malta.

(b) The medicinal product referred to in paragraph

2(a) has to comply in particular with the requirements of the provisions

regarding the classification of medicinal products, laid down in the

Medicines Act, and any regulations made thereunder, and the following

regulations>

(i)

the Medicinal Products (Advertising) Regulations,2005,

(ii) the Medicinal Products (Labelling and Packaging)

Regulations, 2005,

(iii) the Pharmacovigilance Regulations, 2006 and,

(iv) the Wholesale Distribution of Medicinal Products

Regulations, 2005.

(c) Any authorisation issued under this regulation shall

for the purposes of articles 99 to 104 of the Medicines Act be deemed

to be a marketing authorisation.

(d) Before granting such an authorisation the Licensing

Authority shall>

(i) notify the marketing authorisation holder in the Member

State in which the medicinal product concerned is authorised, of

its intention to grant an authorisation under subregulation (2)

hereof, and

(ii) request the competent authority in that Member State

to furnish a copy of the assessment report, and of the marketing

authorisation in force.

(e) (i) The medicinal product to be placed on the

market in Malta shall be that authorised by the Member State referred

to in paragraph (a) of this subregulation.

(ii) An authorisation under this sub-regulation

hereof cannot be used as the basis for a licence in terms of the Parallel

L.N. 437 of 2004.

Importation of Medicinal Products Regulations, 2004.

(iii) An authorisation under this sub-regulation

cannot be used as a reference for an application submitted in accordance

with regulation 7.

(f) The holder of the authorisation in Malta granted in

accordance with this sub-regulation, shall ensure that>

(i) the medicinal product is in accordance with the

marketing authorisation issued by the Member State referred to

above, and includes any variations in particular those affecting

the summary of product characteristics, labelling and package

leaflet of the medicinal product as approved in the said Member

State, and submits the updated documentation to the Medicines

Authority<

(ii) he implements without any delay actions relating to

issues concerning the medicinal product which have resulted in a

product or batch recall as may apply to the medicinal product

authorised in the Member State referred to above.

(g) In the case of a medicinal product, where the

wholesale distributor is not the authorisation holder for the medicinal

product in Malta, the distributor shall, in respect of the product he is

distributing in Malta, furnish to the Medicines Authority an authenticated

copy of the said authorisation together with a letter of access issued by

the authorisation holder granting the wholesale distributor the use of

such an authorisation.

(1) A marketing authorisation may only be granted or Grant or renewal of

renewed if the general conditions applicable to authorisations and the marketing

authorisation.

conditions set out under Directive 2001#83#EC on the Community Code

relating to medicinal products for human use and subsequent

amendments thereto, are fulfilled as follows>

(a) an application for marketing authorisation shall be made

to the Licensing Authority which shall refer such application to

the Authority for processing<

(b) a marketing authorisation may only be granted to an

applicant established in the Community<

(c) the application shall be accompanied by the following

documents and particulars to be submitted in accordance with

Annex I>

(i) the name or corporate name and permanent address

of the applicant and, where applicable, of the manufacturer<

(ii) the name of the medicinal product<

(iii) qualitative and quantitative particulars of all the

constituents of the medicinal product, including the reference

to its international non-proprietary name (INN) recommended

by the World Health Organisation, where an INN for the

medicinal product exists, or a reference to the relevant

chemical name<

(iv) evaluation of the potential environmental risks

posed by the medicinal product. This impact shall be assessed

and, on a case-by-case basis, specific arrangements to limit it

shall be envisaged<

(v) a description of the manufacturing method<

(vi) therapeutic indications, contra-indications and

adverse reactions<

(vii) posology, pharmaceutical form, method and route

of administration and expected shelf life<

(viii) reasons for any precautionary and safety

measures to be taken for the storage of the medicinal product,

its administration to patients and for the disposal of waste

products, together with an indication of potential risks

presented by the medicinal product for the environment<

(ix) description of the control methods employed by

the manufacturer<

(x) results of pharmaceutical (physico-chemical,

biological or microbiological) tests, pre-clinical (toxicological

and pharmacological) tests, clinical trials.

A detailed description of the pharmacovigilance and, where

appropriate, of the risk-management system which the applicant will

introduce.

A statement to the effect that clinical trials carried out outside the

European Union meet the ethical requirements of the Clinical Trials

Regulations, 2004 and of Directive 2001#20#EC of the European L.N. 490 of 2004.

