The Human Medicines (Amendment) (Modular Manufacture and Point of Care) Regulations 2025

PART 3 Amendment of the Medicines for Human Use (Clinical Trials) Regulations 2004

Amendment of regulation 2

39.  In regulation 2(1) (interpretation)(1), at the appropriate places insert—

““manufacturer’s licence (MM)” has the meaning given in regulation 8(1) of the 2012 Regulations;”;

““manufacturer’s licence (POC)” has the meaning given in regulation 8(1) of the 2012 Regulations; ”;

““manufacturing authorisation (MM)” means a manufacturing authorisation that authorises the manufacture or assembly of MM investigational medicinal products;”;

““manufacturing authorisation (POC)” means a manufacturing authorisation that authorises the manufacture or assembly of POC investigational medicinal products;”;

““MM” means modular manufacture;”;

““MM (IMP) control site” means the premises at which the holder of a manufacturing authorisation (MM) supervises and controls the manufacture or assembly of MM investigational medicinal products;”;

““MM (IMP) master file” means a detailed description of the arrangements for manufacture or assembly of an MM investigational medicinal product;”;

““MM investigational medicinal product” means an investigational medicinal product that, for reasons relating to deployment, the licensing authority determines it necessary or expedient to be manufactured or assembled in a modular unit;”;

““modular unit” means a relocatable manufacturing unit;”;

““POC” means point of care;”;

““POC (IMP) control site” means the premises at which the holder of a manufacturing authorisation (POC) supervises and controls the manufacture or assembly of POC investigational medicinal products;”;

““POC (IMP) master file” means a detailed description of the arrangements for the manufacture or assembly of a POC investigational medicinal product;”;

““POC (IMP) site” means a site at which the manufacture or assembly of a POC investigational medicinal product takes place;”;

““POC investigational medicinal product” means an investigational medicinal product that, for reasons relating to method of manufacture, shelf life, constituents or method or route of administration, can only be manufactured at or near the place where the product is to be used or administered;”.

Amendment of regulation 13

40.—(1) Regulation 13 (supply of investigational medicinal products for the purpose of clinical trials)(2) is amended as follows.

(2) In paragraph (2)(b)(i), after “United Kingdom” insert “except for an MM investigational medicinal product or a POC investigational medicinal product”.

(3) After paragraph (2)(b)(i) insert—

“(ia) an MM investigational medicinal product manufactured or assembled in the United Kingdom, the product has been manufactured or assembled in accordance with the terms of a manufacturing authorisation (MM) or assembled under the exemption in regulation 37;

(ib) a POC investigational medicinal product manufactured or assembled in the United Kingdom, the product has been manufactured or assembled in accordance with the terms of a manufacturing authorisation (POC) or assembled under the exemption in regulation 37;”.

Amendment of regulation 36

41.—(1) Regulation 36 (requirement for authorisation to manufacture or import investigational medicinal products)(3) is amended as follows.

(2) In paragraph (1), after “an authorisation” insert “of the appropriate type”.

(3) After paragraph (1) insert—

“(1A) For the purposes of paragraph (1), the appropriate type of authorisation is an authorisation that relates to whichever, or whichever combination, of the following that is appropriate—

(a) manufacture or assembly of investigational medicinal products, except for MM investigational medicinal products and POC investigational medicinal products;

(b) import of investigational medicinal products, except for MM investigational medicinal products and POC investigational medicinal products;

(c) manufacture or assembly of MM investigational medicinal products;

(d) manufacture or assembly of POC investigational medicinal products.”.

(4) After paragraph (2) insert—

“(3) Regulation 36A sets out additional requirements in relation to the manufacture and assembly of MM investigational medicinal products.

(4) Regulation 36B sets out additional requirements in relation to the manufacture and assembly of POC investigational medicinal products.”.

Insertion of new regulations 36A and 36B (manufacture of MM and POC investigational medicinal products)

42.  After regulation 36 (requirement for authorisation to manufacture or import investigational medicinal products) insert—

“Manufacture of MM investigational medicinal products

36A.— (1) No person shall manufacture or assemble an MM investigational medicinal product unless—

(a) the activity and product type is specified in a manufacturing authorisation (MM); and

(b) there is an MM (IMP) master file relating to the product and the product is manufactured and assembled in accordance with that master file.

(2) Paragraph (1) does not apply to the manufacture or assembly of an MM investigational medicinal product to the extent that the manufacture or assembly is in accordance with the terms and conditions of a UK marketing authorisation or a marketing authorisation issued by the competent authority of an EEA State in accordance with Directive 2001/83/EC relating to that product.

