Part III: Stakeholder Comments on FDA’s Interchangeability Guidance for Biosimilars
This post, Part III, of a three-part series (Part I and Part II) on FDA’s interchangeability draft guidance highlights a number of open issues that stakeholders have identified in their comments to FDA. These include the naming and labeling for interchangeable products as well as the relationship between multiple interchangeable products for the same reference product. Biosimilar makers also wanted FDA to make clear that physician-mediated switching is possible for non-interchangeable biosimilar products even if pharmacy-level substitution is not. A number of patient groups, by contrast, expressed concern that payers were in effect mandating pharmacy-level substitution for non-interchangeable biosimilars by taking innovator products off formularies.
- Naming of Interchangeable Biosimilar Products
A number of stakeholders expressed their views on the naming of interchangeable biosimilar products and asked FDA to address this subject in its final interchangeability guidance. FDA issued a final guidance on the naming of biosimilars in January 2017. In that guidance, FDA said that biosimilar and innovator biologic products will have the same core nonproprietary name followed by a distinguishable but meaningless lowercase four-letter suffix. Innovators and biosimilar makers alike had urged FDA to adopt memorable, meaningful suffixes but FDA ultimately stayed with its proposal for suffixes devoid of meaning. The final naming guidance did not address the naming for interchangeable products. Instead, FDA stated that it “is continuing to consider the appropriate suffix format for interchangeable products.” Similarly, the draft interchangeability guidance, which FDA also issued at the same time, did not include FDA’s thinking on this subject.
Many stakeholders urged FDA to use the same naming convention for interchangeable products as it set forth for biosimilar products, particularly since most interchangeable biosimilar products will be first approved as biosimilar products and will already have distinguishable suffixes. PhRMA explained that the suffixes of interchangeable products should remain different from that of the reference product for a further reason: different products that are interchangeable with the same reference product need to be distinguishable from each other for patient safety and tracking. PhRMA elaborated that “[i]f multiple interchangeable versions of a single reference product were assigned the same suffix without an FDA determination that they were interchangeable to each other, there might be inadvertent substitution of these products.” Pfizer, a biosimilar maker and innovator, stressed that it was important for interchangeable products not to have the same suffix as the reference product due to the potential impact of a shared name for interchangeable and innovator products on the uptake of non-interchangeable biosimilar products. Pfizer explained that if “FDA were to recommend interchangeable biological products share the same suffix as their reference product than this could lead to inaccurate perceptions of the quality, safety, and effectiveness of interchangeable products vs biosimilars.”
- Labeling of Interchangeable Biosimilar Products
FDA’s draft interchangeability guidance also did not address labeling. FDA addressed labeling for biosimilars in its draft labeling guidance, including the inclusion of a biosimilarity statement, but it did not address labeling for interchangeable products there. PhRMA and BIO, among others, recommended that labeling for biosimilars also include an interchangeability statement that identifies whether or not interchangeability has been evaluated for the biosimilar and a definition for interchangeability. Amgen, a biosimilar maker and innovator, also noted that “surveys of 400 pharmacists and 400 physicians conducted by the Alliance for Safe Biologic Medicines (ASBM) found that over 80% of those surveyed believe it is important or very important that a product label indicate whether the biosimilar is interchangeable with the originator product.” Pfizer and Amgen also urged FDA to include the clinical data used to demonstrate interchangeability in the labeling. For example, Pfizer stressed that it is “vitally important” to build trust with patients and physicians for successful implementation of the U.S. biosimilars pathway and that “trust depends on transparent disclosure of information.”
- Multiple Interchangeable Biosimilar Products
Stakeholders also asked FDA to address how multiple interchangeable biosimilar products of the same reference product would be treated. BIO asked FDA to “take steps to ensure that only an interchangeable biological product and its reference product are subject to automatic pharmacy substitution.” Amgen urged FDA to include an explicit statement in the guidance that an interchangeability designation for a product “does not reflect any relationship” with another interchangeable product to the same reference product. Genentech explained that different interchangeable products to the same reference product “would likely have even greater differences between them creating a higher likelihood for generating undesirable immune reactions.” Similarly, AbbVie stated that the marketing of multiple products found to be interchangeable with the same reference product raises significant patient safety concerns since physicians, pharmacists and patients may assume that these products are also interchangeable with each other when that may not be the case. It asked FDA to recommend labeling to avoid substitution of interchangeable biosimilar products with each other.
- Physician-mediated Switching vs Pharmacy-level Substitution
A number of stakeholders asked FDA to address confusion about physician-mediated switching, which is possible for interchangeable and non-interchangeable biosimilar products, and pharmacy-level substitution, which is possible for interchangeable biosimilar products. Pfizer urged FDA to make clear that “physician-mediated switching is part of usual medical practice and does not require an interchangeability designation.” The Biosimilars Forum also asked FDA to address this subject in its guidance. In its view “the difference between physician-initiated switching and independent pharmacy-level substitution has been the source of significant confusion that could hinder the uptake of biosimilars in the marketplace.”
Patient groups, by contrast, such as Patients for Biologics Safety & Access (PBSA) asked FDA to take steps to “protect patients from non-medical switching involving non-interchangeable biosimilars.” PBSA noted that some payers and pharmacy benefit managers (PBMs) are removing innovator products from formularies and substituting non-interchangeable biosimilars instead. As a result, patients “covered by these payers are being forced to switch to new products.” According to PBSA, “interchangeability will have no meaning” under these circumstances and biosimilar makers will have no incentive to develop interchangeable biosimilar products. RetireSafe, an advocacy organization for seniors, also urged FDA to address these issues in its interchangeability final guidance to “protect the patient’s safety by eliminating this type of unauthorized substitution.”