21 May saw the MHRA unveil their draft rare disease framework, which is open for consultation until 30 of July. The new framework aims to adapt the regulatory framework for rare diseases, defined as affecting 1 in 50,000 or less people in the UK, as the current development model does not always suit these conditions, since they require greater flexibility in how they are evaluated. Accordingly, the framework emphasises earlier engagement with regulators, flexible evidence requirements, patient centricity, and iterative approvals, with the aim of shortening the time from drug discovery to patient access.
The announcement notes that only 5% of rare diseases have an approved medicinal product, leaving many without a viable treatment. It also acknowledges the difficulties that rare diseases face in fitting into the traditional regulatory model: limited patient populations, lengthy treatment timelines and limited natural history data. The new framework aims to fill this gap, with the dual benefit of speeding up patient access to innovative medicines while supporting the UK’s position as a competitive player in rare disease development.
The framework introduces a new concept: the Investigational Marketing Authorisation (IMA), a single authorisation combining approval to conduct a clinical trial with a continuously reviewed marketing authorisation, allowing controlled patient access earlier in development. The authorisation is contingent on a robust safety and efficacy monitoring plan and is subject to periodic benefit-risk assessments by the MHRA. The IMA is not designed to replace existing routes, such as full, conditional and exceptional marketing authorisations, but rather to provide an alternative where conventional routes aren’t feasible.
The IMA would be delivered through regular contact with the MHRA, via eight proposed:
1. Early engagement meeting
The proposed development plan is discussed and tested against regulatory expectations, reducing uncertainty and helping to shape a proportionate development strategy. This may come with a scientific opinion.
2. Rare disease designation
The MHRA decides whether the applicant is eligible for the framework based on the justification provided. Criteria are not limited to rarity only, but also whether evidence generation is likely to suit current regulatory frameworks.
3. Additional scientific advice
Formal scientific and regulatory advice may be required to agree the foundations of the clinical trials, such as efficacy endpoints, trial design and safety reporting.
4. Ethics considerations
A favourable opinion from a recognised Research Ethics Committee is required, along with robust trial design, transparent risk-mitigation strategies and appropriate medical facilities and trained staff to manage adverse events.
5. IMA application
Applications are reviewed under the clinical trial framework and must follow Good Clinical Practice (GCP) standards, including ICH E6. Data generated from these studies is submitted to the MHRA and contributes to the continuous assessment of the therapy as evidence accumulates.
6. Ongoing clinical monitoring
Evidence must be submitted at a predefined frequency once the IMA is granted, with structured review points, clear decision gates and expectations for continued data generation.
7. Transition to post-authorisation oversight
The MHRA provides clear guidance as to when a product is no longer regulated under the clinical trials framework and instead becomes regulated as an authorised medicinal product.
8. Conversion to MA, restriction or withdrawal
Depending on the data generated, the IMA may be converted into another authorisation type, restricted, or withdrawn.
The IMA is intended to bridge the gap between clinical trial authorisation and full marketing authorisation, allowing incremental evidence generation that is reviewed regularly rather than through the typical discrete regulatory steps, making the process continuous and evolving rather than fixed. The framework is also more accommodating of novel evidence types, such as real-world evidence, adaptive studies and innovative trial designs. Being technology-agnostic, it can be applied to a variety of new technologies, and it aims to align with globally recognised standards to prevent divergence from the global market.
Some of the initiatives within the framework could be applied immediately, while other elements, including the IMA, would require legislative changes. Certain elements can be trialled through pilot programmes, such as regulatory sandboxes. The consultation is open until the end of July for industry to comment, in which many will likely see this as a step in the right direction, a sign that the MHRA is becoming more receptive to innovation and taking a more appropriate approach to regulation.
