S.I. No. 539 of 2007

MEDICINAL PRODUCTS (CONTROL OF MANUFACTURE) REGULATIONS 2007

ARRANGEMENT OF REGULATIONS

1. Citation

2. Commencement

3. Interpretation

4. Requirement for authorisation to manufacture medicinal products (including investigational medicinal products)

5. Exemptions

6. Application for a manufacturer�s authorisation

7. Consideration of an application for a manufacturer�s authorisation

8. Grant or refusal of manufacturer�s authorisation

9. Application and effect of manufacturer�s authorisation

10. Obligations of manufacturers of medicinal products

11. Variation of manufacturer�s authorisation

12. Suspension and revocation of manufacturer�s authorisation

13. Qualified person

14. Particular enforcement obligations

15. Transitional provisions

16. Revocations and amendments

SCHEDULES

1.

Particulars that must accompany an application for a manufacturer�s authorisation

2.

Requirements to be met by an authorisation holder manufacturing medicinal products

3.

Requirements to be met by an authorisation holder importing medicinal products from a third country

4.

Procedural provisions relating to proposals to grant subject to the carrying out of certain obligations, proposals to grant otherwise than in accordance with the application, proposals to refuse to grant or vary, proposals to make the authorisation conditional on the carrying out of certain obligations, and proposals to suspend, vary or revoke a manufacturer�s authorisation

5.

Requirements applicable to qualified persons.

S.I. No. 539 of 2007

MEDICINAL PRODUCTS (CONTROL OF MANUFACTURE) REGULATIONS 2007

Notice of the making of this Statutory Instrument was published in

�Iris Oifigi�il� of 31st July, 2007.

The Minister for Health and Children, in exercise of the powers conferred on her by section 32 of the Irish Medicines Board Act 1995 (No. 29 of 1995), as amended by section 16 of the Irish Medicines Board (Miscellaneous Provisions) Act 2006 (No. 3 of 2006) and as adapted by the Health (Alteration of Name of Department and Title of Minister) Order 1997 ( S.I. No. 308 of 1997 ) and including for the purpose of giving effect to Title IV of Directive 2001/83/EC (as amended by Directive 2004/27/EC), Article 13 of Directive 2001/20/EC ¹ and Chapter 3 of Commission Directive 2005/28/EC ² , hereby make the following regulations-

Citation.

1. These Regulations may be cited as the Medicinal Products (Control of Manufacture) Regulations 2007.

Commencement.

2. These Regulations shall come into force on 23rd July 2007.

Interpretation.

3. (1) In these Regulations-

�Act� means the Irish Medicines Board Act 1995 as amended by the Irish Medicines Board (Miscellaneous Provisions) Act 2006 and by the European Communities (Amendment of the Irish Medicines Board Act 1995 ) Regulations 2007 ( S.I. No. 542 of 2007 );

�authorisation holder� means the holder of a manufacturer�s authorisation;

�authorised medicinal product� means a medicinal product which is the subject of a marketing authorisation, certificate of registration or certificate of traditional-use registration;

�authorised officer� has the meaning assigned to it in section 32A of the Act;

�batch� means a quantity which is homogeneous in character and quality, produced during a given cycle of manufacture;

�Board� means the Irish Medicines Board established by section 3 of the Irish Medicines Board Act 1995 ;

�certificate of registration� means a certificate of registration which is for the time being in force and which has been granted by the Board under the Medicinal Product (Control of Placing on the Market) Regulations 2007 in respect of a homeopathic medicinal product that satisfies the conditions specified in Article 14(1) of the 2001 Directive;

�certificate of traditional-use registration� means a certificate of traditional-use registration which is for the time being in force and which has been granted by the Board under the Medicinal Products (Control of Placing on the Market) Regulations 2007 in respect of a traditional herbal medicinal product;

�Commission� means the Commission of the European Community;

�Community� means the European Community;

�2001 Directive� means Directive 2001/83/EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use ³ as amended by-

(a) Directive 2002/98/EC of the European Parliament and of the Council setting standards of quality and safety for the collection, testing, processing, storage and distribution of human blood and blood components ⁴ ,

(b) Commission Directive 2003/63/EC amending Directive 2001/83/EC on the Community code relating to medicinal products for human use ⁵ ,

(c) Directive 2004/24/EC of the European Parliament and of the Council amending, as regards traditional herbal medicinal products, Directive 2001/83/EC on the Community code relating to medicinal products for human use ⁶ , and

(d) Directive 2004/27/EC of the European Parliament and of the Council amending Directive 2001/83/EC on the Community code relating to medicinal products for human use ⁷ ;

�dispensing pharmacy� means a shop being lawfully kept open for the dispensing or compounding of medical prescriptions under the Pharmacy Acts 1875 to 1977 and includes the pharmaceutical department of a hospital;

�EEA Agreement� means the Agreement on the European Economic Area signed in Oporto on 2 May 1992 as adjusted by the Protocol to that Agreement done at Brussels on 17 March 1993 ⁸ ;

�EEA State� means a State, which is a contracting party to the EEA Agreement;

�European Economic Area� means the European Economic Area created by the EEA Agreement;

�exempt medicinal product� means a medicinal product to which paragraph 2 of Schedule 1 to the Medicinal Products (Control of Placing on the Market) Regulations 2007, or any equivalent legislation in any EEA State other than the State, applies;

�export� means exportation to a third country;

�GMP Directive� means Commission Directive 2003/94/EC ⁹ of 8 October 2003 laying down the principles and guidelines of good manufacturing practice in respect of medicinal products for human use and investigational medicinal products for human use;

�herbal medicinal product� means any medicinal product, exclusively containing as active ingredients one or more herbal substances or one or more herbal preparations, or one or more such herbal substances in combination with one or more such herbal preparations;

�herbal preparations� mean preparations obtained by subjecting herbal substances to treatments such as extraction, distillation, expression, fractionation, purification, concentration or fermentation. These include comminuted or powdered herbal substances, tinctures, extracts, essential oils, expressed juices and processed exudates;

�herbal substances� mean all mainly whole, fragmented or cut plants, plant parts, algae, fungi, lichen in an unprocessed, usually dried, form, but sometimes fresh. Certain exudates that have not been subjected to a specific treatment are also considered to be herbal substances. Herbal substances are precisely defined by the plant part used and the botanical name according to the binomial system (genus, species, variety and author);

�homeopathic medicinal product� means any medicinal product, which may contain a number of principles, 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 an EEA State. The term also includes anthroposophic medicinal products described in an official pharmacopoeia and prepared by a homeopathic method;

�import� means importation from a third country;

�investigational medicinal product� means a pharmaceutical form of an active substance or placebo being tested or used as a reference in a clinical trial, including a medicinal product that is already the subject of a marketing authorisation, but-

(a) is used, formulated or packaged in a way different from the form that is the subject of the authorisation,

(b) is used for an indication that is not included in the summary of product characteristics under the authorisation for the product, or

(c) is used to gain further information about the form of the product that is the subject of the authorisation;

�manufacture� includes total and partial manufacture, and the various processes of dividing up, packaging and presentation;

�manufacturer�s authorisation� means an authorisation which is for the time being in force and which has been granted by the Board in pursuance of Regulation 8;

�marketing authorisation� means an authorisation which is for the time being in force and which has been granted by the Board under the Medicinal Products (Control of Placing on the Market) Regulations 2007 or by the Commission under Regulation (EEC) No. 2309/93 ¹⁰ or Regulation (EC) No 726/2004 ¹¹ and includes a marketing authorisation issued by the competent authority of an EEA State, other than the State, in accordance with the 2001 Directive;

�medicinal product� includes an investigational medicinal product;

�Minister� means the Minister for Health and Children;

�pharmacist� means a registered pharmaceutical chemist or a registered dispensing chemist and druggist, under the Pharmacy Acts 1875 to 1977;

�qualified person� means-

(a) a person with the qualifications and experience specified in Schedule 5, and named in the manufacturer�s authorisation as being responsible at the manufacturer�s premises for the functions set out in Regulation 13(3), or

(b) insofar as the activities of the qualified person are limited to traditional herbal medicinal products, a person who-

(i) on the date of coming into force of these Regulations, without satisfying the requirements referred to in paragraph (a), has been engaged in activities equivalent to those that are to be performed under Regulation 13(3) in respect of traditional herbal medicinal products, and

(ii) is named in the manufacturer�s authorisation as being responsible at the manufacturer�s premises for the functions set out in Regulation 13(3) in respect of traditional herbal medicinal products;

or

(c) insofar as the activities of the qualified person are limited to investigational medicinal products, a person who, without satisfying the requirements referred to in paragraph (a), has been engaged in activities equivalent to those to be performed in accordance with Regulation 13(3) in respect of such products for a period of at least one year prior to 1 May 2004.

