The Human Medicines Regulations 2012

Obligations of holder of marketing authorisation U.K.

Obligation to notify placing on the market etc U.K.

73.—(1) The holder of a UK marketing authorisation must notify the licensing authority of the date on which the product to which the authorisation relates is placed on the market in the United Kingdom, taking account of the various presentations authorised.

(2) A notification under paragraph (1) must be given before the end of the period of two months beginning with the date on which the product is placed on the market.

(3) The holder of a UK marketing authorisation must notify the licensing authority if the product to which the authorisation relates is to be withdrawn from the market in the United Kingdom (whether temporarily or permanently).

(4) A notification under paragraph (3) must be given before the beginning of the period of two months ending with the date on which the product is to be withdrawn from the market unless it is not reasonably practicable to do so.

(5) In that event, the notification must be given as far as is reasonably practicable in advance of the date on which the product is withdrawn from the market.

[F1 (5A) The holder of a UK marketing authorisation must notify the licensing authority forthwith if the holder takes action to—

(a) request the cancellation of the authorisation;

(b) not apply for the renewal of the authorisation; or

(c) withdraw the product to which the authorisation relates from the market in a [F2 country other than the United Kingdom] (whether temporarily or permanently) and the action is based on any of the grounds set out in Article 116 or 117(1) of the 2001 Directive.

(5B) A notification under paragraph (3) or (5A) must include the reasons for the action, in particular declaring if the action is based on any of the grounds set out in Article 116 or 117(1) of the 2001 Directive.

(5C) The holder of a [F3 UKMA(NI) or UKMA(UK)] must also notify the EMA forthwith where the action which is the subject of a notification by the holder under paragraph (3) or (5A) is based on any of the grounds set out in Article 116 or 117(1) of the 2001 Directive.]

(6) The licensing authority may require the holder of a UK marketing authorisation to provide—

(a) information relating to the volume of sales in the United Kingdom of the product to which the authorisation relates; or

(b) information of which the holder is aware relating to the volume of prescriptions in the United Kingdom for the product.

(7) The holder of a UK marketing authorisation must provide the licensing authority with information that it requires under paragraph (6)—

(a) where the period within which the information must be provided is specified in a written notice given to the holder by the licensing authority, before the end of that period; or

(b) otherwise, as soon as is reasonably practicable after receipt of the request.

Textual Amendments

F1 Reg. 73(5A)-(5C) inserted (11.11.2013) by The Human Medicines (Amendment) (No. 2) Regulations 2013 (S.I. 2013/2593), regs. 1(2), 3

F2 Words in reg. 73(5A)(c) substituted (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), regs. 1, 82(2); 2020 c. 1, Sch. 5 para. 1(1)

F3 Words in reg. 73(5C) substituted (31.12.2020) by virtue of S.I. 2019/775, reg. 82(3) (as substituted by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2020 (S.I. 2020/1488), reg. 1, Sch. 2 para. 60)

Obligation to take account of scientific and technical progress U.K.

74.—(1) The holder of a UK marketing authorisation must keep under review the methods of manufacture and control of the product to which the authorisation relates, taking account of scientific and technical progress.

(2) As soon as is reasonably practicable after becoming aware of the need to do so, the holder must apply to vary the marketing authorisation to make any changes to those methods that are required to ensure they are generally accepted scientific methods.

Obligation to provide information relating to safety etc U.K.

75.—(1) The holder of a UK marketing authorisation [F4 or parallel import licence] must provide the licensing authority with any new information that might entail the variation of the authorisation.

(2) The holder [F5 of a UK marketing authorisation] must, in particular, provide the licensing authority with the following information—

(a) information about any prohibition or restriction imposed in relation to the product to which the authorisation relates by the competent authority of any country in which the product is on the market;

(b) positive and negative results of clinical trials or other studies in all indications and populations, whether or not included in the marketing authorisation;

(c) data on the use of the medicinal product where such use is outside the terms of the marketing authorisation; and

(d) any other information that the holder considers might influence the evaluation of the benefits and risks of the product.

[F6 (2A) The holder of a parallel import licence must, in particular, provide the licensing authority with—

(a) information about any prohibition or restriction imposed in relation to the product to which the licence relates by the competent authority of any country in which the product is on the market; and

(b) other information that the holder considers might influence the evaluation of the benefits and risks of the product.]

(3) Information within paragraph (1) [F7 to (2A)] must be provided as soon as is reasonably practicable after the holder becomes aware of it.

(4) The licensing authority may require the holder of a UK marketing authorisation to provide the authority with information that—

(a) is specified by the licensing authority; and

(b) demonstrates that the positive therapeutic effects of the product to which the authorisation relates continue to outweigh the risks of the product to the health of patients or of the public.

[F8 (4A) The licensing authority may require the holder of a parallel import licence to provide further information specified by the licensing authority.]

(5) The information that may be required under paragraph (4) [F9 or (4A)] includes information arising from use of the product—

[F10 (a) in a country other than the United Kingdom;]

(b) outside the terms of the [F11 UK] marketing authorisation,

including use in clinical trials.

