2023 – early regulatory considerations


All those in the pharmaceutical industry hoping to ease themselves into 2023 following the excitement of 2022 (regulatory and otherwise) will face some disappointment. We find that there is a great deal to consider now that we have properly entered the New Year.

First to consider is the industry’s performance in 2022. The US Food and Drug Administration has published its New Drug Therapy Approvals 2022 Report (https://lnkd.in/gSCb8NVz) and it confirms performance concerns. Of only 37 approvals, over half targeted rare diseases, with 12 expanding existing permissions to paediatric populations – good news for those with rare conditions (assuming they can afford the cost of treatment) but not so good for the overall public health. We must hope that performance is better in 2023. It is clear that cybersecurity and digital health, patent challenges and the Medical Device Regulations (MDRs) in Europe will continue to raise challenges in 2023 but below we summarise more immediate concerns:

EU Clinical Trials Regulation implementation 

The regulations around how we conduct clinical trials (CTs) in the European Union (EU) underwent a major change with the instruction of the Clinical Trial Regulation (CTR) EU No 536/2014 on 31 January 2022. However, adoption was slow with most stakeholders deciding to continue submitting under the existing system up to the closing date 12 months later (31 January 2023 – 5 days time). The regulations replace and augment the scope of the existing EU CT Directive (CTD) 2001/20/EC. Critical to implementation was the introduction of the Clinical Trials Information System (CTIS) – the web-based submission hub that enables the CTR’s implementation. It serves as the single-entry point for clinical trial authorisation (CTA), application submission, approval, and supervision in the EU and European Economic Area (EEA). There is a 3-year transition period for ongoing studies but all other trials will require consideration.

In addition to providing what has been billed as a ‘simplified and harmonised procedure,’ the CTR also introduces consideration for ‘low intervention trials’ as a stand-alone category. It also incorporates new rules on the protection of subjects and informed consent, as well as implementing more rigorous greater transparency requirements. Now Sponsors will need to provide greater public and patient involvement, with the introduction of mandatory layperson/patient involvement as well as providing a summary of the protocol and the final report in lay language.

These developments represent a sea change in the way EU trials will be conducted in the future, parties having a longer-term goal of harmonising drug development. Implementation has and will continue to require considerable preparatory work from sponsor organisations. Equally, many agencies have been struggling to meet the minimum requirements. Calls to extend the transition period to minimise disruption to development timelines and ensure both compliance and transparency requirements around CTs are met have been ignored.

Focus of the FDA on accelerated development

The US Food and Drug Administration (FDA) has restated its aim of supporting the industry with the development of complex, novel therapeutic products. Building on existing agency offerings, the FDA is pioneering a chemistry, manufacturing, and controls (CMC) review scheme, including a project specially designed to advance the development of new oncology therapies to the early clinical setting. In the tail-end of 2022, the FDA announced a limited CMC development and readiness pilot programme to expedite the development of breakthrough products targeting unmet medical needs. The scheme, which is slated to begin on 1 April 2023, with recruit nine pilot candidates. The FDA will provide product-specific CMC advice during development, including two additional CMC-focused Type B meetings, as well as a limited number of additional CMC-focused discussions.

There was also an announcement of the FDA’s Project Front Runner, an Oncology Center of Excellence (OCE) initiative intended to facilitate their interaction with pharmaceutical companies in identifying when its most appropriate to seek approval of new cancer drugs for advanced or metastatic disease, focusing on the early clinical setting rather than the more typical approach of seeking approval for treatments in patients who have received numerous prior lines of therapies or have exhausted available treatment options. Interestingly, the FDA noted that trials that support initial approval in the earlier setting may see quicker patient access to new therapies, improve assessment of drug effects, elucidate novel opportunities compared to the established standard of care, and offer potential to improve treatments in the frontline setting.

Overall, Project Front Runner targets better resourced companies, introducing the opportunity to accelerate their therapy development. Smaller biotechs working in the last line setting, for example, may not be able to access such benefits. Few Sponsors will have sufficient funds to run the types of study generally required in early disease. The FDA notes that it is important that incentives remain for Sponsors carrying out work within areas such as rare diseases and developing therapies for unmet need.

United Kingdom trials (and tribulations)

Recent regulatory changes brought about by Brexit, the impact of the pandemic, and the following focus on vaccine research have put considerable pressure on UK pharmaceutical infrastructure and its associated regulatory organisations. The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) continue to face woes with a continued haemorrhaging of key senior company players, a government-imposed funding cut and stories of challenges to review timelines. The number of ILAP reviews and reported successes continue to emerge. New service prices have been announced but the question arises as to whether there is the resource to provide a level of service sufficient to maintain the UK’s competitivity as a place to conduct clinical trials. It may take the MHRA some time to repair the loss of key team members with similarly experienced assessors.

Looking ahead

In conclusion, the regulation of drug development in the UK, EU, and worldwide is undergoing considerable change (and continues to do so). These changes will impact on the breadth of the pharmaceutical stakeholder community. When considering your next move be certain to seek the latest regulatory affairs advice to ensure that all legal requirements are met and that you are taking advantage of any strategic regulatory opportunities. If Sponsors are to prevent delays in development programmes in 2023 and beyond, they are going to need to navigate expertly the challenges ahead.