The Human Medicines Regulations 2012

Conditions for holding a manufacturer's licence U.K.

Conditions for manufacturer's licence U.K.

36.—(1) Regulations 37 to 41 apply to the holder of a manufacturer's licence (referred to in those regulations as “the licence holder”) and have effect as if they were provisions of the licence (but the provisions specified in paragraph (2) do not apply to the holder of a manufacturer's licence insofar as the licence relates to the manufacture or assembly of exempt advanced therapy medicinal products).

(2) Those provisions are regulations [F1 37(3)], 38, 39(6)(a) and (8) , 40 and 41.

(3) The requirements of Part 1 of Schedule 6 apply to the holder of a manufacturer's licence insofar as the licence relates to the manufacture or assembly of exempt advanced therapy medicinal products, and have effect as if they were provisions of the licence.

[F2 (4) [F3 Where a manufacturer’s licence relates to the manufacture or assembly of a medicinal product in, or import of a medicinal product into, Northern Ireland, the requirements] and obligations contained in a provision of Commission Regulation 2016/161 listed in paragraph (5) have effect as if they were [F4 provisions of that] licence under this Part.

(5) The provisions mentioned in paragraph (4) are—

(a) Article 4 (composition of the unique identifier);

(b) Article 5 (carrier of the unique identifier);

(c) Article 6 (quality of the printing of the two-dimensional barcode);

(d) Article 7 (human-readable format);

(e) Article 10 (verification of the safety features) insofar as it relates to manufacturers;

(f) Article 11 (verification of the authenticity of the unique identifier) insofar as it relates to manufacturers;

(g) Article 12 (unique identifiers which have been decommissioned);

(h) Article 13 (reversing the status of a decommissioned unique identifier) insofar as it relates to manufacturers;

(i) Article 14 (verification of the two-dimensional barcode);

(j) Article 15 (record keeping);

(k) Article 16 (verifications to be performed before removing or replacing the safety features);

(l) Article 17 (equivalent unique identifier); and

(m) Article 18 (actions to be taken in case of tampering or suspected falsification).

(6) In distributing a medicinal product by way of wholesale dealing [F5 in Northern Ireland], the requirements and obligations contained in a provision of Commission Regulation 2016/161 listed in paragraph (7) shall apply to the holder of a manufacturer’s licence and have effect as if they were provisions of the licence.

(7) The provisions mentioned in paragraph (6) are—

(a) Article 20 (verification of the authenticity of the unique identifier by wholesalers), subject to the exemption contained in Article 21 (derogations from Article 20(b));

(b) Article 22 (decommissioning of unique identifiers by wholesalers); and

(c) Article 24 (actions to be taken by wholesalers in case of tampering or suspected falsification).]

Textual Amendments

F1 Word in reg. 36(2) substituted (20.8.2013) by The Human Medicines (Amendment) Regulations 2013 (S.I. 2013/1855), regs. 1(1), 10

F2 Reg. 36(4)-(7) inserted (9.2.2019) by The Human Medicines (Amendment) Regulations 2019 (S.I. 2019/62), regs. 1, 4 and reg. 36(4)-(7) inserted (N.I.) (9.2.2019) by The Human Medicines (Amendment) Regulations 2019 (S.R. 2019/10), regs. 1, 4

F3 Words in reg. 36(4) substituted (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), regs. 1, 27(a)(i) (as substituted by S.I. 2020/1488, reg. 1, Sch. 2 para. 17); 2020 c. 1, Sch. 5 para. 1(1)

F4 Words in reg. 36(4) substituted (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), regs. 1, 27(a)(ii) (as substituted by S.I. 2020/1488, reg. 1, Sch. 2 para. 17); 2020 c. 1, Sch. 5 para. 1(1)

F5 Words in reg. 36(6) inserted (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), regs. 1, 27(b) (as substituted by S.I. 2020/1488, reg. 1, Sch. 2 para. 17); 2020 c. 1, Sch. 5 para. 1(1)

[F6 Manufacturing and assembly U.K.

37.— (1) This regulation applies in relation to a manufacturer’s licence relating to the manufacture or assembly of medicinal products.

(2) The licence holder must comply with the principles and guidelines for good manufacturing practice set out in the Good Manufacturing Practice Directive [F7 which apply under or by virtue of regulation B17].

(3) Unless paragraph (10) applies, the licence holder shall use active substances as starting materials only if—

(a) those substances have been manufactured in accordance with good manufacturing practice for active substances; and

(b) those substances have been distributed in accordance with the guidelines on good distribution practice for active substances.

