[author: James DeGiulio]

Last week, the U.S. Food and Drug Administration held a public hearing on the Draft Guidance on Biosimilar Development, where researchers, payors, patient and physician groups, and industry advocates provided their thoughts on the FDA's first attempt to clarify the logistics as to the operation of the Biologics Price Competition and Innovation Act of 2009 (BPCIA).  The panel was headed by Dr. Rachel Sherman, M.D., Associate Director for Medical Policy at CDER, and comprised other agency members Dr. Leah Christl, Ph.D.; Denise Esposito, J.D.; Dr. Steven Kozlowski, M.D.; Diane Maloney, J.D.; Heidi C. Marchand, PharmD; Maryll Toufanian, J.D.; and Robert A. Yetter, Ph.D.  The public hearing follows a 60 day period for comment, where the FDA dockets saw more than 44 different stakeholders represented.

With only eight minutes allotted, most of the speakers used their time to hit the key points of contention from their submitted comments.  As expected, innovator representatives advocated for more clinical studies and stricter standards for identity of products, but what was not expected was the strong support for this position from patient groups as well.  Indeed, patient advocacy groups seemed to be unconvinced that biosimilars would represent products that were just as effective and safe as the brand competitors.  While the groups want the price breaks the follow-on drugs might offer, they are far more concerned about safety, and want to see additional clinical trials.  Representatives from the National Kidney Foundation, Colon Cancer Alliance, and the Alliance for Safe Biologic Medicines warned that seemingly insignificant changes in manufacturing, packaging, handling, and storing of biologics can have unintended consequences that produce a drug that does not work or can be unsafe.

Biosimilar developer representatives used this opportunity to request resources from the FDA for patient education.  Representatives from Momenta focused the discussion on what is demanded in the statute:  clinical trials to establish biosimilarity to the reference product; there is no requirement to independently establish the safety and efficacy of the biosimilar product.  The FDA has stood fast on its position that human clinical trials should not be repeated.  Therefore, clinical trials on a product the FDA determines to be biosimilar could not be justified.  Proving biosimilarity represents an unconventional approach to drug approval.  Indeed, any argument suggesting that a drug's safety and efficacy do not need to be tested will cause unease from patient groups.  Patient advocates and physician groups stated that their constituents will need additional educational materials, including lay summaries of the Guidances, and are interested in interactive presentations from FDA on the appropriate use of these new products.  All of the stakeholders share support for the implementation of an education and communication plan to help the public and other entities understand biosimilars.  For example, the representative from the American Pharmacists Association said pharmacists are unaware of the proper process to follow when they start seeing prescriptions for biosimilar products.

All of the speakers agreed that the FDA should be commended for its scientific and safety-oriented approach in the draft guidance, which begin to pave the way to meeting the need to protect patient safety, encourage product innovation, and create meaningful cost-savings in the biosimilars field.  There were other points of substantive agreement at the hearing, which provides some level of optimism for the FDA's chances of establishing a working protocol for biosimilar approval.  Interestingly, it seems that industry players on both sides of the field are in favor of deferring to the EMA's guidances, which provide detailed guidance for biological products according to classes.  This would provide for harmonization with the rest of the world, as well as preserving FDA resources and speeding approvals.  Despite this supposed harmonization, innovator companies would not agree that referencing a non-US product should be permissible, as it is under the Draft Guidance in certain situations.  Abbott suggested that this was not permitted, citing the language of the statute noting a "single biological product" for biosimilar comparison -- not multiple biological products as would be required.

Stakeholders advocated changes to a wide variety of issues, but biosimilar naming was prominent throughout the hearing.  Patient groups and innovator representatives encouraged the FDA to require unique names for biosimilars, which would help hold manufacturers accountable for their products.  If a common nonproprietary name were used, patients wouldn't know which drug they're getting.  Advocates for a common name raised the possibility of overdosing or misdosing if different names were used, as a patient could inadvertently be prescribed two versions of the same biosimilar.  The FDA has voiced its intent to publish a future guidance on naming, as well as interchangeability, which may account for the extensive testimony on these two key issues, despite their minimal coverage in the Draft Guidance.

The panel was peppered with suggestions for how to improve the Draft Guidances, but few speakers had research available to support their proposed improvements.  For example, several speakers took issue with the FDA's definition of the term "protein," finding that the 40 amino acid cutoff is totally arbitrary.  While some speakers advocated for a more functional definition, such as peptides produced in a cell, the panel stood firm on this definition, emphasizing the need for a bright line rule dictating where polypeptides come under the exclusive coverage of the PHSA.  Without any evidence showing a problem with the current definition, the FDA noted that no matter which definition was chosen, someone would always find it to be arbitrary.  With several topics, the panel charged many of the speakers to support their testimony with additional commentary, including any research that can be located to support their proposed changes to the Guidance.  The panel encouraged these groups to submit their findings and other suggestions on implementation to the docket (FDA-2011-D-0618) at www.regulations.gov.  The FDA will continue to accept comments through May 25.