Unraveling the Biosimilar Paradox
Demonstrating equivalence in a landscape of evolving technologies and regulations
Riding a wave of blockbuster molecule patent expirations, the global biosimilar market grew to nearly $18 billion in 2020. With a total of 26 blockbuster drugs coming off patent in the next five years, the market is expected to reach $75 billion by 2030.1 Biosimilar developers have an opportunity to capture this growing market, but only if they overcome changes in manufacturing requirements, impacts of next-generation assay sensitivity, and increasing pressures to move quickly. 2
Getting ahead with the right bioanalytical strategy
To succeed, developers must establish that their product is highly similar to an innovator reference product (RP), with no clinically meaningful differences in safety, purity, and potency. In preclinical development, structural and functional similarity must be made evident with analytical data. Clinical trials are needed to demonstrate equivalent safety and efficacy, of which pharmacokinetic (PK) and immunogenicity measurement are key components. Thus, having robust, reliable PK and immunogenicity assays in place is paramount to ensuring that clinical studies stay on track and within budget.
Considerations for PK
Historically, PK assays were designed to use multiple standard curves, one for the RP and one for the biosimilar. However, current trends have streamlined design to one assay showing comparability between the standard curves of the RP and biosimilar. While PK assay development may seem straightforward, small differences between the manufacturing processes of the RP and biosimilar can make it difficult to set appropriate QCs for demonstrating comparability. Appropriate control selection can result in streamlined validation and ultimately, faster approval.
Considerations for immunogenicity
Immunogenicity assays are more challenging, commonly requiring a two-assay approach using a single positive control because subtle differences between the RP and biosimilar may result in significant differences in anti-drug antibody (ADA) detection. Separate assays are needed to discern whether differences in immunogenicity are due to process variations or other differences in the underlying molecules. Adding to this complexity are advancements in the technologies used for immunogenicity assessment leading to increased assay sensitivity, as well as changes in regulations. Further, as clinical trial participants may already have been exposed to the RP, there is a heightened chance of pre-existing immunogenicity. Partnering with a CRO who understands and has deep experience addressing these challenges can mean the difference between success and frustration.
For biosimilar developers, finding a bioanalytical partner solely focused on developing fit-for-purpose assays is critical. At BioAgilytix, we understand the impact of variation, the evolution of technology, and the key changes in biosimilar regulation since RP approval, leveraging our expertise to prepare our partners for success and accelerate their time to market.
Learn more about BioAgilytix biosimilar assay development services