�Radiological Protection Institute of Ireland� means the body established under section 6 of the Radiological Protection Act, 1991 (No. 9 of 1991);

�registered dentist� means a person registered in the register established under the Dentists Act 1985 (No. 9 of 1985);

�registered medical practitioner� means a person registered in the register established under the Medical Practitioners Act 1978 (No. 4 of 1978);

�sale by wholesale� means sale or supply for the purposes of sale in the course of a business or for administration to patients in the course of a professional practice and cognate words shall be construed accordingly. Such term shall also include all activities consisting of the procuring, holding or exporting of medicinal products other than activities involving the sale or supply of such products to the public;

�third country� means a country which is not an EEA State;

�traditional herbal medicinal product� means a herbal medicinal product that satisfies the conditions specified in Article 16a of the 2001 Directive;

�wholesaler�s authorisation� means an authorisation granted and in force in pursuance of Regulation 9 of the Medicinal Products (Control of Wholesale Distribution) Regulations 2007 ( S.I. No. 538 of 2007 ).

(2) In these Regulations, unless the context otherwise requires-

(a) any reference to a Regulation or Schedule shall be construed as a reference to a Regulation contained in these Regulations or, as the case may be, to a Schedule thereto,

(b) any reference in a Regulation, or a Schedule, to a paragraph shall be construed as a reference to a paragraph in that Regulation or Schedule,

(c) any reference in a paragraph to a sub-paragraph shall be construed as a reference to a sub-paragraph in that paragraph, and

(d) any reference in a sub-paragraph to a clause shall be construed as a reference to a clause in that sub-paragraph.

(3) A word or expression which is used in these Regulations and which is also used in the 2001 Directive has, unless the context otherwise requires, the same meaning in these Regulations as it has in that Directive.

Requirement for authorisation to manufacture medicinal products (including investigational medicinal products)

4. Subject to the provisions of these Regulations, a person shall not

(a) manufacture for supply in the EEA,

(b) manufacture for export, or

(c) import.

any medicinal product unless he or she is the holder of a manufacturer�s authorisation.

Exemptions.

5. (1) The provisions of Regulation 4 shall not apply to-

(a) the extemporaneous manufacture of a medicinal product in response to a bona fide unsolicited order to fulfil a special need and which is carried out-

(i) in a dispensing pharmacy by or under the personal supervision of a pharmacist

- in accordance with the specifications of a registered medical practitioner or registered dentist for use by his or her individual patients on his or her direct personal responsibility, or

- for the purpose of maintaining a stock of a medicinal product for dispensing exclusively in such pharmacy to meet the orders of the aforementioned registered medical practitioner or registered dentist, or

- in accordance with the prescriptions of a pharmacopoeia for supply to patients attending that pharmacy,

or

(ii) by or under the personal supervision of a registered medical practitioner or a registered dentist for the treatment of one of his or her patients on his or her direct personal responsibility,

and, provided in each case that the medicinal product concerned is not the subject of any advertisement or representation and that no other medicinal product of appropriate composition, that is the subject of a marketing authorisation, is available for use in the circumstances.

(b) the preparation, dividing up, changes in packaging or in the presentation of a medicinal product, where these processes are carried out-

(i) in a dispensing pharmacy by or under the personal supervision of a pharmacist, for supply in or from such pharmacy, or

(ii) by a registered medical practitioner or registered dentist for supply to a patient under his or her care.

(c) a herbal medicinal product that is not industrially produced or manufactured by a method involving an industrial process and the medicinal product so produced is supplied without any written recommendations as to its use and under a designation which specifies only its composition and no other name is applied to the product. For the purposes of this provision, the process that consists only of the drying, crushing or comminuting of herbal plants for use in the production of such herbal medicinal products as aforesaid, shall not be considered as an industrial process.

(d) a homeopathic medicinal product that is not industrially produced or manufactured by a method involving an industrial process and the medicinal product so produced is supplied without any written recommendations as to its use and under a designation which specifies only its composition and no other name is applied to the product. For the purposes of this provision, the process that consists of dilution and succussion or potentisation of homeopathic stocks, for individual patients as part of his or her treatment, shall not be considered as an industrial process.

(e) a medicinal product that is a radiopharmaceutical and which is prepared, at the time at which it is intended to be administered, by or under the responsibility of the person by whom it is to be administered, in accordance with the manufacturer's instructions, exclusively from a kit, generator or precursor (or from more than one of these) in respect of which a marketing authorisation is in force and in an establishment that is licensed by the Radiological Protection Institute of Ireland to use such medicinal products.

(2) In this Regulation:

�generator� means any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and is to be used in a radiopharmaceutical;

�kit� means any product to be reconstituted or combined with radionuclides in a final radiopharmaceutical, usually prior to administration;

�precursor� means a radionuclide produced for the radio-labelling of another substance prior to its administration, other than a radionuclide which is incorporated in or produced from a generator or is included in a radiopharmaceutical;

�radiopharmaceutical� means any medicinal product which, when ready for use, contains one or more radionuclides intended for a medicinal purpose.

(3) Nothing in these Regulations shall permit the handling of a medicinal product which is a radiopharmaceutical, in contravention of the provisions of the Radiological Protection Act, 1991 (Ionising Radiation) Order, 2000 ( S.I. No. 125 of 2000 ) or the administration of any such product in contravention of the provisions of the European Communities (Medical Ionising Radiation Protection) Regulations, 2002 ( S.I. No. 478 of 2002 ).

Application for a manufacturer�s authorisation.

6. (1) An application for the grant of a manufacturer�s authorisation shall-

(a) be made in writing to the Board; and

(b) be signed by or on behalf of the applicant, whether in ink or by means of an electronic signature.

(2) Every application for the grant of a manufacturer�s authorisation shall be accompanied by-

(a) the particulars specified in Schedule 1 to these Regulations;

(b) a written undertaking that in the event of the authorisation being granted, the applicant will ensure fulfillment of the obligations arising by virtue of the terms and conditions of the authorisation, and

(c) any fee which may be payable in connection with that application.

Consideration of application for a manufacturer�s authorisation.

7. (1) Subject to the provisions of this Regulation, the Board shall consider a valid application for a manufacturer�s authorisation and grant or refuse to grant an authorisation within a period not exceeding 90 days from the date the application is received.

(2) Following receipt of an application, the Board shall, by means of inspection or otherwise, confirm the accuracy of the particulars provided in the application as referred to in Regulation 6(2) and may give a notice in writing to the applicant requesting him or her to provide further information relating to the said particulars.

(3) Where the Board gives a notice pursuant to paragraph (2), the period specified in paragraph (1) shall be suspended from the date the notice is given and shall recommence only on receipt of the information requested.

(4) The expiry of the period of 90 days referred to in paragraph (1) shall not be taken to mean that an implicit manufacturer�s authorisation has been granted.

(5) In this Regulation, �valid application� means an application, which complies with the provisions of Regulation 6.

Grant or refusal of a manufacturer�s authorisation.

8. (1) The Board shall grant a manufacturer�s authorisation only if-

(a) the applicant-

(i) has complied with the requirements of Regulation 6,

(ii) has at his or her disposal suitable and sufficient premises, equipment and facilities,

(iii) has appropriate and sufficient staff including a qualified person,

(iv) if a notice has been given under Regulation 7(2), has provided the information requested by the Board; and

(b) it has established that the particulars supplied pursuant to Regulation 6(2) are accurate.

