Assays used to assess biosimilarity of therapies for inflammatory bowel disease

ABSTRACT

Introduction: Biological drugs have revolutionized the treatment of various medical conditions. Recently, upon expiration of patents of a few biological agents, biosimilars are being rapidly developed as an affordable substitute for more expensive biologic drugs, which may serve as a therapeutic alternative for biologics reference medical product (RMP). Prior to approval for use of the biosimilar drug for treatment of RMP indications, a process involving several different assays is required, in which the biosimilar must prove to posses no meaningful differences from an existing approved RMP in terms of purity, safety and potency.

Areas covered: This report describes the different assays which are used to assess biosimilar drugs using CT-P13 infliximab biosimilar as a case-in-point. It covers the assays of physicochemical characterization, biological activity, and immunogenicity and examines their rational along with methodological and conceptual caveats clinicians should be cognizant of.

Expert opinion: The approval of a biosimilar is a complex process that requires several assays, specifically tailored to the characteristics of the RMP. Determining the required assays and the allowable margin of confidence are of great importance but are not sufficient in order to prove that the biosimilar is indeed not inferior in its clinical potency and safety to the RMP.

KEYWORDS:

• Biosimilar
• assays
• infliximab
• CT-P13
• IBD

Article Highlights

• Biologic drugs are complex molecules generated in living cell systems.

• As such, biosimilars are inherently unable to be identical to the reference medicinal product (RMP), and high degree of similarity is instead sought.

• Assays to assess the degree of similarity of biosimilars to their RMP are mostly those that examine physiochemical and structural properties of the compared biologics, and assays assessing biologic function of the molecules in in vitro models.

• The choice of specific assays used, the experimental techniques employed, and the allowable pre-defined non-inferiority margins, all impact the assessment of biosimilarity and have to be considered carefully, acknowledging they may differ between different drugs and even between different disease indications of the same RMP.

• Ultimately, physiochemical and functional assays can only point to possible differences between the molecules, but the clinical impact of such – presumably subtle – differences can only be ascertained by appropriately conducted clinical trials.

This box summarizes key points contained in the article.

Declaration of interest

S Ben-Horin has received consulting and/or advisory board fees from AbbVie, Janssen Pharmaceuticals, Celltrion, Takeda, Pfizer, Ferring, and GlaxoSmithKline. S Ben-Horin has also received research support from AbbVie, Takeda, Janssen, and Celltrion. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.