Manufacture of POC investigational medicinal products

36B.— (1) No person shall manufacture or assemble a POC investigational medicinal product unless—

(a) the activity and product type is specified in a manufacturing authorisation (POC); and

(b) there is a POC (IMP) master file relating to the product and the product is manufactured and assembled in accordance with that master file.

(2) Paragraph (1) does not apply to the manufacture or assembly of a POC investigational medicinal product to the extent that the manufacture or assembly is in accordance with the terms and conditions of a UK marketing authorisation or a marketing authorisation issued by the competent authority of an EEA State in accordance with Directive 2001/83/EC relating to that product.”.

Amendment of regulation 39

43.  After regulation 39(4) (consideration of application for manufacturing authorisation) insert—

“(4A) If the application for a manufacturing authorisation relates (wholly or partially) to an MM investigational medicinal product, the licensing authority shall take into consideration the arrangements for—

(a) supervising and controlling operations at a modular unit specified in the application; and

(b) ensuring that manufacture or assembly is under appropriate control so that the MM investigational medicinal product consistently meets the requirements in the MM (IMP) master file when manufactured at that modular unit.

(4B)  If the application for a manufacturing authorisation relates (wholly or partially) to a POC investigational medicinal product, the licensing authority shall take into consideration the arrangements for—

(a) supervising and controlling operations at any POC (IMP) site specified in the application; and

(b) ensuring that manufacture or assembly is under appropriate control so that the POC investigational medicinal product consistently meets the requirements in the POC (IMP) master file when manufactured at that site.”.

Amendment of regulation 41

44.  In regulation 41(c) (application and effect of manufacturing authorisation), before “the premises,” insert “except in the case of an MM investigational medicinal product or a POC investigational medicinal product,”.

Amendment of regulation 44

45.  After regulation 44(8) (variation of manufacturing authorisation)(4) insert—

“(9) In the case of an application of a type specified in paragraph (11), the information to be provided under sub-paragraph (d) in the definition of “valid application” in paragraph (8) shall include the information specified in paragraph 10 of Schedule 6.

(10) In the case of an application of a type specified in paragraph (12), the information to be provided under sub-paragraph (d) in the definition of “valid application” in paragraph (8) shall include the information specified in paragraph 11 of Schedule 6.

(11) The following types of application are specified for the purpose of paragraph (9)—

(a) an application to vary the licence so that it relates to the manufacture or assembly of MM investigational medicinal products;

(b) an application to vary a manufacturing authorisation (MM) to add a new MM investigational medicinal product.

(12) The following types of application are specified for the purpose of paragraph (10)—

(a) an application to vary the licence so that it relates to the manufacture or assembly of POC investigational medicinal products;

(b) an application to vary a manufacturing authorisation (POC) to add a new POC investigational medicinal product.

(13) In dealing with an application of a type specified in paragraph (11), the licensing authority shall take into consideration the arrangements made or to be made for—

(a) supervising and controlling operations at a modular unit; and

(b) ensuring that manufacturing or assembly is under appropriate control so that the MM investigational medicinal product consistently satisfies the requirements in the MM (IMP) master file when manufactured at a modular unit.

(14) In dealing with an application of a type specified in paragraph (12), the licensing authority shall take into consideration the arrangements made or to be made for—

(a) supervision and controlling operations at a POC (IMP) site specified in the application; and

(b) ensuring that manufacturing or assembly is under appropriate control so that the POC investigational medicinal product consistently satisfies the requirements in the POC (IMP) master file when manufactured at that POC (IMP) site.”.

Insertion of new regulations 44A and 44B (variation of master files)

46.  After regulation 44 (variation of manufacturing authorisation) insert—

“Variation of MM (IMP) master file

44A.   Subject to regulation 45(5), the holder of a manufacturing authorisation (MM) may amend the information in the MM (IMP) master file provided in accordance with paragraph 10(a), (c) and (h) to (k) of Schedule 6 and paragraph 14E(a) of Schedule 7 without applying to the licensing authority for a variation under regulation 44.

Variation of POC (IMP) master file

44B.   Subject to regulation 45(6), the holder of a manufacturing authorisation (POC) may amend the information in the POC (IMP) master file provided in accordance with paragraph 11(a), (b) and (g) to (i) of Schedule 6 and paragraph 14M(a) of Schedule 7 without applying to the licensing authority for a variation under regulation 44.”.