Parliament and of the Council of the 4 th April, 2001 on the approximation

of the laws, regulations and administrative provisions of the Member

States relating to the implementation of good clinical practice in the

conduct of clinical trials on medicinal products on human use<

(xi) a summary, in accordance with regulation 8, of

the product characteristics, a mock-up of the outer packaging,

containing the details provided for in the Medicinal Products

(Labelling and Packaging) Regulations, 2005, and of the

immediate packaging of the medicinal product, containing

the details provided for in those regulations, together with a

package leaflet in accordance with those same regulations<

(xii) a document showing that the manufacturer is

authorised in his own country to produce medicinal products<

(xiii) copies of any authorisation obtained in another

Member State or in a third country to place the medicinal

product on the market, together with a list of those Member

States in which an application for authorisation submitted in

accordance with the provisions of Directive 2001#83#EC, as

amended, is under examination. Copies of the summary of

the product characteristics proposed by the applicant in

accordance with regulation 8 or approved by the competent

authorities of the Member State. Copies of the package leaflet

proposed in accordance with the Medicinal Products

(Labelling and Packaging) Regulations, 2005, or as approved

by the competent authorities of the Member State. Details of

any decision to refuse authorisation, whether in the

Community or in a third country, and the reasons for such a

decision<

(xiv) a copy of any designation of the medicinal

product as an orphan medicinal product under Regulation (EC)

No 141#2000 of the European Parliament and of the Council

of 16 December 1999 on orphan medicinal products,

accompanied by a copy of the relevant Agency opinion<

(xv) proof that the applicant has the services of a

qualified person responsible for pharmacovigilance and has

the necessary means for the notification of any adverse

reaction suspected of occurring either in the Community or

in a third country<

(2) The information under sub-regulation (1)(c)(xiii) hereof

shall be updated on a regular basis.

(3) The documents and information concerning the results

of the pharmaceutical and pre-clinical tests and the clinical trials referred

to in sub-regulation (1)(c)(x) hereof, shall be accompanied by detailed

summaries in accordance with regulation 9.

In the case of an application for a marketing authorisation for

a radionuclide generator, in addition to the requirements set out in

regulations 5 and 7(1), the application shall also contain>

(a) a general description of the system together with a

detailed description of the components of the system which may

affect the composition or quality of the daughter nucleid

preparation< and

(b) qualitative and quantitative particulars of the eluate or

the sublimate.

(1) (a) (i) By way of derogation from regulation 5

(1)(c)(x), and without prejudice to the law relating to the protection of

industrial and commercial property, the applicant shall not be required

to provide the results of pre-clinical tests and of clinical trials if he can

demonstrate that the medicinal product is a generic of a reference

medicinal product which is or has been authorised under Article 6 of

Directive 2001#83#EC and its subsequent amendments for not less than

six years in Malta or in the Community.

(ii) Sub-regulation (1)(a)(i) shall also apply if the

reference medicinal product was not authorised in Malta. In this case,

the applicant shall indicate in the application form the name of the

Member State in which the reference medicinal product is or has been

authorised. At the request of the Licensing Authority, the competent

authority of the other Member State shall transmit within a period of

one month, a confirmation that the reference medicinal product is or

has been authorised, together with the full composition of the reference

product and if necessary other relevant documentation>

Provided that the Licensing Authority shall within one month

provide any information requested by the competent authority of another

Member State in respect of a reference medicinal product authorised in

Malta>

Provided further that for the purposes of this regulation>

“reference medicinal product” means a medicinal product

authorised under regulation 4, in accordance with the provisions

of regulation 5 or authorised under article 8 of Directive

2001#83#EC as amended<

“generic medicinal product” means a medicinal product which

has the same qualitative and quantitative composition in active

substances and the same pharmaceutical form as the reference

medicinal product, and whose bioequivalence with the reference

medicinal product has been demonstrated by appropriate

bioavailability studies. The different salts, esters, ethers, isomers,

mixtures of isomers, complexes or derivatives of an active

substance shall be considered to be the same active substance,

unless they differ significantly in properties with regard to safety

and, or efficacy. In such cases, additional information providing

proof of the safety and, or efficacy of the various salts, esters or

derivatives of an authorised active substance must be supplied by

the applicant. The various immediate-release oral pharmaceutical

forms shall be considered to be one and the same pharmaceutical

form. Bioavailability studies need not be required of the applicant

if he can demonstrate that the generic medicinal product meets the

relevant criteria as defined in the appropriate detailed guidelines.

