Manufacturing of biologicals is more challenging than for traditional small molecule drugs. Even minor changes in manufacturing process can cause significant changes in efficacy or immunogenicity.

A comparison of small-molecule and biological drugs makes it clear as to why there are so many challenges with the production of biosimilars of biologicals compared to the relatively easy task of making a generic of a small molecule drug.

As an example aspirin, which is considered a small molecule drug, measures just 180 daltons and has 21 atoms. It has little ability to initiate an immune response and remains relatively stable over time. In contrast, a typical monoclonal antibody biological drug measures 150,000 daltons, contains 20,000 atoms, degrades over time, and has the ability to generate a significant immune response. Thus, the production of a biological is an inherently unstable situation requiring special handling and storage, see Table 1.

Table 1: Characteristics of small molecule drugs compared to biologicals [1, 2]

API: active pharmaceutical ingredient

The problem with biologicals is also the cost, especially as they are often used for chronic conditions, such as rheumatoid arthritis. Whereas a small molecule drug costs on average US$1 per day, with a generic drug costing just cents, a biological drug costs on average US$22 per day [3].

When considering biosimilars, inherent differences between biosimilars may produce dissimilarities in clinical efficacy, safety, and immunogenicity. Therefore, switching biosimilars should be considered a change in clinical management.

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References

1.  Declerck PJ. Biologicals and biosimilars: a review of the science and its implications. Generics and Biosimilars Initiative Journal (GaBI J). 2012;1(1):13-6. DOI: 10.5639/gabij.2012.0101.005

2.  Schellekens H, et al. Poster #R6341 presented at FIP Pharmaceutical World Congress 2010.

3.  GaBI Online - Generics and Biosimilars Initiative. Opportunities for biosimilar development [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2012 Jun 29]. Available from: www.gabionline.net/Biosimilars/Research/Opportunities-for-biosimilar-development