SummaryIn just two years, on March 23, 2020, biologics currently regulated as drugs will transition to being regulated as biologics. Many aspects of how FDA will implement this transition have yet to be established.
What is a Roll-Over?
For historical reasons, the Food and Drug Administration (FDA) regulates certain biologics as drugs under the Food, Drug and Cosmetic (FD&C) Act rather than as biologics licensed under the Public Health Service (PHS) Act.
Aiming to bring (almost all) biologics under the same legal and regulatory system, the Biologics Price Competition and Innovation Act of 2009 (BPCIA) included the “Deemed to be a License” provision, which states that 10 years after the law’s enactment, on March 23, 2020, applicable biologics approved as drugs under the FD&C Act will automatically be deemed biologics licensed under the PHS Act. This transition (or “roll-over”) carries serious procedural implications for currently approved products and products in development, including changing their nonproprietary names and labels. However, the statute did not provide instructions to FDA on how to accomplish this transition. Therefore, which products transition and how the transition will work is up to the Agency.
The FDA began laying out the process it intends to follow in a draft guidance titled “Implementation of the ‘Deemed to be a License’ Provision of the Biologics Price Competition and Innovation Act of 2009” issued in March 2016 (Draft Guidance). While a definitive list of biologics regulated as drugs to which the transition applies does not exist, the Draft Guidance included a list of examples of products that will be affected by the roll-over (see Table 1).
What are the implications for drug and biologics companies?
For applicable biologics currently approved as drugs, FDA’s actions on March 23, 2020 listed above will require changes in application numbers (from NDA to BLA), product labeling, and possibly a change in non-proprietary name (as FDA’s current scheme requires a unique name, including a suffix, for all biologics). Orange Book designations will have to be changed (and these products will no longer receive therapeutic equivalence ratings), and the new BLAs will be added to FDA’s Lists of Licensed Biological Products with a Reference Product Exclusivity and Biosimilarity or Interchangeability Evaluations (the Purple Book).
For some products, whether FDA will reassign the biologic to a standalone 351(a) product or a 351(k) biosimilar or interchangeable biologic may not be clear, primarily because the approval pathways under the FD&C Act do not align with the approval pathways under the PHS Act (see Figure 1 for possible transition options).
For products in development and pending applications, the disruption to the product life-cycle may be significant given that a pending application that is not approved by March 23, 2020 will have to be re-submitted to the Agency and meet all the regulatory requirements for a new pathway (chosen by the sponsor) – either a 351(a) standalone pathway, or the 351(k) biosimilar or interchangeable biologic pathway. Re-routing the development program for a standalone product may require relatively minimal changes given similar expectations to approve a branded drug or license a branded biologic. However, the differences in data burden and evidentiary requirements between a 505(b)(2), a generic ANDA and a standalone biologic, biosimilar or interchangeable biologic are substantial. Beyond trying to predict development timelines to ensure approval before March 23, 2020 (and little point in filing an application if the approval is likely after the rollover date), trying to re-work a development plan for a completely different regulatory pathway will likely involve significant resources and time. Also, this will bring a whole new significance to the value of regulatory predictability, the importance of user fee goal dates (meetings and decisions), and timeliness in general.
What should companies do to prepare?
Companies can take three actions now to prepare for the events of March 23, 2020:
- Determine if the “Deemed to be a License” provision applies to any of your approved products, pipeline products, or potential acquisitions. Products affected would include both FDA-approved biologics currently regulated as drugs, and applicable biologics in development, including those (e.g., as 505(b)(2)s or generics) that rely on the prior approval of an applicable biologic as their reference product. While the FDA’s Draft Guidance list of products is a start, it is not a comprehensive list. Companies should consult with the Agency to determine the status of their biologic products currently regulated as drugs.
- For applicable biologics, assess timing for development, application, and approval and develop a strategy to meet the March 23, 2020 deadline. Given that any application still pending (including those tentatively approved) on March 23, 2020, will need to be re-submitted under a biologics pathway, timing of developmental milestones is key. If a product’s development timeline, potential for additional cycles of review, and/or unexpired patents or exclusivities will likely delay approval until after March 23, 2020, companies need to develop a strategy as early as possible that may include modifying the product development plan to meet the evidentiary requirements of a biologics pathway (either a standalone application under 351(a) or a biosimilar/interchangeable application under 351(k)). In addition, for a currently approved product, companies should consider preparations to obtain an optimal re-assignment (e.g., a 505(b)(2) approved product obtaining a therapeutic equivalence rating prior to March 23, 2020 and arguing for a re-assignment to an interchangeable biologic). Beyond developing a regulatory strategy, it will be essential that companies keep their customers, payers, physicians, and patients informed regarding the anticipated changes as these rollover products may look different (e.g., with new labels) even though the products themselves remain the same.
- Engage with FDA on these issues. Given that the transition date is now less than two years away and that many aspects of how FDA will implement the transition are unclear, companies should talk to FDA about their products and potential re-assignments, as well as identify options, regulatory requirements, and plans to be ready for March 23, 2020. In addition, companies can engage with the Agency on its policy and implementation plans in this area, for example by submitting comment letters to the Agency on draft guidances.
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