Human medicines Modular Manufacture and Point of Care regulations 2025: Overview

Question 1

1.Introduction

Accepted Answer

POC guidance – legislation

1.1 New types of innovative medicinal products, such as those with very short shelf lives, must be manufactured and supplied at the point where a patient receives care (POC). Up until now, human medicines legislation is geared for medicines which can be manufactured at a very small number of sites and supplied globally. In contrast, POC medicinal products may only have a shelf life of seconds or minutes or need to be highly personalised, so must be manufactured on demand when the patient is present. This could mean manufacturing a POC medicinal product at hundreds of sites across the UK alone. This document provides guidance on the new regulatory framework that will support the manufacture and supply of these innovative products.

1.2 The new regulatory framework is based on and links into the current regulatory systems for human medicine approvals, clinical trials, evaluation of regulatory compliance at manufacturing sites and safety monitoring. The safety, quality and efficacy of POC medicinal products has to remain paramount. This new framework is similar in concept to that established for control of blood products, which delivers regulatory control of quality while delivering the necessary flexibilities for the product type.

1.3 The new regulatory framework supports increased manufacture and supply of new medicinal products manufactured at POC whilst ensuring that they retain equivalent levels of safety, quality and efficacy currently in place for medicinal products manufactured in factory-based locations. The new regulatory framework, tailored to these innovative medicinal products, will improve the availability of novel products, benefiting patients across the UK.

1.4 POC medicinal products can span much of the pharmaceutical spectrum and include:

some types of advanced therapy medicinal products (ATMPs – cell therapy, gene therapy and tissue-engineered products)
3D printed products that can only be printed at the point of care
blood products
medical gases

1.5 Up until now the regulatory framework is primarily geared to the ‘standard model’ of fixed factory-based manufacturing sites, which for any individual product has a relatively small number of sites. The new and broadening spectrum of manufacturing options, sometimes referred to as ‘distributed manufacture’, has a range of manufacturing categories including:

point of care manufacture: medicines manufactured and supplied at the point where a patient receives care - this can include home-based manufacture – some technologies currently permit activities classified as medicinal product manufacture to occur at home, and with technological advances this is set to increase (this is being enabled by increasingly sophisticated manufacturing devices and the ability to control these remotely when the device and supplied starting materials are used by a patient)
modular manufacture: these can be prefabricated manufacturing units which may be totally self-contained or require connection to various services at the new site - they may be moved at intervals measuring months or years, sequentially to different factory or clinical sites
mobile manufacture: mobile micro-factories that can be deployed at clinical centres or military field when required

1.6 This guidance reports on the changes to UK medicines legislation supporting the new framework governing these areas. It does not cover technical aspects of good practices for the supply of such medicines which is covered elsewhere.

1.7 The licensing authority is defined in regulation 6 of the Human Medicines Regulations 2012. The licensing authority consists of the Secretary of State for Health and the Minister for Health in Northern Ireland. By convention, the licensing authority’s functions are performed by the Secretary of State for the whole of the UK and the Secretary of State acts through the MHRA. A reference to the MHRA in this document is a reference to the licensing authority.

Question 2

2.  The Human Medicines Regulations 2012

Accepted Answer

The Human Medicines Regulations 2012 (“HMR 2012”) have been amended to take account of the manufacture of a point of care (POC) medicinal product (this includes home-base manufacture) and modular manufactured (MM) medicinal product (this includes mobile manufacture) by The Human Medicines (Amendment) (Modular Manufacture and Point of Care) Regulations 2025 [SI 2025 No. 87], which come into force on 23 July 2025.

2.1 Interpretation

^{[footnote 1]}

2.1.1 HMR 2012 provides definitions for this new regime: 

“POC” means point of care
“POC medicinal product” means a 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
“manufacturer’s licence (POC)” means a manufacturer’s licence that relates to the manufacture or assembly of the POC medicinal products specified in that licence
“POC control site” means the premises at which the holder of a manufacturer’s licence (POC) supervises and controls the manufacture of POC medicinal products
“POC master file” means a detailed description of the arrangements for the manufacture or assembly of a POC medicinal product
“POC site” means a site at which the manufacture or assembly of a POC medicinal product takes place
“MM” means modular manufacture
“MM medicinal product” means a medicinal product that, for reasons related to deployment, the licensing authority determines it necessary or expedient to be manufactured or assembled in a modular unit
“manufacturer’s licence (MM)” means a manufacturer’s licence that relates to the manufacture or assembly of the MM medicinal products specified in that licence
“MM control site” means the premises at which the holder of a manufacturer’s licence (MM) supervises and controls the manufacture or assembly of MM medicinal products 
“MM master file” means a detailed description of the arrangements for the manufacture or assembly of an MM medicinal product
“modular unit” means a relocatable manufacturing unit

2.1.2 These definitions are used throughout this part of the guidance.

2.2 Manufacture

 ^{[footnote 2]} 

2.2.1 A POC medicinal product or MM medicinal product can be manufactured or assembled under a manufacturer’s licence of the appropriate type. This can be either a manufacturer’s licence (MIA) for a licensed POC medicinal product or MM medicinal product or a manufacturer’s specials licence if the POC medicinal product or MM medicinal product is a special medicinal product.  

2.2.2 You may not manufacture or assemble a POC medicinal product unless it is specified in a manufacturer’s licence (POC) and manufactured or assembled in accordance with that licence and there is a POC master file relating to that product, and it is manufactured or assembled in accordance with that master file.  

2.2.3 Similarly, you may not manufacture or assemble a MM medicinal product unless it is specified in a manufacturer’s licence (MM) and manufactured or assembled in accordance with that licence and there is a MM master file relating to that product and it is manufactured or assembled in accordance with that master file. 

2.2.4 Existing holders of a manufacturer’s licence (MIA) or manufacturer’s specials licence can apply to vary their licence to include the manufacture of a POC medicinal product and name a POC control site or a MM medicinal product and name a MM control site.  

2.3 Exemptions

^{[footnote 3]} 

2.3.1 HMR 2012 sets out some exemptions from the need for a marketing authorisation and or manufacturer’s licence for certain healthcare professionals and some medicines.  

2.3.2 Regulation 3(4) provides where a medicinal product is assembled by a registered nurse, or a registered midwife and the nurse or registered midwife is acting in the course of his or her profession a manufacturer’s licence is not required. The medicinal product must be supplied to a patient in the course of the treatment of that patient and it cannot be manufactured or assembled on a large scale, or by an industrial process.

2.3.3 Regulation 3(5) allows a doctor or dentist to manufacture or assemble a medicinal product without a marketing authorisation or manufacturer’s licence provided the medicinal product is supplied to a patient during the treatment of that patient or to a patient of another doctor or dentist who is a member of the same medical or dental practice. In addition, the medicinal product cannot be manufactured or assembled on a large scale, or by an industrial process.

2.3.4 Regulation 3(6) also provides that a herbal practitioner may manufacture or assembly a herbal medicinal product on their premises (that can exclude the public) without a marketing authorisation or manufacturer’s licence for a person under their care where they have been asked by that person in their presence to use their judgment as to the treatment they require. The medicinal product cannot contain certain specified substances, or be manufactured or assembled on a large scale, or by an industrial process and must be appropriately labelled.

2.3.5 A product that is a radionuclide in the form of a sealed source is excluded from the exemptions set out in regulation 3 referred to above.

2.3.6 Regulation 3A ensures that all professionally justified acts of preparation and assembly of a coronavirus vaccine may be undertaken by or under the supervision of a doctor, nurse or pharmacist, at any location, without precipitating the need for a manufacturer’s licence or marketing authorisation – provided those acts are done under NHS arrangements or arrangements as part of the medical services of His Majesty’s Forces.

2.3.7 Regulation 3A also allows for authorised medicinal products used for the reformulation of coronavirus vaccines (for example, diluents) to be re-assembled at the end of the medicines supply chain without the resultant products needing marketing authorisations in order to be supplied. Provision is also made to allow holders of wholesale dealer’s licences who do not have manufacturer’s licences to label coronavirus vaccines to take account of changes to the shelf life of the vaccines because of the thawing of the product. There is also a change in relation to the application of the packaging and package leaflet requirements of the 2012 Regulations to take account of these other changes. Regulation 3A will cease to have effect on 1st April 2026.