(b) In cases where the medicinal product does not fall

within the definition of a generic medicinal product as provided above

or where the bioequivalence cannot be demonstrated through

bioavailability studies or in case of changes in any active substance,

therapeutic indications, strength, pharmaceutical form or route of

administration, vis-à-vis the reference medicinal product, the results of

the appropriate pre-clinical tests or clinical trials shall be provided.

(c) Where a biological medicinal product which is similar

to a reference biological product does not meet the conditions in the

definition of generic medicinal products, owing to, in particular,

differences relating to raw materials or differences in manufacturing

processes of the biological medicinal product and the reference

biological medicinal product, the results of appropriate pre-clinical tests

or clinical trials relating to these conditions must be provided. The type

and quantity of supplementary data to be provided must comply with

the relevant criteria stated in Annex I and the related detailed guidelines.

The results of other tests and trials from the reference medicinal product’s

dossier shall not be provided.

(d) In addition to the provisions laid down in sub-

regulation (1)(a), where an application is made for a new indication for

a well-established substance, a non-cumulative period of one year of

data exclusivity shall be granted, provided that significant pre-clinical

or clinical studies were carried out in relation to the new indication.

(e) Conducting the necessary studies and trials with a

view to the application of sub-regulation (1)(a),(b),and (c) and the

consequential practical requirements shall not be regarded as contrary

to patent rights or to supplementary protection certificates for medicinal

products.

(f) The periods of protection provided for in sub-

regulation (1)(a), (b), (c) and (d) shall not apply to reference medicinal

products for which an application for authorisation has been submitted

before the date of coming into force of these regulations.

(2) By way of derogation from regulation 5 (1)(c)(x), and

without prejudice to the law relating to the protection of industrial and

commercial property, the applicant shall not be required to provide the

results of pre-clinical tests or clinical trials if he can demonstrate that

the active substances of the medicinal product have been in well-

established medicinal use within the Community for at least ten years,

with recognised efficacy and an acceptable level of safety in terms of

the conditions set out in Annex I. In that event, the test and trial results

shall be replaced by appropriate scientific literature.

(3) In the case of medicinal products containing active

substances used in the composition of authorised medicinal products

but not hitherto used in combination for therapeutic purposes, the results

of new pre-clinical tests or new clinical trials relating to that combination

shall be provided in accordance with regulation 5(1)(c)(x), but it shall

not be necessary to provide scientific references relating to each

individual active substance.

(4) Following the granting of a marketing authorisation, the

authorisation holder may allow use to be made of the pharmaceutical,

pre-clinical and clinical documentation contained in the file on the

medicinal product, with a view to examining subsequent applications

relating to other medicinal products possessing the same qualitative

and quantitative composition in terms of active substances and the same

pharmaceutical form.

(1) The summary of the product characteristics shall contain, Summary

product

in the order indicated below, the following information>

characteristics.

(a) name of the medicinal product followed by the strength

and the pharmaceutical form<

(b) qualitative and quantitative composition in terms of the

active substances and constituents of the excipient, knowledge of

which is essential for proper administration of the medicinal

product. The usual common name or chemical description shall

be used<

(c)

pharmaceutical form<

(d) clinical particulars>

(i) therapeutic indications,

(ii) posology and method of administration for adults

and, where necessary for children,

(iii)

contra-indications,

(iv) special warnings and precautions for use and, in

the case of immunological medicinal products, any special

precautions to be taken by persons handling such products

and administering them to patients, together with any

precautions to be taken by the patient,

(v) interaction with other medicinal products and other

forms of interactions,

(vi) use during pregnancy and lactation,

(vii) effects on ability to drive and to use machines,

(viii) undesirable effects,

(ix) overdose (symptoms, emergency procedures,

antidotes)<

(e)

pharmacological properties>

(i) pharmacodynamic properties,

(ii) pharmacokinetic properties,

(iii) preclinical safety data<

(f)

