REGULATORY CORNER

Those of us working in drug development for several years have likely, at one time or another, focused on the requirements for the development of a combination product. They are listed in 21CFR300.50 Fixed-combination prescription drugs for human use; a regulation dated March 27, 1975 and amended on January 5, 1999. FDA also issued a guideline in 2013, Codevelopment of Two or More New Investigational Drugs for Use in Combination (the 2013 Codevelopment Guidance) that further expands on the information in the regulation.

In August 2025, FDA issued the draft guidance, Approaches to Assessment of Overall Survival in Oncology Clinical Trials. This guidance is based in part on discussions held at a joint FDA, American Association for Cancer Research (AACR), and American Statistical Association (ASA) public workshop held in July 2023. It also puts into writing feedback that I have received from the Agency on oncology clinical trials and guidance that I have related to our oncology clients.

Continuation of marketing approval of a product differs between the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). Marketing applications approved by the EMA are valid for 5 years and must be renewed to continue marketing of the product. If conditional approval was granted by EMA, a yearly reassessment is required. In the US, the situation is quite different. Once an application is approved by FDA, this approval continues unless the company requests that FDA withdraw the application or the FDA initiates a withdrawal process.

When FDA published the guidance, Optimizing the Dosage of Human Prescription Drugs and Biological Products for the Treatment of Oncologic Diseases in August 2024, I read it with great interest. At first, I thought that it was a draft guideline, as this was the first time I had seen a guideline addressing dose selection in the oncology setting. But I quickly realized that this final guidance implements the information gathered in the FDA’s Project Optimus.

When I first read the guideline, Considerations for the Conduct of Clinical Trials of Medical Products During Major Disruptions Due to Disasters and Public Health Emergencies, which FDA issued in September 2023, my initial reaction was, ‘do we really need such a guideline?’ We have just gotten over the impact of the COVID pandemic on clinical trials, and business is getting back to usual or normal or whatever we want to call our new normal. That said, I found some interesting and very useful information in this guidance. Having lived through one pandemic, one thing I have learned is that we need to be prepared for the unexpected. While I hope that I will not experience another pandemic, other natural disasters and disruptions in clinical trial are increasingly more likely, especially in our current environment of global clinical studies.