On November 2 and 3, 2010, the Food and Drug Administration (FDA) held a public hearing concerning the Approval Pathway for Biosimilar and Interchangeable Biological Products. The hearing was well attended on both days, with the FDA hearing testimony from more than 40 presenters representing some of the world’s biggest biotechnology, pharmaceutical and generic companies, patient groups, physician groups, academia, pharmacies and pharmacy groups, the United States Pharmacopeial Convention, the European Medicines Agency, and the office of U.S. Sen. Bernard Sanders. While the two-day hearing highlighted some of the divergent views and complex issues that will require resolution regarding the approval pathway of biosimilar products, no one contested the benefits of having less expensive alternatives to the existing biologic products.

The public offered different perspectives on the issues of safety and efficacy of biosimilar biologics, substitutability of interchangeable biologics with reference biologics, post-marketing studies and pharmacovigilance, ethical considerations and the requirements for clinical and animal studies, and issuance of agency guidances, among others. The patient groups, for example, tried to reconcile having access to lower-cost biologics with the need of assuring reliability, safety and efficacy of biosimilar biologics. All patient groups urged the FDA to require clinical trials and post-marketing surveillance studies to assure reliability and safety of biosimilar biologics. The Immune Deficiency Foundation and American Academy of Pediatrics, however, urged against automatic substitution of biologics at the pharmacy level. The Global Health Living Foundation also argued that biosimilars cannot be considered interchangeable with the reference biologics because, for example, they have the potential to destabilize patients in mid-therapy.

Duke University proposed scientific factors to consider and clinical study design to determine biosimilarity and interchangeability, including recommending parallel clinical study design, using surrogate (pharmacokinetic) and clinical endpoints, focusing on variability, using valid statistical methods for comparing immunogenicity, comparability in manufacturing processes, and establishing product specifications. As for studies to determine interchangeability of products, Duke University recommended using higher-order crossover design and bridging studies using biomarker data.

Intriguing testimony was also heard from academia and analytical laboratories, such as Northeastern University’s Barnett Institute, the Waters Corporation, and Biomedical Consulting International, on the advancements in analytical testing to characterize biologic products. As the analytical testing methods evolve in their sophistication, the biosimilar industry and the FDA would have the tools to procure necessary data in support of efficacy and safety of the follow-on biologic products.

On the issue of the naming of biosimilar products, the public consensus appeared to be split on whether to require unique product names for biosimilars. For example, Express Scripts, Inc., took the position that unique product names for biosimilars serve neither the goal of innovation nor patient interests. Teva and Hospira also proposed that for purposes of substitution at the pharmacy level, biosimilars have the same International Nonproprietary Name (INN) as the innovator. An INN is a non-proprietary or generic name given to a pharmaceutical substance by the World Health Organization to be used worldwide. CVS Caremark Corporation, the Coalition of State Rheumatology Organizations, Novo Nordisk, Merck, Amgen, and Biotechnology Industry Organization (BIO), on the other hand, urged using unique names and different INN numbers to prevent inadvertent substitution, avoid patient confusion and facilitate pharmacovigilance. The ability to track adverse event reporting of biosimilar products was one of the concerns expressed by both the public and the FDA. Thus, to distinguish biosimilars from the reference products, a unique name requirement by the FDA appears likely.

A number of companies, including Novo Nordisk, Teva, Hospira, Watson Pharmaceuticals, and Merck urged the FDA to consider and follow the European experience with the biosimilar approval process and reliance on non-U.S. derived clinical data. Biotechnology companies like Amgen and Novo Nordisk urged the requirement of well-designed clinical trails and licensing of biosimilars only for indications that are justified by the clinical data. Amgen’s Senior Vice President of Research and Development Joseph Miletich urged the FDA to “put patients first and sound policy will follow.”

During a period of open public comment on November 2, a representative from the office of Sen. Sanders read a letter dated the same day to FDA Commissioner Margaret Hamburg, asking the agency to consider the ethical dilemma created by the 12-year exclusivity period awarded to the brand biologics. Namely, in view of a 12-year exclusivity period, requiring a biosimilar applicant to conduct clinical trials in cases in which the data already exists is a violation of Article 20 of the Declaration of Helsinki on clinical trials using human subjects. Sen. Sanders proposed legislation, S.3921, 111th Congress, the Ethical Pathway Act of 2010, to “honor and respect international ethical standards for medical research, including the Declaration of Helsinki by avoiding unnecessary repetition of clinical trials in human subjects. It is pro-patient, pro-research, and pro-taxpayer, while providing for a system of cost sharing for drug registration data that will protect the legitimate financial interests of the innovators.”

All in all, the November 2-3, 2010 public hearing has officially kicked off FDA’s policy-making for the biosimilar and interchangeable biologic product approval process. The FDA is accepting electronic and written submissions until December 31, 2010 on the issues heard at the public hearing and outlined in the Docket No. FDA-2010-N-0477, Federal Register Vol. 75, No. 192, October 5, 2010. The FDA’s process with respect to setting guidelines for the Approval Pathway for Biosimilar and Interchangeable Biological Products promises to be transparent.