FDA hears testimony on approval pathway for biosimilars

After fighting about it for years, Congress included legislation in the mammoth healthcare reform bill that would allow an easier approval path for “biosimilars,” sometimes referred to as generic versions of biologic products.

That bill, among other things, gives manufacturers of innovative biologics 12 years of marketing “exclusivity,” during which time FDA may not make effective the approval of a “biosimilar.”

Faced with implementing the legislation, FDA finds itself dealing with a host of questions arising from the complexity of manufacturing processes and the fact that a biosimilar can never be exactly like the original drug. The agency is asking stakeholders to discuss such questions as: What factors determine that a product is highly similar to the “reference” or “innovator” product? When are animal or clinical studies of a biosimilar unnecessary? What factors should be considered in developing pharmacovigilance for biosimilars?

Biosimilar interchange

At a November meeting in Silver Spring, Md., the agency heard testimony on, for example, a provision in the new law allowing a pharmacist to interchange a product if a biosimilar meets a higher standard than the reference product meets; however, it must be shown that there is no greater risk for a patient switched from the reference product to the biosimilar than if the reference product were used without switching.

Janet S. Wyatt, PhD, RN, CRNP, FAANP, representing the Arthritis Foundation, told the panel, “We believe that there should be no changes in the prescriptive dispensing of the product, based on a pharmacist’s decision to substitute a ‘generic.’”

On the other hand, Rivka Riven-Kreitman, vice president of global innovative research and development for Teva North America, a generic pharmaceutical company, said, “I think that once biosimilarity has been established both on the chemistry level, the clinical level and so forth, interchangeability should be granted,” with no need for additional studies.

Biologist Marie Vodicka, PhD, associate vice president of scientific and regulatory affairs of the Pharmaceutical Research & Manufacturers of America, argued, “Given current science, we do not think it would be safe for patients if FDA were to approve interchangeable biologics now … There is currently no scientific, regulatory, or medical consensus on how the statutory requirement - the same clinical effect in any given patient - would be demonstrated.”

Names and numbers

On the issue of how biosimilars should be named, speaking for the Generic Pharmaceutical Association, Rasmus Rojkjaer, MD, PhD, head of global biologics research and development for Mylan, a generic drug maker, said, “In our view, one of the most unfortunate features of the abbreviated biogeneric pathway is that it does not dictate that the biogeneric have the same name as the reference product.” Both the European Union and the World Health Organization, he said, give biogenerics the same name.

If biogenerics don’t have the same name, “a finding of interchangeability, or biosimilarity for that matter, will count for very little among healthcare providers, diminishing meaningful opportunities for market access,” he said.

Teva’s Riven-Kreitman said that giving biosimilars different INN numbers would be confusing and make exchange at the pharmacy level very complicated.

On the other hand, David I. Bromberg, MD, FAAP, speaking for the American Academy of Pediatrics, said, “The academy’s position is that we provide a system that is as clear as possible for the prescriber, so that they can know exactly what they are working with and what they are prescribing to the patient.”

Testing

There was also an opinion gap on how much testing of biosimilars should occur.

Charles Ebert, PhD, senior vice president of research and development for Watson Pharmaceuticals, said, “Significant advancements have been made on characterizing biosimilars and in developing processes that allow the development of biosimilar products.” When a product has “demonstrated comparability through chemical/biochemical similarity,” the program for the nonclinical testing should be reduced appropriately, he said.

In addition, he argued, “if you have demonstrated chemical, biochemical, and now nonchemical similarity, full ‘clin-pharm’ testing should not be required, which is again consistent with guidances from other regulatory authorities.”

Vodicka countered, “FDA should at a minimum consider the following factors before deciding to waive the clinical data requirement for any indication: molecular mechanism of action, disease mechanism of action, and disease state of the patients.”

The agency is inviting comments until December 31. The Federal Register notice on the issues and the area to comment can be found by searching “biosimilars” at www.regulations.gov.