pharmaceutical particulars>

(i) list of excipients,

(ii) major incompatibilities,

(iii) shelf life, when necessary after reconstitution of

the medicinal product or when the immediate packaging is

opened for the first time,

(iv) special precautions for storage,

(v) nature and contents of container,

(vi) special precautions for disposal of a used medicinal

product or waste materials derived from such medicinal

product, if appropriate<

(g) marketing authorisation holder<

(h) marketing authorisation numbers<

(i) date of the first authorisation or renewal of the

authorisation<

(j) date of revision of the text<

(k) for radiopharmaceuticals>

(i) full details of internal radiation dosimetry<

(ii) additional detailed instructions for extemporaneous

preparation and quality control of such preparation and, where

appropriate, maximum storage time during which any

intermediate preparation such as an eluate or the ready-to-

use pharmaceutical will conform with its specifications.

(2) For the authorisations referred to under regulation 7,

those parts of the summary of product characteristics of the reference

medicinal product referring to indications or dosage forms which were

still covered by patent law at the time when a generic medicine was

marketed need not be included.

(1) The applicant shall ensure that, before the detailed

summaries referred to in the regulation 5 (3) are submitted to the

Licensing Authority, they have been drawn up and signed by experts

with the necessary technical or professional qualifications, which shall

be set out in a brief curriculum vitae.

(2) Persons having the technical and professional

qualifications referred to in the preceding sub-regulation shall justify

any use made of scientific literature under regulation 7(2) in accordance

with the conditions set out in Annex I.

(3) The detailed summaries shall form part of the file which

the applicant submits to the Licensing Authority.

(1) The Authority shall ensure that homeopathic medicinal Specific provisions

applicable to

products manufactured and placed on the market within the Community homeopathic

are registered or authorised in accordance with regulations 10 and 11. medicinal products.

In case of registrations sub-regulations 22(1)(a) to (f) shall apply.

(2) The Authority shall establish a special simplified

registration procedure for the homeopathic medicinal products referred

to in sub-regulation (3).

(3) Only homeopathic medicinal products which satisfy all

of the following conditions may be subject to a special, simplified

registration procedure>

(a)

they are administered orally or externally<

(b) no specific therapeutic indication appears on the

labelling of the medicinal product or in any information relating

thereto<

(c) there is a sufficient degree of dilution to guarantee the

safety of the medicinal product< in particular, the medicinal product

may not contain either more then one part per 10 000 of the mother

tincture or more than 1#100 th of the smallest dose used in allopathy

with regard to active substances whose presence in an allopathic

medicinal product results in the obligation to submit a doctor’s

prescription.

The classification for the dispensing of the medicinal product,

shall be determined by the Authority at the time of registration.

The criteria and rules of procedure provided for in regulations 12,

17, 18, 19, 20 and 21. and articles 4(4), 112, 116 and 125 of Directive

2001#83#EC, as amended, shall apply by analogy to the special,

simplified registration procedure for homeopathic medicinal products

with the exception of the proof of therapeutic efficacy.

(4) An application for special, simplified 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 or stocks

is obtained and controlled, and justifying its homeopathic use, on

the basis of an adequate bibliography<

(c) manufacturing and control file for each pharmaceutical

form and a description of the method of dilution and potentization<

(d) manufacturing authorisation for the medicinal product

concerned<

(e) copies of any registrations or authorisations obtained

for the same medicinal product in other Member States<

(f) one or more mock-ups of the outer packaging and the

immediate packaging of the medicinal products to be registered<

(g) data concerning the stability of the medicinal product.

Homeopathic medicinal products, other than those referred

to in regulation 10 (3), shall be authorised and labelled in accordance

with regulations 5, 7 and 8.

It shall be the duty of the Authority to ensure that the

procedure for granting a marketing authorisation for medicinal products

is completed within a maximum of 210 days after the submission of a

valid application>

Provided that applications for marketing authorisations in two or

more Member States in respect of the same medicinal product shall be

submitted in accordance with the mutual recognition and decentralised

procedures.

Where the Authority notes that another marketing

authorisation application for the same medicinal product is being

examined in another Member State, the Authority shall decline to assess

the application and shall advise the applicant that the mutual recognition

and decentralised procedures apply.

Where the Authority is informed in accordance with Duties of the

regulation 5(1)(c)(xiii) that another Member State has authorised a Authority

receiving the report.

medicinal product, which is the subject of a marketing authorisation

application in Malta, it shall reject the application unless it was submitted

in compliance with the mutual recognition or decentralised procedures.

