Biosimilar Development

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Solutions for Biosimilar Development

We have solutions that provide efficient and cost-effective methods that enable researchers to demonstrate required similarity to the approved reference originator biologic. Explore our solutions for biosimilar development.

How Similar Does a Biosimilar Need to Be to Its Reference Product?

Although the definition of a biosimilar varies, all regulatory bodies state that a biosimilar must be a biologic, have a biologic reference product — the so-called originator that is licensed based on a non-abbreviated drug submission — and be highly similar to the reference product in terms of safety, quality, and efficacy (Choy and Jacobs 2014). Unlike the production of a chemically identical generic small-molecule drug, biologic manufacturing uses a unique cell line and a complex, proprietary manufacturing process that is impossible to replicate entirely. All biologics have microheterogeneity, e.g., in protein isoforms or glycosylation patterns. Changes to the manufacturing process mean that even an originator biologic may not be 100% identical across production batches. Thus, to ensure that quality, safety, and efficacy are unaffected, biologic products undergo physicochemical and functional comparability experiments before and after manufacturing modifications. Similarly, biosimilar development requires extensive physicochemical and biological characterization of the reference originator product using multiple analytical techniques to ensure similarity. Based on the results of this characterization, preclinical studies and clinical trials are undertaken to resolve uncertainty about the similarity of the new biosimilar product.

Demonstrating Biosimilarity

Although regulatory processes for establishing biosimilarity vary among countries, all require the use of a single reference originator product for comparisons of efficacy, safety, and quality. The biosimilar is submitted for both preclinical studies and clinical trials analogous to those for a new drug approval.

Preclinical Studies

In preclinical studies, comparison is required for the proposed vs. the reference originator product to examine protein structure, enzymatic structure, posttranslational modifications, potential protein variations, and intentional chemical modifications in multiple representative lots. In vitro, in vivo, and functional assays should demonstrate that the proposed product has highly similar biologic activity and potency and no clinically meaningful differences from the reference product (Ventola 2013).

Clincal Trials

Authorities generally agree that data on human pharmacokinetic/pharmacodynamic (PK/PD) responses are fundamental for supporting biosimilarity and require a clinically relevant study population, dose, and route of administration.

The design of comparative clinical studies for biosimilars to investigate efficacy, safety, tolerability, and immunogenicity vary based on the findings and limitations of previous testing, the extent to which human PK/PD data predict clinical outcomes, and the extent of clinical experience with the reference originator and proposed biosimilar. An equivalence design is usually used to confirm that the proposed biosimilar is neither inferior nor superior to its reference originator product. Assessment of immunogenicity is critical because it can alter the PK or promote development of antidrug antibodies, thereby affecting safety and efficacy of the proposed drug. Because the required sample size for clinical trials is smaller for biosimilars than for originator biologics, careful monitoring of immunogenicity and other side effects is important in post-marketing surveillance of biosimilars (US FDA 2015).