Clinical trials for medicines: good manufacturing practice and radiopharmaceutical investigational medicinal products
Guidance on good manufacturing practice and the use of radiopharmaceutical investigational medicinal products in clinical trials.
Good manufacturing practice and radiopharmaceutical investigational medicinal products guidance questionnaire
We would like your feedback on whether our new draft guidance is easy to understand and implement. You can feedback via our Good Manufacturing Practice and radiopharmaceutical investigational medicinal products guidance questionnaire.
The deadline for feedback is 11.59pm on Wednesday 25 March 2026. Survey responses will then be aggregated, themed and prioritised.
The Clinical Trials Regulations
The following guidance accompanies the Medicines for Human Use (Clinical Trials) Regulations 2004 (SI 2004/1031, ‘the Clinical Trials Regulations’), as amended by the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025 (SI 2025/538). These amendments come into force on 28 April 2026.
Part 2 of Schedule 1 to the Clinical Trials Regulations (as amended) requires that the investigator and sponsor (and any individual or organisation that the sponsor delegates trial-related activities to) have regard to all relevant guidance with respect to commencing and conducting a clinical trial.
Investigators and sponsors must, therefore, ensure that they are fully aware of the information within this guidance and act accordingly to achieve and maintain regulatory compliance.
This guidance is also relevant to the manufacturing sites that are named in clinical trial application submissions, and involved in the processing of investigational medicinal products.
Good manufacturing practice (GMP) for investigational medicinal products (IMPs) used in clinical trials
GMP definition
The Clinical Trials Regulations (as amended) now states “the principles and guidelines of good manufacturing practice means the principles and guidelines of good manufacturing practice set out in Commission Directive 2003/94/EC in respect of Great Britain or Commission Delegated Regulation 2017/1569 in respect of Northern Ireland”.
This was defined as such as the United Kingdom exited the European Union prior to the implementation date of the Regulation (EU) No 536/2014 on Clinical Trials. Hence the new Commission Directive (EU) 2017/1559 on GMP for IMPs is not directly applicable in Great Britain.
Note that the Commission Delegated Regulation 2017/1569 is supported by GMP Guidelines that are commonly referred to as the revised ‘Annex 13’ of EU GMP.
Guidelines for good manufacturing practice within Great Britain for Investigational Medicinal Products; in line with Directive 2003/94/EC will be published in a separate document. This is intended to reflect the 2010 EU Guidelines Annex 13 GMP for IMPs together with updates due to the implementation of SI 2025/538 and other factors as appropriate. This is not intended to add any additional burden on UK manufacturing sites but will clarify requirements.
Overall, the MHRA remains committed to and aligned with the internationally harmonised standards of Pharmaceutical Inspection Co-operation Scheme (PIC/S) and the EU, including requirements for the Qualified Person.
Labelling requirements
The details with regards to labelling from the 28 April 2026 are now defined within the Clinical Trials Regulations (as amended by the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025). Separate guidance has been generated on this topic and as such this document will not cover those general requirements.
Labels may also include (in small text) a local identification code to manage the generation of artwork and controlled printing, such that unique reference numbers are allocated to each label and version if required to support site quality systems.
Controls and processes for radiopharmaceutical (RP) investigational medicinal products (IMPs) used in clinical trials
A radiopharmaceutical product (‘RP product’) is one that which, when ready for use, contains one or more radionuclides included for a medicinal purpose, as per Regulation 8(1) of the Human Medicines Regulations 2012.
Regulation 37A of the Clinical Trials Regulations (as amended by the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025 has provision for the manufacture and assembly of an RP product that is an IMP (‘RP IMP product’) when used for diagnostic purposes to be carried out at sites in the United Kingdom that hold a manufacturer’s licence, as defined in regulation 8(1) of the 2012 Regulations, which does not relate to the manufacture of investigational medicinal products.
As such this allows those sites that hold an MS (manufacture of specials) or an MIA (manufacturing) licence issued by the MHRA that includes the manufacturing of RP IMP products, as well as the traditional MIA (IMP) (manufacture of IMPs) licenced site.
Note that this does not have any impact on existing ARSAC requirements with regards to the handling of radioactive materials. You should refer to ARSAC’s online information.