2.3.8 Regulation 4, when read with section 10 of the Medicines Act 1968, contain exemptions from the requirements to hold a manufacturer’s licence and a marketing authorisation that relate to extemporaneous preparation. assembly and dispensing of a medicine in accordance with a prescription, undertaken at the end of the medicines supply chain in a registered pharmacy, a hospital, a care home service or a health centre and is done there by or under the supervision of a pharmacist.

2.3.9 Regulation 20 sets out an exemption from the need for a manufacturer’s licence for the mixing of medicines at the bedside used by specified persons. Independent prescribers, supplementary prescribers or a person acting in accordance with the written directions can mix medicine(s) at the bedside for the purposes of administering them to meet the needs of an individual patient. 

2.3.10 Regulation 173 provides an exemption from the requirement of a further marketing authorisation where a radiopharmaceutical is prepared at the time when it is intended to be administered, in accordance with the manufacturer’s instructions and by the person by whom it is to be administered, from radionuclide generators, radionuclide kits and radionuclide precursors in respect of which a marketing authorisation is in force. Where it is for administration in England and Wales and Scotland it must also be in accordance with a licence issued under the Ionising Radiation (Medical Exposure) Regulations 2017 or in Northern Ireland in accordance with a licence issued under the Ionising Radiation (Medical Exposure) Regulations (Northern Ireland) 2018.

General

2.3.11 These exemptions are not applicable for the manufacture of a POC medicinal product or a MM medicinal product. This is because a POC medicinal product and a MM medicinal product must be manufactured by the holder of a manufacturer’s licence for POC or MM which names a POC or MM control site responsible for the POC and MM master file for a specific POC medicinal product or MM medicinal product. 

2.3.12 In the case of regulation 3(4), 3(5) and 3(6) these are restricted so that the medicinal product cannot be manufactured or assembled on a large scale, or by an industrial process. The manufacture of a POC medicinal product or a MM medicinal product will be subject to manufacture by an industrial process.

2.3.13 Whilst regulation 3A allows collaborative working with certain healthcare professions it is limited to acts of preparation and assembly of a coronavirus vaccine. Regulation 3A will cease to have effect on 1st April 2026.

2.3.14 Regulation 4, when read with section 10 of the Medicines Act 1968, remains for extemporaneous preparation, assembly and dispensing of a medicine by or under the supervision of a pharmacist in an appropriate pharmacy healthcare setting which has not changed. Whilst section 10 of the Medicines Act 1968 has not been amended to prohibit the dispensing of a POC or MM medicine if such an activity was required it would have to be under appropriate circumstances.

2.3.15 Regulation 20 sets out an exemption from the need for a manufacturer’s licence for the mixing of medicines at the bedside used by specified persons. Because the activity is carried out at the bedside, it has been made clear by amendment that the exemption does not apply to a POC medicinal product or MM medicinal product. The exemption has not been altered in any other respect. Independent prescribers, supplementary prescribers or a person acting in accordance with the written directions can still mix medicine(s) at the bedside for the purposes of administering them to meet the needs of an individual patient.

Radiopharmaceuticals

2.3.16 In the UK, manufacturers of radiopharmaceuticals for human use are licensed by way of a manufacturer’s licence (MIA or MS “specials”) and inspected to confirm that licence holders are complying with the conditions of their licence, with the provisions of UK human medicines legislation and with the guidance on good manufacturing practice (GMP).

2.3.17 Specifically with respect to unlicensed medicines, the manufacture of an unlicensed radiopharmaceutical may occur at a hospital with a manufacturer’s “specials” licence which is inspected for GMP or in a hospital radio pharmacy, by or under the supervision of a pharmacist, under section 10 of the Medicines Act. Radiopharmaceuticals made up in a hospital radio pharmacy under Section 10 of the Medicines Act can also include licensed radiopharmaceuticals as well.

2.3.18 If the radiopharmaceutical is supplied outside of the hospital’s legal entity the production will have to be covered a manufacturer’s “specials” licence under GMP conditions.

2.3.19 Radiopharmaceuticals have an established supply regime which is not generally affected by the new POC measures. However, any new innovation in this area can be considered by MHRA for POC or MM.

2.4 Applying for a licence / factors relevant to determination of application for manufacturer’s licence

2.4.1 An applicant for a manufacturer’s licence (POC) for a POC medicinal product or manufacturer’s licence (MM) for a MM medicinal product will be asked to provide the address of the POC control site or the address of the MM control site, and a statement of whether any of the medicinal products to be manufactured or assembled are MM medicinal products or POC medicinal products.  

Application dossier

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2.4.2 In addition, the application for a manufacturer’s licence (POC) for a POC medicinal product must be accompanied by a dossier for each POC medicinal product to which the application relates, containing, as a minimum, the following: 

the location of each site at which manufacturing or assembly of the POC medicinal product is to take place
the location of each site at which operations related to the manufacture or assembly of the POC medicinal product are to take place
a description of the process by which the licence holder will approve new POC sites
a description of the processes by which the licence holder will suspend and cease manufacturing or assembly of the product at a POC site
a description of the manufacturing, assembly and product release processes to take place at each POC site
a description of the arrangements for supervision and control by the licence holder of the manufacture or assembly operations at each POC site
a description of the arrangements for reporting of suspected adverse reactions from POC sites to the POC control site
the name and contact details of the person at the POC control site to contact in respect of manufacturing or assembly operations under the licence
the name and contact details of the person to contact in respect of manufacturing or assembly operations at each POC site
the name and contact details of the person at the POC control site to contact in respect of quality operations under the licence
the name and contact details of the person to contact in respect of quality operations at each POC site
a description of the processes by which the licence holder will review and amend the POC master file for the product

2.4.3 In dealing with an application for a manufacturer’s licence (POC) for a POC medicinal product the MHRA will take into consideration the arrangements for supervising and controlling operations at any POC site and ensuring that manufacture or assembly is under appropriate control so that the POC medicine consistently meets the requirements in the POC master file when manufactured at each of those POC sites.^{[footnote 5]}

2.4.4 Similarly, the application relating to a manufacturer’s licence (MM) for a MM medicinal product must be accompanied by a dossier for each MM medicinal product to which the application relates, containing, as a minimum, the following: 

a description and means of identification of each modular unit at which manufacture or assembly of the MM medicinal product is to take place
the location of each unit at which manufacturing or assembly of the MM medicinal product is to take place
the location of each site at which operations related to the manufacture or assembly of the MM medicinal product are to take place
a description of the process by which the licence holder will approve new modular units
a description of the processes by which the licence holder will initiate, suspend or cease manufacturing or assembly of the product at a modular unit
a description of the manufacturing, assembly and product release processes to take place at each modular unit
a description of the arrangements for supervision and control by the licence holder of the manufacture or assembly operations in each modular unit
a description of the arrangements for reporting of suspected adverse reactions from modular units to the MM control site
the name and contact details of the person at the MM control site to contact in respect of manufacturing or assembly operations under the licence
the name and contact details of the person to contact in respect of manufacturing or assembly operations at each modular unit
the name and contact details of the person at the MM control site to contact in respect of quality operations under the licence
the name and contact details of the person to contact in respect of quality operations at each modular unit
a description of the processes by which the licence holder will review and amend the MM master file for the product

2.4.5 In dealing with an application for a manufacturer’s licence (MM) the MHRA will take into consideration the arrangements for supervising and controlling operations at a modular unit specified in the application and ensuring that manufacture or assembly is under appropriate control so that the MM medicinal product consistently meets the requirements in the MM master file when manufactured at that modular unit. ^{[footnote 6]}

2.5 Manufacturing and assembly of POC medicinal products or MM medicinal product - obligations ^{[footnote 7]}

2.5.1 The holder of a manufacturer’s licence (POC) for a POC medicinal product or manufacturer’s licence (MM) for a MM medicinal product must ensure that certain obligations are complied with in relation to manufacturing carried out at the POC sites specified in the POC master file or MM sites specified in the MM master file. This includes that the licence holder: 

must comply with the principles and guidelines for good manufacturing practice, and  
must maintain such staff, premises and equipment as are necessary for the stages of manufacture and assembly of POC medicinal products or MM medicinal product undertaken by the licence holder in accordance with the POC master file or MM master file respectively

