Biosimilar development requires extensive characterization of the innovator drug and the biosimilar.

Booming Market for Biosimilars

Biosimilars are biologic drugs developed to be as similar as possible to an innovator biologic. Like generics, biosimilars provide an important mechanism for lowering drug costs. The U.S. FDA has approved 17 biosimilars to date, the most recent in the beginning of 2019. Ac- cording to market research firm Grand View Research, the global biosimilars market is expanding at a compound annual growth rate of 34.2% from a value of $4.36 billion in 2016.¹ 

Biosimilars vs. Generics

Unlike small molecule generics, which share an exact molecular identity with their branded counterparts, biosimilars exhibit similarity, but not identical chemical composition, to the innovator drug. The complexity of large protein-based drug substances produced by living cells means that manufacturing identical molecules — from batch to batch, let alone from one manufacturer to another — is not realistic.

Demonstrating Biosimilarity

Because there are differences between a biosimilar and the innovator biologic, the goal of biosimilar development is to minimize the differences (in isoforms, impurities, posttranslational modifications, etc.) and determine whether the differences that do exist matter with respect to efficacy and safety.

Biomolecules must attain a minimum level of similarity across a range of critical quality attributes (CQAs) in order to be considered as biosimilar to a reference product. Biosimilar sponsors are encouraged to use a stepwise characterization approach to minimize residual uncertainty between the biosimilar and reference products. The more rigorous the characterization — the extent to which such studies are able to identify differences between the products — the more useful the information is in determining the degree of similarity and additional studies that may be required. When extensive characterization demonstrates a high degree of similarity between the products, with minimal residual uncertainty, a more selective and targeted clinical trial design may be justified.²

While effective characterization and demonstration of analytical similarity is a complex and time-consuming process, it is essential for reducing risk and ensuring product efficacy and patient safety. In addition, a biosimilar development program will often be costlier in the long run if comprehensive characterization is not achieved up-front. For example, the cost of failed manufacturing batches, lengthier engagements with regulatory agencies and unnecessary specifications would likely exceed the cost of thorough up-front characterization.

Importantly, effective characterization of a biosimilar requires nearly the same amount of characterization of the innovator drug. To demonstrate the high degree of similarity needed across a range of CQAs, the reference product must be subjected to all of the same tests as the biosimilar throughout the development process.

The Importance of Risk Assessments Successful biosimilar development requires completion of process and product risk assessments early in development, which then allows for establishment of a fully integrated control strategy. The most important product attributes are identified as CQAs and require greater process and analytical control. Knowledge of the CQAs allows for the development of a quality target product profile (QTPP) and definition of an overall analytical control strategy, including specifications, CQA characterization requirements and stability testing needs. 

Accelerating Biosimilar Development at KBI Biopharma

KBI Biopharma acquired Elion Labs, a CRO specializing in biologics characterization, in January 2018 to strengthen its analytical and biophysical characterization capabilities. Today, KBI is working on a number of initiatives to accelerate the pace of biosimilar development.

KBI is focused on finding ways to create efficiency and reduce biosimilar development timelines. For example, the current biosimilar development paradigm suffers from the high costs of reference product sourcing, lack of reference product availability, lack of statistical independence of reference product lots, and significant underutilization of data. Ultimately, these challenges increase the likelihood of developing a QTPP that does not adequately represent the features of the reference product and an analytical similarity plan that is insufficient in demonstrating that the two products are highly similar. By employing a carefully designed analytical characterization strategy that leverages an information redistribution model, many of these challenges may be overcome, leading to rapid and cost-effective development and licensure of high-quality biosimilar drugs.

References

1. Biosimilars Market Size, Share & Trends Analysis Report By Product, By Application (Oncology, Growth Hormone, Blood Disorders, Chronic & Autoimmune Disorders), By Region, And Segment Forecasts, 2018– Grand View Research. Jul. 2018. Web.
2. FDA Guidance for Industry, Scientific Considerations in Demonstrating Biosimilarity to a Reference Product, https://www.fda.gov/downloads/drugs/guidances/ucm291128.pdf.