The Human Medicines Regulations 2012

[F1 CHAPTER 4 U.K. Importation, manufacture and distribution of active substances

Textual Amendments

F1 Pt. 3 Chs. 3, 4 inserted (20.8.2013) by The Human Medicines (Amendment) Regulations 2013 (S.I. 2013/1855), regs. 1(1), 16

Criteria for importation, manufacture or distribution of active substances U.K.

45M.— (1) A person may not—

(a) import;

(b) manufacture; or

(c) distribute,

an active substance unless that person is registered with the licensing authority in accordance with regulation 45N and the requirements in regulation 45O are met.

(2) Paragraph (1) applies in relation to an active substance which is to be used in an investigational medicinal product only—

[F2 (a) if—

(i) in the case of a product for sale or supply in Great Britain, the product has a UK marketing authorisation, certificate of registration or traditional herbal registration, or

(ii) in the case of a product for sale or supply in Northern Ireland, the product has a marketing authorisation, Article 126a authorisation, certificate of registration or traditional herbal registration, and]

(b) to the extent that the manufacture of the active substance is in accordance with the terms and conditions of that authorisation, certificate or registration.

(3) Paragraph (1)(a) does not apply to a person who, in connection with the importation of an active substance F3 ...—

(a) provides facilities solely for transporting the active substance; or

(b) acting as an import agent, imports the active substance solely to the order of another person who holds a certificate of good manufacturing practice issued by the licensing authority.

Textual Amendments

F2 Reg. 45M(2)(a) substituted (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), regs. 1, 42(2) (as amended by S.I. 2020/1488, reg. 1, Sch. 2 para. 31); 2020 c. 1, Sch. 5 para. 1(1)

F3 Words in reg. 45M(3) omitted (31.12.2020) by virtue of The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), regs. 1, 42(3); 2020 c. 1, Sch. 5 para. 1(1)

Registration in relation to active substances U.K.

45N.— (1) For registration in relation to active substances, the licensing authority must have received a valid registration form from the applicant for import, manufacture or, as the case may be, distribution of an active substance and—

(a) 60 days have elapsed since receipt and the licensing authority have not notified the applicant that an inspection will be carried out; or

(b) the licensing authority—

(i) notified the applicant within 60 days of receipt of a registration form that an inspection will be carried out; and

(ii) within 90 days of that inspection the licensing authority have issued that person with a certificate of good manufacturing practice or, as the case may be, of good distribution practice; and

(c) that person has not instructed the licensing authority to end that person’s registration.

(2) The person applying for registration under paragraph (1) must notify the licensing authority of any changes which have taken place as regards the information in the registration form—

(a) immediately where such changes may have an impact on quality or safety of the active substances that are manufactured, imported or distributed;

(b) in any other case, on each anniversary of the receipt of the application form by the licensing authority.

(3) For the purpose of paragraph (2), changes which are notified in accordance with that paragraph shall be treated as incorporated in the application form.

(4) Any notification to the licensing authority under paragraph (2) must be accompanied by the appropriate fee in accordance with the Fees Regulations.

(5) A registration form is valid for the purpose of paragraph (1) if—

(a) it is provided to the licensing authority; and

(b) is completed in the way and form specified in Schedule 7A.

(6) Paragraph (1) does not apply until 20th October 2013 in relation to a person who had, before 20th August 2013, commenced the activity for which the person would, apart from this provision, need to send a registration form to the licensing authority.

Requirements for registration as an importer, manufacturer or distributor of an active substance U.K.

45O.— [F4 (1) Where principles and guidelines of good manufacturing practice have been published under, or apply by virtue of, regulation C17, which apply to an active substance manufactured in Great Britain, a manufacturer in Great Britain must comply with the principles and guidelines of good manufacturing practice for active substances.