(6) If the information supplied under paragraph (1), (2)[F12 , (4) or (4A)] entails the variation of the UK marketing authorisation [F13 or parallel import licence], the holder must make an application to the licensing authority to that effect as soon as is reasonably practicable after becoming aware of the information.

(7) The licensing authority may require the holder of a UK marketing authorisation to provide the authority with proof of the control methods employed by the manufacturer of the product to which the authorisation relates.

(8) The holder of a UK marketing authorisation [F14 or parallel import licence] must provide the licensing authority with information it requests under paragraphs [F15 (4), (4A) or] (7)—

(a) where the period within which the information must be provided is specified in a written notice given to the holder by the licensing authority, before the end of that period; or

(b) otherwise, as soon as is reasonably practicable after receipt of the request.

Textual Amendments

F4 Words in reg. 75(1) inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 4 and words in reg. 75(1) inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 4(2)(l)

F5 Words in reg. 75(2) inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 14(2) and words in reg. 75(2) inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 14(2)

F6 Reg. 75(2A) inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 14(3) and reg. 75(2A) inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 14(3)

F7 Words in reg. 75(3) substituted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 14(4) and words in reg. 75(3) substituted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 14(4)

F8 Reg. 75(4A) inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 14(5) and reg. 75(4A) inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 14(5)

F9 Words in reg. 75(5) inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 14(6) and words in reg. 75(5) inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 14(6)

F10 Reg. 75(5)(a) substituted (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), regs. 1, 83(a); 2020 c. 1, Sch. 5 para. 1(1)

F11 Word in reg. 75(5)(b) inserted (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), regs. 1, 83(b); 2020 c. 1, Sch. 5 para. 1(1)

F12 Words in reg. 75(6) substituted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 14(7) and words in reg. 75(6) substituted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 14(7)

F13 Words in reg. 75(6) inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 4 and words in reg. 75(6) inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 4(2)(l)

F14 Words in reg. 75(8) inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 4 and words in reg. 75(8) inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 4(2)(l)

F15 Words in reg. 75(8) substituted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 14(8) and words in reg. 75(8) substituted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 14(8)

Obligation in relation to product information U.K.

76.—(1) The holder of a UK marketing authorisation [F16 or parallel import licence] for a medicinal product must ensure that the product information relating to the product is kept up to date with current scientific knowledge.

[F17 (2) In this regulation “current scientific knowledge” includes the conclusions of the assessment and recommendations made public by means of—

(a) in the case of a medicinal product authorised for sale or supply by a UKMA(NI) or a UKMA(UK)—

(i) the European medicines web-portal established in accordance with Article 26 of Regulation (EC) No 726/2004, and

(ii) the UK web-portal established in accordance with regulation 203(1);

(b) in the case of a medicinal product authorised for sale or supply by a UKMA(GB), the UK web-portal established in accordance with regulation 203(1).]

Textual Amendments

F16 Words in reg. 76(1) inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 4 and words in reg. 76(1) inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 4(2)(m)

F17 Reg. 76(2) substituted (31.12.2020) by S.I. 2019/775, reg. 84 (as substituted by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2020 (S.I. 2020/1488), reg. 1, Sch. 2 para. 61)

Record-keeping obligations U.K.

77.  The holder of a marketing authorisation [F18 or parallel import licence] must keep any documents or information that will facilitate the withdrawal or recall from sale or supply of any product to which the authorisation relates.

Textual Amendments

F18 Words in reg. 77 inserted (E.W.S.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.I. 2014/1878), regs. 1, 4 and words in reg. 77 inserted (N.I.) (1.10.2014) by The Human Medicines (Amendment) (No. 2) Regulations 2014 (S.R. 2014/324), regs. 1(1), 4(2)(n)

Obligation to ensure appropriate and continued supplies U.K.

78.  The holder of a marketing authorisation must take all reasonable steps to ensure appropriate and continued supplies of the product to which the authorisation relates to pharmacies and persons authorised to supply the product so that the needs of patients in the United Kingdom are met.

[F19 Post authorisation requirements in relation to UK marketing authorisations to which paediatric specific provisions apply U.K.

78A.— (1) Paragraph (2) applies where—

(a) a holder of a UK marketing authorisation intends to discontinue supply of the product to which that authorisation relates;

(b) the holder of the authorisation benefited from a reward or incentive under regulation 58A(3) or (8) or 58D(5) in relation to the product; and

(c) the period of protection provided pursuant to those regulations has expired.

(2) Where this paragraph applies, the holder of the UK marketing authorisation must—

(a) either—

(i) transfer the UK marketing authorisation to another person who has declared an intention to continue to supply the product; or

(ii) allow such a person to use the pharmaceutical, pre-clinical and clinical documentation contained in the file on that product in accordance with regulation 56; and

(b) notify the licensing authority of its intention to cease to supply the product before the beginning of the period of six months ending immediately before the day on which the holder does so.

(3) Paragraph (4) applies to the holder of a UK marketing authorisation if—

(a) that authorisation includes a paediatric indication following completion of an agreed paediatric investigation plan; and

(b) the product was placed on the market for other indications before that holder obtained that paediatric indication.