(1) In order to examine the application submitted in Examination of

application.

accordance with regulations 5 and 7 of these regulations, the

Authority –

(a) shall verify whether the particulars submitted by the

applicant are in terms of the provisions of these regulations and

examine whether the conditions for issuing a marketing

authorisation are complied with<

(b) may submit the medicinal product, its starting materials

and, if need be, its intermediate products or other constituent

materials, for testing by an Official Medicines Control Laboratory

or by a laboratory designated for that purpose by the Authority in

order to ensure that the control methods employed by the

manufacturer and described in the particulars accompanying the

application in accordance with regulation 5(1)(c)(ix) are

satisfactory<

(c) may, where appropriate, require the applicant to

supplement the particulars accompanying the application in respect

of the items listed under regulations 5(1)(c) and 7, in which case,

the two hundred and ten days referred to under regulation 12 shall

be suspended until such time as the supplementary information

required has been provided. Likewise, these time limits shall be

suspended when the applicant is given the opportunity of providing

an oral or written explanation.

(2) The Authority>

(a) shall verify that manufacturers and importers of

medicinal products coming from third countries are able to carry

out manufacture in compliance with the particulars supplied

pursuant to regulation 5(1)(c)(v) and, or to carry out controls

according to the methods described in the particulars accompanying

the application in accordance with regulation 5(1)(c)(ix)<

(b) may allow manufacturers and importers of medicinal

products coming from third countries, in justifiable cases, to have

certain stages of manufacture and, or certain of the controls referred

to in regulation 15(2)(a) carried out by third parties< in such cases,

the verifications by the Authority shall also be made in the

establishment designated.

(a) When the marketing authorisation is issued it shall be

subject to the conditions as specified in the Marketing Authorisation,

the Act and any regulations made thereunder as well as to any conditions

that the Licensing Authority may deem necessary, and the holder shall

be informed by the Authority of the summary of the product

characteristics as approved by it.

(b) The Authority shall>

(i) 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<

(ii) make publicly available without delay the marketing

authorisation together with the summary of the product

characteristics for each medicinal product which it has authorised<

(iii) draw up an assessment report and comments on the

file as regards the results of the pharmaceutical and pre-clinical

tests and the clinical trials of the 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 medicinal product concerned<

(iv) make publicly accessible the assessment report, together

with the reasons for its opinion, after deletion of any information

of a commercially confidential nature. The justification shall be

provided separately for each indication applied for.

In exceptional circumstances and following consultation with

the applicant, the authorisation may be granted subject to a requirement

for the applicant to meet certain conditions, in particular concerning

the safety of the medicinal product, notification to the Authority of any

incident relating to its use, and action to be taken. This authorisation

may be granted only for objective, verifiable reasons and must be based

on one of the grounds set out in Annex I. Continuation of the

authorisation shall be linked to the annual reassessment of these

conditions. The list of these conditions shall be made publicly accessible,

together with deadlines and dates of fulfilment.

(1) After an authorisation has been issued, the authorisation

holder must, in respect of the methods of manufacture and control

provided for in regulation 5(1)(c)(v) and (ix), take account of any

scientific and technical progress and introduce any changes which may

be required to enable the medicinal product to be manufactured and

checked by means of generally accepted scientific methods. These

changes shall be subject to the approval of the Authority.

(2) (a) The authorisation holder shall forthwith supply to

the Authority any new information which might entail the amendment

of the particulars or documents referred to in regulations 5(1)(c), 7 and

8 or Article 32(5) of Directive 2001#83#EC, and its subsequent

amendments or Annex I of that Directive.

(b) In particular, he shall forthwith inform the

Authority of any prohibition or restriction imposed by the competent

authorities of any country in which the medicinal product for human

use is marketed and of any other new information which might influence

the evaluation of the benefits and risks of the medicinal product for

human use concerned.

(3) In order that the risk-benefit balance may be

continuously assessed, the Authority may at any time ask the holder of

the marketing authorisation to forward data demonstrating that the risk-

benefit balance remains favourable.

(4) After a marketing authorisation has been granted, the

holder of the authorisation shall inform the Authority of the date of

actual marketing of the medicinal product for human use in Malta, taking

into account the various presentations authorised. The holder shall also

notify the Authority if the product ceases to be placed on the market in

Malta, either temporarily or permanently. Such notification shall,

otherwise than in exceptional circumstances, be made no less than two

months before the interruption in the placing on the market of the

product.