(4) The licence holder shall verify—

(a) that the manufacturer or distributor of an active substance used by the licence holder has complied with the requirements of good manufacturing practice and good distribution practice for active substances by means of audits performed—

(i) directly by the licence holder, or

(ii) by a person acting on behalf of the licence holder under a contract;

[F8 (b) that unless the active substance is imported into Great Britain from a country other than an approved country for import or into Northern Ireland from a country other than an EEA State from a third country, any manufacturers, importers or distributors supplying active substances to the licence holder—

(i) in the case of a product imported into Great Britain, are registered with the appropriate authority for the registration of such persons in the approved country for import, and

(ii) in the case of a product imported into Northern Ireland, are registered with the competent authority of a member State in which they are established; and]

(c) the authenticity and quality of the active substance.

(5) The licence holder shall ensure that—

(a) excipients are suitable for use in a medicinal product by—

(i) ascertaining what the appropriate good manufacturing practice is, and

(ii) ensuring that the ascertained good manufacturing practice is applied;

(b) the suitability of the excipient is ascertained on the basis of a formalised risk assessment as described [F9 in the case of a product for sale or supply in Great Britain [F10 (including a listed NIMAR product for sale or supply from Great Britain to Northern Ireland)], in the guidelines which apply under or by virtue of regulation C17 and, in the case of a product for sale or supply in Northern Ireland,] in paragraph 5 of Article 47 of the 2001 Directive;

(c) the assessment under sub-paragraph (b) takes account of—

(i) the source,

(ii) requirements under other quality systems,

(iii) intended use of the excipients, and

(iv) previous instances of quality defects,

(d) the authenticity and quality of any excipient used is verified; and

(e) the measures taken under this paragraph are documented by the licence holder.

(6) The licence holder must maintain such staff, premises and equipment as are necessary for the stages of manufacture and assembly of medicinal products undertaken by the licence holder in accordance with—

(a) the manufacturer’s licence; F11 ...

[F12 (aa) in the case of a product for supply as an EAMS medicinal product, the conditions attached to the EAMS scientific opinion in respect of the product; and]

(b) [F13 in the case of a product for sale or supply—

(i) in Great Britain [F14 (including a listed NIMAR product for sale or supply from Great Britain to Northern Ireland)], the UKMA(GB), UKMA(UK), COR(GB), COR(UK), THR(GB) or THR(UK), or

(ii) in Northern Ireland, the UKMA(NI), UKMA(UK), COR(NI), COR(UK), THR(NI), THR(UK), EU marketing authorisations or Article 126a authorisations,

applying to the medicinal products.]

(7) The licence holder must not manufacture or assemble medicinal products, or classes of medicinal products, other than those specified in the licence.

(8) The licence holder must not manufacture or assemble medicinal products on premises other than those specified in the licence as approved by the licensing authority for the purpose.

(9) The licence holder must ensure that blood, or blood components, imported into the United Kingdom and used as a starting material or raw material in the manufacture of a medicinal product meet—

(a) the standards of quality and safety specified in [F15 the Blood Quality and Safety Regulations 2005]; or

(b) equivalent standards.

(10) The requirements in paragraphs (3) to (5) do not apply in relation to the manufacture or assembly of special medicinal product to which regulation 167 (supply to fulfil special needs) applies [F16 or an EAMS medicinal product to which regulation 167E(1) to (4) (EAMS medicinal product: manufacture, assembly, importation, distribution and supply) applies].

(11) The licence holder must immediately inform the [F17 licensing authority] and, where applicable, the [F18 UK] marketing authorisation holder, of medicinal products which come within the scope of manufacturing authorisation which the licence holder—

(a) knows or suspects; or

(b) has reasonable grounds for knowing or suspecting,

to be falsified.]

Textual Amendments

F6 Reg. 37 substituted (20.8.2013) by The Human Medicines (Amendment) Regulations 2013 (S.I. 2013/1855), regs. 1(1), 11

F7 Words in reg. 37(2) inserted (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), regs. 1, 28(1A) (as inserted by S.I. 2020/1488, reg. 1, Sch. 2 para. 18(a)); 2020 c. 1, Sch. 5 para. 1(1)

F8 Reg. 37(4)(b) substituted (31.12.2020) by S.I. 2019/775, regs. 1, 28(2) (as substituted by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2020 (S.I. 2020/1488), reg. 1, Sch. 2 para. 18(b))

F9 Words in reg. 37(5)(b) inserted (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), regs. 1, 28(3) (as substituted by S.I. 2020/1488, reg. 1, Sch. 2 para. 18(c)); 2020 c. 1, Sch. 5 para. 1(1)

