Biosimilars: controversies as illustrated by rhGH

Abstract

The validity of the current criteria for comparability and interchangeability of biosimilars and their reference products remains controversial. The authors conclude that long-term clinical investigations and systematic monitoring of the efficacy and tolerability of rhGH biosimilars in all indications are needed. In addition, the medico-economical environment should allow physicians to take a free and informed decision about the type of rhGH to be prescribed.

Biosimilars: what clinicians should know

“…38 Another, more theoretical concern regarding automatic substitution is the possibility that repeated switches between the biosimilar and the reference product may increase immunogenicity with potentially negative effects on the safety and/or efficacy of the products. 13,36 This would, however, also apply to switches between different originator biologicals of the same class. Automatic substitution may be difficult from a practical viewpoint, especially for patients selfadministering the medicinal product, in case of differences in injection devices, preparation and handling of the biosimilar, which may increase the risk of medication errors or impair treatment compliance.…”

“…Concerns have been expressed that the safety database of biosimilars could be insufficient at the time of approval, with immunogenicity being a particular concern. [12][13][14][15][16][17][18][19] For a biosimilar, an extensive comparability exercise with the reference product is required, including human efficacy and safety data. Based on similarity being demonstrated with the reference product, the biosimilar can also refer to the safety experience gained with the reference product.…”

Market access of biosimilars: not only a cost issue

“…molecular weights of interferon beta is 19,000 Daltons, in contrast to the 180 Daltons of molecules such as aspirin). Currently available analytical techniques are insufficient to fully characterize biological products [2], first because structural variability is very diverse or subtle, and this complexity is highly dependent on the manufacturing process. For instance, even though biosimilar Valtropin-which referenced the growth hormone Humatrope-was found to be similar to the originator's biologic product, different precautions were required because different cell lines were used for the production of the two products (yeast for Valtropin and E. coli for Humatrope).…”

Biologicals and biosimilars: a review of the science and its implications

“…In some cases, PK/PD studies alone might be considered sufficient [15] and in other cases, for example, where it is assumed that the mechanism of action of the drug is only dependent on its interaction with one single binding partner as the target, therapeutic similarity demonstrated in one indication may be extrapolated to other indications of the reference product. Extrapolation, however, remains a matter of debate especially when different indications imply the use of significant different doses [19], or different patient populations, for example, children versus adults, or when extrapolation to use in healthy individuals is concerned, for example, use of filgrastim for stem cell mobilisation and collection in healthy donors.…”