(1A) Where the Commission has adopted principles and guidelines of good manufacturing practice under the third paragraph of Article 47 of the 2001 Directive which applies to an active substance manufactured in Northern Ireland, a manufacturer in Northern Ireland must comply with the principles and guidelines of good manufacturing practice for active substances.]

[F5 (2) Where principles and guidelines of good distribution practice have been published under, or apply by virtue of, regulation C17, which apply to an active substance distributed in Great Britain, a distributor in Great Britain must comply with the principles and guidelines of good distribution practice for active substances.

(2A) Where the Commission has adopted principles and guidelines of good distribution practice under the fourth paragraph of Article 47 of the 2001 Directive which applies to an active substance distributed in the Northern Ireland, a distributor in Northern Ireland must comply with the principles and guidelines of good distribution practice for active substances.]

(3) Without prejudice to regulation 37(4) (manufacture and assembly in relation to active substances) and paragraph 9A of Schedule 8 (material to accompany an application for a UK marketing authorisation in relation to an active substance), where the Commission has adopted principles and guidelines of good manufacturing practice under the third paragraph of Article 47 of the 2001 Directive which applies to an active substance imported into [F6 Northern Ireland] and where an active substance is imported [F7 into Northern Ireland from a country other than an EEA State]—

(a) the importer must comply with good manufacturing practice and good distribution practice in relation to the active substance;

(b) the active substances must have been manufactured in accordance with standards which are at least equivalent to good manufacturing practice; and

(c) the active substances must be accompanied by a written confirmation from the competent authority of the [F8 exporting country] of the following—

(i) the standards of manufacturing practice applicable to the plant manufacturing the exported active substance are at least equivalent to good manufacturing practice,

(ii) the manufacturing plant concerned is subject to regular, strict and transparent controls and to the effective enforcement of standards of manufacturing practice at least equivalent to good manufacturing practice, including repeated and unannounced inspections, so as to ensure a protection of public health at least equivalent to that in [F9 Northern Ireland], and

(iii) in the event of findings relating to non-compliance, information on such findings is supplied by the [F8 exporting country] to the Union without any delay.

[F10 (3A) Without prejudice to regulation 37(4) and paragraph 9A of Schedule 8, where principles and guidelines of good manufacturing practice have been published under, or apply by virtue of, regulation C17, which apply to an active substance imported into Great Britain other than from Northern Ireland and where an active substance is so imported—

(a) the importer must comply with good manufacturing practice and good distribution practice in relation to the active substance,

(b) the active substances must have been manufactured in accordance with standards which are at least equivalent to good manufacturing practice, and

(c) the active substances must be accompanied by a written confirmation from the competent authority of the exporting country of the following—

(i) the standards of manufacturing practice applicable to the plant manufacturing the exported active substance are at least equivalent to good manufacturing practice,

(ii) the manufacturing plant concerned is subject to regular, strict and transparent controls and to the effective enforcement of standards of manufacturing practice at least equivalent to good manufacturing practice, including repeated and unannounced inspections, so as to ensure a protection of public health at least equivalent to that in Great Britain, and

(iii) in the event of findings relating to non-compliance, information on such findings is supplied by the exporting country to the licensing authority without any delay.]

(4) Paragraph [F11 (3)(c) and (3A)(c) do] not apply—

(a) where the country from where the active substance is exported is included in the list referred to in Article 111b of the 2001 Directive [F12 (in the case of an import into Northern Ireland) or paragraph (6) (in the case of an import into Great Britain)]; or

(b) for a period not exceeding the validity of the certificate of good manufacturing practice, where—

(i) in relation to a plant where active substances are manufactured where the competent authority of a member State [F13 or licensing authority (in the case of an import into Northern Ireland) or licensing authority or an appropriate authority responsible for the licensing of medicinal products in a country included in a list under paragraph (6) (in the case of an import into Great Britain)] has found, upon inspection, that a plant complies with the principles and guidelines of good manufacturing practice, and

(ii) the licensing authority is of the opinion that it is necessary to waive the requirement to ensure availability of the active substance.