(5) Upon request by the Authority, particularly in the context

of pharmacovigilance, the marketing authorisation holder shall provide

it with all data relating to the volume of sales of the medicinal product,

and any data in his possession relating to the volume of prescriptions.

(1) Without prejudice to sub-regulations (4) and (5), a Validity of

marketing

marketing authorisation shall be valid for five years.

authorisation.

(2) The marketing authorisation may be renewed after five

years on the basis of a re-evaluation of the risk-benefit balance by the

Authority. To this end, the marketing authorisation holder shall provide

the Authority with a consolidated version of the file in respect of quality,

safety and efficacy, including all variations introduced since the

marketing authorisation was granted, at least six months before the

marketing authorisation ceases to be valid in accordance with sub-

regulation (1).

(3) Once renewed, the marketing authorisation shall be valid

for an unlimited period, unless the Authority decides, on justified

grounds relating to pharmacovigilance, to proceed with one additional

five-year renewal in accordance with sub-regulation (2).

(4) Any authorisation granted by the Authority which within

three years of its granting is not followed by the actual placing on the

market of the authorised product in Malta shall cease to be valid.

(5) When an authorised product previously placed on the

market in Malta is no longer actually present on the market for a period

of three consecutive years, the authorisation for that product shall cease

to be valid.

(6) The Authority may, in exceptional circumstances and

on public health grounds grant exemptions from sub-regulations (4)

and (5) provided that such exemptions are duly justified.

An authorisation or licence for placing a medicinal product

on the market shall not affect the civil and criminal liability of the

manufacturer and, where applicable, of the marketing authorisation

holder who has placed such medicinal product on the market in any

European Union or European Economic Area state. Such manufacturer

or marketing authorisation holder shall in particular remain liable for

any deficiencies in quality, safety and efficacy of such medicinal

products.

(1) The marketing authorisation of a medicinal product shall

be refused if, after verification of the particulars and documents listed

in regulations 5 and 7 it is clear that>

(a) the risk-benefit balance is not considered to be

favourable, or

(b) the therapeutic efficacy of the medicinal product is

insufficiently substantiated by the applicant, or

(c) the qualitative and quantitative composition of the

medicinal product is not as declared.

(2) Authorisation shall likewise be refused if any particulars

or documents submitted in support of the application do not comply

with the provisions of regulations 5 and 7.

(3) The applicant or the holder of a marketing authorisation

shall be responsible for the accuracy of the documents and the data

submitted.

(a) With a view to the granting of a marketing authorisation Mutual recognition

and decentralised

for a medicinal product in more than one Member State, including Malta, procedure.

an applicant shall submit an application to the Authority, based on a

dossier identical to that submitted in the other Member States. The

dossier shall contain the information and documents referred to in

regulations 5, 7 and 8. The documents submitted shall include a list of

Member States concerned by the application.

The applicant shall request one Member State to act as “reference

Member State” and to prepare an assessment report on the medicinal

product in accordance with paragraphs (b) and (c) hereof.

(b) Where the medicinal product has already received a

marketing authorisation at the time of application, if Malta is a concerned

Member State, the Authority shall recognise the marketing authorisation

granted by the reference Member State. To this end, the marketing

authorisation holder shall request the reference Member State either to

prepare an assessment report on the medicinal product or, if necessary,

to update any existing assessment report. If Malta is the reference

Member State, the Authority shall prepare or update the assessment

report within 90 days of receipt of a valid application. The assessment

report together with the approved summary of product characteristics,

labelling and package leaflet shall be sent to the concerned Member

States and to the applicant.

(c) In cases where the medicinal product has not received a

marketing authorisation at the time of application, the applicant shall

request the reference Member State to prepare a draft assessment report,

a draft summary of product characteristics and a draft of the labelling

and package leaflet. If Malta is the Reference Member State, the

Authority shall prepare these draft documents within 120 days after

receipt of a valid application and shall send them to the concerned

Member States and to the applicant.

(d) If Malta is a concerned Member State, within 90 days

of receipt of the documents referred to in paragraphs (b) and (c) hereof,

the Authority shall approve the assessment report, the summary of

product characteristics and the labelling and package leaflet and shall

inform the reference Member State accordingly. If Malta is the reference

Member State, the Authority shall record the agreement of all parties,

close the procedure and inform the applicant accordingly.

