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The Clinical Trials Regulations听

The following guidance听accompanies听the听听(SI 2004/1031,听鈥榯he Clinical Trials Regulations鈥�), as amended by听the听听(厂滨听2025/538).听

Part 2 of Schedule 1 to听the听Clinical Trials听Regulations听(as amended)听requires that the听听(and any individual or organisation that the听sponsor听delegates听trial-related activities to)听have regard to all relevant guidance with respect to听commencing听and conducting a clinical trial.听听

Investigators and sponsors must,听therefore,听ensure that they are fully aware of the information within this guidance and act accordingly to听achieve and听maintain听regulatory compliance.听

This guidance is also relevant to the听manufacturing sites that are named in听clinical trial application听submissions,听and听involved in the processing of听investigational medicinal听products.听

Good听manufacturing听practice (GMP)听for investigational medicinal products (IMPs) used in clinical trials听

GMP 诲别蹿颈苍颈迟颈辞苍听

The听Clinical Trials听Regulations听(as amended)听now states听鈥渢he principles and guidelines of good manufacturing practice听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鈥�.听听

This听was听defined as such as听the听United Kingdom听exited听the European Union prior to the implementation date听of the Regulation (EU) No 536/2014 on Clinical Trials.听听Hence听the new听Commission Directive (EU) 2017/1559 on GMP听for IMPs听is听not听directly听applicable in听Great Britain.听听

Note that the听Commission Delegated Regulation 2017/1569听is supported by听GMP听听that are听commonly referred to as听the听.听

Guidelines听for听good manufacturing practice听within Great Britain听for听Investigational Medicinal Products;听in line with Directive 2003/94/EC听will be published in a separate document. This is intended to听reflect the听听Annex 13听GMP听for IMPs together with updates due to the听implementation of SI 2025/538听and other factors as听appropriate.听This is not intended to add any additional burden on UK manufacturing sites but will clarify requirements.

Overall,听the MHRA听remains听committed to听and aligned with the internationally harmonised standards of听Pharmaceutical Inspection Co-operation Scheme (PIC/S)听and the EU, including requirements for the Qualified Person.听

Labelling requirements鈥兲�

The听details with regards to labelling听from the听28 April 2026听are now defined within听the听Clinical Trials Regulations听(as amended by the听).听Separate听guidance听has been generated on this topic and as such this听document will not cover those听general听requirements.听

Labels may also include (in small text) a local identification code to manage the听generation of artwork and controlled printing, such that unique reference numbers are听allocated听to each label and version if听required听to support site quality systems.听

Controls听and processes for听radiopharmaceutical (RP) investigational medicinal products (IMPs) used in clinical trials听

A听radiopharmaceutical product听(鈥�RP product鈥�)听is one that听which, when ready for use,听contains听one or more radionuclides included for a medicinal purpose, as per听Regulation 8(1) of the听.听

Regulation听37A of听the听Clinical Trials Regulations (as amended by the听 has听provision听for the manufacture and assembly of听an听RP product听that is an IMP (鈥�RP IMP product鈥�)听when used for听diagnostic purposes听to听be carried out at听sites听in the United Kingdom听that hold听a manufacturer鈥檚 licence, as defined in regulation 8(1) of the 2012 Regulations, which does not relate to the manufacture of investigational medicinal products.听听

As such this allows those sites听that hold an MS听(manufacture of听specials)听or an MIA (manufacturing)听licence issued by the MHRA听that includes the听manufacturing听of RP听IMP听products, as well as the traditional MIA (IMP) (manufacture of IMPs) licenced site.听

Note听that听this听does not have any impact on existing ARSAC requirements with regards to the handling of radioactive materials.听听You should听refer to听ARSAC鈥檚 online information.听

This provision听is restricted to听RP听IMP听products that are manufactured for听use for diagnostic purposes only (not therapeutic purposes). The RP听IMP听product听may听be manufactured within a licenced facility, such that they can supply听a hospital or health centre which is a trial location or taking part in the trial.听听