(5) The criteria in this regulation apply regardless of whether an active substance is intended for export.

[F14 (6) The licensing authority may publish a list of countries which it is satisfied have a regulatory framework applicable to active substances exported to Great Britain that is equivalent to the regulatory framework in Great Britain, in that the respective control and enforcement activities in those countries ensures an equivalent level of protection of public health.

(7) Before including a country in the list under paragraph (6), the licensing authority must assess the equivalence referred to in that paragraph by—

(a) reviewing relevant documentation; and

(b) unless the country is included in the approved country for batch testing list, carrying out—

(i) an on-site review of the country's regulatory system, and

(ii) if the licensing authority considers it necessary, an inspection of one or more of that country's manufacturing sites for active substances.

(8) In carrying out an assessment under paragraph (7) the licensing authority must in particular take account of the—

(a) country's rules for good manufacturing practice;

(b) regularity of inspections to verify compliance with good manufacturing practice;

(c) effectiveness of enforcement of good manufacturing practice; and

(d) regularity and rapidity of information provided by that country relating to non-compliant producers of active substances.

(9) The licensing authority must—

(a) review the list under paragraph (6) to determine if a country included in it still satisfies the requirements for inclusion in the list, and if it is not so satisfied, remove that country; and

(b) undertake such a review at least every three years, beginning with the date on which a country is included in the list .]

Textual Amendments

F4 Reg. 45O(1)(1A) substituted for reg. 45O(1) (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), regs. 1, 44(2) (as amended by S.I. 2020/1488, reg. 1, Sch. 2 para. 32(a)); 2020 c. 1, Sch. 5 para. 1(1)

F5 Reg. 45O(2)(2A) substituted for reg. 45O(2) (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), regs. 1, 44(3) (as amended by S.I. 2020/1488, reg. 1, Sch. 2 para. 32(b)); 2020 c. 1, Sch. 5 para. 1(1)

F6 Words in reg. 45O(3) substituted (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), regs. 1, 44(4)(a) (as amended by S.I. 2020/1488, reg. 1, Sch. 2 para. 32(c)); 2020 c. 1, Sch. 5 para. 1(1)

F7 Words in reg. 45O(3) substituted (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), regs. 1, 44(4)(b) (as amended by S.I. 2020/1488, reg. 1, Sch. 2 para. 32(c)); 2020 c. 1, Sch. 5 para. 1(1)

F8 Words in reg. 45O(3) substituted (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), regs. 1, 44(4)(c) (as amended by S.I. 2020/1488, reg. 1, Sch. 2 para. 32(c)); 2020 c. 1, Sch. 5 para. 1(1)

F9 Words in reg. 45O(3)(c)(ii) substituted (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), regs. 1, 44(4)(d) (as amended by S.I. 2020/1488, reg. 1, Sch. 2 para. 32(c)); 2020 c. 1, Sch. 5 para. 1(1)

F10 Reg. 45O(3A) inserted (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), regs. 1, 44(4A) (as inserted by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2020 (S.I. 2020/1488), reg. 1, Sch. 2 para. 32(d))

F11 Words in reg. 45O(4) substituted (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), regs. 1, 44(5)(a) (as amended by S.I. 2020/1488, reg. 1, Sch. 2 para. 32(e)); 2020 c. 1, Sch. 5 para. 1(1)

F12 Words in reg. 45O(4)(a) inserted (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), regs. 1, 44(5)(b) (as amended by S.I. 2020/1488, reg. 1, Sch. 2 para. 32(e)); 2020 c. 1, Sch. 5 para. 1(1)

F13 Words in reg. 45O(4)(b)(i) inserted (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), regs. 1, 44(5)(c) (as amended by S.I. 2020/1488, reg. 1, Sch. 2 para. 32(e)); 2020 c. 1, Sch. 5 para. 1(1)

F14 Reg. 45O(6)-(9) inserted (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), regs. 1, 44(6) (as amended by S.I. 2020/1488, Sch. 2 para. 32(f)); 2020 c. 1, Sch. 5 para. 1(1)

Provision of information U.K.

