Analytical Approach for Biosimilar Development: Special Focus on Monoclonal Antibody Biosimilars

Abstract

Long-term safety and efficacy of biosimilars are approved by using abbreviated methods and clinical studies may not always adequate to ensure comparability of biosimilar mAbs comparing to its reference product. Therefore, the analytical strategy of the physicochemical comparison of a biosimilar to its reference product becomes an important data to indicate clinical similarity in safety and efficacy. FDA recommended that demonstration of biosimilarity between reference and biosimilar versions is based upon data derived from analytical studies to show "high similarity" to the reference product not withstanding minor differences in clinically inactive components. Therefore, the physicochemical analytical comparison between biosimilar and its reference product is the primary consideration during biosimilar development. In these review, the approach for physicochemical characterization, biological activity and impurities assessment were reviewed.

Practical Strategies for Advanced Practitioners Streamlining the Integration of Oncology Biosimilar Therapies Into Practice

“…The biosimilar approval process is rigorous but differs from that for novel biologics ( Figure 2 ). The biosimilar pathway relies on extensive comparative analytical testing to demonstrate high similarity in structure and biological function to the reference product, which has already been extensively studied in humans and has a well-understood clinical profile ( Janjigian et al, 2018 ; Yuan et al, 2018 ). After these characteristics, which are known to impact safety and efficacy, have been thoroughly compared and shown to be highly similar, an abbreviated comparative clinical program can be implemented to answer any unresolved questions arising from preclinical development ( Janjigian et al, 2018 ).…”

“…PD = pharmacodynamic; PK = pharmacokinetic; US = United States. Information from Christl & Lim (2018) ; McClellan et al (2019) ; Stebbing et al (2020) ; Yuan et al (2018) .…”

“…All US-licensed and European (EU)-approved biosimilars are required to demonstrate no clinically meaningful differences in safety, purity/pharmaceutical quality, and potency with respect to the reference product ( European Medicines Agency, 2019 ; FDA, 2015). Biosimilars are an attractive therapeutic option because of their potential to contribute to the alleviation of affordability and accessibility issues associated with originator biologics, which can largely benefit underserved patient populations (Biosimilars Council, 2017 ; Lyman et al, 2018 ; Transparency Market Research, 2016 ; Vulto & Jaquez, 2017 ; Yuan et al, 2018 ). Accordingly, biosimilars are emerging as a practical reality across health-care systems under growing economic pressure ( Kobberling, 2017 ).…”

Biosimilar-to-Biosimilar Switching: What is the Rationale and Current Experience?

“…Using state-of-the-art methods and technology, analytical biosimilarity must first be demonstrated via extensive in vitro and/or in vivo functional activity characterizations and structural analyses to evaluate product-related variants, stability, and impurities [ 29 , 99 – 101 ]. In the event that uncertainty exists following in vitro assessments with respect to potential for in vivo toxicity, animal data may be required before clinical pharmacology studies are conducted to test pharmacokinetic and pharmacodynamic equivalence in an adequately sensitive population [ 12 , 60 , 75 ].…”

Comparative biosimilar quality studies between a rituximab product and MabThera

“…A biosimilar testing requires an extensive analytical characterization to prove its similarity to the originator product but less of the expensive clinical studies. The analytical biosimilarity exercise involves a set of head-tohead characterization methods using the proposed biosimilar product and the originator product under the same experimental conditions [10,11]. These characterizations involve methods for characterizing the protein amino acid sequence, which should be the same as the originator product.…”