As a follow-up to NDA’s previous post on the latest news ‘MHRA to streamline clinical trial approvals in the biggest overhaul of trial regulation in 20 years,’ here we provide a high-level discussion on how the legislative changes will position the UK amongst its EU counterparts, highlighting also special considerations for industry.
A series of new measures will be introduced by the Medicines and Healthcare products Regulatory Agency (MHRA), with support from partners, to make it faster and easier to gain approval and to run clinical trials in the UK.
These changes, which follow a public consultation in partnership with the Health Research Authority (HRA) and the Department of Health in Northern Ireland, have been made possible with the help of the public and the research community.
Comprehensive new guidance, co-designed with stakeholder groups, will be introduced to accompany the new legislative measures. This will ensure that UK clinical trials work in partnership with patients and the public and are representative of the diversity of people who may benefit from the medicine if the data generated ultimately lead to regulatory approval. The guidance will outline how to include patients meaningfully into the design and conduct of trials, and how to achieve diversity in trials in a way that is proportionate and achieves the best results.
The UK and EU regulatory landscapes have seen numerous changes. How do the proposed changes compare to the EU's Clinical Trials Regulation, which mandated the use of the "Clinical Trials Information System" (CTIS) for all new trials in the EU from January 31, 2023
Here we introduce four Pillars underpinning the MHRA overhaul and compare and contrast to the EU counterparts.
1. Proportionate, streamlined and flexible regulatory environment
‘Under the new framework, clinical trials application processes in the UK will be more proportionate, streamlined, and flexible without compromising on safety, helping to cement the UK as an attractive destination for trials, including global “multi-site” trials. For example, the integration of the regulatory and ethics reviews of clinical trial applications (the combined ways of working), which in pilot phase halved the approval times for studies and cut the time from application to recruiting a first patient by 40 days, will be embedded into the new regulation’.
Regulatory Considerations for Industry –
A proposal to embed a proportionate, streamlined, and flexible regulatory framework into the UK regulatory landscape may allow for quicker trial start up times as demonstrated by the combined ways of working implementation. A streamlined framework is attractive, given it can help speed the route to market and deliver medicines to those that need them quicker.
It is less clear, at this stage, how the UK will address the proportionate and flexible regulatory aspects of the new framework. That said, the UK national response to the pandemic (amongst the first countries to approve safe and effective clinical trials and vaccines) demonstrated how proportionate, streamlined, and flexible the UK regulator can be.
In the UK the clinical trial application is a mandatory combined regulatory and ethics submission and approval process, enabling a streamlined approach to receiving Requests for Information (RFI) and final approval.
In the EU, industry has the option to choose to submit the Part I (co-ordinated assessment) and Part II (National assessment) applications either sequentially or in parallel.
Both the UK and the EU, however, offer a single application portal for clinical trials, which reduces administrative burden for sponsors and speeds up the approval process.
2. Timelines
‘The MHRA will implement a timeline for completion of an application review within a maximum 30 days in general, with a maximum 10 calendar days for a decision to be granted once the regulator has received any final information’.
Regulatory Considerations for Industry –
The UK proposal offers a relatively quick turnaround time from the point of submission to the regulatory outcome decision. This could be a very attractive incentive for industry.
Industry needs to be prepared and have robust internal processes in place to address agency questions to make best use of these timelines.
The UK proposals will also implement an extended timeframe for responding to questions with a nominal maximum 60-day timeframe (with flexible extension) for responses whereas in the EU the response timelines are fixed to a maximum of 12 calendar days.
The importance of pre-empting regulatory questions in preparedness for responding to them can’t be emphasised enough. Prior to submitting a clinical trial application consideration should be given to seeking scientific advice from the regulator to maximise the opportunities for regulatory buy in to the clinical and regulatory strategy proposed.
3. Future proof framework: trial design and trial conduct
‘The legislative changes will result in a regulatory framework that is as future-proof as possible, responsive to different types of trials and innovative designs, and supportive of new ways of carrying out trials such as decentralised trials’.
Regulatory Considerations for Industry –
The proposal demonstrates that the MHRA are embracing a pragmatic culture encouraging novel and innovative trial designs.
Similarly in the EU, the Accelerating Clinical Trials initiative (ACT EU) aims to develop the European Union further as a competitive centre for innovative clinical research, with one objective being to facilitate innovation in clinical trial methods and further develop guidance on decentralised clinical trials.
When preparing a regulatory road map, consideration should be given to a number of varied trial design options, with a view to adopting the trial that enables meaningful results to be collected in the most efficient manner.
Early engagement with regulatory experts is advisable to discuss innovative trial designs and their acceptability to UK and EU regulators.
4. Transparency
‘On transparency, the framework will introduce a legal mandate to register the trial in a World Health Organisation (WHO) public register, and a requirement to publish a summary of results within 12 months of the end of the trial. Sharing trial findings with participants in a timely manner and suitable format will also be required by law’.
Regulatory Considerations for Industry –
This is a new UK requirement as current UK legislation is silent on transparency requirements. In comparison, the EU regulatory framework requires the publication of most documents that are submitted to CTIS.
Both the UK and the EU CTR requires that all clinical trial results be publicly disclosed within one year of trial completion, which helps to ensure that patients, researchers, the public and healthcare professionals have access to complete and accurate information on clinical trials.
Conclusions
Overall, whilst there are some differences between the UK and EU clinical trials regulation, they remain aligned in the main, with a focus on facilitating timely and efficient access to new therapies for patients whilst conducting safe and ethically sound clinical trials. The involvement of people who have relevant experience as a patient, family member or carer, in the design, management, conduct and dissemination of clinical trials underpins both the UK and EU regulatory frameworks.
Proposals for change are refreshing and welcomed globally. Industry now has more options with regard to routes to market and what this actually looks like. Options will both enable and encourage innovation and scientific advancement, bringing medicines to those that need them quicker.
Are you wondering how the new legislative measures will impact your drug development? Contact us by using the form below to learn more.