Biosimilarity Assessment of Biosimilar Therapeutic Monoclonal Antibodies

As biosimilars continue to integrate into pharmacologic arsenals around the world, they are expected to abate medical expenses, allowing patients to access the drug therapies needed for treatment. In this review, published in Science Direct, authors introduced the concept of biosimilar development as well as pharmacokinetic (PK) data, which they obtained via clinical and non-clinical studies of biosimilar therapy, while also providing some future perspectives on biosimilar monoclonal antibodies (mAbs).

Biosimilars were conceptualized in the early 2000s in the European Union (EU), with current regulations for biosimilars existing in the United States and Japan, among other nations. The initial biosimilar mAb to receive approval was the biosimilar for infliximab, a biologic that is used for treating rheumatoid arthritis (RA), psoriatic arthritis (PA), Crohn’s disease (CD), and ulcerative colitis (UC), to name a few. As of September 2018, biosimilars for adalimumab, rituximab, bevacizumab, and trastuzumab, and etanercept have also passed the approval process, with biosimilars for ranibizumab and omalizumab in the developmental stage.

The development phase of manufacturing any biosimilar is stringent, as the product is extensively tested up against its original reference. In creating a biosimilar, the company must first establish the manufacturing process, ensuring that the reference product goes undisclosed, making the process quite different from that of an originator product. However, any biosimilar must be highly comparable to the referenced product as it pertains to attributes such as structure, physiochemical and biological properties. The drug’s developers must justify any deviations in quality attributes to ensure there are no clinical differences between the biosimilar and the reference drug in terms of efficacy and safety.

For the assessment the comparability of any biosimilar to the original product, a stepwise approach is often implemented consisting of comparative quality, clinical, and non-clinical studies. Because the formulation of the biosimilar is not identical to that of the reference, differences are usually discovered in the comparative quality testing phase, and subsequently, in in vitro or in vivo clinical studies conducted to ensure that safety and efficacy.

An integral part in developing any biosimilar is the clinical PK profile, which is usually the first step in the comparative clinical study.  Potential PK-related quality attributes include isoelectric point, charge variant contents and glycan structure and antigen binding, the latter of which can affect the PK profile by accelerating the clearance of immune complexes. For the inaugural mAb biosimilar of infliximab (CT-P13), PK efficacy and safety were concomitantly studied in the patient population. In two clinical trials, results indicated that the differences in quality attributes between the reference product and biosimilar had little impact on their PK, exhibiting a favorable comparability with the biosimilar next to its originator.

The increased future development of biosimilar mAbs is expected to lessen health care expenditures, thus facilitating an easier path for patients to access and purchase the medicines they need. In 2018, the FDA released the Biosimilar Action Plan, intended to foster innovation and competition among biologics while spurring the development of more biosimilars. Concluding their review, the authors remarked that from a scientific viewpoint, “elucidating the factors regulating the PK profile of mAbs and other biologics in humans may contribute to more efficient development of biosimilars and next generation innovative mAbs.”