Dr Julie Warner is Vice President of Regulatory Affairs at global drug development consultancy, Boyds. In this article, she provides her expert insights into the key regulatory developments likely to shape the global drug development industry this year.
Implementation of the EU Clinical Trials Regulation
The way clinical trials (CTs) are conducted in the European Union (EU) underwent a major change when the Clinical Trial Regulation (CTR) EU No 536/2014 came into force on 31 January 2022. The CTR replaced and expanded on the scope of the existing EU CT Directive (CTD) 2001/20/EC.
In addition, a new system – the Clinical Trials Information System (CTIS) – was introduced to enable the implementation of the CTR. From its ‘go-live date’ of 31 January 2022, CTIS became the single-entry point for clinical trial authorisation (CTA), application submission, approval, and supervision in the EU and European Economic Area (EEA), with a three-year transition period for ongoing studies.
As well as offering a simplified and harmonised procedure, the CTR also provides a category for ‘low-intervention trials’, new rules on the protection of subjects and informed consent, and greater transparency requirements.
Notably, sponsors will be required to ensure greater involvement of the public and patients, with the mandatory introduction of layperson(s) or patient organisations into the testing team and the publication of a final report in lay language.
The new developments represent a major change in the way CTs are carried out in Europe, with the longer-term goal of harmonising drug development timelines. However, this evolution has and will continue to demand a great deal of preparation work from sponsor organisations over the transition period in order to minimise disruption to development timelines and ensure both compliance and transparency requirements around CTs are met.
Increased FDA focus on accelerated development
The US Food and Drug Administration (FDA) has recently increased its focus on supporting drug developers with complex therapeutic products. Building on existing offerings from the agency, the FDA has introduced a chemistry, manufacturing, and controls (CMC) review pilot, and a new project specifically designed to advance the development of new oncology therapies to the early clinical setting.
On 31 October 2022, the FDA announced a limited CMC development and readiness pilot (CDRP) programme to expedite the development of breakthrough products that address an unmet medical need. The FDA will accept nine applications for the pilot, which is slated to begin on 1 April 2023.
Under the pilot, 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.
The FDA has also announced Project FrontRunner, an Oncology Center of Excellence (OCE) initiative designed to encourage drug sponsors to consider when it may be appropriate to first develop and seek approval of new cancer drugs for advanced or metastatic disease in an earlier clinical setting, rather than the usual approach to seek approval for treatment of patients who have received numerous prior lines of therapies or have exhausted available treatment options.
The FDA notes that designing trials that support initial approval in the earlier setting may provide earlier access to new therapies, improve assessment of drug effects, elucidate drug effects of new therapies compared to the established standard of care, and offer potential to improve treatments in the frontline setting.
While Project FrontRunner offers resource rich companies 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, and not all sponsors will have the funds to run larger studies along the lines of those generally required in early disease. It is important that incentives remain for sponsors carrying out work within areas such as rare diseases and developing therapies for unmet need.
Conclusion
In summary, there has – and will continue to be – a great amount of change with regards to the regulation of drug development across the UK, EU, and the globe. It’s important to remember that the drug development community is all in this together, and companies unsure about the changes should seek external regulatory affairs support and expertise to ensure full compliance with legislation and to maximise potential opportunities.
The industry and its regulatory agencies have been under significant strain in recent times, with the regulatory changes brought about by Brexit, coupled with the pandemic’s impact and the subsequent focus on vaccine development, causing delays across many clinical development programmes.
A willingness to adapt and be agile is essential if the industry and its sponsors are to avoid further disruption to drug development timelines and make positive progress in 2023 and beyond.
About the author
Dr Julie Warner is Vice President of Regulatory Affairs at drug development consultancy Boyds and leads its regulatory team. Warner has a wealth of experience in EU and US regulatory affairs, and a special interest in orphan drugs.
