Six months since implementation of the UK’s new clinical trials regulations

How to avoid delays when submitting clinical trial application assessments

The UK's new clinical trial regulations came into force on 28 April 2026, introducing a more flexible and risk-proportionate approach to clinical trial assessment. Sponsors now submit a single clinical trial application for review by both the MHRA and a Research Ethics Committee (REC) through the Integrated Research Application System (IRAS). The aim is simple: to help potentially life-changing medicines to reach patients faster, while maintaining the highest standards of safety and oversight.

• Six months on, the new framework is already supporting a more responsive application process. Improvements include: updates for applicants as their application moves through the assessment process.
• More flexible timelines of up to 60 days for responding to requests for information (RFI).
• Final decisions within just 10 days of receiving a response to a request for information. Relevant expert consultation with the Commission for Human Medicines (CHM) for higher risk investigational medicinal products (IMPs), including some advance therapy investigational medicinal products (ATIMPs).

Getting it right first time

The quality and completeness of every application remain essential to making the process work as efficiently as possible. By reviewing the guidance, using the available checklists and providing the right information first time, sponsors can help avoid unnecessary requests for information and support a smoother assessment. In this blog we highlight some common issues encountered by sponsors during assessment and share practical steps you can take to prepare a high-quality application.

Delays to application assessments: Common Issues

In many cases, delays occur for relatively simple reasons, such as missing documentation, unsigned forms or files that don’t meet Optical Character Recognition (OCR) requirements. Approximately 3 to 5 percent of applications fail validation for these reasons. Our website has more information on common validation issues: https://www.gov.uk/government/publications/common-issues-identified-during-clinical-trial-applications/common-issues-validation) .

Check before submitting

The validation stage can take up to seven days, but once validated, applications enter the assessment phase, which can take up to 30 calendar days until a decision is communicated. This is often completed faster when the submission is complete and of good quality.

The most common reason for delays is incomplete documentation. Submission of an inadequate application package, such as a missing document or failing to provide the required information for approval, may result in a request for information (RFI) being issued by the MHRA and/or REC leading to a delay in the approval timeline.

Before you submit, make sure all required documents are included and correctly completed.
You can find full list of documents required for an application for clinical trial approval on our website.

Common pharmaceutical issues

• Missing investigational medicinal products (IMPs) or placebos from the medicine information form.
• Missing justifications for IMP labelling.
• Manufacturing site information that is unclear, incomplete or absent.
• Missing or incomplete GMP information and/or Qualified Person (QP) declarations.

You can find a list of Common issues associated with Pharmaceuticals on our website.

Common medical issues

• Contraception requirements: Applications sometimes fail to align with Clinical Trials Facilitation Group (CTFG) guidance, particularly regarding the duration of contraception following the final dose of the IMP.
• Emergency unblinding procedures: Protocols must clearly state how investigators can access treatment allocation information in a medical emergency and ensure they retain the primary right to break the blind when necessary.
• Safety reporting: Protocols should clearly specify that investigators must report serious adverse events (SAEs) to sponsors within 24 hours.

You will find a list of Common issues identified in CT applications on our website.

Common non-clinical issues

• Lack of information about pivotal safety studies that have been submitted in support of the application, including whether studies were conducted in an OECD MAD member country.
• When compiling the contraceptive advice for a clinical trial, the Sponsor should consult the Clinical Trial Coordination Group Recommendations related to contraception and pregnancy testing in clinical trials.
• Lack of justification for the starting and maximum dose in humans from a safety perspective.
• Missing description of the analytical methods used in the pharmacokinetic and toxicology studies.

You can find more information about this on our Common issues: Non-clinical - GOV.UK webpage

Common Notifiable Trials submission issues

Taking the time to review published guidance, complete relevant checklists and verify that all supporting documentation is included, can prevent invalidation and/or unnecessary RFIs and help ensure your application progresses smoothly.

Before submitting, review the published guidance and application checklists to ensure:

• You are applying through the correct regulatory route.
• Your submission meets all eligibility requirements.
• All required information and supporting documents have been included.

To avoid delays, ensure you can answer ‘yes’ to the following questions before submission:

• Have you selected the correct Notifiable Trial condition?
• Is the supporting first-in-human (FTIH) programme complete?
• If relying on approval from another regulator, do the protocol, Investigator's Brochure (IB) and Investigational Medicinal Product Dossier (IMPD) match versions submitted to other regulators?
• Have you avoided introducing UK-specific requirements that require additional MHRA assessment?
• Are you following standard quality requirements, including labelling guidance?

Route B substantial modifications: making low-risk changes faster

Since 28 April 2026 sponsors must use the Route B process for substantial modifications when their application meets the eligibility criteria. There is no alternative route for eligible modifications.

The key eligibility requirement is that, after making reasonable enquiries, the sponsor is not aware of any significant new safety concerns relating to the investigational medicinal product that have arisen since the trial was originally approved.

The benefit

Following a six-month pilot, Route B has delivered impressive efficiencies:

• Average validation time: 3 days
• Average review time: 4 days
• Average end-to-end approval time: 7 days

This compares favourably with the regulatory maximum timeline for Route B substantial modifications of 21 days (up to 7 days for the validation period, and up to 14 days for the review period).

Common Route B substantial modification issues

Most objections arise where proposed changes affect safety information, particularly modifications to the Reference Safety Information (RSI), where new expected adverse reactions are included.

You can find out more about verifying and reporting of safety events on our website.  

Before submitting, check:

• Does the proposed modification clearly fit one of the published Route B categories?
• Have you completed the Route B confirmation form in full?
• Are all changes clearly described and appropriately justified in your cover letter, including a clear statement that the application is being submitted via Route B?
• If relying on a previously approved submission, have you provided identical document versions and supporting evidence?
• Have you confirmed that the changes do not require reassessment of the trial's approved safety profile or risk-benefit balance?
• Your Reference Safety Information (RSI), should list the nature of ‘expected’ SARs by body organ system class and using preferred terms (PTs), so that it can be used as a point of reference for determining expedited SUSAR reporting and assessment.

Further guidance

Visit the Clinical Trials Hub, Medicines: clinical trials hub - GOV.UK which brings together the latest information, guidance and resources for sponsors and researchers. You can also contact the Clinical Trials Helpline if you have questions about the application process or eligibility requirements.

Stay up to date by signing up for MHRA clinical trials email updates and visiting the Clinical Trials Hub regularly for new guidance and resources.

If you still can’t find the information you require, get in touch with us  clintrialhelpline@mhra.gov.uk.