New preparations comprising recombinant human growth hormone: deliberations on the issue of biosimilars.

Manufactured recombinant human GH (rhGH) has been available for more than 25 years. In the meantime, the GH produced by various manufacturers has been approved for application in replacement therapy in children and adults with GH deficiency or a number of disorders involving small stature in children. Until recently approval for each individual diagnosis was only granted after extensive studies on the long-term efficacy (e.g. adult height reached) and safety of the various products. Meanwhile, the European approving agency, the European Medicines Evaluation Agency (EMEA), has relinquished this restrictive stance. Thus, new rhGH preparations can count on gaining approval for existing indications even without conducting standard clinical studies of their efficacy and safety for each of these indications. The EMEA's reconsideration is apparently based on the rationale that recombinant GH can, in effect, be considered equivalent to the tried and tested preparations in wide use, provided certain specifications are met. The term 'biosimilars' was coined to denote the similarities between the products rather than their parity, as is the case with generics for instance. The higher complexity of biopharmaceuticals relates not only to the substances themselves but also to the manufacturing process. It is generally believed that modifications to a manufacturing process - which are a prerequisite for a patent - may cause modifications of the active substance which then may lead to different long-term effects. Thus, the term 'biosimilar' does not indicate that complex biopharmaceuticals deriving from the same substance are entirely identical, nor does the approval of a 'biosimilar' ensure this. The factual information provided here is offered towards clarification of some uncertainties and as a contribution towards resolving open questions relating to the topic of biosimilars. The final choice of product to be prescribed must be made by the informed, independent physician.