This provision is restricted to RP IMP products that are manufactured for use for diagnostic purposes only (not therapeutic purposes). The RP IMP product may be manufactured within a licenced facility, such that they can supply a hospital or health centre which is a trial location or taking part in the trial.
Regulation 37A applies to the manufacture and assembly of the diagnostic RP IMP products. However, it does not override nor include any provision that removes the requirement to continue to comply with all release requirements. This includes the release by a Qualified Person (QP) in line with current legislation and guidance.
The Sponsor must ensure the clinical trial approval application includes details for both the MIA (IMP) licenced facility that is undertaking final batch release and QP certification, as well as the MS (or MIA) licenced facility that is undertaking the radiolabelling.
Technical agreements should be in place between the Sponsor, MIA (IMP) and licenced facilities to confirm quality oversight and responsibilities.
Note that Regulation 37A applies an exemption to Regulation 36 which relates to the requirement for authorisation to manufacture of investigational medicinal products. As such this applies to IMPs only, and not ‘non-investigational’ products (NIMPs) associated with a trial.
These NIMPs will continue to be assessed within any clinical trial application on a case-by-case basis, where for example NIMPs are allowed to be manufactured at sites that hold MS licences.
Radiolabelling of diagnostic ‘cold kit’ IMPs
Where an IMP is manufactured at a MIA (IMP) licenced facility, this may be considered a ‘cold kit’ in that this is the finished product that requires radiolabelling to ensure that the IMP can fulfil the diagnostic scanning requirements.
The cold kit is a non-radioactive preparation (with no radioactivity) and is certified by the Qualified Person at the MIA(IMP) licenced facility.
This final cold kit IMP may be provided to an MS licenced facility to be radiolabelled via the addition of the appropriate radioisotope. Any further physical labelling should be applied as required by the Clinical Trials Regulations (as amended) and labelling guidance document.
The Sponsor should ensure that the quality systems at the MS licence holder are suitable for the management of IMPs and that physical labelling controls are in place.
As the cold kit has been QP certified, no further QP certification is required for the radiolabelled IMP. Release of the radiolabelled IMP can follow existing release controls at the MS licenced facility.
This is a similar approach to the radiolabelling of authorised ‘cold kit’ medicines that are released in line with the approved marketing authorisation and then radiolabelled for administration.
Full manufacture and radiolabelling of diagnostic IMPs
Where no IMP exists prior to purification, synthesis and radiation activity steps, such as some radiotracers used in Positron Emission Tomography (PET) scans, then a Qualified Person must ensure that all requirements are met for the release of the IMP. This must be line with the clinical trial application, the product specification file and their legal duties.
The physical processing for manufacture and assembly may occur at an MS licenced facility, where this site acts as a contract acceptor to the MIA (IMP) licence holder. The QP at the MIA(IMP) licence holder is responsible for batch activities undertaken at the MS licenced facility and QP certification.
This includes the QP conditionally certifying the product before it is used, as well as final QP certification following completion of all applicable tests, following the requirements of EU GMP Annex 3 for the manufacture of radiopharmaceuticals.
The QP should assure themselves of the suitability and competence of the Contract Acceptor to carry out these activities successfully, in line with the requirements of EU GMP Chapter 7 for outsourced activities.
Labelling specifics for radiopharmaceutical (RP) investigational medicinal products (IMPs) used for diagnostic purposes
The Regulations 46(3) and 46(4) of the Clinical Trials Regulations (as amended by the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025) and labelling guidance documentation includes provisions for the minimal labelling of diagnostic radiopharmaceutical IMPs.
Where IMPs are handled at a radiopharmaceutical (RP) site holding an MS licence, the labelling requirements remain the same as those stated in Regulations 46(3) and 46(4). Note that the MS licence number should not be included within labels for any IMPs as these are not unlicenced medicines but investigational medicinal products.
Note that is not anticipated that any diagnostic RP IMP would be used as a blinded product within a trial, as such no specific guidance has been defined. Any such trial should be clearly identified and controls defined in the relevant application.
Radiolabelling of therapeutic IMPs
Where a radiolabelled product is designated a therapeutic IMP, this must continue to be manufactured at a MIA (IMP) licenced facility. This is outside the scope of the Regulation 37A exemptions.