On February 4, 2014, the U.S. Federal Trade Commission ("FTC") held a Workshop entitled: "Follow-On Biologics Workshop: Impact of Recent Legislative and Regulatory Naming Proposals on Competition". The Workshop was well attended and sought to solicit a variety of views on the marketing of follow-on biologics, currently referred to as "biosimilars" under the Biologics Price Competition and Innovation Act ("BPCIA").
Briefly, the BPCIA defines "biosimilarity" as "[T]he biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components" and "there are no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product." A biosimilar is submitted as a 351(k) application, which must contain, among other things, information demonstrating that the biological product is biosimilar to a reference product based upon data derived from analytical studies, animal studies, and a clinical study or studies, unless FDA determines, in its discretion, that certain studies are unnecessary. To meet a higher standard of "interchangeability," an applicant must provide sufficient information to demonstrate biosimilarity, and also to demonstrate that the biological product can be expected to produce the same clinical result as the reference product in any given patient and, if the biological product is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between the use of the biological product and the reference product is not greater than the risk of using the reference product without such alternation or switch. According to the BPCIA, interchangeable biosimilar products may be substituted for the reference product without the intervention of the prescribing healthcare provider.
As explained by Edith Ramirez, FTC Commissioner, many state legislatures have either passed or are considering legislation to explain how to handle biosimilars that are not interchangeable (and sometimes including interchangeable biosimilars), which may affect competition for the market at this juncture before even one biosimilar has been approved. In particular, many of the state laws or bills include provisions for prescriber notification of possible biosimilar substitution for the referenced innovator biologic product. FDA and other regulatory bodies are still considering universal nomenclature for biosimilars, which may either create the same or similar names for biosimilars and their referenced innovator biologic products. The FTC sees similarities between biosimilars and how generics were first perceived and opportunities to either facilitate or hinder acceptance of biosimilars in the market that they wanted to explore in this Workshop.
As expected, the Workshop provided an avenue for a variety of stakeholders to express their views, rising to the level of heated debate during some panel discussions. A sampling of points discussed included:
- Aaron Kessleheim, M.D., J.D., M.P.H., Assistant Professor of Medicine, Brigham and Women's Hospital / Harvard Medical School, explaining that physicians continue to prescribe by brand name but rely on automatic substitution for generic drug products as applicable, where the generic name is critical for such substitution to occur.
- Emily Shacter, Ph.D., Independent Consultant, ThinkFDA, LLC (former Chief, Laboratory of Biochemistry, Division of Therapeutic Proteins of the Office of Biotechnology Products, FDA Center for Drug Evaluation and Research) opining that FDA would not waive any requirements if there were any proposed biosimilar that differed clinically from the referenced biological product, resulting in "virtual interchangeability" for any approved biosimilar. In her experience, analytics have progressed to a point where small differences in biologics are unavoidable and detectable, and clinical studies cannot overcome any big analytical differences, but analytics cannot fully predict immunogenicity and folding (yet).
- Geoffrey Eich, M.B.A., Executive Director, R&D Policy, Amgen, Inc. asserting that it would be misguided and not lead to a robust market to frame the biosimilar debate as similar to Hatch-Waxman generic drugs. Instead, Eich explained that Amgen believes that state laws should only allow substitution when interchangeable and that for purposes of making prescribing decisions and post-market surveillance, it is important to have unique names for different biosimilars to prevent ambiguous or inaccurate records in patients' medical records, noting that Amgen "believes in and not or."
- Steven B. Miller, M.D., M.B.A., Senior Vice President & Chief Medical Officer, Express Scripts, stating that studies reveal that doctors do not want to know when patients pick up their medications or whether prescribed innovator medications are substituted for generic versions, and do not want to keep patient dispensing records for adverse event tracking. Rather, Miller believes that for biosimilars, doctors would prefer pharmacies tracking such information, which is what they are already able and by-in-large doing.
- Bruce Leicher, J.D., Senior Vice President & General Counsel, Momenta Pharmaceuticals, Inc. providing his view that many of the state biosimilar notification laws are part of a "campaign" to make biosimilars look "biodifferent" than interchangeable biosimilars, which he believes will make biosimilar innovation less attractive. Leicher thinks the next "tactic" will be to raise concerns about pharmacovigilance with biosimilars. The state notification laws provide a competitive advantage to innovators with large sales forces, Leicher argues, and are designed to encourage physician intervention and may violate the BPCIA.