(2) Subject to paragraph (1), the Board may grant a manufacturer�s authorisation in respect of any or all of-

(a) the medicinal products and pharmaceutical forms,

(b) the premises, and

(c) the manufacturing or importation operations,

specified in the application made pursuant to Regulation 6.

(3) Subject to paragraph (1), the Board may-

(a) grant a manufacturer�s authorisation in accordance with the application,

(b) grant a manufacturer�s authorisation in accordance with the application, but subject to the carrying out of certain obligations by the authorisation holder,

(c) grant a manufacturer�s authorisation otherwise than in accordance with the application, or

(d) refuse to grant a manufacturer�s authorisation.

(4) The provisions of Schedule 4 shall have effect where the Board-

(a) proposes to grant a manufacturer�s authorisation in accordance with the application, but subject to the carrying out of certain obligations by the authorisation holder,

(b) proposes to grant a manufacturer�s authorisation otherwise than in accordance with the application, or

(c) proposes to refuse to grant a manufacturer�s authorisation.

(5) Where the Board-

(a) grants a manufacturer�s authorisation in accordance with the application, but subject to the carrying out of certain obligations by the authorisation holder,

(b) grants a manufacturer�s authorisation otherwise than in accordance with the application, or

(c) refuses to grant a manufacturer�s authorisation,

the Board shall give the applicant a notice in writing stating in detail the reasons on which its decision is based.

Application and effect of manufacturer�s authorisation.

9. A manufacturer�s authorisation shall apply only in relation to-

(a) the medicinal products and pharmaceutical forms,

(b) the manufacturing or importation operations, and

(c) the premises,

specified in the application made pursuant to Regulation 6 and in respect of which the authorisation has been granted.

Obligations of manufacturers of medicinal products.

10. (1) Subject to the provisions of these Regulations, an authorisation holder shall not-

(a) manufacture for supply in the EEA, or for export, any medicinal product except in accordance with the requirements set down in Schedule 2, and the principles and guidelines of good manufacturing practice, set down in the GMP Directive, or

(b) import any medicinal product except in accordance with the requirements set down in Schedule 3, and the principles and guidelines of good manufacturing practice set down in the GMP Directive, insofar as those principles and guidelines are applicable to such importation.

(2) An authorisation holder shall comply with the terms of the authorisation and any further conditions or obligations as may be imposed in the authorisation.

Variation of manufacturer�s authorisation.

11. (1) The Board may vary a manufacturer�s authorisation, whether on the application of the authorisation holder or otherwise.

(2) Subject to the following provisions of this Regulation, if the authorisation holder makes a valid application to vary the manufacturer�s authorisation, the Board shall consider the application and-

(a) in a case where the effect of the variation would be to change the-

(i) medicinal products or pharmaceutical forms,

(ii) the premises or equipment, or

(iii) the manufacture, control or storage facilities,

in respect of which the authorisation has been granted, may vary or refuse to vary the authorisation within a period not exceeding 30 days from the date the application is received;

(b) in any other case, may vary or refuse to vary the authorisation within such period as the Board considers appropriate, being a period not exceeding 60 days.

(3) If the application falls within paragraph (2)(a), but it appears to the Board to be necessary to conduct an inspection of any premises to which the variation relates, the Board may vary or refuse to vary the authorisation within a period not exceeding 90 days from the date the application is received.

(4) Following receipt of a valid application to vary a manufacturer�s authorisation, the Board may give a notice in writing to the applicant requesting him or her to provide further information relating to the contents of the application or any particulars relevant to the application.

(5) Where the Board gives a notice pursuant to paragraph (4), and a period specified in paragraph (2) or paragraph (3) applies, that period shall be suspended from the date the notice is given and shall recommence only on receipt of the information requested.

(6) The Board may vary a manufacturer�s authorisation where it considers it necessary to do so for the purpose of securing compliance with the 2001 Directive, or in the case of an authorisation relating to an investigational medicinal product, Directive 2001/20/EC ¹² , and the Board may make a manufacturer�s authorisation conditional on the carrying out of certain obligations.

(7) The provisions of Schedule 4 shall have effect where the Board-

(a) proposes to vary a manufacturer�s authorisation, otherwise than in accordance with a valid application by the authorisation holder;

(b) proposes to make a manufacturer�s authorisation conditional on the carrying out of certain obligations by the authorisation holder, or

(c) proposes to refuse to vary a manufacturer�s authorisation, after consideration of the application of the holder.

(8) Where the Board-

(a) varies a manufacturer�s authorisation, otherwise than in accordance with a valid application by the authorisation holder; or

(b) makes a manufacturer�s authorisation conditional on the carrying out of certain obligations by the authorisation holder, or

(c) after consideration of the application of the holder, refuses to vary a manufacturer�s authorisation,

the Board shall notify the holder of that authorisation in writing, stating in detail the reasons on which its decision is based.

(9) In this Regulation, �valid application� means an application-

(a) made to the Board in writing and signed by or on behalf of the applicant, whether in ink or by means of an electronic signature;

(b) specifying the variation requested by the applicant;

(c) accompanied by-

(i) such particulars and supporting documentation as are necessary to enable the Board to consider the application, and

(ii) any fee which may be payable in connection with that application.

Suspension and revocation of manufacturer�s authorisation.

12. (1) The Board may by a notice in writing to the authorisation holder, forthwith or from a date specified in the notice, suspend the authorisation for such period as the Board may determine, or revoke the authorisation, on one or more of the following grounds-

(a) the holder is not carrying out, or has indicated by a notice in writing that he or she is no longer to carry out, the manufacturing or importation operations to which the authorisation relates;

(b) the matters specified in the application in accordance with Regulation 6(2), were false or incomplete in a material particular;

(c) a material change of circumstances has occurred in relation to any of those matters or particulars;

(d) the authorisation holder has failed to any material extent to comply with his or her obligations under Regulation 10;

(e) the holder has manufactured or imported medicinal products otherwise than in accordance with the terms of the authorisation;

(f) the authorisation holder does not have the staff, premises, equipment or facilities necessary for carrying out properly the handling, storage or distribution activities to which the authorisation relates, and

(g) the authorisation holder has failed to carry out an obligation imposed by the Board pursuant to Regulation 8(3)(b) or Regulation 11(6).

(2) The suspension or revocation of a manufacturer�s authorisation under this Regulation may be-

(a) total; or

(b) limited to medicinal products-

(i) of one or more descriptions, or

(ii) manufactured, handled, stored or distributed at or from any particular premises or particular part of any premises.

(3) The provisions of Schedule 4 shall have effect where the Board proposes to suspend or revoke a manufacturer�s authorisation in accordance with this Regulation.

(4) Where the Board suspends or revokes a manufacturer�s authorisation in accordance with this Regulation, it shall notify the authorisation holder in writing, stating in detail the reasons on which its decision to suspend or revoke the authorisation is based.

Qualified Person.

13. (1) The authorisation holder shall have permanently and continuously at his disposal the services of at least one qualified person.

(2) If the authorisation holder personally fulfils the requirements set down in respect of a qualified person, the holder may himself act as the qualified person.

