Pharmacovigilance of biosimilars - Why is it different from generics and innovator biologics?

The invent of biosimilar compounds has revolutionized the access of biological drugs to the patients for various indications. Oza et al., in their review, have narrated the differences in pharmacovigilance of biosimilar compounds as compared with innovator compounds and generic drugs.[1] The biological effects (efficacy and safety) of biosimilar compounds may be different from those of innovator compounds because of the differences in their manufacturing process, which could cause structural variations and impact their stability. Moreover, the parenteral nature of the biosimilar agents could also affect their immunogenicity. These clinically important differences highlight that pharmacovigilance of biosimilar compounds is equally necessary as for innovator compounds. Apart from their manufacturing, it is also important to mention that the development of biosimilar compounds does not undergo full clinical development process and usually omits the phase II trials. This shortened clinical development process warrants for more vigilance for their effects post-marketing in the patients.[2] Similarly, in guidelines, indication extrapolation is permissible and a biosimilar compound needs to be tested in one of the chief indications in phase III studies following which it can be used in other indications as for the innovator compound. This has a lot of implications for pharmacovigilance as immunogenicity for the same compound may be different in patients with different diseases for various reasons like route of administration of the drug, concomitant medicine use, and disease indication.[3] Lastly, the regulations governing the use of biosimilar compounds in different countries are different. The EULAR (European League Against Rheumatism) recommendations on the use of biosimilar agents in rheumatic diseases recommend switching from the innovator compound to biosimilars even for non-medical reasons.[4] However, evidence for switching between different biosimilar compounds of the same innovator molecule is not strong. In India where any such recommendations to guide switching and interchangeability are not in place, cost governs the use of biosimilar agents to a large extent and “cycling” of biological agents (switching as well as substitution) is not infrequent. In multiple studies, it has been shown that such cycling of biosimilar agents leads to loss of duration of the efficacy for the subsequent biosimilar.[5] Hence, in any system like that of ours, monitoring of duration and degree of drug efficacy in pharmacovigilance may become more important and very complex than for innovator molecules and generic compounds.

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