2.5.2 The holder of a manufacturer’s licence (POC) for a POC medicinal product must:^{[footnote 8]}

ensure only the POC medicinal products specified in the licence are manufactured or assembled at the POC sites specified in the POC master file and a POC medicinal product specified in the licence is only manufactured or assembled on premises specified in the POC master file
ensure that the medicinal products specified in the licence are not handled, controlled, stored or distributed on any premises other than the POC control site and those specified in the POC master file (this does not apply to anything done in the course of the business of a hospital that consists of dealing with a medicine or making it ready for use for the purposes of its final supply or administration to a patient)
inform the licensing authority before making a material alteration to the premises or facilities at the POC control site, or to the purposes for which those premises or facilities are used

2.5.3 The holder of a manufacturer’s licence (MM) must:^{[footnote 9]}

ensure that only the MM medicinal products specified in the licence are manufactured or assembled in the modular units specified in the MM master file
ensure that the medicinal products specified in the licence are not handled, controlled, stored or distributed on any premises other than the MM control site and the modular units specified in the MM master file (this does not apply to anything done in the course of the business of a hospital that consists of dealing with a medicine or making it ready for use for the purposes of its final supply or administration to a patient)
inform the licensing authority before making a material alteration to the premises or facilities at the MM control site, or to any modular unit specified in the MM master file, or to the purposes for which those premises or facilities are used

2.5.4 The manufacturer’s licence (POC) holder for a POC medicinal product must maintain a POC master file for each POC medicinal product specified in the licence. Each POC master file may relate to one POC medicinal product only.^{[footnote 10]}

2.5.5 A POC master file must contain, as a minimum, the information specified in the application dossier (see paragraph 2.4.2) and the location of any POC sites at which manufacturing or assembly of the POC medicinal product has commenced, has been suspended or has ceased, the date on which manufacturing or assembly commenced or ceased, and the dates on which it was suspended.  

2.5.6 The manufacturer’s licence (POC) holder for a POC medicinal product must: 

ensure that the information contained in the POC master file is kept up to date, and consistent with any UK marketing authorisation for the product, at all times
make the POC master file available to the licensing authority at all times on request 
submit to the MHRA, at annual intervals, an update of any changes to the POC 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 manufacturer’s licence (POC) was granted
keep under review the arrangements for supervision and control of the manufacture or assembly operations at each POC site and, if the arrangements are found to be inadequate, ensure that appropriate remedial action is taken as soon as reasonably practicable
record all suspected adverse reactions to the POC medicinal product which are brought to its attention
not refuse to consider reports of suspected adverse reactions to the product received electronically or by any other appropriate means from patients or from health care professionals
report suspected adverse reactions identified to the holder of any UK marketing authorisation, or the EAMS scientific opinion holder (if applicable), relating to the POC medicinal product, as soon as reasonably practicable after the licence holder gained knowledge of the reaction

2.5.7 The manufacturer’s licence (MM) holder must maintain a MM master file for each MM medicinal product specified in the licence. Each MM master file may relate to one MM medicinal product only.  

2.5.8 The MM master file must contain, as a minimum, the following information:

the information specified in the application dossier (see paragraph 2.4.4) 
the location and identification of any modular unit at which manufacturing, or assembly of the MM medicinal product has commenced, has been suspended or has ceased, the date on which manufacturing or assembly commenced or ceased, and the dates on which it was suspended

2.5.9 The manufacturer’s licence (MM) holder must: 

ensure that the information contained in the MM master file is kept up to date, and consistent with any marketing authorisation for the product, at all times 
make the MM master file available to the MHRA at all times on request
submit to the MHRA, at annual intervals, an update of any changes to the MM 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 manufacturer’s licence (MM) was granted
keep under review the arrangements for supervision and control of the manufacture or assembly operations at each modular unit and, if the arrangements are found to be inadequate, ensure that appropriate remedial action is taken as soon as reasonably practicable
record all suspected adverse reactions to the MM medicinal product which are brought to the licence holder’s attention
not refuse to consider reports of suspected adverse reactions to the product received electronically or by any other appropriate means from patients or from health care professionals
report suspected adverse reactions identified to the holder of the UK marketing authorisation, or the EAMS scientific opinion holder (as applicable), relating to the MM medicinal product as soon as reasonably practicable after the licence holder gains knowledge of the reaction

2.6 Qualified persons^{[footnote 11]}

2.6.1 The qualified person named on a manufacturer’s licence is responsible for securing that each batch of medicinal products manufactured in Great Britain and Northern Ireland has been manufactured and checked in accordance with the manufacturing provisions in the HMR 2012 and the requirements of the authorisation to market relating to those products.

2.6.2 In the case of an MM medicinal product or a POC medicinal product, the above obligations of the QP (in paragraphs 12(1)(a) and 12A(1)(a) of schedule 7 of HMR 2012) may be satisfied by securing that each product has been manufactured and checked in accordance with the regulations and the requirements of the marketing authorisation relating to the product.

2.7 Variation of a manufacturer’s licence ^{[footnote 12]}

2.7.1 In the case of an application to vary a manufacturer’s licence so that it relates to the manufacture or assembly of POC medicinal products or an application to vary a manufacturer’s licence (POC) for a POC medicinal product to add a new POC medicinal product, the application must be accompanied by a dossier for each POC medicinal product to which the application relates, containing, as a minimum, the following (also referred to in paragraph 2.4.2) (1B(2) of Schedule 3): 

the location of each site at which manufacturing or assembly of the POC medicinal product is to take place
the location of each site at which operations related to the manufacture or assembly of the POC medicinal product are to take place
a description of the process by which the licence holder will approve new POC sites
a description of the processes by which the licence holder will suspend and cease manufacturing or assembly of the product at a POC site
a description of the manufacturing, assembly and product release processes to take place at each POC site
a description of the arrangements for supervision and control by the licence holder of the manufacture or assembly operations at each POC site
a description of the arrangements for reporting of suspected adverse reactions from POC sites to the POC control site
the name and contact details of the person at the POC control site to contact in respect of manufacturing or assembly operations under the licence
the name and contact details of the person to contact in respect of manufacturing or assembly operations at each POC site
the name and contact details of the person at the POC control site to contact in respect of quality operations under the licence
the name and contact details of the person to contact in respect of quality operations at each POC site
a description of the processes by which the licence holder will review and amend the POC master file for the product

2.7.2 The MHRA must take into consideration the arrangements made or to be made for:^{[footnote 13]}

supervising and controlling operations at a POC site specified in the application
ensuring that manufacturing or assembly is under appropriate control so that the POC medicinal product consistently satisfies the requirements in the POC master file when manufactured at that POC site

2.7.3 In the case of an application to vary a manufacturer’s licence so that it relates to the manufacture or assembly of MM medicinal products or an application to vary a manufacturer’s licence (MM) to add a new MM medicinal product, the application must be accompanied by a dossier for each MM medicinal product to which the application relates, containing, as a minimum, the following (also referred to in paragraph 2.4.2): ^{[footnote 14]}

a description and means of identification of each modular unit at which manufacture or assembly of the MM medicinal product is to take place
the location of each site at which manufacturing or assembly of the MM medicinal product is to take place
the location of each site at which operations related to the manufacture or assembly of the MM medicinal product are to take place
a description of the process by which the licence holder will approve new modular units
a description of the processes by which the licence holder will suspend or cease manufacturing or assembly of the product at a modular unit
a description of the manufacturing, assembly and product release processes to take place at each modular unit
a description of the arrangements for supervision and control by the licence holder of the manufacture or assembly operations in each modular unit
a description of the arrangements for reporting suspected adverse reactions from modular units to the MM control site
the name and contact details of the person at the MM control site to contact in respect of manufacturing or assembly operations under the licence
the name and contact details of the person to contact in respect of manufacturing or assembly operations at each modular unit
the name and contact details of the person at the MM control site to contact in respect of quality operations under the licence
the name and contact details of the person to contact in respect of quality operations at each modular unit
a description of the processes by which the licence holder will review and amend the MM master file for the product