(3) The functions of the qualified person shall be-

(a) in the case of medicinal products, other than investigational medicinal products and products to which sub-paragraph (b) refers, to ensure that every batch of a medicinal product to which the authorisation relates has been manufactured and checked in compliance with-

(i) the laws in force in the State in respect of such product,

(ii) the provisions of the manufacturer�s authorisation, and

(iii) the provisions of the marketing authorisation, certificate of registration, certificate of traditional-use registration or other standard which relates to the said product;

(b) in the case of medicinal products that have been imported by the authorisation holder, other than investigational medicinal products, to ensure that every batch of such products has undergone a full qualitative analysis, a quantitative analysis of at least all of the active ingredients and all other tests or checks necessary to ensure that the quality of the medicinal products is in accordance with the requirements of the relevant marketing authorisation, certificate of registration or certificate of traditional-use registration;

(c) in the case of investigational medicinal products, other than investigational medicinal products to which either of sub-paragraphs (d) or (e) refers, to ensure that every batch of a medicinal product has been manufactured and checked in compliance with the requirements of the GMP Directive, the product specification file and the information notified to the Board pursuant to Regulation 15 of the European Communities (Clinical Trials on Medicinal Products for Human Use) Regulations 2004 ( S.I. No. 190 of 2004 ) (as amended);

(d) in the case of investigational medicinal products manufactured in a third country, to ensure that each production batch has been manufactured and checked in accordance with standards of good manufacturing practice at least equivalent to those laid down in the GMP Directive, in accordance with the product specification file, and that each production batch has been checked in accordance with the information notified to the Board pursuant to Regulation 15 of the European Communities (Clinical Trials on Medicinal Products for Human Use) Regulations 2004;

(e) in the case of an investigational medicinal product which is a comparator product from a third country, and which is the subject of a marketing authorisation, where the documentation certifying that each production batch has been manufactured in conditions at least equivalent to the standards of good manufacturing practice referred to above cannot be obtained, to ensure that each production batch has undergone all relevant analyses, tests or checks necessary to confirm its quality in accordance with the information notified to the Board pursuant to Regulation 15 of the European Communities (Clinical Trials on Medicinal Products for Human Use) Regulations 2004 (as amended);

(f) in all cases, to certify in a register, or other equivalent document appropriate for the purpose, whether each production batch of the medicinal product to which the authorisation relates satisfies the requirements set out in sub-paragraphs (a), (b), (c), (d) or (e) and to ensure that such register or other document is regularly maintained and in particular that the appropriate entries in such register or other document are made as soon as practicable after each such batch has been manufactured or imported.

(4) (i) Except in the case of investigational medicinal products, the batches of medicinal products which have undergone the controls referred to in paragraph (3) in another EEA State shall be exempt from such controls if they are marketed in the State, accompanied by the control reports signed by the qualified person.

(ii) In the case of investigational medicinal products, the batches of medicinal products which have undergone the controls referred to in paragraph (3) in another EEA State shall be exempt from such controls if they are imported into the State, accompanied by the batch release certificates signed by the qualified person.

(5) In the case of medicinal products imported from a third country, where appropriate arrangements, in the form of a Mutual Recognition Agreement, have been made by the Community with that country, ensuring that the manufacturer of the medicinal product applies standards of good manufacturing practice at least equivalent to those laid down by the Community, and ensuring that the controls referred to in paragraph (3)(b) have been carried out in the exporting country, the qualified person shall be relieved of responsibility for carrying out those controls.

(6) Where, after giving the authorisation holder and the person acting as the qualified person the opportunity of making representations (either orally or in writing), the Board is of the opinion that the person so acting is failing to carry out the functions specified in paragraph (3) and has notified the authorisation holder accordingly in writing, the holder shall not permit that person to continue to act as the qualified person so long as the said notification has not been withdrawn by the Board.

(7) The Board may require the authorisation holder temporarily to suspend the person acting as such qualified person upon the commencement of administrative or disciplinary proceedings against him or her for failure to fulfil his or her functions as required under paragraph (3) and the authorisation holder shall not permit that person to act as the qualified person pending the determination of such proceedings. However, nothing in this paragraph shall affect the right of the qualified person pursuant to his or her contract of employment to receive full pay during the period of any such suspension.

(8) The authorisation holder shall not be required to comply with the requirements of this regulation in relation to any activity carried out in pursuance of his or her authorisation and which consists of the manufacture or import of a medicinal product pursuant to his or her manufacturer's licence insofar as such activity is limited to the manufacture or importation of a medicinal product which-

(a) is an exempt medicinal product, or

(b) may be placed on the market in any EEA State without a marketing authorisation by virtue of legislation adopted by that State under Article 5.2 of the 2001 Directive.

Particular Enforcement Obligations.

14. Whether acting through authorised officers appointed under section 32B of the Act or in any other way, and without prejudice to the generality of the provisions of the Act, the Board shall in particular investigate the following:

(a) that all manufacturers and importers of medicinal products have obtained an authorisation pursuant to an application under Regulation 6,

(b) that manufacturers and importers of medicinal products are complying with the terms and conditions of any such authorisation,

(c) that the manufacturer or importer has at his or her disposal the qualified person specified in the application (or another qualified person which has been approved by the Board) and that such qualified person meets the requirements set down in in respect of such person and is fulfilling the obligations imposed on qualified persons pursuant to Regulation 13, and

(d) that the manufacturer or importer is complying with his or her obligations pursuant to Regulation 10.

Transitional provisions.

15. (1) Subject to paragraph (2), any manufacturer�s licence granted under-

(a) Regulation 7(1) of the Medical Preparations (Licensing of Manufacture) Regulations 1993 (as amended) or

(b) Regulation 33 of the European Communities (Clinical Trials on Medicinal Products for Human Use) Regulations 2004,

and in force on the coming into force of these Regulations, shall continue in force until the date of expiry of such licence, as if granted under these Regulations.

(2) The holders of the licences referred to in paragraph (1) shall make application for a manufacturer�s authorisation under Regulation 6, not later than three months before the date on which the said manufacturer�s licence is due to expire and where such application has been made, the said licence shall continue in force pending the decision of the Board on that application.

(3) An application made in respect of the grant or renewal of a manufacturer�s licence under the Medical Preparations (Licensing of Manufacture) Regulations 1993, or under the European Communities (Clinical Trials on Medicinal Products for Human Use) Regulations 2004, and which has not been determined prior to the date of coming into force of these Regulations, shall be considered as if it were an application made under Regulation 6 of these Regulations. In all such cases, where the information provided in such applications is not sufficient, the Board may require that the applicant shall update his or her application to conform to the provisions of Regulation 6.

Revocations and amendments.

16. (1) The Medical Preparations (Licensing of Manufacture) Regulations 1993 ( S.I. No. 40 of 1993 ), the Medical Preparations (Licensing of Manufacture) Regulations 1993 (Amendment) Regulations 1993 ( S.I. No. 68 of 1993 ) and the Medical Preparations (Licensing of Manufacture) (Amendment) Regulations 1996 ( S.I. No. 42 of 1996 ) are hereby revoked.

(2) The European Communities (Clinical Trials on Medicinal Products for Human Use) Regulations 2004 are hereby amended-

(a) by the deletion therefrom of Part 6, and of Schedules 4, 5 and 6;

(b) in Regulation 4(1)-

(i) by deleting the definition of �qualified person�; and

(ii) by substituting the following definition for the definition of �manufacturing authorisation�:

�manufacturing authorisation� means a manufacturer�s authorisation which is for the time being in force and which has been granted by the Board in pursuance of Regulation 8 of the Medicinal Products (Control of Manufacture) Regulations 2007 ( S.I. No. 539 of 2007 );�;

(c) in Regulation 11(1), by deletion of the words �other than in accordance with the terms of any marketing authorisation in force in relation to the product concerned,�; and

(c) in Regulation 11(2), by substituting �Regulation 13(3) of the Medicinal Products (Control of Manufacture) Regulations 2007� for �Regulation 40�.

[Regulation 6(2)]

SCHEDULE 1 Particulars that must accompany an application for a manufacturer�s authorisation

1. The name and address of the applicant, and, where the applicant is not the proposed authorisation holder, the name and address of the proposed holder.

2. A statement setting out the medicinal products and the pharmaceutical forms to which the application relates.

3. A statement of the manufacturing, packaging, labelling or importation operations to which the authorisation is to relate, including a statement whether they include one or more of the following-

(a) the manufacture of medicinal products;

(b) the dividing up, packaging, labelling or presentation of medicinal products;

(c) the importation of medicinal products.

4. A statement, where relevant as in the case of viral or non-conventional agents� inactivation, of the manufacturing process.

