FDA recently issued a new draft guidance titled Scientific Considerations in Demonstrating Biosimilarity to a Reference Product: Updated Recommendations for Assessing the Need for Comparative Efficacy Studies, which proposes omitting comparative efficacy studies (CES) where appropriate “based on the totality of the evidence” to instead rely only on analytical, PK/PD, and immunogenicity data to inform biosimilarity determinations. As the agency explains, it has gained substantial experience with comparative analytical assessments (CAA) and now wants to update its framework for determining when a CES may not be necessary to support biosimilarity.
This guidance reflects FDA’s ongoing efforts to streamline biosimilar data requirements as its experience with the class continues to mature. Innovator and biosimilar developers broadly should stay abreast of FDA’s approaches here both for their impacts on development programs as well as on related asset protection strategies, including intellectual property (IP) portfolios.
The draft frames a “streamlined” approach: where the CAA shows the proposed biosimilar is highly similar, an appropriately designed human PK similarity study plus an immunogenicity assessment may be sufficient (i.e., no CES needed). FDA recommends sponsors consider this approach when the following three parameters are met:
- The reference and proposed biosimilar are manufactured from clonal cell lines, are highly purified, and are well-characterized analytically
- The relationship between quality attributes and clinical efficacy is generally understood and evaluable in the CAA
- A human PK similarity study is feasible and clinically relevant
While FDA notes that circumstances will remain for which a CES remains necessary to show biosimilarity, FDA makes clear that there is no bright-line rule and invites developers to engage with the agency in early stages of biosimilar product development before the initiation of clinical studies.
This is not an entirely new approach. For example, FDA published draft guidance in 2019 for biosimilar insulin products, which proposed a similar CAA approach that would, under some circumstances, allow an applicant to forgo comparative clinical immunogenicity studies. Following in the footsteps of FDA’s evolving approach with respect to switching studies for biosimilar applications, it is also consistent with the general trend of FDA leveraging its experience and technological advances to reduce the burdens of biosimilar development programs and likely marks another milestone in the maturation of FDA’s approach to biosimilar development programs. FDA has signaled that stakeholders should expect continued evolution of FDA approaches in the biosimilar space.
For biosimilar developers, the most direct potential impact of FDA’s updated thinking on this matter is improved development efficiency. For programs meeting the specified parameters, biosimilar sponsors may be able to accelerate timelines and reduce budgets to the extent they are able to avoid conducting a CES. This will also affect prospective product pipelines, with biosimilar developers targeting those product categories that are more amenable to CAA and for which the streamlined pathway will be available. Stakeholders should remain watchful of FDA’s evolving approaches to ensure that the standards adopted by FDA are appropriate and scientifically sound.
For all medical product development programs, including biologics and biosimilars, FDA approval requirements and data thresholds are inextricably tied to IP interests and other asset protection strategies for innovator and follow-on developers alike. While FDA’s streamlined approach most directly drives regulatory and product development strategies, it also shifts the strategic landscape for portfolio coverage of related technologies. This dynamic will have long-term implications for both novel biologics developers and biosimilar developers. Because FDA’s approach with respect to biosimilar development remains active and dynamic, the corresponding strategies and approaches to related asset protection and IP issues will also remain in flux for the foreseeable future as markets and participants react to evolving regulatory standards.
Biosimilar developers will likely find reference products or product categories amenable to the streamlined pathway more attractive for development, while innovators will want to anticipate this shift and adapt strategies accordingly. Innovators should also consider ways to leverage related portfolio portions (such as platforms or other ancillary IP) that could be helpful in developing asset protection strategies.
It will be key to monitor how FDA specifically approaches streamlining in future decisions, paying particular attention to any guidance on whether a biosimilar developer may have “fallen short” in availing itself of the streamlined process. Overall, this implicates all stages of portfolio strategy, including early-stage research and development invention identification, prosecution strategies, and licensing opportunities, as well as enforcement programs.
While FDA’s biosimilars guidance is new, the trend towards lowering the data burdens for biosimilar development programs continues. Stakeholders who stay abreast of this ongoing evolution and incorporate changes into their strategies early may reap hefty benefits down the line. Our FDA and IP teams will continue to monitor these developments as they continue.