MANUFACTURE AND IMPORTATION OF MEDICINAL PRODUCTS FOR HUMAN USE REGULATIONS

SUBSIDIARY LEGISLATION 458.36

MANUFACTURE AND IMPORTATION OF

MEDICINAL PRODUCTS FOR HUMAN USE

REGULATIONS

30th October, 2005

LEGAL NOTICE 381 of 2005, as amended by Legal Notices 252 of 2009

476 of 2012 and 234 and 283 of 2022.

The title of these regulations is the Manufacture and

Importation of Medicinal Products for Human Use Regulations.

For the purposes of these regulations -

"Act" means the Medicines Act;

"active substance (API)" means any substance or mixture of

substances intended to be used in the manufacture of a medicinal

product and that, when used in its production, becomes an active

ingredient of that product intended to exert a pharmacological,

immunological or metabolic action with a view to restoring, correcting

or modifying physiological functions or to make a medical diagnosis;

"the Agency" means the European Medicines Agency established

by Regulation (EC) No. 726/2004;

"the Commission" means the Commission in accordance with

Council Decision 1999/468/EC of 28th June, 1999;

"the Community" means the European Community and the

European Economic Area;

"imported medicinal products" means medicinal products

ob t a in e d f r o m a s o ur c e o u t s i d e t h e Eu r o p e a n U n i o n o r t h e

European Economic Area;

"Member State" me ans a State w hich is a member o f the

European Union and includes Iceland, Norway and Liechtenstein.

(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, or

Directive 2001/20/EEC of the European Parliament

and of the Council of the 4th 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;

(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)(a) No medicinal product, biological active substance, or

active substance to be used directly as an

investigational medicinal product, may be

manufactured in Malta unless there is, in respect of

such product or substance, a manufacturing licence,

hereinafter referred to as "licence", to that effect. This

manufacturing licence shall also be required for the

processes of sterilisation of active substances.

(b) This manufacturing licence shall be

required

notwithstanding that the medicinal

products

manufactured are intended for export.

(2)

(a) A licence, which shall remain in force for a period to

be determined by the Licensing Authority, hereinafter

referred to as "the Authority", shall be required for

both total and partial manufacture, and for the various

processes of dividing up, packaging or presentation.

(b) A licence shall not be required for preparation,

dividing up, changes in packaging or presentation

where such processes are carried out solely for retail

supply by pharmacists in pharmacies, or by persons

legally authorised to carry out such processes.

(3) An importer’s licence, hereinafter also referred to as

"licence", shall be required for the importation of medicinal

products.

(4) A licence shall include a licence to distribute by wholesale

the medicinal products in respect of which the licence has been

issued.

(5) The Authority shall forward to the Agency a copy of the

licence referred to in subregulation (1).

(6) The Authority shall enter the information relating to the

licence referred to in sub-regulation (1) in the European Union

database referred to in Article 111(6) of Directive 2001/83/EC as

amended.

(1) Importers and manufacturers of active substances who

are established in Malta shall register their activity with the

Licensing Authority.

(2) The registration form shall include, at least, the following

information

(a) name or corporate name and permanent address;

(b) the active substances which are to be imported or

manufactured;

(c) particulars regarding the premises and the technical

equipment for their activity

Provided that the persons referred to in sub-regulation (1)

shall submit the registration form to the Licensing Authority at

least sixty days prior to the intended commencement of their

activity.

(3) The Licensing Authority may, based on a risk assessment,

decide to carry out an inspection. If the Licensing Authority

notifies the applicant within sixty days of the receipt of the

registration form that an inspection will be carried out, the activity

shall not begin before the Licensing Authority has notified the

applicant that he may commence the activity. If within sixty days of

the receipt of the registration form the Licensing Authority has not

notified the applicant that an inspection will be carried out, the

applicant may commence the activity.

(4) The persons referred to in sub-regulation (1) shall

communicate annually to the Licensing Authority an inventory of

the changes which have taken place as regards the information

provided in the registration form. Any changes that may have an

impact on the quality or safety of the active substances that are

manufactured or imported shall be notified immediately.

(5) Persons referred to in sub-regulation (1) who had

commenced their activity before 2 January 2013 shall submit the

registration form to the competent authority by 2 March 2013.

(6) Member States shall enter the information provided in

accordance with sub-regulation (2) in the European Union database

referred to in Article 111(6) of Directive 2001/83/EC, as amended.

(7) This regulation shall be without prejudice to articles 101

and 102 of the Medicines Act.