(e) The Authority shall adopt a decision in conformity with

the approved assessment report, the summary of product characteristics

and the labelling and package leaflet as approved, within 30 days after

acknowledgement of the agreement.

(f) If, within the period laid down in paragraph (d) hereof,

the Authority cannot approve the assessment report, the summary of

product characteristics, the labelling and the package leaflet on the

grounds of potential serious risk to public health, it shall give a detailed

exposition of the reasons for its position to the reference Member State,

to the other Member States concerned and to the applicant. The points

of disagreement shall be forthwith referred to the coordination group.

Within such co-ordination group, the Authority shall use its best

endeavours to reach agreement on the action to be taken and it shall

allow the applicant the opportunity to make his point of view known

orally or in writing. If, within 60 days of the communication of the

points of disagreement, all Member States reach an agreement, if Malta

is the Reference Member State, the Authority shall record the agreement,

close the procedure and inform the applicant accordingly and paragraph

(e) hereof shall apply>

Provided that if Member States fail to reach an agreement within

the co-ordination group, within such 60-day period, and if the Authority

has approved the assessment report, the draft summary of product

characteristics and the labelling and package leaflet of the reference

Member State, the Authority may, at the request of the applicant,

authorise the medicinal product without waiting for the outcome of the

procedure laid down in Article 32 of Directive 2001#83#EC as amended

by Directive 2004#27#EC. In that event, the authorisation granted shall

be without prejudice to the outcome of that procedure.

(1) If two or more applications submitted in accordance

with regulations 5, 7 and 8 have been made for marketing authorisation

for a particular medicinal product, and if Member States have adopted

divergent decisions concerning the authorisation of the medicinal

product or its suspension or revocation, the Authority, the Commission

or the applicant or the marketing authorisation holder may refer the

matter to the Committee for Medicinal Products for Human Use,

hereinafter referred to as the Committee, for the application of the

procedure laid down in Articles 32, 33 and 34 of Directive 2001#83 as

amended by Directive 2004#27.

(2) In order to promote harmonisation of authorisations for

medicinal products authorised in the Community, the Authority shall,

each year, forward to the coordination group a list of medicinal products

for which a harmonised summary of product characteristics should be

drawn up.

(3) The Authority or the Commission, in agreement with

the Agency and taking into account the views of interested parties, may

refer these products to the Committee in accordance with sub-regulation

(1).

(4) The Authority or the Commission or the applicant or

the marketing authorisation holder shall, in specific cases where the

interests of the Community are involved, refer the matter to the

Committee for application of the procedure laid down in Articles 32,

33 and 34 of Directive 2001#83#EC as amended by Directive

2004#27#EC, before any decision is reached on a request for a marketing

authorisation or on the suspension or revocation of an authorisation, or

on any other variation to the terms of a marketing authorisation which

appears necessary, in particular to take account of the information

collected in accordance with the Pharmacovigilance Regulations, 2005.

(5) The Authority or the Commission shall clearly identify

the question which is referred to the Committee for consideration and

shall inform the applicant or the marketing authorisation holder.

(6) The Authority and the applicant or the marketing

authorisation holder shall supply the Committee with all available

information relating to the matter in question.

(1) A marketing authorisation holder may apply to vary Application for

the marketing authorisation, which has been granted in accordance with variation.

regulations 22 and 23, and such application shall be submitted to the

Authority and to all other Member States which have previously

authorised the medicinal product concerned.

(2) Where the Authority considers that a variation of a

marketing authorisation which has been granted in accordance with the

provisions relating to the mutual recognition or decentralised procedure,

or its suspension or withdrawal is necessary for the protection of public

health, the Authority shall forthwith refer the matter to the Agency for

the application of the procedures laid down in Articles 32, 33 and 34 of

Directive 2001#83#EC as amended by Directive 2004#27#EC>

Provided that, without prejudice to regulations 23(4), (5) and

(6), in exceptional cases, when urgent action needs to be taken in the

interest of public health, the Licensing Authority may suspend the

marketing and use of the medicinal product concerned and inform the

Commission and other Member States not later than the following

working day, giving reasons for its decision.

