The MHRA’s proposed rare disease therapies regulatory framework (“the Proposed Framework”) represents an ambitious attempt to redesign medicines regulation around the realities of rare disease development.

On 21 May 2026, the MHRA launched its consultation on the Proposed Framework, representing a significant step in the UK’s ambition to become a global leader in the development of therapies for rare diseases.

The initiative reflects the scale of unmet need: around 1 in 17 people will be affected by a rare disease during their lifetime, equating to over 3.5 million people in the UK, yet only around 5% of rare diseases have an approved treatment.

The consultation acknowledges that traditional regulatory approaches, designed for common diseases with large patient populations and well‑established trial paradigms, are often unsuitable for rare disease therapies.  Against this backdrop, the Proposed Framework aims to enable earlier patient access to promising therapies, reduce development burden, and incentivise innovation, while maintaining the UK’s standards of safety, quality and efficacy.

The MHRA requests responses from industry, patient organisations and other stakeholders. The consultation closes on 30 July 2026.

A shift towards a tailored and flexible regulatory model

The Proposed Framework is primarily designed for therapies targeting conditions with a prevalence in the UK of typically <1 in 50,000 where there are quantifiable barriers to conducting an existing clinical development programme or obtaining a standard regulatory approval. Elements of the Proposed Framework may apply to conditions with higher prevalence when randomised controlled trials are not feasible or are impractical.

The consultation recognises several structural challenges in rare disease development, including:

• slow disease progression may result in modest efficacy signals;
• small, heterogeneous patient populations making randomised controlled trials impractical;
• traditional development timelines are too long to meet the often urgent clinical need of patients;
• rare diseases may require highly personalised medicines and gene and cell therapies, creating complexity around manufacturing, durability of efficacy, and long-term safety.
• financial incentives may not be sufficient due to very small patient populations and uncertain returns on investment.

While some flexibility exists today, the MHRA’s proposals go further in embedding flexibility across the entire lifecycle of development and authorisation.

The Investigational Marketing Authorisation

The central feature of the Proposed Framework is the introduction of the Investigational Marketing Authorisation (“IMA”). This is a novel pathway that would combine clinical trial authorisation and progressive marketing authorisation into a single, adaptive regulatory route.  Under the IMA, therapies may be authorised based on limited but compelling evidence, allowing patients to gain earlier access while data continues to be generated. Data is reviewed on a rolling, iterative basis, rather than at fixed dossier submission points. This would allow a medicine to be used in the treatment of patients for specific rare indications where the available evidence supports a positive benefit-risk balance but is not yet sufficient for a full marketing authorisation.

This approach aims to reduce the development timeline through more targeted trials, smaller datasets, and earlier decisions to reduce late stage attrition. The MHRA hopes that the Proposed Framework will encourage large pharmaceutical companies to diversify their product portfolio to include very rare indications, through supporting greater commercial viability.

A more flexible evidence framework

The approach under the IMA is intended to enable data to be accumulated incrementally rather than through a fixed development programme, such that the conditions of the authorisation can be expanded, narrowed, or converted to a different type of authorisation, as knowledge about the medicine develops.

The MHRA has signalled a willingness to accept a wider variety of data during the course of an IMA, such as:

• Prior knowledge, including platform data, previous clinical experience, natural history studies, in silico or preclinical evidence.
• Predictive knowledge,  to address risk in patients through novel methodologies
• Projected safety profile based on non-clinical toxicology studies
• Innovative trial designs, including novel, validated methodologies and endpoints where randomised controlled trials are not feasible
• Real-world evidence
• Alternative sources, including patient video assessments if they support evaluation of clinical benefit.

If implemented, the IMA could represent one of the more flexible and adaptive licensing models currently available. However, important practical questions remain, including how reimbursement pathways, post-authorisation obligations, and international regulatory recognition would operate in practice.

Lifecycle regulation

The IMA is designed to be a dynamic authorisation, allowing for the scope to be expanded or narrowed as data evolves, additional data obligations to be imposed via a clinical monitoring plan and ultimately for the IMA to be converted into a full or conditional marketing authorisation, or be withdrawn in the risk-benefit profile changes.

The  clinical monitoring plan is intended to set out requirements for long-term safety and efficacy follow-up during the trial or for a subsequent trial. The requirements for adverse event reporting as ordinarily apply in clinical trials would also apply under the IMA. The approach reflects a broader move towards lifecycle‑based regulation, where approval is not a single decision point but an ongoing regulatory process.