The Authority, shall only grant or renew a licence, if the

applicant

(a) specifies the medicinal products and pharmaceutical

forms which are to be manufactured or imported and

the place where they are to be manufactured and, or

controlled;

(b) has at his disposal, for the manufacture or import of

medicinal products, suitable and sufficient premises,

technical equipment and control facilities complying

with requirements set by the Authority;

(c) has at his disposal the services of at least one qualified

MANUFACTURE AND IMPORTATION OF

MEDICINAL PRODUCTS FOR HUMAN USE

person within the meaning of regulation 8; and

(d) provides all necessary documentation in support of his

application.

(1)(a) The Authority shall issue the licence after verifying

the contents of the application but in any case not later

than ninety days from receipt of the application.

(b) This time period shall be suspended when the

Authority requests additional information from the

applicant.

(c) The Authority may grant a conditional licence subject

to the carrying out of certain obligations imposed on

the applicant.

(2) The licence shall apply only to the premises, medicinal

products and pharmaceutical forms specified in the application.

When the holder of the licence requests a change in the

particulars specified in regulation 4(a) and 4(b), the process of

verification of such information shall not exceed thirty days.

However, in exceptional cases, this period of time may be extended

to ninety days.

(1) The holder of the licence, apart from his obligations in

article 44 of the Act, shall

(a) comply with the Community principles and guidelines

of good manufacturing practice and any annexes

thereof for medicinal products and use only active

substances which have been manufactured in

accordance with the Community guidelines on good

manufacturing practice for active substances and

distributed in accordance with good distribution

practices for active substances. To this end, the holder

of the manufacturing authorisation shall verify

compliance by the manufacturer and distributors of

active substances with good manufacturing practice

and good distribution practices by conducting audits at

the manufacturing and distribution sites of the

manufacturer and distributors of active substances.

The holder of the manufacturing authorisation shall

verify such compliance either by himself or, without

prejudice to his responsibility as provided for in these

regulations and in the Act , through an entity acting on

his behalf under a contract;

(b) ensure that the excipients are suitable for use in

medicinal products by ascertaining what the

appropriate good manufacturing practice is. This shall

be ascertained on the basis of a formalised risk

assessment in accordance with the applicable

guidelines referred to in the fifth paragraph of Article

47 of Directive 2001/83/EC, as amended. Such risk

assessment shall take into account requirements under

other appropriate quality systems as well as the source

and intended use of the excipients and previous

instances of quality defects. The holder of the

manufacturing authorisation shall ensure that the

appropriate good manufacturing practice, so

ascertained, is applied. The holder of the

manufacturing authorisation shall document the

measures taken under this paragraph;

(c) inform the competent authority and the marketing

authorisation holder immediately if he obtains

information that medicinal products which come under

the scope of his manufacturing authorisation are, or

are suspected of being, falsified irrespective of

whether those medicinal products were distributed

within the legal supply chain or by illegal means,

including illegal sale by means of information society

services;

(d) verify that the manufacturers, importers or distributors

from whom he obtains active substances are registered

with the competent authority of the Member State in

which they are established;

(e) verify the authenticity and quality of the active

substances and the excipients.

(2) For the purposes of this regulation, manufacture of active

substances used as starting materials shall include both total and

partial manufacture or import of an active substance used as a

starting material as defined in Part I, point 3.2.1.1 (b) Annex I of

Directive 2001/83, and the various processes of dividing up,

packaging or presentation prior to its incorporation into a medicinal

product, including repackaging or re-labelling, such as are carried

out by a distributor of starting materials.

(3) The safety features referred to in regulation 3(o) of the

Medicinal Products (Labelling and Packaging) Regulations shall

not be removed or covered, either fully or partially, unless the

following conditions are fulfilled

(a) the manufacturing licence holder verifies, prior to

partly or fully removing or covering those safety

features, that the medicinal product concerned is

authentic and that it has not been tampered with;

(b) the manufacturing licence holder complies with

regulation 3(o) of the Medicinal Products (Labelling

and Packaging) Regulations, by replacing those safety

features with safety features which are equivalent as

regards the possibility to verify the authenticity,

identification and to provide evidence of tampering of

the medicinal product. Such replacement shall be

conducted without opening the immediate packaging.

Safety features shall be considered equivalent if they

(i)

comply with the requirements as may be adopted

by the European Union Commission pursuant to

Article 54a(2) of Directive 2001/83/EC as

amended; and

(ii) are equally effective in enabling the verification

of authenticity and identification of medicinal

products and in providing evidence of tampering

with medicinal products;

(c) the replacement of the safety features is conducted in

accordance with applicable good manufacturing

practice for medicinal products; and

(d) the replacement of the safety features is subject to

supervision by the Licensing Authority through

inspections or any other means as may be determined

by the same Authority.

