Common issues identified during clinical trial applications
This guidance identifies common issues with validation and assessment of clinical trial applications and how to avoid them.
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The Medicines and Healthcare products Regulatory Agency (MHRA) receives between 950 and 1,000 clinical trial authorisation (CTA) applications for investigational medicinal products (IMPs) per year. The great majority (up to 95%) of these are approved; however, more than half of all applications require additional information to be submitted before they are considered approvable.
Many of the requests for further information or ‘grounds for non-acceptance’ (GNA), are common and are avoidable if available guidance is followed or if a satisfactory justification for not following the applicable guidance is provided in the application.
The statutory timeframe for initial assessment of a CTA application is 30 days with an MHRA internal target of an average of 14 days for assessment of phase 1 applications.
Currently, MHRA conducts an initial assessment of phase 1 applications within approximately 12 days and within approximately 22 days for all other phases. When GNA points are raised it can add up to 21 days to the final approval time for a phase 1 application and 23 days for other phases, depending on the time taken for the applicant to submit their response and MHRA assessment of that response.
Whilst these timeframes remain competitive and are well within the statutory 60 day period for final determination of a CTA application for a clinical trial of a general medicinal product, reducing any avoidable delays to the authorisation of a clinical trial is of benefit to trial sponsors and, ultimately, patients.
This guidance aims to assist applicants in understanding the common reasons for MHRA requiring additional information and provides direction to where further information and guidance can be found.
While this guidance covers many of the common reasons for MHRA requiring additional information during validation and review of a CTA application, it should not be seen as a ‘tick-box’ guide.
Every trial will have its own peculiarities and each is assessed on a case by case basis, which may lead to questions needing to be asked on specific areas. By the same token, sponsors who do not comply with some of the issues raised in this guidance might not necessarily receive a GNA if they have provided an acceptable scientific (safety) justification for not complying with guidance.
Applicants are reminded that you can ask for scientific advice from MHRA at any stage of the development of your medicine. Details on the types of advice we offer and how to submit a request for advice can be found on our website.
Advice on specific scientific or regulatory aspects of a clinical trial can also be obtained via the Clinical Trials Helpline at clintrialhelpline@mhra.gov.uk. If you have any specific feedback on the issues raised you can also let us know via the Clinical Trials Helpline.
Last updated 6 November 2023 + show all updates
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Updated to include a new link to updated guidance on Recommendations related to contraception and pregnancy testing in clinical trials.
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The Common issues: Clinical section has been updated to include reference to the latest guidance on strategies to mitigate risks for early phase trials and to provide further guidance on safety reporting requirements.
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Edited 'Common issues: Pharmaceutical' publication. Added new information under 'Manufacturer’s Authorisation' regarding the copies and declarations which need to be provided in the event of a cross-referral or if a certificate is not accepted.
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Added information about reference to an Active Substance Master File to the page 'Common issues: Pharmaceutical'
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Information about proof of payment is no longer relevant and has been removed from the page.
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First published.