5. (1) The address of each of the premises where the manufacturing, dividing up, packaging, labelling, presentation or importation operations to which the application relates, including any testing and controls associated with such activities, that are or are to be carried out.

(2) The address of each of the premises where the proposed authorisation holder proposes to store medicinal products or from which he or she proposes to distribute them.

(3) A statement indicating the equipment and facilities available at each of the premises referred to in sub-paragraphs (1) and (2), for storing the medicinal products on, and distributing them from or between, such premises.

(4) A separate statement in respect of each of the premises referred to in sub-paragraphs (1) and (2), of the manufacturing, dividing up, packaging, labelling, presentation or importation operations capable of being carried out at those premises with their existing facilities. Each statement shall specify the classes of medicinal products to which the operations are relevant.

(5) A separate statement in respect of each of the premises referred to in sub-paragraphs (1) and (2), of the equipment available at those premises for carrying out each stage of the manufacturing, dividing up, packaging, labelling, presentation or importation operations described in sub-paragraph (4).

(6) The information required under this paragraph may be supported by a copy of the relevant Site Master File, which shall contain information about the site and the operations being carried out on the site.

6. A statement of any manufacturing operations, other than those to which the manufacturing authorisation is to relate, that are carried on by the proposed authorisation holder on or near each of the premises referred to in paragraph 4, and of the substances or articles which are the subject of any such operation.

7. (1) The name and address and qualifications and experience of the qualified person who is to carry out the duties referred to in Regulation 13(3).

(2) In the case of an authorisation relating to manufacture, dividing up, packaging, labelling or presentation, the name and address and qualifications and experience of the production manager or other person whose duty it will be to supervise the production operations at each of the premises referred to in paragraph 5, and the name and function of the person to whom he or she is responsible.

(3) In the case of an authorisation relating to manufacture, dividing up, packaging, labelling or presentation-

(a) the name and degrees, diplomas or other qualifications and experience of the person to be in charge of quality control over all the premises referred to in paragraph 5;

(b) the extent of the authority to be delegated to him or her to reject unsatisfactory batches of medicinal products, and

(c) the name and function of the person to whom he or she is responsible.

8. A description of the arrangements for the identification and storage of materials and ingredients before and during manufacture and for the storage of medicinal products after their manufacture, dividing up, packaging, labelling, presentation or importation.

9. A description of the arrangements at each of the premises where the authorisation holder stores or proposes to store medicinal products for ensuring, so far as practicable, whether by maintaining records or other means, a satisfactory turn-over of stocks of medicinal products.

10. A description of the arrangements-

(a) for maintaining production or importation records;

(b) for maintaining records of analytical and other testing procedures applied in the course of manufacture, dividing up, packaging, labelling, presentation or importation for ensuring compliance of materials used in the manufacture of any medicinal products with the specification of such materials or medicinal products;

(c) for keeping reference and retention samples of materials used in the manufacture of any medicinal products and of the medicinal products; and

(d) for the withdrawal or recall from sale, supply or exportation of any medicinal product to which the authorisation relates, as may be required.

11. In this Schedule, the reference to medicinal products in paragraph 2 includes blood products, immunological products, cell therapy products, gene therapy products, biotechnology products, human or animal extracted products, herbal products, homeopathic products, radiopharmaceutical products and products containing chemical agents.

[Regulation 10(1)(a)]

SCHEDULE 2 Requirements to be met by an authorisation holder manufacturing medicinal products

1. In this Schedule, the term �marketing authorisation� includes a certificate of registration and a certificate of traditional-use registration.

2. The authorisation holder shall-

(a) provide and maintain such staff, premises, equipment and facilities as are necessary for the carrying out, in accordance with the terms of his or her authorisation and relevant marketing authorisation, of such stages of manufacture as are undertaken by him or her;

(b) not use for such purposes premises other than those specified in his or her authorisation or which may be approved in writing from time to time by the Board; and

(c) in the distribution of medicinal products, comply with the principles and guidelines on good distribution practice for medicinal products ¹³ published by the Commission under Article 84 of the 2001 Directive;

13 OJ No. C 63, 1.03.1994, p.4.

3. The authorisation holder shall-

(a) provide and maintain such staff, premises, installations and equipment for the handling, storage and distribution of medicinal products that he or she handles, stores or distributes under his or her authorisation as are necessary to maintain the quality of the medicinal products to which the authorisation relates; and

(b) not use for such purposes premises other than those specified in his or her authorisation or which may be approved in writing from time to time by the Board.

4. The authorisation holder shall conduct all manufacturing operations in such a way as to ensure that the medicinal products conform with the standards of strength, quality and purity applicable to them whether under the relevant marketing authorisation, or under any pharmacopoeial standard or other specification to which they may be manufactured.

5. The authorisation holder shall at all times provide and maintain such staff, premises, equipment and facilities as will enable the qualified person at his or her disposal pursuant to Regulation 13(1) to carry out the duties referred to in Regulation 13(3).

6. The authorisation holder shall give prior notice to the Board of any changes he or she may wish to make to any of the particulars supplied in his or her application made pursuant to Regulation 6 and Schedule 1.

7. The authorisation holder shall immediately inform the Board if the qualified person referred to in Regulation 13 is replaced unexpectedly.

8. The authorisation holder shall place the quality control system referred to in Article 11.1 of the GMP Directive under the authority of the person notified to the Board in accordance with paragraph 7(3) of Schedule 1.

9. The authorisation holder may use a contract laboratory pursuant to Article 11.2 of the GMP Directive if such laboratory and the person operating it has been approved by the Board.

10. The authorisation holder shall inform the Board-

(a) before making any material change in the premises, installations or equipment used under his authorisation, or in the operations for which they are used; and

(b) of any change that he or she proposes to make in the personnel named in his authorisation as respectively-

(i) responsible for supervising production operations; or

(ii) responsible for quality control of the medicinal products being manufactured, divided up, packaged, labelled or presented, including the person named as the qualified person for the purposes of Regulation 13.

11. (1) The authorisation holder shall-

(a) keep readily available for inspection by an authorised officer, the batch documentation pursuant to Article 9.1 of the GMP Directive; and

(b) permit the authorised officer to take copies or make extracts from such documentation.

(2) Such records shall be retained for at least one year after the expiry date of the batches to which they relate or at least 5 years from the date of certification, by the qualified person, as referred to in Regulation 13(3)(f), whichever is the longer period.

(3) In the case of investigational medicinal products, such records shall be retained for at least five years after completion or formal discontinuation of the last clinical trial in which the batch was used.

12. The authorisation holder shall maintain a system for recording and reviewing complaints concerning reported defects associated with any medicinal product to which his authorisation relates and of the outcome to any investigation carried out in respect of each such complaint.

13. The authorisation holder shall keep such documents as will facilitate the withdrawal or recall from sale, supply or exportation of any medicinal product to which the authorisation relates. Such documents shall be readily available for inspection by an authorised officer.

14. The authorisation holder shall keep an adequate sample of each batch and of each active constituent used in the manufacture of such medicinal product to which the authorisation relates, for the period which ends one year after the labelled expiry date of the product, and shall furnish on request by the Board a sufficient sample of each such batch for the purpose of any test, examination or analysis which may be requested by the Board.

15. The authorisation holder shall ensure that any tests for determining conformity with the standards and specifications applying to any product used in the manufacture of a medicinal product shall, except insofar as the specifications for that product otherwise provide, be applied to samples taken from the medicinal product after all manufacturing processes have been completed, or at such earlier stage(s) in the manufacture as may be required or approved in writing by the Board.

16. Except in the case of exempt medicinal products, the authorisation holder shall use as starting materials only active substances, which have been manufactured in accordance with the detailed guidelines on good manufacturing practice for starting materials.

17. For the purposes of paragraph 16, the 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) of Annex I of the 2001 Directive, 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.

18. The authorisation holder shall ensure that any human blood or blood component imported into the State and used by him or her as a starting material or as a raw material in the manufacture of a medicinal product shall meet the equivalent standards of quality and safety to those laid down in Commission Directive 2004/33/EC ¹⁴ , implementing Directive 2002/98/EC of the European Parliament and of the Council as regards certain technical requirements for blood and blood components.