(4) Manufacturing licence holders, including those performing

the activities referred to in sub-regulation (3), shall be regarded as

producers and therefore held liable for damages in the cases and

under the conditions set forth in the Consumers Affairs Act.

(5)

It shall be the duty of the importer to ensure that

(a) in the case of medicinal products and investigational

medicinal products imported from third countries, these

have been manufactured in accordance with standards

which are at least equivalent to the good manufacturing

practice standards laid down by the Community;

(b) in the case of medicinal products, such products have

been manufactured by manufacturers duly authorised

for the purpose; and

(c) in the case of investigational medicinal products, such

products have been manufactured by a manufacturer

notified to the competent authorities and accepted by

them for that purpose.

(1) The holder of the licence shall have permanently and

continuously at his disposal the services of at least one qualified

person, in accordance with the conditions laid down in regulation 9,

responsible in particular for carrying out the duties specified in

regulation 11.

(2) If the manufacturing licence holder personally has the

qualifications laid down in regulation 9, then he may himself

assume the responsibility of a qualified person.

For a person to be designated as qualified person, he must

possess the following qualifications

(a)

(i)

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, extending

over a period of at least four years of theoretical

and practical study in any of the following

scientific disciplines: pharmacy, medicine,

veterinary medicine, chemistry, pharmaceutical

chemistry and technology, biology;

(ii) where the course is followed by a period of

theoretical and practical training of a minimum

duration of one year and including a training

period of at least six months in a pharmacy open

to the public, such period being corroborated by

an examination at university level, then the

minimum duration of the university course may

be three and half years;

(iii) where two university courses or two courses

recognised as equivalent co-exist in a Member

State, and where one of these extends over four

years and the other over three years, the three-

year course leading to a diploma, certificate or

other evidence of formal qualifications awarded

on completion of a university course or its

recognised equivalent shall be considered to

fulfil the condition of duration referred to above,

in so far as the diplomas, certificates or other

evidence of formal qualifications awarded on

completion of both courses are recognised as

equivalent;

(b) the course shall include theoretical and practical study

on at least the following basic subjects

(i)

experimental physics;

(ii)

general and inorganic chemistry;

(iii)

organic chemistry;

(iv)

analytical chemistry;

(v)

pharmaceutical chemistry, including analysis of

medicinal products;

(vi)

general and applied biochemistry (medical);

(vii) physiology;

(viii) microbiology;

(ix) pharmacology;

(x)

pharmaceutical technology;

(xi)

toxicology;

(xii) pharmacognosy (study of the composition and

effects of the natural active substances of plants

and animal origin);

(c) studies in these subjects shall be so balanced as to

enable the qualified person to fulfil the obligations

specified in regulation 11;

(d) in those cases where diplomas, certificates or other

evidence of formal qualifications do not fulfil the

criteria above mentioned, the Authority shall ensure

that the person concerned provides evidence of

adequate knowledge of the subjects involved;

(e)

(i)

the qualified person shall have acquired

practical experience over at least two years, in

one or more undertakings which are authorised

to manufacture medicinal products, 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 medicinal

products;

(ii) 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.

(1) 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, in a scientific

discipline allowing him to perform the duties of a qualified person,

may, if he began his course prior to the 21st May, 1975, be

considered as qualified to carry out the duties of a qualified person,

provided that he was, for at least two years before the 21st May,

1985, engaged with one or more undertakings authorised to

manufacture, and as having carried out the duties of production

supervision and, or qualitative and quantitative analysis of active

substances, and the necessary testing and checking under the direct

authority of a qualified person in order to ensure the quality of the

medicinal products.

(2) If the person concerned has acquired the practical

experience referred to in subregulation (1) before the 21st May,

1965, a further one year’s practical experience in accordance with

the conditions referred to in subregulation (1) will be required to be

completed immediately before he engages in such activities.

(3) A person engaging in the activities of a qualified person

from the time of the application of Directive 75/319/EEC in a

Member State without complying with the provisions of regulation

9 shall be eligible to continue to engage in those activities within

the Community.

(1) The qualified person, without prejudice to his

relationship with the holder of the licence, shall be responsible to

ensure that

(a) each batch of medicinal products manufactured in

Malta has been manufactured and checked in terms of

the laws in force and is in accordance with the

requirements of the marketing authorisation;

(b) in the case of medicinal products coming from third

countries, irrespective of whether the product has been

manufactured in the Community, each production

batch has undergone in a Member State a full

qualitative analysis, a quantitative analysis of at least

all the active substances and all the other tests or

checks necessary to ensure the quality of the medicinal

product in accordance with the requirements of the

marketing authorisation

Provided that when the batches of medicinal products have

already undergone the controls above mentioned in a Member

State, they shall be exempt from further controls if they are

accompanied by the control reports signed by the qualified person,

and are marketed within the Community.

