WHO Develops Clinical Trials Tailoring Approach for Biosimilars

The Center for Biosimilars® spoke recently with Marta Baldrighi, PhD, policy and science officer for Medicines for Europe, a trade organization of generics and biosimilars producers, about the World Health Organization’s ongoing revision of its guidelines for evaluation of biosimilars. Baldrighi was a presenter on the topic at the recent Terrapinn Festival of Biologics meeting in Basel, Switzerland.

The WHO’s revisions will help to clarify the evidence requirements that developers of “similar biological products,” or biosimilars, should aim to satisfy when developing these molecules. Regulatory authorities in the United States and the European Union are moving toward a streamlined or clinical trial (CT) “tailored approach” that allows biosimilar developers to focus on the most advanced analytical technologies for characterization of biosimilars (ie, ensuring equivalence with reference drug molecules) and avoid comparative clinical trials that are not as precise and contribute little, if anything, to the sum of significant evidence for judging equivalence between highly similar biologic medicines.

The WHO, in conducting this review process, is moving in step with advances in the United States and European Union and providing an implied endorsement of CT tailoring. Following a public comment period this year, the WHO in November 2021 released the second draft of the guidance, Baldrighi explains.

The inclusion of CT tailoring holds out significant potential for adding constructive flexibility to biosimilar development that could make it more achievable for manufacturers to develop orphan biosimilars (for rare diseases) and other types of molecules that, owing to prior regulatory standards, may have been too costly to produce, Baldrighi says.

Advanced molecular characterization techniques lower the cost of biosimilar development and can substitute for in-human clinical trials that may be difficult or impossible for companies to perform in cases where patients with these diseases or conditions are scarce, she explains.

The WHO is not a regulator in the sense that it reviews and authorizes investigational medicines for use, but it maintains a list of essential medicines that it judges are qualified for safe and efficacious use, and its recommended medicines are adopted by medical authorities and countries worldwide. These guidelines on evaluation of biosimilar medicines will provide biosimilar developers with the assurance that the evidence basis upon which their molecules are founded will be satisfactory to the WHO when it decides what medicines to endorse.