Biosimilars: A Regulatory Review
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Biosimilars: A Regulatory Review Pia Furlani, PhD Member, SIAR (Italian Association for Regulatory Activities)
Key Words Biosimilar; Biosimilarity; Generic medicine; Substitutability; Biological products Correspondence Address Pia Furlani, PhD, Regulatory Affairs Manager, DOC Generici Srl, Via Manuzio 7, 20124 Milano, Italy (email: [email protected]).
INTRODUCTION: DIFFERENCES BETWEEN CHEMICAL GENERICS AND BIOSIMILARS Chemical entities have well-defined, easy-tocharacterize molecular structures with impurity profiles that depend on their synthetic route of manufacture. In vivo safety and efficacy are unrelated to product origin. Produced by living cells, biologics are 100- to 1,000-fold larger than chemically synthesized products, with sophisticated three-dimensional structures, and can be mixtures of isoforms rather than pure homogeneous entities (1). Therefore, routine chemical analysis is not sufficient to compare a biosimilar to its originator product. Just as for conventional chemical products, the prerequisites for marketing authorization of a biosimilar are proof of quality, safety, and efficacy, but this could imply appropriate additional requirements based on the experience gained with the reference medicinal product, against which appropriate studies and comparisons are made. The demonstration of approvability for biosimilars differs therefore from the standard generics approach as it is based on a comparability exercise rather than on demonstration of bioequivalence. Quality differences (quality characterization) can impact the amount of nonclinical and clinical data needed for full demonstration of comparability. It is not simply
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This article summarizes the regulatory situation of biosimilar medicinal products from their first appearance to the recent approvals and the present situation in the European Union and the United States. The rationale behind the classification of a generic molecule as a biosimilar, comparability, therapeutic equivalence, and substitutability are discussed together with the new opportunities, both for the growth of the generic industry and for the control of national health care expenditure, made possible by biosimilars. The EU’s competitive advantage over other countries and its level of preparedness in research, development, and production of biosimilar medicines are also addressed.
a case of proving chemical identity and bioequivalence against a reference drug, as with traditional generics. Comparability studies are needed to generate evidence substantiating the similar nature, in terms of quality, safety, and efficacy, of the new similar biological medicinal product and the chosen reference medicinal product authorized in the European Community. Hence the need to establish on a caseby-case basis how heavy the burden of proof has to be. The biological origin is not considered a sufficient reason per se for requiring preclinical or clinical data. In order to fulfill the legal definition of “biological substance,” a substance should fulfill both of the follow
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