45P.— (1) In this regulation—

“R” means a person who is, or has applied to the licensing authority to become, a registered importer, manufacturer or distributor of active substances;

“reporting year” means a period of twelve months ending on 31st March.

(2) On or before the date specified in paragraph (3), R must submit a report to the licensing authority which—

(a) includes a declaration that R has in place an appropriate system to ensure compliance with regulations 45N, 45O and this regulation; and

(b) details the system which R has in place to ensure such compliance.

(3) The date specified for the purposes of this paragraph is—

(a) in relation to any application made before 31st March 2014, the date of the application; and

(b) in relation to each subsequent reporting year, 30th April following the end of that year.

(4) R must without delay notify the licensing authority of any changes to the matters in respect of which evidence has been supplied in relation to paragraph (2) which might affect compliance with the requirements of this Chapter.

(5) Any report or notification to the licensing authority under paragraph (2) or (4) must be accompanied by the appropriate fee in accordance with the Fees Regulations.

(6) The licensing authority may give a notice to R, requiring R to provide information of a kind specified in the notice within the period specified in the notice.

(7) A notice under paragraph (6) may not be given to R unless it appears to the licensing authority that it is necessary for the licensing authority to consider whether the registration should be varied, suspended or removed from the active substance register.

(8) A notice under paragraph (6) may specify information which the licensing authority thinks necessary for considering whether the registration should be varied, suspended or removed from the active substance register.

Power to suspend or vary or remove an active substance registration U.K.

45Q.— (1) The licensing authority may in accordance with regulation 45R—

(a) suspend an active substance registration for such period as the authority thinks fit;

(b) vary an active substance registration; or

(c) remove a person from the active substance register.

(2) The suspension of registration may be—

(a) total;

(b) limited to active substances of one or more descriptions; or

(c) limited to active substances imported, manufactured, assembled or stored on specified premises or a specified part of any premises.

(3) The powers conferred by this regulation may not be exercised in relation to an active substance registration except on one or more of the following grounds—

(a) the information in the application as a result of which the active substance registration was granted was false or incomplete in a material respect;

(b) a material change of circumstances has occurred in relation to any of the matters stated in the application;

(c) the person with an active substance registration has materially contravened a criterion of registration; or

(d) the person with an active substance registration has without reasonable excuse failed to supply information to the licensing authority with respect to active substances of a description to which the registration relates when required to do so under regulation 45P(6).

Procedure where licensing authority proposes to suspend or vary an active substance registration or remove a person from the active substance register U.K.

45R.— (1) This regulation applies where—

(a) the provisions of regulation 45S do not apply; and

(b) the licensing authority proposes to exercise the power in regulation 45Q(1).

(2) The licensing authority must notify the person with an active substance registration in writing of—

(a) its proposal;

(b) the reasons for it; and

(c) the date (which must be no earlier than 28 days from the notice given by the licensing authority) on which it is proposed that the suspension, variation or removal from the active substance register should take effect.

(3) The person with an active substance registration may before the date specified in the notice—

(a) make written representations to the licensing authority with respect to the proposal; or

(b) notify the licensing authority that the person wishes the licensing authority to submit the proposal to review upon oral representations.

(4) If the person with an active substance registration makes written representations in accordance with sub-paragraph (3)(a) the licensing authority must take those representations into account before making a decision in the matter.

(5) If the person with an active substance registration notifies the licensing authority that the person wishes the licensing authority to submit the proposal to review upon oral representations in accordance with paragraph (3)(b)—

(a) Schedule 5 has effect; and

(b) the person with an active substance registration must pay a fee for a review upon oral representations in accordance with the Fees Regulations.