Amendment of regulation 45

47.—(1) Regulation 45 (suspension and revocation of manufacturing authorisation)(5) is amended as follows.

(2) In paragraph (2)—

(a) at the end of sub-paragraph (a) delete “or”; and

(b) after sub-paragraph (b) insert—

“(c) in the case of a manufacturing authorisation (MM), limited to modular units specified in an MM (IMP) master file associated with the authorisation; or

(d) in the case of a manufacturing authorisation (POC), limited to POC (IMP) sites specified in a POC (IMP) master file associated with the authorisation.”.

(3) After paragraph (4) insert—

“(5) If the licensing authority suspends or revokes a manufacturing authorisation (MM) in accordance with paragraph (2)(c) so that manufacturing or assembly is suspended, or no longer authorised, at a modular unit, the holder of the authorisation may not approve that unit for the purpose of manufacturing or assembly of the MM investigational medicinal product other than by way of an application under regulation 44.

(6) If the licensing authority suspends or revokes a manufacturing authorisation (POC) in accordance with paragraph (2)(d) so that manufacturing or assembly is suspended, or no longer authorised, at a POC (IMP) site, the holder of the authorisation may not approve that site for the purpose of manufacturing or assembly of the POC investigational medicinal product other than by way of an application under regulation 44.”.

Amendment of regulation 46

48.  After regulation 46(2) (labelling of investigational medicinal products)(6) insert—

“(3) Paragraph (1) does not apply to a POC investigational medicinal product that is to be administered in its entirety immediately after manufacture.”.

Amendment of regulation 48

49.  In regulation 48(4) (infringement notices)(7), for “31A and 32 to 35” substitute “31A, 32 to 35, 36A and 36B”.

Amendment of regulation 49

50.  In regulation 49(1) (offences)(8), after sub-paragraph (k) insert—

“(ka) regulation 36A;

(kb) regulation 36B;”.

Amendment of Schedule 6

51.—(1) Schedule 6 (particulars that must accompany an application for a manufacturing authorisation)(9) is amended as follows.

(2) In paragraph 2, after “forms” insert “and whether any of them is an MM investigational medicinal product or a POC investigational medicinal product”.

(3) In paragraph 3—

(a) in sub-paragraph (a), after “products” insert “, including specifically MM investigational medicinal products or POC investigational medicinal products”;

(b) in sub-paragraph (b), after “products” insert “, including specifically MM investigational medicinal products or POC investigational medicinal products”; and

(c) in sub-paragraph (c), after “products” insert “except for MM investigational medicinal products and POC investigational medicinal products”.

(4) In paragraph 4—

(a) in sub-paragraph (1), at the beginning insert “Except where the application relates to an MM investigational medicinal product or a POC investigational medicinal product,”;

(b) after sub-paragraph (1) insert—

“(1A) Where the application relates to an MM investigational medicinal product, the address of the MM (IMP) control site and the location of any testing associated with manufacture or assembly that is, or is to be, carried out.

(1B) Where the application relates to a POC investigational medicinal product, the address of the POC (IMP) control site and the location of any testing associated with manufacture or assembly that is, or is to be, carried out.”;

(c) after sub-paragraph (2) insert—

“(2A) Where the application relates to an MM investigational medicinal product, the address of each of the premises other than the MM (IMP) control site where the proposed holder of the manufacturing authorisation (MM) proposes to store components or equipment to be used in the manufacturing process.

(2B)  Where the application relates to a POC investigational medicinal product, the address of each of the premises other than the POC (IMP) control site where the proposed holder of the manufacturing authorisation (POC) proposes to store components or equipment to be used in the manufacturing process.”; and

(d) in sub-paragraphs (3), (4) and (5), for “(1) and (2)” substitute “(1) to (2B) (as applicable)”.

(5) After paragraph 9 insert—

“10.   Where the application relates to an MM investigational medicinal product, the application for each product must be accompanied by a dossier which includes, as a minimum, the following:

(a) a description and means of identification of each modular unit at which manufacture or assembly of the MM investigational medicinal product is to take place;

(b) the location of each unit at which manufacturing or assembly of the MM investigational medicinal product is to take place;

(c) the location of each site at which operations related to the manufacture or assembly of the MM investigational medicinal product are to take place;

(d) a description of the process by which the proposed holder of the authorisation will approve new modular units;

(e) a description of the processes by which the proposed holder of the authorisation will initiate, suspend and cease manufacturing or assembly of the product at a modular unit;