(4) Where this paragraph applies, the holder of the UK marketing authorisation must place the product on the market taking account of the paediatric indication before the end of the period of two years beginning immediately after the day on which the paediatric indication is authorised.

(5) Paragraph (6) applies if—

(a) a decision by the licensing authority in respect of a paediatric investigation plan is addressed to a person (“PIP sponsor”); and

(b) the plan refers to clinical trials carried out in a country other than the United Kingdom (“non-UK clinical trials”).

(6) Where this paragraph applies, the PIP sponsor must send to the licensing authority the details set out in Article 11 of the Clinical Trials Directive in relation to the non-UK clinical trials within whichever is the later of—

(a) the period of one month beginning after the day on which the decision was received; or

(b) the period of one month beginning after the day on which the necessary permission to conduct the clinical trial was received from the competent authorities in the country where the clinical trial is to take place.

(7) Where paragraph (6) applies, the PIP sponsor must submit the results of those clinical trials to the licensing authority within the period of twelve months beginning with the day on which the last of those trials ended, subject to paragraph (8).

(8) Paragraph (7) does not apply in the case of a clinical trial which forms part of a paediatric study to which paragraph (12) applies.

(9) Paragraph (10) applies in relation to the sponsor of a paediatric clinical trial in the United Kingdom in respect of a medicinal product if—

(a) the product has a UK marketing authorisation but the sponsor is not the holder of the authorisation; or

(b) the product does not have a UK marketing authorisation.

(10) Where this paragraph applies, the sponsor of the clinical trial must submit the results of the trial to the licensing authority within the period of twelve months beginning with the day on which the trial ended.

(11) Paragraph (12) applies in relation to the holder of a UK marketing authorisation who sponsors a paediatric clinical trial in respect of the medicinal product to which that authorisation relates.

(12) Where this paragraph applies, the holder of the UK marketing authorisation must submit the results of the trial to the licensing authority within the period of six months beginning with the day on which the trial ended.

(13) Paragraph (14) applies in relation to the holder of a UK marketing authorisation who sponsors a study which involves the use in the paediatric population of a medicinal product to which that UK marketing authorisation relates, irrespective of whether or not—

(a) the studies are conducted in accordance with an agreed paediatric investigation plan; or

(b) the marketing authorisation holder intends to apply for a marketing authorisation for a paediatric indication in relation to the product.

(14) Where this paragraph applies, the holder of the UK marketing authorisation must submit the results of the study to the licensing authority within the period of six months beginning with the day on which the study ended.

(15) Where the licensing authority has granted a deferral of the initiation or completion of some or all of the measures set out in a paediatric investigation plan, in accordance with regulation 50C, the person to whom that decision was addressed must submit to the licensing authority an annual report providing an update on progress with the paediatric studies to which the deferral relates.

(16) The first report referred to in paragraph (15) must be submitted within the period of twelve months beginning with the date on which the licensing authority granted the deferral.

Textual Amendments

F19 Regs. 78A, 78B inserted (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), regs. 1, 87 (as amended by S.I. 2020/1488, reg. 1, Sch. 2 para. 64); 2020 c. 1, Sch. 5 para. 1(1)

Post authorisation requirements in relation to UKMA(GB) for advanced therapy medicinal products U.K.

78B.— (1) The holder of a UKMA(GB) in respect of an advanced therapy medicinal product must—

(a) establish and maintain a system ensuring that the individual product and its starting raw materials, including all substances coming into contact with the cells or tissues it may contain, can be traced through the sourcing, manufacturing, packaging, storage, transport and delivery to the hospital, institution or private practice where the product is used;

(b) where the product contains human tissues or cells, ensure that the traceability system is complementary to and compatible with requirements imposed pursuant to—

(i) as regards gametes and embryos, sections 12(3), and 33A to 33D of, and paragraph 1 of Schedule 3A to, the Human Fertilisation and Embryology Act 1990,

(ii) as regards blood cells, regulations 8, 9(e) and 14 of the Blood Safety and Quality Regulations 2005, and

(iii) as regards other cells and tissues, regulations 13 and 16 of, and paragraph 1 of Schedule 2 to, the Human Tissue (Quality and Safety for Human Application) Regulations 2007;

(c) keep the data referred to in paragraph (a) for a minimum of 30 years after the expiry of the date of the product, or longer if required by the licensing authority as a term of the UKMA(GB); and

(d) in the event of the UKMA(GB) holder's bankruptcy or liquidation occurring within the period of time for which that holder is required to keep the data referred to in paragraph (a), transfer that data to another person or the licensing authority.

(2) The holder of a UKMA(GB) who is subject to the obligations in paragraph (1) remains subject to them even if the UKMA(GB) is suspended or revoked.]

Textual Amendments

F19 Regs. 78A, 78B inserted (31.12.2020) by The Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (S.I. 2019/775), regs. 1, 87 (as amended by S.I. 2020/1488, reg. 1, Sch. 2 para. 64); 2020 c. 1, Sch. 5 para. 1(1)