UK: Public Consultation on new Clinical Trials Legislation and Impact on IMPs

With the start of the application of the EU CTR on 31 January 2022, the MHRA (UK Medicines and Healthcare products Regulatory Agency) has launched a public consultation on proposals for legislative changes for clinical trials (CTs). Due to the Brexit, the CTR is not (directly) applicable in UK. 

UK requirements will remain unchanged pending completion of the consultation. However, the UK “will remain aligned with the internationally harmonized standards of PIC/S and the EU, including requirements for the Qualified Person“, says the agency. The revised Annex 13 changes the approach to the management of issues at the interface between GMP and GCP. These include the two-step release procedure, handling and shipping of IMPs and contractual arrangements between the sponsor and the IMP manufacturer. There are also changes to the labelling of IMPs (e.g., changing the approach to providing expiry information, moving labelling requirements from GMP guidance into the text of the CTR).

According to the agency, the UK consultation particularly relates to CTs and Investigational Medicinal Products (IMPs). The proposals are to update the current UK legislation that governs CTs, The Medicines for Human Use (Clinical Trials) Regulations (SI 2004/1031), which transposed the former EU Clinical Trials Directive 2001/20 into UK law. The proposal is based on feedback from stakeholders and an Expert Working Group, which included representatives from academia, industry, and patient groups. The consultation will close on 14 March 2022.

Good Clinical Practice (GCP)

The current UK legislation on CTs sets out that the GCP principles must be followed to conduct a CT, and the MHRA conducts GCP inspections to ensure sponsors conduct trials according to GCP and the trial protocol. But what are these GCP principles?

ICH E6 on GCP is usually followed where trials are conducted to support a marketing authorization, although this is not a UK legislative requirement. The agency is proposing to maintain a requirement for compliance with broad GCP principles to protect the rights and well-being of trial participants and the reliability of the trial results. However, the agency is not proposing to adopt a specific set of GCP requirements or move to legislate for ICH E6 in its entirety. UK GCP principles would be written into legislation to ensure that they are flexible and can be applied to a broad range of CTs. They will include identification of critical quality factors, risk proportionality, and will support more efficient approaches to trial design and conduct. However, sponsors will still be able to choose to follow ICH E6.

Electronic Systems

Regarding the use of electronic systems (e.g., electronic case report forms (eCRFs), web portals for documentation sharing and training, etc.) the agency recognizes that these systems can have a direct impact on patient safety, data integrity and protocol compliance. Currently these systems may be designed or controlled by external service providers, and GCP may not be applied. The MHRA would like to future proof the applicability of GCP for electronic systems by introducing into legislation clarity over the design and control of electronic systems that have an impact on safety and results. This would include that service providers of electronic systems should also be required to follow GCP principles.  

Labelling

The current clinical trial regulations set out requirements for the manufacture and import of IMPs to be used in CTs, as well as how these products should be labelled. The MHRA says that it is not intended to align with the upcoming European CTR Annex 6 labelling requirements. Instead the agency proposes to allow the sponsor to suggest risk adapted labelling. Moreover, it is planned to introduce risk-proportionate requirements in UK legislation for the labelling of IMPs such as those with a marketing authorization and medicines manufactured at the point of care. This provision would allow for such products to have reduced or no clinical trial specific labelling if justified.

Implementation in the UK

Pending completion of the UK’s future clinical trial legislation, the UK will continue to apply the January 2010 version of Annex 13 with respect to:

  • Labelling requirements,
  • Two-step release procedure,
  • Handling and shipping of IMPs,
  • Contractual arrangements between the sponsor and IMP manufacturer.

More information is available here: Public Consultation on new Clinical Trials Legislation in the MHRA Inspectorate Blog.