F10 Words in reg. 37(5)(b) inserted (1.1.2022) by The Human Medicines (Amendment) (Supply to Northern Ireland) Regulations 2021 (S.I. 2021/1452), regs. 1(2), 8

F11 Word in reg. 37(6)(a) omitted (15.4.2022) by virtue of The Human Medicines (Amendments Relating to the Early Access to Medicines Scheme) Regulations 2022 (S.I. 2022/352), regs. 1(2), 5(2)(a) (with reg. 19)

F12 Reg. 37(6)(aa) inserted (15.4.2022) by The Human Medicines (Amendments Relating to the Early Access to Medicines Scheme) Regulations 2022 (S.I. 2022/352), regs. 1(2), 5(2)(b) (with reg. 19)

F13 Reg. 37(6)(b) substituted (31.12.2020) by S.I. 2019/775, regs. 1, 28(4) (as substituted by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2020 (S.I. 2020/1488), reg. 1, Sch. 2 para. 18(d))

F14 Words in reg. 37(6)(b)(i) inserted (1.1.2022) by The Human Medicines (Amendment) (Supply to Northern Ireland) Regulations 2021 (S.I. 2021/1452), regs. 1(2), 8

F15 Words in reg. 37(9)(a) substituted (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), regs. 1, 28(5); 2020 c. 1, Sch. 5 para. 1(1)

F16 Words in reg. 37(10) inserted (15.4.2022) by The Human Medicines (Amendments Relating to the Early Access to Medicines Scheme) Regulations 2022 (S.I. 2022/352), regs. 1(2), 5(3) (with reg. 19)

F17 Words in reg. 37(11) substituted (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), regs. 1, 28(6)(a); 2020 c. 1, Sch. 5 para. 1(1)

F18 Word in reg. 37(11) inserted (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), regs. 1, 28(6)(b); 2020 c. 1, Sch. 5 para. 1(1)

Imports from states other than EEA States [F19 / countries other than approved countries for import] U.K.

38.—(1) This regulation applies in relation to a manufacturer's licence relating to the import of medicinal products.

(2) The licence holder must comply with the conditions set out in this regulation in relation to the import of medicinal products [F20 from—

(a) in the case of an import into Great Britain, a country other than an approved country for import, or

(b) in the case of an import into Northern Ireland, a country other than an EEA State].

(3) The licence holder must—

(a) comply with the principles and guidelines on good manufacturing practice in the Good Manufacturing Practice Directive in so far as they are relevant to the import of medicinal products; and

(b) ensure that active substances have been used as starting materials in the manufacture of medicinal products, other than special medicinal products, imported from [F21 , in the case of an import into Great Britain, a country other than an approved country for import and in the case of an import into Northern Ireland, a country other than an EEA State] only if those substances have been manufactured or assembled in accordance with [F22 good manufacturing practice for active substances].

Textual Amendments

F19 Words in reg. 38 heading inserted (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), regs. 1, 29(2) (as substituted by S.I. 2020/1488, reg. 1, Sch. 2 para. 19(a)); 2020 c. 1, Sch. 5 para. 1(1)

F20 Reg. 38(2)(a)(b) substituted for words in reg. 38(2) (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), regs. 1, 29(3) (as amended by S.I. 2020/1488, reg. 1, Sch. 2 para. 19(b)); 2020 c. 1, Sch. 5 para. 1(1)

F21 Words in reg. 38(3)(b) substituted (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), regs. 1, 29(4) (as amended by S.I. 2020/1488, reg. 1, Sch. 2 para. 19(c)); 2020 c. 1, Sch. 5 para. 1(1)

F22 Words in reg. 38(3)(b) substituted (E.W.S.) (1.10.2015) by The Human Medicines (Amendment) (No. 3) Regulations 2015 (S.I. 2015/1503), regs. 1, 4 and words in reg. 38(3)(b) substituted (N.I.) (1.10.2015) by The Human Medicines (Amendment) (No.3) Regulations 2015 (S.R. 2015/354), regs. 1, 4

Further requirements for manufacturer's licence U.K.

39.—(1) This regulation applies in relation to any manufacturer's licence.

(2) The licence holder must maintain such staff, premises, equipment and facilities for the handling, control, storage and distribution of medicinal products under the licence as are appropriate in order to maintain the quality of the medicinal products.

(3) The licence holder must ensure that any arrangements made for the handling, control, storage and distribution of medicinal products are adequate to maintain the quality of the products.

(4) The licence holder must not handle, control, store or distribute medicinal products on any premises other than those specified in the licence as approved by the licensing authority for the purpose.