(f) a description of the manufacturing, assembly and product release processes to take place at each modular unit;

(g) a description of the arrangements for supervision and control by the proposed holder of the authorisation of the manufacture or assembly operations at each modular unit;

(h) a description of the arrangements for reporting of suspected adverse reactions from modular units to the MM (IMP) control site;

(i) the name and contact details of the person at the MM (IMP) control site who is to be contacted in respect of manufacturing or assembly operations under the authorisation;

(j) the name and contact details of the person to be contacted in respect of manufacturing or assembly operations at each modular unit;

(k) the name and contact details of the person at the MM (IMP) control site who is to be contacted in respect of quality operations under the authorisation;

(l) the name and contact details of the person to be contacted in respect of quality operations at each modular unit; and

(m) a description of the processes by which the proposed holder of the authorisation will review and amend the MM (IMP) master file for the product.

11.   Where the application relates to a POC investigational medicinal product, the application for each product must be accompanied by a dossier which includes, as a minimum, the following:

(a) the location of each site at which manufacturing or assembly of the POC investigational medicinal product is to take place;

(b) the location of each site at which operations related to the manufacture or assembly of the POC investigational medicinal product are to take place;

(c) a description of the process by which the proposed holder of the authorisation will approve new POC (IMP) sites;

(d) a description of the processes by which the proposed holder of the authorisation will suspend and cease manufacturing or assembly of the POC investigational medicinal product at a POC (IMP) site;

(e) a description of the manufacturing, assembly and product release processes to take place at each POC (IMP) site;

(f) a description of the arrangements for supervision and control by the proposed holder of the authorisation of the manufacture or assembly operations at each POC (IMP) site;

(g) a description of the arrangements for reporting of suspected adverse reactions from POC (IMP) sites to the POC (IMP) control site;

(h) the name and contact details of the person at the POC (IMP) control site who is to be contacted in respect of manufacturing or assembly operations under the authorisation;

(i) the name and contact details of the person to be contacted in respect of manufacturing or assembly operations at each POC (IMP) site;

(j) the name and contact details of the person at the POC (IMP) control site who is to be contacted in respect of quality operations under the authorisation;

(k) the name and contact details of the person to be contacted in respect of quality operations at each POC (IMP) site; and

(l) a description of the processes by which the proposed holder of the authorisation will review and amend the POC (IMP) master file for the product.”.

Amendment of Schedule 7

52.—(1) Part 2 of Schedule 7 (standard provisions for manufacturing authorisation)(10) is amended as follows.

(2) In paragraph 1—

(a) for sub-paragraph (a) substitute the following—

“(a) provide and maintain such staff, premises and plant (including technical equipment) as are necessary for the carrying out of such stages of the manufacture and assembly of the investigational medicinal products or EAMs medicinal products as are undertaken by the holder, in accordance with the following—

(i) the holder’s authorisation;

(ii) the product specification;

(iii) the MM (IMP) master file, in the case of an MM investigational medicinal product; and

(iv) the POC (IMP) master file, in the case of a POC investigational medicinal product; ” and

(b) in sub-paragraph (b), at the beginning insert “except in the case of an MM investigational medicinal product and a POC investigational medicinal product,”.

(3) In paragraph 2(b), after “authorisation” insert “or, in the case of an MM investigational medicinal product, the MM (IMP) master file and in the case of a POC investigational medicinal product, the POC (IMP) master file,”.

(4) After paragraph 2 insert—

“2A.   The holder of a manufacturing authorisation (MM) shall not use premises other than the MM (IMP) control site and the modular units specified in the MM (IMP) master file for the purposes specified in paragraph 2(a).

2B.   The holder of a manufacturing authorisation (POC) shall not use premises other than the POC (IMP) control site and the sites specified in the POC (IMP) master file for the purposes specified in paragraph 2(a).”.

(5) In paragraph 6(a), at the beginning insert “except in the case of an MM investigational medicinal product or a POC investigational medicinal product,”.

(6) After paragraph 6 insert—

“6A.   The holder of the authorisation shall inform the licensing authority before making a material alteration to the premises or plant used at the MM (IMP) control site or to any modular unit specified in the MM (IMP) master file, or to the operations for which they are used.

6B.   The holder of the authorisation shall inform the licensing authority before making a material alteration to the premises or plant used at the POC (IMP) control site, or to the operations for which they are used.”.