2.7.4 The MHRA must take into consideration the arrangements made or to be made for:^{[footnote 15]}

supervising and controlling operations at a modular unit
ensuring that manufacture or assembly is under appropriate control so that the MM medicinal product consistently satisfies the requirements in the MM master file when manufactured at a modular unit

2.8 Variation of POC master file or MM master file^{[footnote 16]}  

2.8.1 The holder of the manufacturer’s licence (POC) for a POC medicinal product or a manufacturer’s licence (MM) for a MM medicinal product is not required to apply to the MHRA for a variation to amend the POC master file or the MM master file, where matters relate to:

a) POC master file:^{[footnote 17]}

the location of each site at which manufacturing or assembly of the POC medicinal product is to take place
the location of each site at which operations related to the manufacture or assembly of the POC medicinal product are to take place
a description of the arrangements for reporting of suspected adverse reactions from POC sites to the POC control site
the name and contact details of the person at the POC control site to contact in respect of manufacturing or assembly operations under the licence
the name and contact details of the person to contact in respect of manufacturing or assembly operations at each POC site
the name and contact details of the person at the POC control site to contact in respect of quality operations under the licence

b) MM master file:^{[footnote 18]}

a description and means of identification of each modular unit at which manufacture or assembly of the MM medicinal product is to take place
the location of each site at which operations related to the manufacture or assembly of the MM medicinal product are to take place
a description of the arrangements for reporting of suspected adverse reactions from modular units to the MM control site
the name and contact details of the person at the MM control site to contact in respect of manufacturing or assembly operations under the licence
the name and contact details of the person to contact in respect of manufacturing or assembly operations at each modular unit
the name and contact details of the person at the MM control site to contact in respect of quality operations under the licence

2.8.2 However, if the MHRA suspends or varies a manufacturer’s licence (POC) for a POC medicinal product or a manufacturer’s licence (MM) for a MM medicinal product, so that manufacturing or assembly is suspended, or no longer authorised, at a POC site or at a modular unit, the licence holder may not approve that POC site or modular unit for the purpose of manufacturing or assembly of the POC medicinal product or MM medicinal product other than by way of an application to MHRA.^{[footnote 19]} 

2.9 Applications for marketing authorisation for POC medicinal products and MM medicinal products

2.9.1 In addition to the information referred to in Part 1, paragraph 1.2, fourth paragraph of Annex 1 to the 2001 Directive, an applicant for the grant of a UK marketing authorisation for an MM medicinal product or a POC medicinal product must also provide a copy of the MM master file for that product or a copy of the POC master file for that product respectively.^{[footnote 20]}

2.9.2 The applicant for a UK marketing authorisation for a POC medicinal product must, in addition to the accompanying material specified in regulation 50 of HMR 2012, provide to the MHRA information about the measures the applicant envisages putting in place to ensure the follow up of the efficacy of the product and of any adverse reactions to it.^{[footnote 21]}

2.9.3 The holder of a UK marketing authorisation relating to a POC medicinal product must provide the holder of the manufacturer’s licence (POC) relating to that product with information (relating to methods of manufacture and control) in order to enable the licence holder to ensure that the manufacturer’s licence (POC) and POC master file relating to the product are consistent with the marketing authorisation at all times.^{[footnote 22]}

2.9.4 The holder of a UK marketing authorisation relating to an MM medicinal product must provide the holder of the manufacturer’s licence (MM) relating to that product with information (relating to methods of manufacture and control) in order to enable the licence holder to ensure that the manufacturer’s licence (MM) and MM master file relating to the product are consistent with the marketing authorisation at all times.

2.10 Material to accompany an application for a UK marketing authorisation

^{[footnote 23]}

2.10.1 In the case of a POC medicinal product, the written confirmation that the manufacturer of the medicinal product has verified compliance of the manufacturer of the active substance with the principles and guidelines of good manufacturing practice is removed.

2.10.2 An application for a marketing authorisation for a POC medicinal product that will be administered immediately after manufacture does not require a mock-up of the outer packaging of the medicinal product, or the immediate packaging of the medicinal product. A mock-up of the package leaflet for the medicinal product is still required.

2.11 Pharmacovigilance 

2.11.1 The MHRA retains responsibility for pharmacovigilance across the UK and will:

take all appropriate measures to encourage the reporting to it of suspected adverse reactions
facilitate reporting by providing web-based and alternative reporting formats
take all appropriate measures to obtain accurate and verifiable data for the scientific evaluation of suspected adverse reaction reports
ensure that the public is given important information on pharmacovigilance concerns relating to the use of a medicinal product in a timely manner, through publication on the UK web-portal, and through other means of publicly available information as necessary

2.11.2^{[footnote 24]} In relation to a MM medicinal product and a POC medicinal product, the MHRA will ensure that all appropriate measures are taken to identify any biological medicinal product, MM medicinal product and POC medicinal product (including name and batch number, or other product identifier if no batch number is available) prescribed, dispensed or sold in the United Kingdom which is the subject of a suspected adverse reaction report through:

the methods for collecting data
where necessary, the follow-up of suspected adverse reaction reports

2.11.3 The MHRA may establish a list of any POC medicinal products or any MM medicinal products that are subject to additional monitoring.

2.11.4 The holder of a UK marketing authorisation must, in relation to the product in Northern Ireland:

submit a report electronically to the MHRA on all serious suspected adverse reactions that occur in the UK and countries other than the UK before the end of the period of 15 days beginning on the day following the day on which the holder gained knowledge of the reaction
submit a report electronically to the MHRA on all non-serious suspected adverse reactions that occur in the UK before the end of the period of 90 days beginning on the day following the day on which the holder gained knowledge of the reaction
establish procedures in order to obtain accurate and verifiable data for the scientific evaluation of suspected adverse reaction reports
collect follow-up information on reports submitted and submit it electronically to the MHRA by way of an update to the original report within the specified time period
collaborate with the MHRA in the detection of duplicates of suspected adverse reaction reports

2.11.5 In the case of an MM medicinal product or a POC medicinal product, ensure that all appropriate measures are taken to identify the product by batch number or other product identifier if no batch number is available.

2.11.6 The holder of a UKMA(UK)(Category 2), and a UKMA(NI) must, in relation to the product:

submit a report electronically to the Eudravigilance database on all serious suspected adverse reactions that occur in the UK and other countries before the end of the period of 15 days beginning on the day following the day on which the holder gained knowledge of the reaction
submit electronically to the Eudraviligance database a report on all non-serious suspected adverse reactions that occur in an EEA State or Northern Ireland before the end of the period of 90 days beginning on the day on which the holder gained knowledge of the reaction
collect follow-up information on reports submitted and submit it electronically to the Eudravigilance database by way of an update to the original report within the specified time period
collaborate with the EMA and the competent authorities of the EEA states in the detection of duplicates of suspected adverse reaction reports

2.11.7 In the case of an MM medicinal product or a POC medicinal product, ensure that all appropriate measures are taken to identify the product by batch number or other product identifier if no batch number is available.

2.11.8 In the case of an MM medicinal product, the periods of 15 and 90 days begin on the day following the day on which the holder of the marketing authorisation gained knowledge of the reaction.

2.11.9 In the case of a POC medicinal product, the periods of 15 and 90 days begin on the day following the day on which the holder of the marketing authorisation gained knowledge of the reaction.  

2.12 Specials and pharmacovigilance requirements

^{[footnote 25]}

2.12.1 HMR 2012 provides an exemption from the need for a marketing authorisation for a medicinal product which is:  

supplied in response to an unsolicited order;
manufactured and assembled in accordance with the specification of a person who is a doctor, dentist, nurse independent prescriber, pharmacist independent prescriber or supplementary prescriber
for use by a patient for whose treatment that person is directly responsible to fulfil the special needs of that patient
meets certain conditions specified in the exemption (regulation 167(2)-(9))

2.12.2 In the case of a POC medicinal product, it is a condition that the product is manufactured or assembled by the holder of a manufacturer’s licence (POC) for a POC medicinal product that relates specifically to the manufacture or assembly of special medicinal products and in accordance with the POC master file relating to the product.   

2.12.3 Similarly in the case of an MM medicinal product, it is a condition that the product is manufactured or assembled by the holder of a manufacturer’s licence (MM) that relates specifically to the manufacture or assembly of special medicinal products and in accordance with the MM master file relating to the product. 