Scientific Opinions

Scientific Opinions will be offered as part of the Proposed Framework. These are formal statements setting out the MHRA’s position on scientific, technical or methodological aspects of the product’s development. They are intended to be an additional regulatory tool to support alignment between the MHRA and developers throughout the lifecycle of an IMA, maintaining continuous oversight of benefit–risk. Although they do not replace statutory regulatory decisions, they are intended to: reduce uncertainty through ensuring the developer receives regulator feedback from the MHRA throughout the development process, provide reference points for planning development, and help clarify expectations on sufficient evidence at each stage and what further data may be required.  

In practice, Scientific Opinions could become an important mechanism for de-risking development programmes by providing greater regulatory predictability earlier in the product lifecycle.

Interaction with existing frameworks

The Proposed Framework does not replace existing routes to approval, but sits alongside them as an alternative where the  conventional approaches are not feasible. Early engagement with the MHRA is encouraged to determine the most suitable route.

The Proposed Framework is distinct from orphan designation and products can benefit from both the Proposed Framework and orphan incentives.

Other considerations

Individualised Medicines Framework

In addition to the Proposed Framework, the MHRA has signalled that it is considering the development of a separate legal framework covering individualised therapies for serious or life‑threatening conditions with unmet medical need. Aspects of this approach have been outlined for mRNA cancer immunotherapies (see our related blog here), but the current proposal would formalise and expand on this to apply to other types of individualised medicines, including (but not limited to) rare diseases.

The approach would enable a single marketing authorisation covering multiple patient‑specific product variants, based on a validated manufacturing and design process, providing greater regulatory certainty for therapies with variable components tailored to individual patients.

This is particularly relevant given the growing importance of gene and cell therapies, oligonucleotide therapies, and AI‑driven, patient‑specific treatments.

The proposal reflects a recognition that “one product, one authorisation” models are increasingly incompatible with personalised medicine.

The MHRA is proposing that an eligibility review would be carried out in advance of the marketing authorisation application, such that developers are given clarity early on in the development cycle.

GMP and Master File Considerations

The MHRA acknowledges that Good Manufacturing Practice (“GMP”) requirements for rare disease therapies should be applied in a risk-based and proportionate manner, recognising the unique manufacturing characteristics of these products, including small batch sizes, limited patient populations, short shelf lives, decentralised manufacture, and the need for rapid patient access.  The Proposed Framework therefore signals a move away from a purely compliance-driven approach towards greater emphasis on process understanding, robust control strategies and real-time quality assurance tailored to the specific risks of the product and manufacturing process. Early engagement with the MHRA is encouraged to ensure alignment.

In addition, the MHRA proposes expanding the use of the “master file” concept to support more efficient regulatory management of common materials and components across multiple MA holders. This could support increased efficiency in dossier compilation and submissions such that the regulatory assessment is based on a single, integrated submission.

Platform technologies

The MHRA also recognises “platform technologies” as a means of streamlining development and regulatory assessment for innovative therapies. Many advanced therapies are developed using common delivery systems, manufacturing processes, vectors, or technological backbones across multiple products. Rather than reassessing the same foundational data for each product, the Proposed Framework contemplates greater reliance on prior knowledge and platform-based evidence where the underlying technology has already been characterised and validated. This could reduce duplication across development and regulatory submissions, particularly for sponsors developing multiple therapies using the same manufacturing or delivery platform.

The consultation suggests that data relating to manufacturing processes, analytical methods, vectors, delivery systems, or other core platform elements could be leveraged across products, allowing regulatory focus to shift towards the novel or product-specific aspects of the therapy. The proposals also recognise the need for a more iterative and collaborative regulatory model, with early scientific engagement and ongoing dialogue likely to play an important role in determining how platform data may be relied upon and what additional evidence may be required for individual products. Overall, the approach signals a more flexible and innovation-friendly regulatory environment that better reflects modern platform-based product development.

Concluding remarks

While many elements of the Proposed Framework remain conceptual and will require further operational detail, the consultation signals a clear strategic direction from the MHRA towards more adaptive, lifecycle-based regulation for rare disease therapies. If implemented effectively, the proposals could materially strengthen the UK’s attractiveness as a development and launch market for innovative therapies, particularly in areas where conventional regulatory models are poorly suited to the realities of small patient populations and highly personalised medicines.