14 OJ No. L.91, 30.3.2004, p.25.

19. The authorisation holder, who is not the holder of a marketing authorisation in respect of a medicinal product to which the authorisation relates, shall comply with any provisions of such authorisation which relate to the sale or supply of that medicinal product and shall, by means of a label or otherwise, communicate the particulars of such provisions as they relate to method of sale or supply or restriction as to sale or supply to any person to whom the authorisation holder sells or supplies that medicinal product.

20. (1) Subject to subparagraph (2), the authorisation holder shall not supply a medicinal product that is the subject of a marketing authorisation except to persons-

(a) who are themselves the holders of a wholesaler�s authorisation, or

(b) who are the holders of an authorisation granted by the competent authority of another EEA State authorising the wholesale distribution of those products, or

(c) who are authorised or entitled to lawfully supply the said medicinal product to the public, or

(d) who are lawfully entitled to administer the said medicinal product to patients in the course of a professional practice, or business as a hospital,

and, the supply of the said product is in conformity with the provisions of its relevant marketing authorisation.

(2) The provisions of this paragraph shall not apply to investigational medicinal products supplied in accordance with Regulation 11 of the European Communities (Clinical Trials on Medicinal Products for Human Use) Regulations 2004 (as amended).

21. The authorisation holder shall, in the distribution of authorised medicinal products to which his or her authorisation relates, within the limits of his or her responsibility as a distributor of such medicinal products, ensure appropriate and continued supplies of such products to the persons referred to in paragraph 20(c) and (d), so that the needs of patients in the State in respect of such products are covered.

22. (1) The authorisation holder, in making a sale by wholesale to persons referred to in paragraph 20(c) and (d), shall enclose with the medicinal product a document that makes it possible for such persons to ascertain:

- the date on which the sale took place,

- the name and pharmaceutical form of the product supplied,

- the quantity of the product supplied, and

- the name and address of the supplier and consignor.

(2) Such records shall be retained for at least 5 years from the date on which it was supplied and during that period shall be available for inspection by officers of the Board.

23. (1) Subject to subparagraph (2), the authorisation holder shall not sell by wholesale any medicinal product-

(a) other than a product to which the authorisation relates,

(b) unless there has been granted in respect of such product, a marketing authorisation which is for the time being in force, and

(c) unless the sale of such product is in conformity with the provisions of its marketing authorisation.

(2) Subparagraph (1)(b) and (c) shall not apply-

(a) until 30 April 2011, to the sale by wholesale of any traditional herbal medicinal product that was already on the market in the State, on the date of the coming into force of these Regulations;

(b) to the sale by wholesale of an exempt medicinal product;

(c) to the export to an EEA State, or supply for the purposes of such export, of a medicinal product which may be placed on the market in that State without a marketing authorisation by virtue of legislation adopted by that State under Article 5.2 of the 2001 Directive; and

(d) to investigational medicinal products supplied in accordance with Regulation 11 of the European Communities (Clinical Trials on Medicinal Products for Human Use) Regulations 2004 (as amended).

24. The authorisation holder shall supply such information as may be requested by the Board for the purposes of these Regulations about the medicinal products currently being manufactured and about the operations being carried out in relation to such manufacture.

25. The authorisation holder shall for the purpose of enabling the Board-

(a) to verify any statement contained in an application for a manufacturer�s authorisation or marketing authorisation, or

(b) to ascertain whether there are any grounds for suspending, revoking or amending any such authorisation,

permit, and provide all necessary facilities to enable, authorised officers to enter and inspect his or her premises at any time and to take such samples or to take copies of any documents in relation to any such application or authorisation as may be required.

26. The authorisation holder shall from time to time permit such inspection and make available such information as may be required to satisfy the Board that the conditions of the authorisation are being complied with.

27. Where the authorisation holder has been informed by the Board that any part of a batch of a medicinal product to which his authorisation relates has been found not to conform as regards strength, quality or purity with the specifications of the relevant product he or she shall, if so directed by the Board, immediately withhold the remainder of that batch from sale, supply or exportation and, insofar as may be practicable, immediately recall all supplies already sold, supplied or exported from that batch.

28. Where the authorisation holder has been informed by the Board that a medicinal product to which his or her authorisation relates has been found to give rise to concerns in regard to its safety or efficacy, he or she shall, if so directed by the Board, immediately withhold that product from sale, supply or exportation and, insofar as may be practicable, immediately recall all supplies of such product already sold, supplied or exported.

29. Where the authorisation holder has been informed by the Board that any batch of a medicinal product, or part thereof, to which his authorisation relates, has not been manufactured in accordance with the principles and guidelines of good manufacturing practice set out in the GMP Directive, he or she shall, if so requested by the Board, immediately withhold that product from sale, supply or exportation and, insofar as may be practicable, immediately recall all supplies of such product already sold, supplied or exported.

30. Where the authorisation holder decides for whatever reason to recall a particular batch of a medicinal product manufactured by him or her, or part thereof, he or she shall forthwith inform the Board of the decision to recall and of the reason for such recall.

31. Where the authorisation holder considers that there may be grounds for the recall, or for the imposition of an abnormal restriction on the supply of a particular medicinal product manufactured by him or her, or of a batch or part of batch thereof, he or she shall consult with the Board in relation to the action which may be considered appropriate in the circumstances.

[Regulation 10(1)(b)]

SCHEDULE 3 Requirements to be met by an authorisation holder importing medicinal products from a third country

1. In this Schedule, the term �marketing authorisation� includes a certificate of registration and a certificate of traditional-use registration.

2. The authorisation holder shall-

(a) provide and maintain such staff, premises, equipment and facilities as are necessary for the handling, control, storage and distribution of medicinal products which he or she handles, stores and distributes under his or her authorisation, as are necessary to maintain the quality of those medicinal products;

(b) not use for such purposes premises other than those specified in his or her authorisation or which may be approved in writing from time to time by the Board;

(c) at all times provide and maintain such staff, premises, equipment and facilities as will enable the qualified person at his or her disposal pursuant to Regulation 13(1) to carry out the duties referred to in Regulation 13(3);

(d) give prior notice to the Board of any changes he or she may wish to make to any of the particulars supplied in his or her application made pursuant to Regulation 6 and Schedule 1;

(e) immediately inform the Board if the qualified person referred to in Regulation 13 is replaced unexpectedly;

(f) inform the Board-

(i) before making any material change in the premises, installations or equipment used under his authorisation, or in the operations for which they are used; and

(ii) of any change that he or she proposes to make in the personnel named in his authorisation as responsible for quality control of the medicinal products being imported by him or her, including the person named as the qualified person for the purposes of Regulation 13;

(g) in his or her distribution of medicinal products, comply with the principles and guidelines on good distribution practice for medicinal products published by the Commission under Article 84 of the 2001 Directive.

3. (1) Subject to subparagraph (2), the authorisation holder shall not supply a medicinal product that is the subject of a marketing authorisation except to persons-

(a) who are themselves the holders of a wholesaler�s authorisation, or

(b) who are the holders of an authorisation granted by the competent authority of another EEA State authorising the wholesale distribution of those products, or

(c) who are authorised or entitled to lawfully supply the said medicinal product to the public, or

(d) who are lawfully entitled to administer the said medicinal product to patients in the course of a professional practice or business as a hospital,

and, the supply of the said product is in conformity with the provisions of its relevant marketing authorisation.

(2) The provisions of this paragraph shall not apply to investigational medicinal products supplied in accordance with Regulation 11 of the European Communities (Clinical Trials on Medicinal Products for Human Use) Regulations 2004 (as amended).

4. The authorisation holder shall, in the distribution of authorised medicinal products to which his or her authorisation relates, within the limits of his or her responsibility as a distributor of such medicinal products, ensure appropriate and continued supplies of such products to the persons referred to in paragraph 3(c) and (d), so that the needs of patients in the State in respect of such products are covered.

