The UK Medicines and Healthcare products Regulatory Agency (MHRA) receives approximability 1000 clinical trial authorization (CTA) applications a year. These are for investigational medicinal products of which >95% are approved. However, >50% still need additional information to be submitted in order to get approved. The majority of the requests for additional information, including “grounds for non-acceptance (GNA)”, are common and somewhat avoidable provided sponsors follow the guidelines. The UK MHRA’s guidance on the ‘Common issues identified during clinical trial applications’ published in 2017 has assisted applicants in understanding the need for, and reasons behind, the UK MHRA requesting for additional information. Recently, the guidance was updated on recommendations related to contraception and pregnancy testing in clinical trials. These recommendations made by the Clinical Trial Facilitation Group address critical points related to contraception.
Common issues identified during clinical trial applications
The guidance covers common issues related to clinical, nonclinical, validation, and pharmaceutical aspects. It also provides useful resources including the template for qualified person’s declaration. The process of handling CTAs presents challenges, including the need for careful planning, preparation and adherence to MHRA regulations. The MHRA has identified issues that arise in CTAs encompassing aspects such as validation, non-clinical studies, clinical trials and pharmaceutical considerations. It is crucial to address these issues in order to avoid any delays in obtaining approval.
According to the guidelines set forth by the MHRA, the initial assessment timeframe for CTAs is set at 30 days. For phase 1 applications specifically, there is a target of completing the assessment within 14 days. Currently phase 1 assessment are taking 12 days on average while assessments for phases require approximately 22 days. Delays can occur when additional information is requested during the review process and can add up to 21 days, for phase 1 assessments and 23 days for assessments pertaining to other phases.
Key Documents Required for MHRA Submission
A comprehensive set of documents is essential for a successful MHRA submission. These include:
- Cover letter
- Clinical trial protocol
- Investigator’s brochure
- Investigational medicine product dossier
- Manufacturer’s authorization
- Patient information sheet and inform consent form.
- Clinical trial insurance certificate
- Suitability of the investigator document
Each trial is unique, requiring a case-by-case assessment. Thus, the UK MHRA’s guidance document provides applicants with the initial direction & guidance on where to find further information. It is important to note that compliance with the guidance is not strictly a ‘tick-box’ process, and acceptable scientific justifications may prevent grounds for GNAs even if not all guidance is followed, thus reducing avoidable delays benefits trial sponsors and, ultimately, patients.
The UK stands as a prominent destination for global clinical trials, emphasising the significance of understanding the CTA process. Successful navigation requires careful preparation of required documents, and addressing common issues highlighted by the MHRA. Collaboration with experienced partners that have experience in supporting applicants for CTAs can enhance the efficiency of the approval process, ensuring timely commencement of clinical trials in the UK.
DDReg is leading regulatory and pharmacovigilance service provider that has supported its customers with submissions to the UK MHRA. The team is well-versed with the regulations and have in-depth knowledge & experience of the ever-evolving clinical trial landscape in the UK and around the world. Missed the previous blog? Read more from the experts on Fostering Bilateral Trade and Harmonized Efforts in Medicine Regulation.