Feature Article: Addressing Product Improvement Using Chemical Modification In Biopharmaceutical Manufacture

By Roger L. Lundblad and Ralph A. Bradshaw, BioProcess International

Any modification of a natural protein (by either chemical means or site-directed mutagenesis) for use as a biotherapeutic immediately raises the issue of immunogenicity and, to a lesser extent, stability. Indeed, development of antibodies against therapeutics is receiving increased study. Immune reactions secondary to administration of protein therapeutics is not a new problem and was a major issue with animal-derived insulin products (2). The specific problems with those drugs (due more to immunogenicity of contaminating proinsulin than to insulin itself) mostly disappeared with the development of recombinant human insulin. However, with the advent of recombinant protein biologicals as drugs and their increasing presence in the human pharmacopoeia, immunogenic issues have resurfaced as a major problem.