Regulation听37A听applies to the听manufacture and assembly听of the听diagnostic听RP听IMP products.听However,听it does not override听nor include any provision that removes听the听requirement to听continue to听comply with听all release requirements. This听includes听the release by a Qualified Person听(QP)听in line with current legislation and guidance.听

The Sponsor must ensure the clinical trial approval application includes details for both the MIA (IMP) licenced facility that is undertaking听final batch听release听and QP听certification, as well as the MS听(or MIA)听licenced facility that is undertaking the radiolabelling.听

Technical agreements should be in place between the听Sponsor,听MIA (IMP)听and licenced facilities to confirm quality oversight and responsibilities.听

Note听that听Regulation听37A听applies an exemption to Regulation听36 which relates to the听requirement for authorisation to manufacture听of听investigational medicinal products.听听As such this applies to IMPs only, and not听鈥榥on-investigational鈥櫶齪roducts (NIMPs)听associated with a trial.听听

These听NIMPs听will continue to be assessed within any听clinical听trial application听on a case-by-case basis, where for example NIMPs are allowed to be manufactured at sites that hold MS licences.听

Radiolabelling of听diagnostic听鈥榗old听kit鈥櫶齀MPs听

Where an IMP is manufactured at a MIA (IMP) licenced facility, this may be considered a听鈥榗old kit鈥櫶齣n that this is the finished product that requires radiolabelling听to ensure that the IMP can fulfil the diagnostic scanning requirements.听听

The cold kit听is a听non-radioactive preparation听(with听no radioactivity)听and is听certified听by the Qualified Person at the MIA(IMP)听licenced听facility.听

This final cold kit IMP听may听be provided to an MS licenced facility to be radiolabelled听via the addition of听the听appropriate radioisotope. Any听further听physical听labelling should be applied听as required听by听the Clinical Trials Regulations听(as amended)听and听labelling guidance document.听

The Sponsor听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.听

As the cold kit has been QP certified, no further QP certification is听required听for the radiolabelled听IMP. Release of the radiolabelled IMP can follow existing release controls at the MS licenced facility.听

This is a similar approach to the radiolabelling of听authorised听鈥榗old kit鈥櫶齧edicines that are released in line with the听approved听marketing听authorisation and then radiolabelled听for administration.听

Full manufacture and radiolabelling of听diagnostic听IMPs听

Where no IMP exists prior to听purification,听synthesis听and radiation activity steps,听such as听some听radiotracers used in Positron Emission Tomography (PET) scans, then听a Qualified Person must ensure that all requirements are met for the release of the IMP. This must be听line with the听clinical听trial听application, the听product听specification听file听and their legal duties.听

The听physical processing听for听manufacture and assembly听may occur at an MS licenced facility, where this site acts as a contract acceptor to the MIA (IMP) licence holder.听The QP at the听MIA(IMP) licence holder听is responsible for听batch听activities undertaken at the听MS licenced facility听and QP听certification.听

This includes听the听QP听conditionally certifying听the product before it听is used, as well as听final听QP certification following completion of all听applicable听tests, following the requirements of EU听听for the听manufacture of radiopharmaceuticals.听

The QP should assure themselves of the听suitability and competence of the Contract Acceptor to听carry out听these听activities successfully, in line with听the requirements of EU听听for听outsourced activities.听

Labelling specifics for radiopharmaceutical (RP) investigational medicinal products (IMPs) used for diagnostic purposes听

The听Regulations 46(3) and 46(4) of the Clinical Trials Regulations听(as amended by the听)听and听labelling听guidance documentation includes provisions for the minimal labelling of diagnostic radiopharmaceutical IMPs.听听

Where IMPs are handled at a radiopharmaceutical (RP) site holding an MS licence, the labelling requirements听remain听the same听as those听stated听in Regulations听46(3) and 46(4). Note听that the MS licence number should not be included within labels for any IMPs as these are not unlicenced medicines but investigational medicinal products.听

Note听that听is not听anticipated听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听identified听and听controls defined in the relevant application.听

Radiolabelling of听therapeutic听IMPs听

Where a听radiolabelled product听is听designated听a therapeutic IMP, this must continue to be听manufactured at a MIA (IMP) licenced facility.听This is outside the scope of the听Regulation听37A听exemptions.