MM medicinal products: pharmacovigilance requirements

^{[footnote 26]}

2.12.4 Where the sale or supply of an MM medicinal product relies on the exemption in regulation 167, the person who sells or supplies the product must maintain a record of the following information from the date that sale or supply first takes place until a date that is at least five years from the date on which supply of the product is discontinued:

the source from which, and the date on which, the person obtained the product
the person to whom, and the date on which, the sale or supply was made
the quantity of the sale or supply
the product’s batch number from which the sale or supply was made, or other product identifier if no batch number is available
details of any suspected adverse reaction to the product so sold or supplied of which the person is aware or subsequently becomes aware

2.12.5 The person must make the record available for inspection by the MHRA on request.

2.12.6 The person must submit electronically to the MHRA:

a report on all serious suspected adverse reactions to the product that occur within 15 days of the day following the day on which the person gained knowledge of the reaction
a report on all non-serious suspected adverse reactions to the product that occur in the United Kingdom within 90 days of the day following the day on which the person gained knowledge of the reaction

2.12.7 The person must ensure that the reports submitted electronically to the MHRA:

are in the format and have the content specified in Part 6 of Schedule 12A of HMR 2012
include the product’s batch number, or other product identifier if no batch number is available

2.12.8 The person must, at the written request of the MHRA, set up a risk management system designed to identify, characterise, prevent or minimise risks relating to the product.

POC medicinal products: pharmacovigilance requirements

^{[footnote 27]}

2.12.9 Where the sale or supply of a POC medicinal product relies on the exemption in regulation 167, the person who sells or supplies the product must maintain a record of the following information from the date that sale or supply first takes place until a date that is at least 5 years from the date on which supply of the product is discontinued:

the source from which, and the date on which, the person obtained the product
the person to whom, and the date on which, the sale or supply was made
the quantity of the sale or supply
the product’s batch number from which the sale or supply was made, or other product identifier if no batch number is available
details of any suspected adverse reaction to the product so sold or supplied of which the person is aware or subsequently becomes aware

2.12.10 The person must make the record available for inspection by the MHRA on request.

2.12.11 The person must submit electronically to the MHRA:

a report on all serious suspected adverse reactions to the product that occur within 15 days of the day following the day on which the person gained knowledge of the reaction
a report on all non-serious suspected adverse reactions to the product that occur in the United Kingdom within 90 days of the day following the day on which the person gained knowledge of the reaction

2.12.12 The person must ensure that the reports submitted electronically to the MHRA:

are in the format and have the content specified in Part 6 of Schedule 12A of HMR 2012
include the product’s batch number, or other product identifier if no batch number is available

2.12.13 The person must, at the written request of the MHRA, set up a risk management system designed to identify, characterise, prevent or minimise risks relating to the product.

2.13 EAMS

^{[footnote 28]}

2.13.1 The Early Access to Medicines (EAMS) scientific opinion holder must comply with the following pharmacovigilance requirements in respect of an EAMS medicinal product:

a risk management system must be agreed with the MHRA and operated by the EAMS scientific opinion holder in accordance with the risk management plan
the EAMS scientific opinion holder must record and maintain adverse reaction reports in respect of the EAMS medicinal product and must ensure that these reports are accessible (electronically or physically) at a single point within the UK
the EAMS scientific opinion holder must submit electronically to the MHRA:
- a report on all serious suspected adverse reactions that occur within 15 days of receipt
- a report on all non-serious suspected adverse reactions that occur in the UK within 90 days of receipt
ensure that the reports on all serious suspected adverse reactions that occur within 15 days of receipt, and on all non-serious suspected adverse reactions that occur in the United Kingdom within 90 days of receipt, are in the format and content specified by Part 6 of Schedule 12A of HMR 2012 and in the case of an MM medicinal product or a POC medicinal product, include the product’s batch number or other product identifier

2.13.2 In the case of an MM medicinal product, the periods of 15 and 90 days begin on the day following the day on which the holder of the scientific opinion gained knowledge of the reaction.

2.13.3 In the case of a POC medicinal product, the periods of 15 and 90 days begin on the day following the day on which the holder of the scientific opinion, gained knowledge of the reaction.

2.14 Labelling

^{[footnote 29]}

2.14.1 Nothing in regulation:

257 (Packaging requirements: general), applies to a POC medicinal product that is the subject of a UKMA(UK)(Category 1)
257C (Packaging requirements: advanced therapy medicinal products), applies to an advanced therapy medicinal product that is a POC medicinal product, if the product is to be administered immediately after manufacture, or
258 (Packaging requirements: specific provisions) or Schedule 25, applies to a POC medicinal product

2.14.2 Regulation 257CA^{[footnote 30]} sets out packaging requirements for a POC medicinal product that is the subject of a UKMA(UK)(Category 1) and not:

an advanced therapy medicinal product, and
is to be administered in its entirety immediately after manufacture

2.14.3 The information specified in Part 6 of Schedule 24 of HMR 2012 must appear on the outer packaging of a POC medicinal product to which this regulation applies and on the immediate packaging of that product (See below).

2.14.4 Where the packaging is in the form of a blister pack and is placed in outer packaging which complies with the requirements of Part 6 of Schedule 24 or the packaging is too small to display the information required by Part 6 of Schedule 24, information specified in Part 7 of Schedule 24 must appear on the immediate packaging (See below).

Packaging and information requirements (Schedule 24)

^{[footnote 31]}

Part 6 of Schedule 24 of HMR 2012 Outer and Immediate Packaging: POC Medicinal Products for sale or supply in Great Britain only provides:

the name of the medicinal product
the strength and pharmaceutical form of the product
where appropriate, whether the product is intended for babies, children or adults
the expiry date in clear terms, including the year and month and, if applicable, the day or time in hours and minutes
where the product contains up to three active substances, the common name of each active substance
a statement of the active substances in the product, expressed qualitatively and quantitatively per dosage unit or according to the form of administration for a given volume or weight, using their common names
the pharmaceutical form and the contents by weight, by volume or by number of doses of the product
a list of:
- where the product is injectable or is a topical or eye preparation, all excipients, or
- in any other case, those excipients known to have a recognised action or effect and included in the guidance published under regulation 257D that is applicable to such products
the method of administration of the product and if necessary the route of administration
where appropriate, space for the prescribed dose to be indicated
a warning that the product must be stored out of the reach and sight of children
any special warning applicable to the product
any special precautions relating to the disposal of an unused product or part of a product, or waste derived from the product, and reference to any appropriate collection system in place
the name and address of the holder of the UK marketing authorisation relating to the product and, where applicable, the name of the holder’s representative
the number of the UK marketing authorisation for placing the product on the market
the manufacturer’s batch number
the patient’s name and unique patient identifier

Part 7 of Schedule 24 of HMR 2012 Immediate Packaging: Blister Packs and Small Packaging (POC Medicinal Products for sale or supply in Great Britain only) provides:

the name of the medicinal product
the strength and pharmaceutical form of the product
where appropriate, whether the product is intended for babies, children or adults
the expiry date in clear terms, including the year and month and, if applicable, the day or time in hours and minutes
where the product contains up to 3 active substances, the common name of each active substance
the method of administration of the product and if necessary the route of administration
the name of the holder of the UK marketing authorisation relating to the product
the manufacturer’s batch number
the contents of the packaging by weight, by volume or by unit
the patient’s name and unique patient identifier

Question 3

3.  The Medicines for Human Use (Clinical Trials) Regulations 2004

Accepted Answer

The Medicines for Human Use (Clinical Trials) Regulations 2004 (“CT Regulations”) are amended to take account of the manufacture of a point of care (POC) medicinal product (which includes home-based manufacture) and modular manufactured (MM) medicinal product (which includes mobile manufacture) by the The Human Medicines (Amendment) (Modular Manufacture and Point of Care) Regulations 2025 [SI 2025 No. 87], which come into force on 23 July 2025.