5. The authorisation holder shall place the quality control system referred to Article 11.1 of the GMP Directive under the authority of the person notified to the Board in accordance with paragraph 7(3) of Schedule 1.

6. The authorisation holder may use a contract laboratory pursuant to Article 11.2 of the GMP Directive, if such laboratory and the person operating it has been approved by the Board.

7. (1) The authorisation holder shall-

(a) keep readily available for inspection by an authorised officer, the batch documentation pursuant to Article 9.1 of the GMP Directive; and

(b) permit the authorised officer to take copies or make extracts from such documentation.

(2) Such records shall be retained for at least one year after the expiry date of the batches to which they relate or at least 5 years from the date of certification, by the qualified person, as referred to in Regulation 13(3)(f), whichever is the longer period.

(3) In the case of investigational medicinal products, such records shall be retained for at least five years after completion or formal discontinuation of the last clinical trial in which the batch was used.

8. The authorisation holder shall maintain a system for recording and reviewing complaints concerning reported defects associated with any medicinal product to which his authorisation relates and of the outcome to any investigation carried out in respect of each such complaint.

9. The authorisation holder shall keep such documents as will facilitate the withdrawal or recall from sale, supply or exportation of any medicinal product to which the authorisation relates. Such documents shall be readily available for inspection by an authorised officer.

10. The authorisation holder shall keep an adequate sample of each batch to which the authorisation relates, for the period which ends one year after the labelled expiry date of the product, and shall furnish on request by the Board a sufficient sample of each such batch for the purpose of any test, examination or analysis which may be requested by the Board.

11. The authorisation holder shall ensure that any tests for determining conformity with the standards and specifications applying to any product used in the manufacture of a medicinal product shall, except insofar as the specifications for that product otherwise provide, be applied to samples taken from the medicinal product after all manufacturing processes have been completed, or at such earlier stage(s) in the manufacture as may be required or approved in writing by the Board.

12. (1) Subject to subparagraph (2) and paragraph 25, the authorisation holder shall not sell by wholesale any medicinal product-

(a) other than a product to which the authorisation relates,

(b) unless there has been granted in respect of such product, a marketing authorisation which is for the time being in force, and

(c) unless the sale of such product is in conformity with the provisions of its marketing authorisation.

(2) Subparagraph (1)(b) and (c) shall not apply-

(a) until 30 April 2011, to the sale by wholesale of any traditional herbal medicinal product that was already on the market in the State, on the date of the coming into force of these Regulations;

(b) to the sale by wholesale of an exempt medicinal product;

(c) to the export to an EEA State, or supply for the purposes of such export, of a medicinal product which may be placed on the market in that State without a marketing authorisation by virtue of legislation adopted by that State under Article 5.2 of the 2001 Directive; and

(d) to investigational medicinal products supplied in accordance with Regulation 11 of the European Communities (Clinical Trials on Medicinal Products for Human Use) Regulations 2004 (as amended).

13. (1) The authorisation holder, in making a sale by wholesale to persons referred to in paragraph 3(c) and (d), shall enclose with the medicinal product a document that makes it possible for such persons to ascertain:

- the date on which the sale took place,

- the name and pharmaceutical form of the product supplied,

- the quantity of the product supplied, and

- the name and address of the supplier and consignor.

(2) Such records shall be retained for at least 5 years from the date on which it was supplied and during that period shall be available for inspection by officers of the Board.

14. The authorisation holder, who is not the holder of a marketing authorisation in respect of a medicinal product to which the authorisation relates, shall comply with any provisions of such authorisation which relate to the sale or supply of that medicinal product and shall, by means of a label or otherwise, communicate the particulars of such provisions as they relate to method of sale or supply or restriction as to sale or supply to any person to whom the authorisation holder sells or supplies that medicinal product.

15. The authorisation holder shall supply such information as may be requested by the Board for the purposes of these Regulations about the medicinal products being imported and about the operations being carried out in relation to such products.

16. The authorisation holder shall for the purpose of enabling the Board-

(a) to verify any statement contained in an application for a manufacturer�s authorisation or marketing authorisation, or

(b) to ascertain whether there are any grounds for suspending, revoking or amending any such authorisation,

permit, and provide all necessary facilities to enable, authorised officers to enter and inspect his or her premises at any time and to take such samples or to take copies of any documents in relation to any such application or authorisation, as may be required.

17. The authorisation holder shall from time to time permit such inspection and make available such information as may be required to satisfy the Board that the conditions of the authorisation are being complied with.

18. Where the authorisation holder has been informed by the Board that any part of a batch of a medicinal product to which his or her authorisation relates has been found not to conform as regards strength, quality or purity with the specifications of the relevant product, he or she shall, if so directed by the Board, immediately withhold the remainder of that batch from sale, supply or exportation and, insofar as may be practicable, immediately recall all supplies already sold, supplied or exported from that batch.

19. Where the authorisation holder has been informed by the Board that a medicinal product to which his or her authorisation relates has been found to give rise to concerns in regard to its safety or efficacy, he or she shall, if so directed by the Board, immediately withhold that product from sale, supply or exportation and, insofar as may be practicable, immediately recall all supplies of such product already sold, supplied or exported.

20. Where the authorisation holder has been informed by the Board that any batch of a medicinal product, or part thereof, to which his or her authorisation relates, has not been manufactured in accordance with the principles and guidelines of good manufacturing practice set out in the GMP Directive, he or she shall, if so requested by the Board, immediately withhold that product from sale, supply or exportation and, insofar as may be practicable, immediately recall all supplies of such product already sold, supplied or exported.

21. Where the authorisation holder decides for whatever reason to recall a particular batch of a medicinal product imported by him or her, or part thereof, he or she shall forthwith inform the Board of the decision to recall and of the reason for such recall.

22. Where the authorisation holder considers that there may be grounds for the recall, or for the imposition of an abnormal restriction on the supply of a particular medicinal product imported by him or her, or of a batch or part of batch thereof, he or she shall consult with the Board in relation to the action which may be considered appropriate in the circumstances.

23. The authorisation holder shall ensure that medicinal products (other than exempt medicinal products) imported by him or her, use as starting materials only active substances, which have been manufactured in accordance with the detailed guidelines on good manufacturing practice for starting materials.

24. For the purposes of paragraph 23, the 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) of Annex I of the 2001 Directive, 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.

25. (1) Where and insofar as the authorisation relates to medicinal products to which paragraph 2 of Schedule 1 to the Medicinal Products (Control of Placing on the Market) Regulations 2007 apply, the authorisation holder shall only import such products from a third country-

(a) in response to an order, or in anticipation of an order, which satisfies the requirements of paragraph 2 of Schedule 1 to those Regulations; and

(b) where the conditions set out in subparagraphs (2) to (9) are complied with.

(2) The authorisation holder shall, in the case of each importation of an exempt medicinal product, make, and keep available for inspection by officers of the Board, for a period of not less than five years, written records showing the following particulars-

(a) the name of the medicinal product, being the brand name or the common name, or the scientific name, and any name, if different, under which the particular medicinal product is to be sold or supplied in the State;

(b) the dosage form;

(c) the trading style or name of the manufacturer of the medicinal product;

(d) in respect of each active constituent of the medicinal product, any international non-proprietary name or the monograph name or, where that constituent does not have an international non-proprietary name, the accepted scientific name or any other name descriptive of the true nature of that constituent;

(e) the quantity of medicinal product which has been imported;

(f) the batch number of the medicinal product which has been imported; and

(g) the name and address of the manufacturer of that medicinal product in the form in which it was imported and, if the person who supplied the medicinal product for importation is not the manufacturer, the name and address of such supplier.

(3) Where the authorisation holder sells or supplies an exempt medicinal product, he or she shall, in addition to those records mentioned in sub-paragraph (2), make and maintain written records relating to-

(a) the batch number of the batch of the product from which each sale or supply was made;

(b) details of any suspected adverse reaction to the product so sold or supplied of which he or she becomes aware; and

(c) details of any quality defect relating to the product so sold or supplied of which he or she becomes aware.

