Development of biosimilars is not an easy matter

Biosimilars/Research | Posted 28/10/2011 post-comment0 Post your comment

By 2020 biological products with sales of around US$23 billion in the EU and US$29 billion in the US will be exposed to biosimilar competition [1]. As more and more biologicals lose their patent protection, it is no wonder that Big Pharma, the biotechnology industry and generics manufacturers, as well as regulatory agencies, are becoming increasingly interested in biosimilars [2].

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While small molecule drugs are ideal for generics replication, biological drugs are not so simple. Biological drugs are usually large, complex molecular structures derived from or produced through a living organism, making them very difficult to replicate.

Development of biologicals is difficult and often variable, as even small changes in the manufacturing process can cause changes in the final product, making things even more complicated for potential biosimilars [3]. The complexity and heterogeneity of the molecular structure, complicated manufacturing process, different analytical methods, and possibility of severe immunogenicity reactions make quantitative evaluation of biosimilars a challenge for both the scientific community and regulatory agencies.

Biosimilars are known to be variable and very sensitive to environmental conditions, such as light and temperature. Even a small variation may affect safety and efficacy. Some of the major differences between small molecule drugs and biologicals are summarised in Table 1.

Table 1: Fundamental differences between small molecule drugs and biologicals

Small molecule drugs Biologicals
Synthesis Chemical Made in living cells
Structure Well-defined


Mixtures of related molecules

Characterisation Easy Difficult
Stability Relatively stable


Sensitive to environmental conditions, e.g. light and temperature

Immunogenicity Not an issue Can be a problem
Method of dosing Orally Injection
Prescribing Doctor Specialist

In the two articles that follow, an overview of current criteria, study design and statistical methods for quantitative evaluation of bioequivalence for traditional small molecule generics and biosimilarity for biosimilar products are given. In addition, the concept of interchangeability, along with switching and alternating between biosimilar and originator products are discussed.


1. GaBI Online - Generics and Biosimilars Initiative. Biosimilars: barriers to entry and profitability in the EU and US []. Mol, Belgium: Pro Pharma Communications International; [cited 2011 October 28]. Available from:

2. Chow SC. Quantitative evaluation of bioequivalence/biosimilarity. J Bioequiv Availab. 2011; S1. doi:10.4172/jbb.S1-002

3. GaBI Online - Generics and Biosimilars Initiative. Current status of biosimilar development []. Mol, Belgium: Pro Pharma Communications International; [cited 2011 October 28]. Available from:

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