Area Coordinators: Arunrag Rathore and Rob Gronke
Name: Russell Shpritzer
Name: Narendra Chirmule
As noted in FDA guidance, the manufacturer of a proposed biosimilar product will likely have a different manufacturing process from that of the reference product and no direct knowledge of the manufacturing process for the reference product. Additionally, biosimilar formulations may be utilized that do not match that of the reference product and analytical methods must be developed to enable demonstration of “finger-print like similarity”. The development of these manufacturing processes, formulations and analytical methods each present many challenges.
This session will explore these challenges. Examples and case studies discussing strategies used in the development of biosimilar processes, formulations and analytics are requested. Some questions that are of interest:
· What points are considered in developing the Quality Target Product Profile of the intended biosimilar?
· What are the considerations when choosing a platform host cell line versus matching the host cell line used by the reference product?
· What tools have been used in cell line selection and cell culture process design to target difficult-to-match product quality attributes?
· How much is the upstream process relied upon to meet product quality endpoints versus using the downstream process to dial in certain attributes?
· Where have downstream platforms been able to meet the needs of a biosimilar manufacturing process? Where have deviations from platforms been required?
· What are the considerations when choosing to match the reference product formulation versus developing a new formulation?
· Where has the analytical toolbox needed to be expanded in order to meet the needs of a similarity assessment?
· How has reference product from different ICH regions, and the different presentations, been combined in the biosimilarity, prospective and side-by-side analyses?
· What is the relative significance of structure-functions studies in the biosimilarity package?
· What statistical approaches have been used to establish similarity? Are covariate analyses applied to establish equivalence?
Name: Mark Byers
Name: Marjorie Shapiro
Regulatory agencies intend to consider the totality of the evidence provided by the sponsor to support demonstration of biosimilarity and an appropriate statistical analysis is required for the demonstration of analytical similarity. In this session, we will discuss global regulatory expectations for establishing biosimilarity as well as the approaches taken by various agencies and sponsors in establishing analytical similarity. Additionally, abstracts pertaining to challenges sponsors have had in gaining regulatory acceptance of their biosimilar CMC package would be of particular interest. These could also include challenges in manufacturing, and strategies dealing with current or future process, scale or site changes.
· For regulators, any recent trends or “hot topics” that are emerging from the biosimilars applications seen to date that the sponsors need to be aware of (especially CMC-related)?
· For sponsors, what strategies have been taken with respect to scale, site, and process for non-clinical tox and Phase 1 manufacture?
· Is the process “locked down” as early as Phase 1 manufacture, or are changes considered between Phase 1 and commercial launch? If changes are made, how is the analytical similarity assessment impacted?
· Are the commercial scale and commercial site utilized starting with the initial manufacture or not until Phase 3 or PQ runs?
· What strategies have the sponsors taken for validation of a commercial biosimilar process that is different from an innovator type approach?
· How have varying guidance from global health authorities impacted the strategies for establishing similarity?
· Is the communication between a sponsor and regulator the same or different throughout the biosimilar clinical development period? If different, how so?
· What key negotiations between regulators and sponsors have permitted the acceptance of a biosimilar license application (e.g. specifications or changes allowed)?
· What strategies have the biosimilar manufacturer used to supply autoinjector/devices during clinical development, especially when the innovator’s is not available?