3.1 Interpretation

^{[footnote 32]}

3.1.1 The CT Regulations provides definitions for this new regime:

“POC” means point of care
“manufacturer’s licence (POC)” has the meaning given in regulation 8 of the 2012 Regulations
“POC investigational medicinal product” means an investigational medicinal product that: 

(a) for reasons relating to 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

(b) for reasons relating to method of manufacture, can only be manufactured at or near the place where the product is to be used or administered 
“POC (IMP) control site” means the premises at which the holder of a manufacturing authorisation (POC) supervises and controls the manufacture 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
“manufacturing authorisation (POC)” means a manufacturing authorisation that authorises the manufacture of POC investigational medicinal products
MM” means modular manufacture
“modular unit” means a relocatable manufacturing unit
“manufacturer’s licence (MM)” has the meaning given in regulation 8 of the 2012 Regulations
“manufacturing authorisation (MM)” means a manufacturing authorisation that relates to the manufacture or assembly of MM investigational medicinal products
“MM investigational medicinal product” means an investigational medicinal product that, for reasons related to deployment, the licensing authority determines it necessary or expedient to be manufactured in a modular unit
“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

3.1.2 These definitions are used throughout this part of the guidance.

3.2 Supply of investigational medicinal products for the purpose of clinical trials

^{[footnote 33]}

3.2.1 No person shall, in the course of a business carried on by him, sell or supply any investigational medicinal product to an investigator, a healthcare professional who is a member of an investigator’s team, a person who provides or is to provide health care under the direction or control of a specified person or a subject, for the purpose of administering that product in a clinical trial, unless certain conditions are met.  

3.2.2 Where a POC investigational medicinal product or a MM investigational medicinal product is manufactured or assembled in the UK, the product has to have been manufactured or assembled in accordance with the terms of a manufacturing authorisation (POC) or a manufacturing authorisation (MM) respectfully or assembled under the exemption for hospitals and health centres in regulation 37 (See section 3.4)

3.3 Requirement for authorisation to manufacture or import investigational medicinal products^{[footnote 34]}.

3.3.1 POC investigational medicinal products or MM investigational medicinal products can be manufactured or assembled under a manufacturing authorisation (MIA(IMP)). 

3.3.2 A person shall not manufacture or assemble a POC investigational medicinal product, or a MM investigational medicinal unless the activity and product type is specified in a manufacturing authorisation (POC) or in a manufacturing authorisation (MM) and carried out in accordance with that authorisation and there is a POC (IMP) master file or a MM (IMP) master file relating to the product and the product is manufactured and assembled in accordance with that master file. 

3.3.4 This does not apply to the manufacture or assembly of an MM investigational medicinal product or 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.

3.4 Exemption for hospitals and health centres

^{[footnote 35]}

3.4.1 The CT Regulations provide an exemption from the need for a hospital or health centre to hold a manufacturing authorisation to assemble an investigational medicinal product in a hospital or health centre, when the “assembly” is carried out by a doctor or pharmacist, or under the supervision of a pharmacist. “Assembly” is related to packaging and labelling, and not to the preparation of medicines from their ingredients. The exemption applies only if the product is to be used exclusively in that hospital or health centre or any other that is a trial site for the clinical trial in which the product is to be used. This exemption also applies to the assembly of MM investigational medicinal products and POC investigational medicinal products in line with the exemptions for medics and pharmacists in HMR 2012. 

3.5 Applying for a manufacturing authorisation

^{[footnote 36]}

3.5.1 An applicant for a manufacturing authorisation for an investigational medicinal product will be asked to provide:

a statement describing the types of investigational medicinal product in respect of which the authorisation is required, including their pharmaceutical forms and whether any of them is an MM investigational medicinal product or a POC investigational medicinal product
a statement of the manufacturing, assembling or importation operations to which the authorisation is to relate, including a statement whether they include one or more of the following:
- the manufacture of investigational medicinal products, including specifically MM investigational medicinal products or POC investigational medicinal products
- the assembly of investigational medicinal products, including specifically MM investigational medicinal products or POC investigational medicinal products
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
- 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
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
- 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
a statement indicating the facilities and equipment available at each of the premises referred to above (as applicable), for storing the investigational medicinal products on, and distributing them from or between, such premises
a separate statement in respect of each of the premises referred to above (as applicable), of the manufacturing, assembling or importation operations capable of being carried out at those premises with their existing facilities - each statement shall specify the classes of investigational medicinal products to which the operations are relevant
a separate statement in respect of each of the premises referred to above (as applicable), of the facilities and equipment available at those premises for carrying out each stage of the manufacturing, assembling operations

3.5.2 In addition, the application for a POC investigational medicinal product must be accompanied by a dossier for each POC investigational medicinal product to which the application relates, which includes, as a minimum, the following: 

the location of each site at which manufacturing or assembly of the POC investigational medicinal product is to take place
the location of each site at which operations related to the manufacture or assembly of the POC investigational medicinal product are to take place
a description of the process by which the proposed holder of the authorisation will approve new POC (IMP) sites
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
a description of the manufacturing, assembly and product release processes to take place at each POC (IMP) site
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
a description of the arrangements for reporting of suspected adverse reactions from POC (IMP) sites to the POC (IMP) control site
the name and contact details of the person at the POC (IMP) control site to contact in respect of manufacturing or assembly operations under the licence
the name and contact details of the person to contact in respect of manufacturing or assembly operations at each POC (IMP) site
the name and contact details of the person at the POC (IMP) control site to contact in respect of quality operations under the authorisation
the name and contact details of the person to contact in respect of quality operations at each POC (IMP) site
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

3.5.3 An application relating to an MM investigational medicinal product must be accompanied by a dossier for each MM investigational medicinal product to which the application relates, which includes, as a minimum, the following: 

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
the location of each unit at which manufacturing or assembly of the MM investigational medicinal product is to take place
the location of each site at which operations related to the manufacture or assembly of the MM investigational medicinal product are to take place
a description of the process by which the proposed holder of the authorisation will approve new modular units
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
a description of the manufacturing, assembly and product release processes to take place at each modular unit
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
a description of the arrangements for reporting of suspected adverse reactions from modular units to the MM (IMP) control site
the name and contact details of the person at the MM (IMP) control site to contact in respect of manufacturing or assembly operations under the licence
the name and contact details of the person to contact in respect of manufacturing or assembly operations at each modular unit
the name and contact details of the person at the MM (IMP) control site to contact in respect of quality operations under the authorisation
the name and contact details of the person to contact in respect of quality operations at each modular unit
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

3.6 Consideration of an application for a manufacturing authorisation

^{[footnote 37]}

3.6.1 The MHRA will consider a valid application for a manufacturing authorisation and grant, or refuse to grant, an authorisation within a specified period.  

3.6.2 If the application for a manufacturing authorisation relates (wholly or partially) to a POC investigational medicinal product, the MHRA shall take into consideration the arrangements for supervising and controlling operations at any POC (IMP) site specified in the application and ensure that the 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 each of that site. 

3.6.3 If the application for a manufacturing authorisation relates (wholly or partially) to an MM investigational medicinal product, the MHRA shall take into consideration the arrangements for supervising and controlling operations at a modular unit specified in the application and ensuring that the 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. 

3.7 Standard provisions for manufacturing authorisations

^{[footnote 38]}

3.7.1 In addition to the standard provisions, the holder of a manufacturing authorisation must provide and maintain such staff, premises and plant (including technical equipment) necessary to carry out the stages of manufacture and assembly of the investigational medicinal products undertaken by the holder, in accordance with:

the holder’s authorisation
the product specification
the MM (IMP) master file, in the case of an MM investigational medicinal product
the POC (IMP) master file, in the case of a POC investigational medicinal product

3.7.2 The manufacturing authorisation holder shall not use for such purposes premises other than those specified in the case of a POC investigational medicinal product, the POC (IMP) master file and, in the case of an MM investigational medicinal product, the MM (IMP) master file, or which may be approved from time to time by MHRA. 

