Does the committee agree that based on the totality of the evidence, EP2006 should receive licensure for each of the 5 indications for which US-licensed Neupogen is currently licensed?Following a day-long public meeting that heard from diverse stakeholders, the ODAC unanimously approved the submission. This meeting and its vote shows that the pathway for biosimilar approval has officially been activated in the U.S., but these initial questions of biosimilarity for approval are not the only hurdles in the regulatory scheme. Left for another day is the key question of whether an approved biosimilar will be greenlighted as “interchangeable” with the approved brand name product, thus making it available for substitution when filling prescriptions. The FDA defines interchangeability:
An “interchangeable” biological product is biosimilar to the reference product, and can be expected to produce the same clinical result as the reference product in any given patient. If administered more than once to an individual (as many biological products are), the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product will not be greater than the risk of using the reference product without such alternation or switch. Once determined “interchangeable” two biological products will thus be able to be substituted for each other (i.e., interchanged) by a pharmacist without the intervention of the health care provider. Pharmacists will be responsible for knowing which biological products are interchangeable and which will require prescriber prescription before substitution.Substitution laws for pharmaceuticals are state laws, and because biosimlar substitution is now on the radar screen, some states have already seen legislative action which is quite early considering that no biosimilars have completed regulatory review and will not for some time. Obviously, the standards for substitution will govern whether any approved biosimilar can compete for distribution with an already approved and well-known original biologic. The logic of any generic drug marketplace is to offer lower-cost options to high-priced brand-name drugs; for the scheme to work, a proposed substitute must provide the same therapeutic benefit to a consumer. In contrast to traditional chemically-based pharmaceutical synthesis, biologic drugs are produced in biological systems, which can introduce some differences in various cycles of production; any differences in a biosimilar must not degrade the overall clinical benefit in order to replace the existing pioneer biologic. That requirement and its implementation will surely test how well the BPCIA was designed to establish a true biosimilar approval process that results in a more competitive marketplace for biologics.