(7) After paragraph 14A insert—

“Part 2A Manufacturing authorisation (MM)

14B.   The provisions of paragraphs 14C to 14I are incorporated as additional standard provisions of a manufacturing authorisation (MM).

14C.   The holder of the authorisation shall maintain and make available on request of the licensing authority an MM (IMP) master file for each MM investigational medicinal product to which the authorisation relates.

14D.   Each master file may relate to one MM investigational medicinal product only.

14E.   An MM (IMP) master file shall contain, as a minimum, the following information:

(a) the information specified in paragraph 10 of Schedule 6; and

(b) the location of any modular units at which manufacturing or assembly of the MM investigational medicinal product has commenced, has been suspended or has ceased, and the date on which manufacturing or assembly commenced, the dates on which it is suspended, or the date from which it has ceased.

14F.   The holder of the authorisation shall ensure that the information in the MM (IMP) master file is kept up to date at all times.

14G.   The holder of the authorisation shall submit to the licensing authority at annual intervals an update of any changes to the MM (IMP) master file made in the previous 12 month period, the first update being required to be submitted no later than the date that is 12 months from the date on which the manufacturing authorisation (MM) was granted.

14H.   The holder of the authorisation shall conduct regular reviews of the arrangements for supervision and control of the manufacture or assembly operations at each modular unit and ensure that, where appropriate, remedial action is taken as soon as reasonably practicable.

14I.   The holder of a manufacturing authorisation (MM) shall ensure that—

(a) the requirements of paragraphs 1 to 14 and 14C to 14H are complied with in relation to manufacturing carried out at the modular units specified in the MM (IMP) master file;

(b) only the MM investigational medicinal products specified in the MM (IMP) master file are manufactured or assembled at those modular units; and

(c) an MM investigational medicinal product specified in the MM (IMP) master file is only manufactured on premises specified in the MM (IMP) master file.

Part 2B manufacturing authorisation (POC)

14J.   The provisions of paragraphs 14K to 14Q are incorporated as additional standard provisions of a manufacturing authorisation (POC).

14K.   The holder of the authorisation shall maintain and make available on request of the licensing authority a POC (IMP) master file for each POC investigational medicinal product to which the authorisation relates.

14L.   Each master file may relate to one POC investigational medicinal product only.

14M.   A POC (IMP) master file shall contain, as a minimum, the following information:

(a) the information specified in paragraph 11 of Schedule 6; and

(b) the location of any POC (IMP) sites at which manufacturing or assembly of the POC investigational medicinal product has commenced, has been suspended or has ceased, and the date on which manufacturing or assembly commenced, the dates on which it is suspended, or the date from which it has ceased.

14N.   The holder of the authorisation shall ensure that the information in the POC (IMP) master file is kept up to date at all times.

14O.   The holder of the authorisation shall submit to the licensing authority at annual intervals an update of any changes to the POC (IMP) master file made in the previous 12 month period, the first update being required to be submitted no later than the date that is 12 months from the date on which the manufacturing authorisation (POC) was granted.

14P.   The holder of the authorisation shall conduct regular reviews of the arrangements for supervision and control of the manufacture or assembly operations at each POC (IMP) site and ensure that, where appropriate, remedial action is taken as soon as reasonably practicable.

14Q.   The holder of a manufacturing authorisation (POC) shall ensure that—

(a) the requirements of paragraphs 1 to 14 and 14K to 14P are complied with in relation to manufacturing carried out at the POC (IMP) sites specified in the POC (IMP) master file;

(b) only the POC investigational medicinal products specified in the authorisation are manufactured or assembled at those sites; and

(c) a POC investigational medicinal product specified in the authorisation is only manufactured at a POC (IMP) site specified in the POC (IMP) master file.”.

(1)

Amended by S.I. 2019/744. There are other amendments but none is relevant.

(2)

Paragraph (2)(b) was substituted by S.I. 2019/775. There are other amendments but none is relevant.

(3)

There are amendments but none is relevant.

(4)

Regulation 44(8) was substituted by S.I. 2006/1928.

(5)

There are amendments but none is relevant.

(6)

There are amendments but none is relevant.

(7)

Regulation 48 has been amended by S.I. 2006/1928. There are other amendments but none is relevant.

(8)

Regulation 49 has been amended by S.I. 2006/1928. There are other amendments but none is relevant.

(9)

Paragraph 2 was substituted by S.I. 2006/1928. There are other amendments but none is relevant.

(10)

Paragraphs 1 and 2 were amended by S.I. 2022/352. There are other amendments but none is relevant.