Piecing together the biosimilar puzzle: Physicochemical & Functional Analytics

27th March 2017

Category: Bioanalytical / Biosimilars

Tags: , , , , , , , ,

By: Dr Terry Gray, Field Marketing Manager,

Part two

Read Part One.

A fundamental feature of a mAb is its biological structure, as this defines the functional output of the biologic, as illustrated by Figure 2.

Figure 2 – The interplay between the structure of a monoclonal antibody, the affinity for interaction and the resulting functional activity.

Fundamentally, the sequence of a biosimilar must match the innovator mAb; in turn this forms the basis for the many molecule interactions which define the antibody’s 3-dimensional organisation to form the functional antibody. Properties such as:

  • High molecular weight and low molecule weight products
  • Proportion of basic and acidic species
  • Heterogeneity of the recombinant mAb

These are all influencing factors of the interaction between the mAb and the antigen (or mAb and effector molecules) and thus should be evaluated at an early stage of biosimilar development prior to final lead molecule identification.

In particular, the carbohydrate profile is important for the evaluation of complex effector functions, including Antibody-dependent Cell-mediated Cytotoxicity (ADCC) and Complement-dependent cytotoxicity (CDC).

The glycosylation profile of a mAb can vary in terms of:

  • Monosaccharide composition
  • Linkage
  • Branching pattern

Techniques to evaluate the distribution of carbohydrates are fundamental to demonstrating the biosimilarity; major divergences can impact the function, efficacy, immunogenicity and pharmacokinetics of the drug and so the glycan profile is often considered a critical quality attribute of therapeutic IgGs.

Continue to Part Three.

To view our case study on this subject you can download our whitepaper here.

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