On 22nd March 2017, the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) published a guidance (“Guidance“) identifying the most common issues that the Agency has encountered during the validation and review of Clinical Trial Authorisation (CTA) applications. The Guidance is intended to assist clinical trial sponsors in identifying avoidable delays, to the benefit of both clinical trial sponsors and patients.
The MHRA has published background information in relation to the Guidance. According to this information, the MHRA receives more than 1000 CTA applications each year. Additional information is requested for more than half of the CTA applications before their assessment and approval.
The MHRA explains that these requests for additional information result in unnecessary delays, which could be disadvantageous for the applicants and, eventually, patients. The MHRA explains that it initially reviews applications within between 12 to 22 days. However, when non-acceptance points are raised, the review of CTA applications can be extended by up to a further 23 days.
MHRA states that although the final determination of a CTA application does not exceed the statutory timeframe of 60 days, the reduction of any unnecessary delays of the CTA process is beneficial for applicants and patients.
The different elements of the Guidance
The Guidance provides information concerning the most common reasons leading the MHRA to request additional information to applicants. As an example, MHRA states that 15% of the CTA applications are declined at the validation step before even reaching an assessor. As a result, common issues discussed in the validation document include the failure to supply an XML file of the completed CTA application form and the absence of mandatory accompanying documentation.
Clinical and non-clinical issues that are also common grounds for non-acceptance of applications. The absence of information about acceptable risk mitigation strategies, or the lack of data related to crucial safety studies can lead to rejection.
The relevant documents provide guidance on several matters including the statement of compliance with OECD GLP for studies; risk mitigation strategies; and contraceptive requirements. The Guidance also provides recommendations on how to avoid potential delays related to these requests for additional information. The Guidance consists of the five documents indicating the most common issues with regard to application validation, non-clinical and clinical data, pharmaceutical; and a list of useful resources.
The MHRA underlines that the issues mentioned in the above documents should not be considered as an exhaustive list.