POC

3.7.3 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
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

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

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

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

where the application relates to a POC investigational medicinal product, the application for each product must be accompanied by a dossier (See paragraph 3.5.2) containing, as a minimum, the following^{[footnote 39]}:
- the location of each site at which manufacturing or assembly of the POC investigational medicinal product is to take place
- the location of each site at which operations related to the manufacture or assembly of the POC investigational medicinal product are to take place
- a description of the process by which the licence holder will approve new POC (IMP) sites
- a description of the processes by which the licence holder will suspend and cease manufacturing or assembly of the POC investigational medicinal product at a POC (IMP) site; a description of the manufacturing, assembly and product release processes to take place at each POC (IMP) site
- a description of the arrangements for supervision and control by the licence holder of the manufacture or assembly operations at each POC (IMP) site
- a description of the arrangements for reporting of suspected adverse reactions from POC (IMP) sites to the POC (IMP) control site
- the name and contact details of the person at the POC (IMP) control site to contact in respect of manufacturing or assembly operations under the licence
- the name and contact details of the person to contact in respect of manufacturing or assembly operations at each POC (IMP) site
- the name and contact details of the person at the POC (IMP) control site to contact in respect of quality operations under the licence
- the name and contact details of the person to contact in respect of quality operations at each POC (IMP) site
- a description of the processes by which the licence holder will review and amend the POC (IMP) master file for the product
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 dates on which manufacturing or assembly commenced, is suspended, or has ceased

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

3.7.8 The holder of the authorisation shall submit to the MHRA, at annual intervals, an update of any changes to the POC (IMP) master file made in the previous 12 month period. The first update must be submitted no later than 12 months from the date on which the manufacturing authorisation (POC) was granted.

3.7.9 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 where appropriate remedial action is taken as soon as reasonably practicable.

3.7.10 The holder of a manufacturing authorisation (POC) shall ensure that:

these requirements are complied with in relation to manufacturing carried out at the POC (IMP) sites specified in the POC (IMP) master file
only the POC investigational medicinal products specified in the manufacturing authorisation are manufactured or assembled at those sites
a POC investigational medicinal product specified in the manufacturing authorisation is not manufactured or assembled on premises other than those specified in the POC (IMP) master file

MM

3.7.10 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
inform the licensing authority before making a material alteration to the premises or plant used at the MM (IMP) control site or modular units, or to the operations for which they are used

3.7.11 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.

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

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

where the application relates to an MM investigational medicinal product, the application for each product must be accompanied by a dossier (See paragraph 3.5.3) containing, as a minimum, the following^{[footnote 40]}:
- 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
- the location of each unit at which manufacturing, or assembly of the MM investigational medicinal product is to take place
- the location of each site at which operations related to the manufacture or assembly of the MM investigational medicinal product are to take place
- a description of the process by which the licence holder will approve new modular units
- a description of the processes by which the licence holder will initiate, suspend and cease manufacturing or assembly of the product at a modular unit
- a description of the manufacturing, assembly and product release processes to take place at each modular unit
- a description of the arrangements for supervision and control by the licence holder of the manufacture or assembly operations at each modular unit
- a description of the arrangements for reporting of suspected adverse reactions from modular units to the MM (IMP) control site
- the name and contact details of the person at the MM (IMP) control site to contact in respect of manufacturing or assembly operations under the licence
- the name and contact details of the person to contact in respect of manufacturing or assembly operations at each modular unit
- the name and contact details of the person at the MM (IMP) control site to contact in respect of quality operations under the licence
- the name and contact details of the person to contact in respect of quality operations at each modular unit
- a description of the processes by which the licence holder will review and amend the MM (IMP) master file for the product
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 dates on which manufacturing or assembly commenced, is suspended, or has ceased

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

3.7.15 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 must be submitted no later than 12 months from the date on which the manufacturing authorisation (MM) was granted.

3.7.16 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 where appropriate remedial action is taken as soon as reasonably practicable.

3.7.17 The holder of a manufacturing authorisation (MM) shall ensure that:

these requirements are complied with in relation to manufacturing carried out at the modular units specified in the MM (IMP) master file
only the MM investigational medicinal products specified in the MM (IMP) master file are manufactured or assembled at those modular units
an MM investigational medicinal product specified in the MM (IMP) master file is not manufactured or assembled on premises other than those specified in the MM (IMP) master file

3.8 Variation of manufacturing authorisation

^{[footnote 41]}

3.8.1 The MHRA may vary a manufacturing authorisation (POC) or manufacturing authorisation (MM), whether on the application of the holder of the authorisation or otherwise. 

3.8.2 In the case of an application to vary the manufacturing authorisation (POC) so that it relates to the manufacture or assembly of POC investigational medicinal products; or an application to vary a manufacturing authorisation (POC) to add a new POC investigational medicinal product, the application for each product must be accompanied by a dossier (see paragraph 3.5.2) which includes, as a minimum, the following^{[footnote 42]}:

the location of each site at which manufacturing or assembly of the POC investigational medicinal product is to take place
the location of each site at which operations related to the manufacture or assembly of the POC investigational medicinal product are to take place
a description of the process by which the licence holder will approve new POC (IMP) sites
a description of the processes by which the licence holder will suspend and cease manufacturing or assembly of the POC investigational medicinal product at a POC (IMP) site
a description of the manufacturing, assembly and product release processes to take place at each POC (IMP) site
a description of the arrangements for supervision and control by the licence holder of the manufacture or assembly operations at each POC (IMP) site
a description of the arrangements for reporting of suspected adverse reactions from POC (IMP) sites to the POC (IMP) control site
the name and contact details of the person at the POC (IMP) control site to contact in respect of manufacturing or assembly operations under the licence
the name and contact details of the person to contact in respect of manufacturing or assembly operations at each POC (IMP) site
the name and contact details of the person at the POC (IMP) control site to contact in respect of quality operations under the licence
the name and contact details of the person to contact in respect of quality operations at each POC (IMP) site
a description of the processes by which the licence holder will review and amend the POC (IMP) master file for the product

3.8.3 The MHRA shall take into consideration the arrangements made or to be made for:

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

3.8.4 In the case of an application to vary the manufacturing authorisation (MM) so that it relates to the manufacture or assembly of MM investigational medicinal products or to vary a manufacturing authorisation (MM) to add a new MM investigational medicinal product, the application for each product must be accompanied by a dossier (see paragraph 3.5.3) which includes, as a minimum, the following^{[footnote 43]}:

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
the location of each unit at which manufacturing, or assembly of the MM investigational medicinal product is to take place
the location of each site at which operations related to the manufacture or assembly of the MM investigational medicinal product are to take place
a description of the process by which the licence holder will approve new modular units
a description of the processes by which the licence holder will initiate, suspend and cease manufacturing or assembly of the product at a modular unit
a description of the manufacturing, assembly and product release processes to take place at each modular unit
a description of the arrangements for supervision and control by the licence holder of the manufacture or assembly operations at each modular unit
a description of the arrangements for reporting of suspected adverse reactions from modular units to the MM (IMP) control site
the name and contact details of the person at the MM (IMP) control site to contact in respect of manufacturing or assembly operations under the licence
the name and contact details of the person to contact in respect of manufacturing or assembly operations at each modular unit
the name and contact details of the person at the MM (IMP) control site to contact in respect of quality operations under the licence
the name and contact details of the person to contact in respect of quality operations at each modular unit
a description of the processes by which the licence holder will review and amend the MM (IMP) master file for the product.

3.8.5 The MHRA shall take into consideration the arrangements made or to be made for:

supervising and controlling operations at a modular unit
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

3.9 Variation of a POC (IMP) master file and MM (IMP) master file

^{[footnote 44]}

3.9.1 The holder of a manufacturing authorisation (POC) may amend the following information in the POC (IMP) master file without applying to the MHRA for a variation^{[footnote 45]}:

the location of each site at which manufacturing or assembly of the POC investigational medicinal product is to take place
the location of each site at which operations related to the manufacture or assembly of the POC investigational medicinal product are to take place
a description of the arrangements for reporting of suspected adverse reactions from POC (IMP) sites to the POC (IMP) control site
the name and contact details of the person at the POC (IMP) control site to contact in respect of manufacturing or assembly operations under the authorisation
the name and contact details of the person to contact in respect of manufacturing or assembly operations at each POC (IMP) site

3.9.2 If the MHRA suspends or revokes a manufacturing authorisation (POC) limited to POC (IMP) manufacturing sites specified in a POC (IMP) master file associated with the authorisation 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 for variation.^{[footnote 46]}

3.9.3 The holder of a manufacturing authorisation (MM) may amend the following information in the MM (IMP) master file without applying to the MHRA for a variation^{[footnote 47]}:

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
the location of each site at which operations related to the manufacture or assembly of the MM investigational medicinal product are to take place
a description of the arrangements for reporting of suspected adverse reactions from modular units to the MM (IMP) control site
the name and contact details of the person at the MM (IMP) control site to contact in respect of manufacturing or assembly operations under the licence
the name and contact details of the person to contact in respect of manufacturing or assembly operations at each modular unit
the name and contact details of the person at the MM (IMP) control site to contact in respect of quality operations under the authorisation

3.9.4 If the MHRA suspends or revokes a manufacturing authorisation (MM) limited to modular units specified in an MM (IMP) master file associated with the authorisation 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 medicinal product other than by way of an application for variation.^{[footnote 48]}

3.10 Labelling

^{[footnote 49]}

3.10.1 An investigational medicinal product has to be labelled in accordance with Article 15 of Commission Directive 2003/94/EC. This does not apply to a POC investigational medicinal product that is to be administered in its entirety immediately after manufacture.

