The UK Medicines and Healthcare products Regulatory Agency (MHRA) has published an analysis of common issues with clinical trial applications (CTAs) showing that over half of the 1000 CTAs that the MHRA receives each year are delayed because insufficient information has been submitted.
The MHRA generally completes the initial assessment for phase 1 trials within 12 days and other phases within 22 days, but this can easily double if additional information has to be supplied by the applicant. Such delays can often be avoided if applicants follow the published guidance and either provide the data required or an adequate justification for not doing so.
The MHRA has analysed the issues which commonly require them to issue a ‘grounds for non-acceptance’ letter (GNA) requesting further information. Their advice on how applicants can avoid submitting deficient applications covers 4 main areas: Validation, Non-Clinical, Clinical and Pharmaceutical.
Validation – applicants frequently do not include an xml file of the CTA application form or provide scanned copies of documents rather than searchable (OCR) versions, or omit mandatory documents.
Non-Clinical – insufficient information about pivotal studies or analytical methods is a common problem. Applicants should ensure they comply with published guidelines on Good Laboratory Practice and include a justification for the proposed dose.
Clinical – the main issue is insufficient detail on how risks will be mitigated. Strategies on when to stop dosing trial participants, clear study and treatment endpoints and unblinding procedures if a clinical emergency arises should all be provided.
Pharmaceutical – advice is provided on how to adequately address the Quality aspects of the CTA. This includes providing sufficient information on the structure and characteristics of the drug substance, supplying a tabulated summary of analytical method validation results and providing full Manufacturing Authorisations [MIA(IMP)] for all sites in the trial. Batch analysis data from all sites is often missing. A justification for all specification limits, including impurities, should be provided and the proposed re-test period and a shelf life should also be stated clearly.
There is plenty of guidance available on all aspects of the CTA application and the advice is to follow it! Regulis can support you with this and prepare and submit CTAs across Europe.
Despite often having to request additional information, the MHRA’s final decision on CTA applications are generally issued well within the 60 day statutory timeline, which is good news.
Click here to access the advice on the MHRA’s analysis.