(2) The qualified person need not carry out the controls above

mentioned in the case of imported medicinal products, where

a r r a n g e m e n t s h a v e b e e n m a de b y t h e C o m m u n i t y w i t h t h e

exporting country to ensure that the manufacturer of the medicinal

products applies standards of good manufacturing practice at least

equivalent to those laid down by the Community, and to ensure that

the control s r eferred t o above have been carried o ut in t he

exporting country.

(3) The qualified person shall, in the case of medicinal

products intended to be placed on the market in the European

Union, ensure that the safety features referred to in regulation 3(o)

of the Medicinal Products (Labelling and Packaging) Regulations

have been affixed on the packaging.

With regard to quality control testing, carried out in parts of

the United Kingdom other than Northern Ireland, regarding

medicinal products included in the list referred to in regulation 5A

of the Medicines (Marketing Authorisation) Regulations other than

those authorised by the Commission, until the 31st December 2024,

the Licensing Authority, may consider there is a justifiable case

within the meaning of regulation 11(1)(b), without carrying out a

case-by-case assessment provided that

(a) each batch of the medicinal products concerned is

released by a qualified person on a site in the Union or

in Northern Ireland or by a qualified person on a site in

parts of the United Kingdom other than Northern

Ireland applying quality standards that are equivalent

to those laid down in regulation 11;

(b) the establishment designated by the third party

conducting the quality control testing is supervised by

the competent authority of the United Kingdom,

including by performing on-the-spot checks;

(c) where the batch release is carried out by a qualified

person who resides and operates in parts of the United

Kingdom other than Northern Ireland, the

manufacturing authorisation holder declares that it

does not have at its disposal a qualified person who

resides and operates in the Union on the 20th April

2022.

By way of derogation from sub-regulations 1(a) and (b) of

regulation 3, until the 31st December 2024, the Licensing

Authority shall allow medicinal products to be imported from parts

of the United Kingdom other than Northern Ireland by holders of a

wholesale distribution authorisation as referred to in regulation 4 of

the Wholesale Distribution and Brokering of Medicinal Products

and Active Substances Regulations, that are not in possession of a

relevant manufacturing authorisation provided that all of the

following conditions are fulfilled

(a)

the medicinal products have undergone quality

control testing, either in the Union, as provided for in regulation

12 or in parts of the United Kingdom other than Northern

Ireland in compliance with regulation 11(1)(b);

(b)

the medicinal products have been subject to batch

release by a qualified person in the Union in accordance with

regulation 11(1) or, for medicinal products authorised by the

Licensing Authority and the United Kingdom in respect of

Northern Ireland, in parts of the United Kingdom other than

Northern Ireland applying quality standards that are equivalent to

those laid down in regulation 11(1);

(c)

the marketing authorisation for the medicinal

product concerned has been granted in accordance with Union

law, by the competent authority of a Member State or by the

Commission or, as regards medicinal products placed on the

market in Northern Ireland, by the competent authority of the

United Kingdom in respect of Northern Ireland;

(d)

medicinal products are only made available to

patients or end-consumers in Malta;

(e)

the medicinal products bear the safety features

referred to in regulation 3(o) of the Medicinal Products

(Labelling and Packaging) Regulations.

For batches of medicinal products exported to parts of the

United Kingdom other than Northern Ireland from a Member State

and subsequently imported into Malta until the 31st December

2 0 24 t he c o nt r o ls u p o n i m p or t a t i o n r e f e rr e d t o i n th e su b -

regulations (1) and (2) of regulation 11, shall not be required,

provided that those batches have undergone such controls in a

Member State prior to being exported to parts of the United

Kingdom other than Northern Ireland and that they are

accompanied by the control reports referred to in the said

regulation.

Where the manufacturing authorisation is granted by the

competent authority of the United Kingdom in respect of Northern

Ireland, the qualified person referred to regulation 11(1) may reside and

operate in parts of the United Kingdom other than Northern Ireland,

unless the manufacturing authorisation holder already has at its disposal

a qualified person who resides and operates in the Union on 20 April

2022.

(1) It shall be the duty of the qualified person to keep a

register to document and certify that each production batch satisfies

the provisions of these regulations.

(2) The said register shall be kept up to date as operations are

carried out and must be made available for inspection by the

Authority for at least five years.

Any breaches of

(a) regulations 3 and 3A shall be an offence and shall be

liable to penalties under article 99(1)(a) of the Act;

(b) regulations 7 and 8 shall be an offence and shall be

liable to penalties under article 99(1)(b) of the Act;

(c) regulations 11 and 12 shall be an offence and shall be

liable to penalties under article 99(1)(c) of the Act.