3.11 Infringement notices

^{[footnote 50]}

3.11.1 If the MHRA has objective grounds for considering that any person has contravened any provision to which the Clinical Trial Regulations apply, they may serve upon that person an infringement notice which will be in writing. This will apply in cases of regulation:

36A - manufacturing of MM investigational medicinal products
36B - manufacturing of POC investigational medicinal products

3.12 Offences

^{[footnote 51]}

3.12.1 Any person who contravenes regulation 36A - manufacturing of MM investigational medicinal products, or 36B - manufacturing of POC investigational medicinal products, shall be guilty of an offence.

Question 4

Further information

Accepted Answer

Licence application forms are available from the MHRA website. Alternatively applicants can email pcl@mhra.gsi.gov.uk.

Copies of relevant statutory instruments are also available from the legislation.gov.uk website or The Stationery Office, Publications Centre, PO Box 29, Norwich NR3 1GN, telephone 0870-600 5522.

Question 5

Glossary of legislation

Accepted Answer

The Human Medicines Regulations 2012 (SI 2012/1916)

Replaces nearly all UK medicines legislation – most of the Medicines Act 1968 and over 200 statutory instruments. The Regulations set out a comprehensive regime for the authorisation of medicinal products for human use; for the manufacture, import, distribution, sale and supply of those products; for their labelling and advertising and for pharmacovigilance.

The Medicines (Products for Human Use) (Fees) Regulations 2016 (SI 2016/190)

These Regulations make provision for the fees payable under the Medicines Act 1971 in respect of marketing authorisations, licences and certificates relating to medicinal products for human use.

The Medicines for Human Use (Clinical Trials) Regulations 2004 (SI 2004/1031)

The Medicines for Human Use (Clinical Trials) Regulations 2004 (the Regulations) regulate clinical trials in the UK since they came into force on the 1 May 2004. They replaced the clinical trial provisions of the Medicines Act 1968 and its secondary legislation and transposed Directive 2001/20/EC1 into UK law.

(Amendment of regulation 8) ↩
(Amendment of regulation 17) (Insertion of new regulations 17A and 17B (manufacturing of MM and POC medicinal products)) ↩
(Regs 3, 3A,4, 20,173 and s.10) ↩
By amendment to schedule 3 ↩
(Amendment of regulation 22) ↩
(Amendment of regulation 22) ↩
(Reg 37 and Insertion of new regulations 37A and 37B (manufacturing and assembly of MM and POC medicinal products: additional requirements)) and (Amendment of regulation 39) ↩
(Reg 37B and 39) ↩
(Reg 37A and 39) ↩
(by amendment to Schedule 4) ↩
(by amendment to Schedule 7) ↩
(Amendment of regulation 29) ↩
(Amendment of regulation 29) ↩
(1A(2) of Schedule 3) ↩
(Amendment of regulation 29) ↩
(Insertion of new regulations 29A and 29B (variation of MM and POC master files)) ↩
(Paragraph 1B(2)(a), (b) and (g) to (j) of Schedule 3) ↩
(Paragraph 1A(2)(a), (c) and (h) to (k) of Schedule 3) ↩
(Insertion of new regulation 27A (effect of suspension or variation relating to modular unit or POC site)) ↩
(Amendment of regulation 50) ↩
(Insertion of new regulation 50K (applications relating to POC medicinal products)) ↩
(Insertion of new regulations 74A and 74B (obligations to provide information relating to methods of manufacture and control)) ↩
(Amendment of Schedule 8) ↩
(Amendment of regulation 188) ↩
(Amendment of regulation 167) ↩
Insertion of new regulations 170A and 170B (pharmacovigilance requirements: MM and POC medicinal products)) ↩
Insertion of new regulations 170A and 170B (pharmacovigilance requirements: MM and POC medicinal products)) ↩
(Amendment of regulation 167G) ↩
(Amendment of regulation 257, Amendment of regulation 257C and Amendment of regulation 258) ↩
(Insertion of new regulation 257CA (packaging requirements: POC medicinal products)) ↩
(Amendment of Schedule 24) ↩
(Amendment of regulation 2) ↩
(Amendment of regulation 13) ↩
(Amendment of regulation 37 and Insertion of new regulations 36A and 36B (manufacture of MM and POC investigational medicinal products) ↩
(Regulation 37) ↩
(Amendment of Schedule 6) ↩
(Amendment of regulation 39) ↩
(Amendment of Schedule 7) ↩
The information specified in paragraph 11 of Schedule 6 ↩
The information specified in paragraph 10 of Schedule 6 ↩
(Amendment of regulation 44) ↩
(paragraph 11 of Schedule 6) ↩
(paragraph 10 of Schedule 6) ↩
(Insertion of new regulations 44A and 44B (variation of master files)) ↩
(paragraph 11(a), (b) and (g) to (i) of Schedule 6 and paragraph 14M(a) of Schedule 7) ↩
(Amendment of regulation 45) ↩
(paragraph 10(a), (c) and (h) to (k) of Schedule 6 and paragraph 14E(a) of Schedule 7) ↩
Amendment of regulation 45 ↩
(Amendment of regulation 46) ↩
(Amendment of regulation 48) ↩
(Amendment of regulation 49) ↩

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1.Introduction

POC guidance – legislation

2. The Human Medicines Regulations 2012

2.1 Interpretation

2.2 Manufacture

2.3 Exemptions

General

Radiopharmaceuticals

2.4 Applying for a licence / factors relevant to determination of application for manufacturer’s licence

Application dossier

2.5 Manufacturing and assembly of POC medicinal products or MM medicinal product - obligations [footnote 7]

2.6 Qualified persons[footnote 11]

2.7 Variation of a manufacturer’s licence [footnote 12]

2.8 Variation of POC master file or MM master file[footnote 16]

2.9 Applications for marketing authorisation for POC medicinal products and MM medicinal products

2.10 Material to accompany an application for a UK marketing authorisation

2.11 Pharmacovigilance

2.12 Specials and pharmacovigilance requirements

MM medicinal products: pharmacovigilance requirements

POC medicinal products: pharmacovigilance requirements

2.13 EAMS

2.14 Labelling

Packaging and information requirements (Schedule 24)

3. The Medicines for Human Use (Clinical Trials) Regulations 2004

3.1 Interpretation

3.2 Supply of investigational medicinal products for the purpose of clinical trials

3.4 Exemption for hospitals and health centres

3.5 Applying for a manufacturing authorisation

3.6 Consideration of an application for a manufacturing authorisation

3.7 Standard provisions for manufacturing authorisations

POC

MM

3.8 Variation of manufacturing authorisation

3.9 Variation of a POC (IMP) master file and MM (IMP) master file

3.10 Labelling

3.11 Infringement notices

3.12 Offences

Further information

Glossary of legislation

The Human Medicines Regulations 2012 (SI 2012/1916)

The Medicines (Products for Human Use) (Fees) Regulations 2016 (SI 2016/190)

The Medicines for Human Use (Clinical Trials) Regulations 2004 (SI 2004/1031)

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2.5 Manufacturing and assembly of POC medicinal products or MM medicinal product - obligations ^{[footnote 7]}

2.6 Qualified persons^{[footnote 11]}

2.7 Variation of a manufacturer’s licence ^{[footnote 12]}

2.8 Variation of POC master file or MM master file^{[footnote 16]}  

2.11 Pharmacovigilance 