Biosimilars advancements: Moving on to the future

Abstract

in Wiley Online Library (wileyonlinelibrary.com) Many patents for the first biologicals derived from recombinant technology and, more recently, monoclonal antibodies (mAbs) are expiring. Naturally, biosimilars are becoming an increasingly important area of interest for the pharmaceutical industry worldwide, not only for emergent countries that need to import biologic products. This review shows the evolution of biosimilar development regarding regulatory, manufacturing bioprocess, comparability, and marketing. The regulatory landscape is evolving globally, whereas analytical structure and functional analyses provide the foundation of a biosimilar development program. The challenges to develop and demonstrate biosimilarity should overcome the inherent differences in the bioprocess manufacturing and physicochemical and biological characterization of a biosimilar compared to several lots of the reference product. The implementation of approaches, such as Quality by Design (QbD), will provide products with defined specifications in relation to quality, purity, safety, and efficacy that were not possible when the reference product was developed. Actually, the need to prove comparability to the reference product by the biosimilar industry has increased the knowledge about the product and the production-process associated by the use of powerful analytical tools. The technological challenges to make copies of biologic products while attending regulatory and market demands are expected to help innovation in the direction of attaining more productive manufacturing processes.

Current advances in the development of high-throughput purification strategies for the generation of therapeutic antibodies

“…The antibody needs to be purified from materials originating in the host cell (proteins, DNA), potential contaminants (endotoxin, viruses) and incorrectly formed product (aggre-gate, incorrect post-translation modification, degradation) [15]. In the case of biosimilar production, where an innovator product must be as closely matched as possible, small differences in manufacturing can have a large effect on the final product possibly leading to unwanted side effects [16].…”

Biosimilars are coming: ready or not

“…The TGA has developed a set of strict guidelines (which have been adopted from the EMA guidelines) to govern the assessment and approval of biosimilars . Analytical assays are used to establish the physicochemical similarity between the biosimilar and the reference product through the comparison of primary and higher‐order structure, size, charge and post‐translational modifications, while cell‐based assays are used to compare function and biological activity . The level of similarity established through physicochemical and biological characterisation then determines the nature and extent of the preclinical and clinical studies required, but such studies are usually much less demanding than those required for a novel biologic.…”

A Primer on Biosimilars: FDA-Approved and those in the Pipeline

“…In general, two phases of clinical studies are required: phase I studies to demonstrate similar pharmacokinetics and pharmacodynamics and phase III studies to demonstrate similar efficacy, safety, and immunogenicity to the reference biologic [23]. The following evidence is required for comparison with a licensed reference product: structure, function, nonclinical studies (animal studies and toxicity assessment), human PK/PD, clinical safety, clinical effectiveness, immunogenicity and pharmacovigilance [24][25][26][27].…”