(5) The licence holder must inform the licensing authority before making a material alteration to the premises or facilities used under the licence, or to the purposes for which those premises or facilities are used.

(6) The licence holder must inform the licensing authority of any proposed change to—

(a) the qualified person; and

(b) any person named in the licence as having responsibility for quality control.

(7) For the purposes of enabling the licensing authority to determine whether there are grounds for suspending, revoking or varying the licence, the licence holder must permit a person authorised in writing by the licensing authority to do anything that the licensing authority could have done for the purposes of verifying a statement made in an application for a licence.

[F23 (8) In distributing a medicinal product by way of wholesale dealing, the licence holder must comply with the following as if they are a holder of a wholesale dealer’s licence—

(a) regulations 43(1), (2) and (5), 43ZA and 44(5) and (6), and

(b) regulation 43A, if applicable, where the product is being distributed in NI.]

Textual Amendments

F23 Reg. 39(8) substituted (1.1.2022) by The Human Medicines (Amendment) (Supply to Northern Ireland) Regulations 2021 (S.I. 2021/1452), regs. 1(2), 9

Obligation to provide information relating to control methods U.K.

40.—(1) This regulation applies in relation to any manufacturer's licence.

(2) The licensing authority may require the licence holder to provide the authority with proof of the control methods employed by the holder in relation to a medicinal product.

Requirements as to qualified persons U.K.

41.—(1) This regulation applies in relation to any manufacturer's licence.

(2) The licence holder must ensure that there is at the disposal of the holder at all times at least one qualified person who is responsible for carrying out, in relation to medicinal products manufactured, assembled or imported under the licence, the duties specified in Part 3 of Schedule 7.

(3) If the licence holder satisfies the requirements of Part 1 or 2 of Schedule 7 the licence holder may act as a qualified person.

(4) A qualified person may be treated by the licence holder as satisfying the requirements of Part 1 or 2 of Schedule 7 if that person produces evidence that he or she—

(a) is a member of a body specified in paragraph (5); and

(b) is regarded by that body as satisfying those requirements.

(5) Those bodies are—

(a) the Society of Biology;

(b) the Royal Pharmaceutical Society;

(c) the Pharmaceutical Society of Northern Ireland;

(d) the Royal Society of Chemistry; and

(e) such other body as may be specified by the licensing authority for the purpose of this paragraph.

(6) Where the qualified person changes, the licence holder must give the licensing authority advance notification of—

(a) that change; and

(b) the name, address and qualifications of the new qualified person.

(7) The licence holder must not permit any person to act as a qualified person other than the person named in the licence or another person notified to the licensing authority under paragraph (6).

(8) Paragraph (9) applies if the licensing authority thinks, after giving the licence holder and a person acting as a qualified person the opportunity to make representations (orally or in writing), that the person—

(a) does not satisfy the requirements of Part 1 or 2 of Schedule 7 in relation to qualifications or experience;

(b) does not satisfy paragraph (b) of the definition of “qualified person” in regulation 8; or

(c) is failing to carry out the duties referred to in paragraph (2) adequately or at all.

(9) Where this paragraph applies, the licensing authority must notify the licence holder in writing that the person is not permitted to act as a qualified person.

(10) The licence holder must at all times provide and maintain such staff, premises and equipment as are necessary to enable the qualified person to carry out the duties referred to in paragraph (2).

(11) The licence holder is not obliged to meet the requirements of this regulation in relation to any activity under the licence which relates to special medicinal products or [F24 , unless conditions attached in accordance with regulation 174A(1) provide otherwise,] to products authorised on a temporary basis under regulation 174 (supply in response to spread of pathogenic agents etc).

[F25 (12) The licence holder is not obliged to meet the requirements of this regulation in relation to any activities under the licence which relate to EAMS medicinal products, unless the conditions attached to the scientific opinion in respect of that product in accordance with regulation 167C(2)(c) provide otherwise.]

Textual Amendments

F24 Words in reg. 41(11) inserted (6.11.2020) by The Human Medicines (Coronavirus and Influenza) (Amendment) Regulations 2020 (S.I. 2020/1125), regs. 1(2), 5 and words in reg. 41(11) inserted (N.I) (6.11.2020) by The Human Medicines (Coronavirus and Influenza) (Amendment) Regulations 2020 (S.R. 2020/349), regs. 1(2), 5

F25 Reg. 41(12) inserted (15.4.2022) by The Human Medicines (Amendments Relating to the Early Access to Medicines Scheme) Regulations 2022 (S.I. 2022/352), regs. 1(2), 6 (with reg. 19)