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Abstract: Uncertainties remain the key issue surrounding biosimilars, although decisions regarding their use must be made. The challenges for policymakers, doctors, patients and others seeking to navigate in the uncharted waters of biosimilars must be clarified. At the most basic level, scientific understanding of the issue remains limited and when making decisions, policymakers must consider all those affected by health policy decisions, particularly the ultimate recipients of these medicines: the patients. The biosimilar-value chain relies on measurement of comparabilities. The goal is to demonstrate how, from a molecular perspective, closely similar they are or are not and how potential small differences may be relevant to clinical outcomes. To critically understand these points, this conceptual paper will present a knowledge-value chain and discuss each dimension assigning value in the decision making process re-utilization of biosimilars. [Copyright &y& Elsevier]

In the EU, the EMA has been working with biosimilars since 1998. This experience is crystallized in the extensive set of guidelines, which range from basic principles to details of clinical trials. While the guidance may appear complicated, it has enabled the development of biosimilars, of which 21 have managed to get marketing authorization. Currently marketed biosimilars in the EU have a good track record in safety and traceability. No biosimilars have been withdrawn from the market because of safety concerns. The most controversial issues with biosimilars are immunogenicity and extrapolation of therapeutic indications. The available data for these topics do not raise concerns among EU regulators. Interchangeability and substitution are regulated by individual EU member states. [ABSTRACT FROM AUTHOR]

Similar to the low molecular weight traditional drugs, biopharmaceuticals are capable of producing not only therapeutic effects but also side effects provided if the dose of these compounds exceeds certain concentration and/or if the exposure duration of these compounds at subtoxic doses is being lengthened. In addition, a major drawback of biopharmaceuticals is the risk of antibody formation. Following the administration of biopharmaceuticals into human body, the formation of antidrug–antibody (ADA) or neutralizing antibody and other general immune system effects (including allergy, anaphylaxis, or serum sickness) are of clinical concern regarding therapeutic efficacy and patient safety. For example, drug-induced neutralizing antibodies to erythropoietin (EPO) result in pure red cell aplasia, whereas drug-induced acquired anti-factor VIII antibodies worsen the pathology associated with hemophilia. Since most of the already developed or under development biopharmaceuticals are to some extent immunogenic, the regulatory agencies insist to conduct potential ADA formation during the drug development process itself. This review encompasses a short overview on the clinical concerns of immunogenicity produced at cellular levels by growth hormone, interferon-α, EPO, factor VIII, and factor IX following their parenteral administration into human body. Clinical concerns related to immunogenicity produced by the biosimilar versions of these drugs are also presented wherever possible. [ABSTRACT FROM AUTHOR]