- Marissa Schlaifer, M.S., R.Ph., Head of Policy, CVS Caremark, noting that the state laws were unnecessary given that biosimilar substitution would only be allowed if interchangeable and would result in unnecessary communication between pharmacies and physician offices, possibly leading to some confusion that interchangeable biosimilars could not be substituted. She thought FDA should maintain a book of innovator biologics and biosimilars similar to the Orange Book rather than each state making their own (also advocated by Angela Long, M.S., Senior Vice President, Global Alliances & Organizational Affairs, United States Pharmacopeia).
- Krystalyn Weaver, Pharm.D., Director of Policy and State Relations, National Alliance of State Pharmacy Associations, noting that state notification rules would be expected to increase innovator product use (and slow acceptance of generic versions), as was seen in Tennessee with epilepsy drugs.
- Sumant Ramachandra, M.D., Ph.D., M.B.A., Senior Vice President and Chief Scientific Officer, Hospira, Inc., calling biosimilars a "market forming event" where communication will help to foster confidence. He agreed with Eich/Amgen that the generic drug paradigm should not be used. Ramachandra thought, however, that biosimilar product development is not about driving to the lowest cost but about obtaining greater access with appropriate incentives for participating in the market. For example, Hospira noticed in Europe that reimbursement helps drive uptake of biosimilar products and different naming can have an impact.
- Mark McCamish, M.D., Ph.D., Global Head, Biopharmaceutical Development, Sandoz International GmbH, noting that a sales force will be more critical if different states have different approaches to substitution and notification for biosimilars. According to Sandoz's data with biosimilars in Europe, there has been no sign of adverse events for switches from the innovator product to biosimilars (later echoed by Ramachandra/Hospira). McCamish said that proprietary product names, not INN names (Europe's version of generic naming) have been used in reports of Sandoz's European biosimilar products (also echoed by Ramachandra/Hospira).
- Helen Hartman, Ph.D., Director, Worldwide Regulatory Strategy, Pfizer Inc., reporting on a product identification study conducted by Pfizer that indicated proprietary names are most important for pharmacovigilance. Hartman concluded that since not every country has a requirement for proprietary names, there should be a unique identifier for each biosimilar product (not INN, which is the same for biosimilars in Europe).
- Emily Alexander, J.D., Director of U.S. Regulatory Affairs, Biologics Strategic Development, AbbVie Inc., reporting on a study that demonstrated the correct product (innovator versus generic) is often not reported in adverse event report forms (or verified by FDA) suggesting the need for related but distinguishable names for all biologics.
- Harry Travis, B.S. Pharm., M.B.A., Vice President, General Manager, Aetna Specialty and Home Delivery Pharmacy, reporting that specialty pharmaceuticals are becoming an ever-increasing share of payor budgets, causing increased costs for non-specialty drugs with larger population-changing effects, such as cholesterol-lowering products, and physician benefits. Travis said this suggests the need to develop a vigorous, competitive market for specialty drugs including biologics.
For those interested in this topic, the FTC has archived the webcast for the Workshop and included the presentations in the "Event Speaker" tab found in the link above. While it is unclear how the FTC could change or influence the key topics discussed, the Workshop provided a venue for many of the stakeholders to present their opinions. Some thoughts that did not appear to be raised or discussed in much detail here but have been raised in other contexts included: 1) if unique names for each biologic are adopted, how would they change if a biosimilar is first approved as a "regular" biosimilar and later an interchangeable biosimilar, 2) what effect will FDA's pending rulemaking for generic drug adverse event reporting have on biosimilar pharmacovigilance and labeling, 3) what would it take for FDA to be able to mandate proprietary names for all biologics/biosimilars (since the consensus was that is how adverse events are usually reported), and 4) to the extent each state maintains its own board of pharmacy, what would it take for more uniform pharmacovigilance data collection at a federal level to collect desired information for biosimilars and other dispensed products?