Bioequivalence and the immunogenicity of biopharmaceuticals

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Abstract
The first patents of recombinant-DNA-derived biopharmaceuticals will expire in the near future, which should allow the marketing of 'generics'. With classical drugs, generics can be marketed on the basis of limited documentation that shows physicochemical and pharmaceutical similarity to the innovator product. Clinical data from a crossover volunteer study will generally suffice. However, for biopharmaceuticals, which are in general large proteins, the biological and clinical properties cannot be completely predicted by current analytical methods, such as mass spectroscopy. As illustrated by the problem of immunogenicity, the properties of a biopharmaceutical are dependent on many factors, which include downstream processing and formulation. Even if the same genes are expressed in the same host cells, and identical production methods are used, this does not necessarily lead to a similar degree of immunogenicity. Although the induction of antibodies is in many cases harmless, serious clinical consequences might occur, as shown by the current epidemic of the antibody-induced severe anaemia that is associated with the use of a specific form of recombinant erythropoietin. So, the concept of generics cannot be extrapolated to biopharmaceuticals, and the term 'biogenerics' should not be used.