This regulation shall apply by analogy to medicinal products

authorised by the Authority following an opinion of the Committee

given in accordance with Article 4 of Directive 87#22#EEC before 1

January, 1995.

Applications for marketing authorisations which have been

referred to the Committee for Proprietary Medicinal Products before

the 1 January, 1995 in accordance with Article 2 of Directive 87#22#EEC

and in respect of which the Committee concerned has not given an

opinion by 1 January, 1995, shall be considered in accordance with

Regulation (EC) No 726#2004.

Regulation 22(1)(f) second paragraph, regulation 23 and Articles

32 to 34 of Directive 2001#83#EC and its subsequent amendments, shall

not apply to homeopathic medicinal products referred to in sub-

regulations (1), (2) and (3) of regulation 10.

(1) When a marketing authorisation is granted, the

Authority shall specify the classification of the medicinal product into>

(a)

a medicinal product subject to medical prescription,

(b) a medicinal product not subject to medical prescription.

To this end, the criteria laid down in regulation 27(1) shall apply.

(2) The Authority may fix sub-categories for medicinal

products which are available on medical prescription only. In that case,

they shall refer to the following classification>

(a) medicinal products on medical prescription for

renewable or non-renewable delivery<

(b) medicinal products subject to special medical

prescription<

(c) medicinal products on “restricted” medical prescription,

reserved for use in certain specialised areas>

Provided that where the Authority does not designate

medicinal products into sub-categories, it shall nevertheless take

into account the criteria referred to in sub-regulations (2) and (3)

of regulation 27 in determining whether any medicinal product

shall be classified as a prescription-only medicine.

(1) Medicinal products shall be subject to medical

prescription where they>-

(a) are likely to present a danger either directly or indirectly,

even when used correctly, if utilized without medical supervision,

or

(b) are frequently and to a very wide extent used incorrectly,

and as a result are likely to present a direct or indirect danger to

human health, or

(c) contain substances or preparations thereof, the activity

and any adverse reactions of which require further investigation,

or

(d) are normally prescribed by a doctor to be administered

parenterally.

(2) For the sub-category of medicinal products subject to

special medical prescription, the Authority shall take account of the

following factors>

(a) the medicinal product contains, in a non-exempt quantity,

a substance classified as a narcotic or a psychotropic substance

within the meaning of the international conventions in force, such

as the United Nations Conventions of 1961 and 1971, or

(b) the medicinal product is likely, if incorrectly used, to

present a substantial risk of medicinal abuse, to lead to addiction

or be misused for illegal purposes, or

(c) the medicinal product contains a substance which, by

reason of its novelty or properties, could be considered as belonging

to the group envisaged in sub-regulation (b), as a precautionary

measure.

(3) For the sub-category of medicinal products subject to

restricted prescription, the Authority shall take account of the following

factors>

(a) the medicinal product, because of its pharmaceutical

characteristics or novelty or in the interests of public health, is

reserved for treatments which can only be followed in a hospital

environment<

(b) the medicinal product is used in the treatment of

conditions which must be diagnosed in a hospital environment or

in institutions with adequate diagnostic facilities, although

administration and follow-up may be carried out elsewhere, or

(c) the medicinal product is intended for outpatients but its

use may produce very serious adverse reactions requiring a

prescription drawn up as required by a specialist and special

supervision throughout the treatment.

(4) The Authority may waive application of sub-regulations

(1), (2) and (3) having regard to>

(a) the maximum single dose, the maximum daily dose, the

strength, the pharmaceutical form, certain types of packaging< and,

or

(b) other circumstances of use which it has specified.

Medicinal products not subject to prescription shall be those

which do not meet the criteria listed in regulation 27 of these regulations.

The Authority shall draw up a list of the medicinal products

subject to medical prescription, specifying, if necessary, the category

of classification, and it shall update this list annually.

(1) When new facts are brought to its attention, the

Authority shall examine and, as appropriate, amend the classification

of a medicinal product by applying the criteria listed in regulation 27 of

these regulations.

(2) Where a change of classification of a medicinal product

has been authorised on the basis of significant pre-clinical tests or

clinical trials, the Authority shall not refer to the results of those tests or

trials when examining an application by another applicant or holder of

marketing authorisation for a change of classification of the same

substance for one year after the initial change was authorised.

The Medicines (Marketing Authorisation) Regulations, 2004

are hereby repealed.

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