Systematic Analytical Characterization of Innovator and Biosimilar Products with the Focus on Post-translational Modifications

摘要

ABSTRACT Since the FDA approval of Zarxio®, a biosimilar for filgrastim, in 2015, many big pharma companies have begun adding a biosimilars portfolio to their pipeline. As of April 2022, there are now 35 biosimilars for 11 products sponsored by well-known companies such as Sandoz, Amgen, Pfizer, etc. Cost savings are already being realized and will continue to grow in upcoming years as more innovator biologics lose their exclusivity. Biosimilars resulted in $8B in savings to the US healthcare system in 2020 and it is estimated there will be anywhere from $38B - $133B in biosimilars-related savings come 2025[1] Owing to these large savings and, subsequently, reduced patient out-of-pocket expenses, the expanding biosimilar market is expected to increase patient access to these life-changing products[2]. Within the last year we saw even further advancements in the biosimilar field with the approval of two interchangeable products – Semglee® (insulin glargine) and Cyltezo® (adalimumab). With this interchangeable status, Semglee® (insulin glargine) and Cyltezo® (adalimumab), can be automatically switched for the innovator product by pharmacists without consulting the prescriber. Understandably, the need for biosimilars and/or interchangeable products from all stakeholders (i.e. physicians, patients, pharmacists, payers, pharmaceutical industry) is immense. Owing to this need, there are over 90 reported biosimilars under development within companies' pipelines. Given the number of biosimilars in development, there is an urgent need for robust, established and accessible methodologies for companies to implement when characterizing key attributes of biosimilars such as physicochemical properties, efficacy, immunogenicity, interchangeability. By applying for this BsUFA funded grant, we seek to aid in the development, implementation and standardization of methods that can be applied to multiple biosimilar types. As such, we are proposing five aims to conduct research on multiple biosimilar/innovator pairs in the following areas relevant to BsUFA: 1) structural features; 2) higher order structure; 3) aggregation and its effect on stability and immunogenicity; 4) glycosylation and its impact on functionality; 5) technical and regulatory hurdles for interchangeable approval. Our lab's extensive background in biosimilar analytical comparisons, in addition to our close collaborations with members from the FDA, industry, and the UM hospital system on several ongoing projects in this area, make us a strong candidate to perform the proposed aims in support of efficient biosimilar development.