(4) The authorisation holder shall not issue any advertisement, catalogue, price list or circular relating to the exempt medicinal product or make any representations in respect of that product.

(5) The authorisation holder shall inform the Board forthwith of any matter, including suspected adverse reactions and quality defects, coming to his or her attention, in respect of an exempt medicinal product imported by him or her.

(6) The authorisation holder shall cease importing or supplying an exempt medicinal product if he or she has received a notice in writing from the Board directing that, as from a date specified in that notice, a particular product or class of products shall no longer be imported or supplied.

(7) The authorisation holder shall, on being informed by the Board, or by the manufacturer or person who supplied the medicinal product for importation, that the medicinal product can not be regarded either as a product which can safely be administered to human beings or as a product which is of satisfactory quality or efficacy for such administration, immediately withdraw any supplies of that product held by him or her and immediately recall all supplies already sold or distributed.

(8) With effect from the 1 January 2008, the authorisation holder shall, not later than seven days of his or her importation of an exempt medicinal product, notify the Board of each such importation. Each such notification shall include the particulars set out in subparagraph (2).

(9) With effect from the 1 January 2009, the notifications referred to in subparagraph (8) shall, except in exceptional circumstances, be communicated electronically to the Board and within a timeframe of two working days from the date of each such importation.

(10) In this paragraph-

�common name� means the international non-proprietary name, or, if one does not exist, the usual common name;

�international non-proprietary name� means the international non-proprietary name recommended by the World Health Organisation; and

�monograph name� means the name or approved synonym which appears at the head of a monograph in the current edition of the European Pharmacopoeia or the British Pharmacopoeia, or a foreign or international compendium of standards and �current� in this definition means current at the time the notice is sent to the Board.

[Regulations 8(4), 11(7) and 12(3)]

SCHEDULE 4 Procedural provisions relating to proposals to grant subject to the carrying out of certain obligations, proposals to grant otherwise than in accordance with the application, proposals to refuse to grant or vary, proposals to make the authorisation conditional on the carrying out of certain obligations, and proposals to suspend, vary or revoke a manufacturer�s authorisation

1. In this Schedule-

�authorisation� means a manufacturer�s authorisation; and

�time allowed� means the period of 28 days or such extended period as the Board may in any particular case allow.

2. Subject to paragraph 6, if the Board proposes-

(a) not to grant an authorisation,

(b) to grant an authorisation subject to the carrying out of certain obligations,

(c) to grant an authorisation other than in accordance with the application,

(d) to revoke, vary or suspend an authorisation,

(e) not to vary an authorisation on the holder�s application to vary, or

(f) to make an authorisation conditional on the carrying out of certain obligations,

the Board shall notify the applicant or authorisation holder accordingly.

3. Any notification given under paragraph 2 shall include-

(a) a statement of the proposals of the Board;

(b) a statement setting out in detail the reasons on which the said proposals are based, and

(c) a statement that the applicant or authorisation holder has the right to make representations to the Board in response to the notification.

4. A person to whom notification has been given under paragraph 2 may, within the time allowed after the notification was given, give notice to the Board of his or her wish to do so, and make representations to the Board with respect to the decision or proposal referred to in the notification.

5. The Board shall, after considering the representations, decide whether to grant the authorisation, revoke, vary or suspend an authorisation or confirm or alter its decision, as the case may be.

6. (1) Paragraph 2 shall not apply to the suspension of an authorisation where it appears to the Board that, in the interests of safety, it is necessary to suspend the authorisation with immediate effect for a period not exceeding 3 months.

(2) If, after the aforementioned suspension has taken effect, it appears to the Board that the authorisation should be further suspended or revoked, the Board shall proceed in accordance with the provisions of paragraphs 2 to 5.

[Regulations 3(1) and 13]

SCHEDULE 5 Requirements applicable to qualified persons

A person shall only have the capacity to act as a qualified person if he or she fulfils the conditions of qualification at one of (a), (b) or (c) below-

(a) He or she is 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 Board, extending over a period of at least four years of theoretical and practical study in one of the following scientific disciplines: pharmacy, medicine, veterinary medicine, chemistry, pharmaceutical chemistry and technology, biology. However, a university course of shorter duration may suffice if either of the conditions set out in clause (i) or (ii) are satisfied-

(i) 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 a minimum duration of one year and including a training period of at least six months in a pharmacy open to the public, corroborated by an examination at university level;

(ii) Where two university courses or two courses recognised by the State in question as equivalent co-exist in an EEA 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 at clause (i) above insofar as the diplomas, certificates or other evidence of formal qualifications awarded on completion of both courses are recognised as equivalent by the State in question.

Where qualification is dependent on clause (i) or (ii), it must be shown that the course included theoretical and practical study bearing upon at least the following basic subjects:

Experimental physics,

General and inorganic chemistry,

Organic chemistry,

Analytical chemistry,

Pharmaceutical chemistry including analysis of medicinal products,

General and applied biochemistry (medical),

Physiology,

Microbiology,

Pharmacology,

Pharmaceutical technology,

Toxicology,

Pharmacognosy (study of the composition and effects of the natural active substances of plant and animal origin).

Studies in these subjects should be balanced so as to enable the person concerned to fulfil the obligations specified in Regulation 13.

Where a qualification under paragraph (a) is not dependent on clause (i) or (ii), the Board shall ensure that the person in question provides evidence of adequate knowledge of the aforementioned basic subjects.

All persons qualifying under this paragraph 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. 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.

(b) He or she has engaged in the activities of a qualified person from the time of the application of Council Directive 75/319/EEC ¹⁵ in an EEA State without complying with the requirements of paragraph (a).

15 OJ No. L 147, 9.6.1975, p. 13.

(c) He or she is 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 Board - in a scientific discipline allowing him or her to engage in the activities of a qualified person, may- if he or she began his or her course before 21 May 1975 - be considered as qualified to carry out within the State the duties of a qualified person provided that he or she has previously engaged in the following activities for at least two years before 21 May 1985 at one or more undertakings authorised to manufacture medicinal products: 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 to ensure the quality of the medicinal products.

If the person concerned has acquired this practical experience before 21 May 1965, a further one year�s practical experience of this kind will be required to be completed immediately before such person may act as a qualified person for the purposes of these Regulations.

GIVEN under the Official Seal,

20 July 2007

MARY HARNEY.

Minister for Health and Children.

EXPLANATORY NOTE.

(This note is not part of the Instrument and does not purport to be a legal interpretation).

The main purpose of these Regulations is to implement TITLE IV of Directive 2001/83/EC (as amended by Directive 2004/27/EC) relating to the manufacture and importation of medicinal products for human use.

The Regulations also implement Article 13 of Directive 2001/20/EC and Chapter 3 of Directive 2005/28/EC, which relate to the manufacture and import of investigational medicinal products. The Regulations also fully implement Commission Directive 2003/94/EC laying down the principles and guidelines of good manufacturing practice in respect of medicinal products for human use.

The Regulations also consolidate all the controls relating to the manufacture of medicinal products and investigational medicinal products into one set of Regulations.

1 OJ No. L. 121, 1.5.2001, p. 34

2 OJ No. L.91, 9.4.2005, p. 13.

3 OJ No. L. 311, 28.11.2001, p.67.

4 OJ No. L. 33, 8.02.2003, p.30.

5 OJ No. L. 159, 27.06.2003, p.46.

6 OJ No. L. 136, 30.04.2004, p.85.

7 OJ No. L. 136, 30.4.2004, p.34.

8 OJ No. L 1, 3.01.1994, p.572.

9 OJ No. L 262, 14.10.2003, p. 22.

10 OJ No. L.214, 24.08.1993, p.1

11 OJ No. L 136, 30.04.2004, p. 1.

12 OJ No. L. 121, 1.5.2001, p. 34.

13 OJ No. C 63, 1.03.1994, p.4.

14 OJ No. L.91, 30.3.2004, p.25.

15 OJ No. L 147, 9.6.1975, p. 13.