(6) If the licensing authority proceeds to suspend or vary a registration or remove a person from the active substance register in accordance with the provisions of regulation 45Q it must give a notice to that person.

(7) The notice must—

(a) give particulars of the suspension, variation or removal; and

(b) give reasons for the decision to suspend, vary or remove a person’s entry on the active substance register.

(8) Paragraphs (6) and (7) are without prejudice to any requirement of Schedule 5 as to notification.

Suspension of an active substance registration in cases of urgency U.K.

45S.— (1) The licensing authority may immediately suspend a person’s active substance registration for a period not exceeding three months where it appears to the licensing authority that in the interests of safety it is appropriate to do so.

(2) This paragraph applies where—

(a) a person’s active substance registration has been suspended under paragraph (1); and

(b) it appears to the licensing authority that it is necessary to consider whether a person’s active substance registration should be—

(i) further suspended or varied, or

(ii) removed from the active substance register.

(3) Where paragraph (2) applies, the licensing authority must proceed as set out in regulation 45R (but this is subject to paragraph (4)).

(4) Paragraph (5) applies where, in circumstances where paragraph (2) applies, the licensing authority proceeds as set out in regulation 45R and any proceedings under that regulation have not been finally disposed of before the end of the period for which the registration was suspended under paragraph (1) or further suspended under paragraph (5).

(5) If it appears to the licensing authority to be necessary in the interests of safety to do so, the authority may further suspend the registration for a period which (in the case of each further suspension) is not to exceed three months.

(6) In the event that any challenge against a decision under regulation 45R to suspend, vary or remove a person’s active substance registration is made on an application to the High Court under regulation 322(4), paragraph (5) shall apply, but this is without prejudice to regulation 322(6)(a) (validity of decisions and proceedings).

Variation of an active substance registration on an application from the registered person U.K.

45T.— (1) This regulation applies if a person with an active substance registration applies to the licensing authority for a variation of the registration.

(2) The application must—

(a) be in writing;

(b) specify the variation requested;

(c) be signed by or on behalf of the applicant;

(d) be accompanied by such information as may be required to enable the licensing authority to consider the application; and

(e) include the appropriate fee in accordance with the Fees Regulations.

(3) The licensing authority must vary an active substance registration or refuse to vary it within 30 days beginning with the day after the date when the licensing authority receives the application.

(4) The licensing authority may give a notice to the applicant requiring the applicant to supply further information in connection with the application within the period specified in the notice.

(5) If a notice under paragraph (4) requires the applicant to provide the licensing authority with information, the information period is not to be counted for the purposes of paragraph (3).

(6) In paragraph (5), the “information period” means the period—

(a) beginning with the day on which notice is given; and

(b) ending with the day on which the licensing authority receives the information or the applicant shows to the licensing authority’s satisfaction that the applicant is unable to provide it.

(7) Nothing in this regulation affects the powers conferred by regulations 45Q and 45S.

Offences: breach of regulations and false information U.K.

45U.— (1) A person is guilty of an offence if the person imports, manufactures or distributes an active substance in breach of regulation 45M(1).

(2) A person is guilty of an offence if the person knowingly gives false information in—

(a) a registration form received by the licensing authority under regulation 45N(1);

(b) a notification to the licensing authority under regulation 45N(2) or 45P(4);

(c) an application for a variation under regulation 45T(2); or

(d) response to a notice under regulation 45T(4).

(3) A person is guilty of an offence if, without reasonable excuse, the person fails to comply with a notice under regulation 45P(6) or 45T(4).

Penalties U.K.

45V.— (1) A person guilty of an offence under regulation 45U(1) or (2) is liable—

(a) on summary conviction to a fine not exceeding the statutory maximum; or

(b) on conviction on indictment to a fine, to imprisonment for a term not exceeding two years, or to both.

(2) A person guilty of an offence under regulation 45U(3) is liable on summary conviction to a fine not exceeding level 3 on the standard scale.]