Quality considerations for recombinant DNA-derived biological therapeutic products: a control perspective on...

Biological therapeutics, particularly those produced by the biotechnology industry, have been perceived as highly complex, novel and having 'unknown' adverse potential. This has led to the rapid growth of biological regulatory control of such products, with a plethora of regulations (often originally based on classical chemical drugs) in addition to case-by-case treatment by control authorities. There is a need for a relationship between industry and regulators using a scientifically based dialogue in order to establish appropriate scientifically based guidelines. These guidelines need to take into account increasing experience in manufacturing, sophisticated analytical techniques and the clinical use of biotherapeutics. Such dialogue must include a rationale of risk/benefit that is not unique to these products and therefore redresses the concept that complexity equates to potential hazard. Current regulatory issues are focused on the use of scientific experience and understanding to relate regulations produced during the early development of the bioindustry to the present use of these materials in the clinic and the realistic potential for difficulties when compared to chemical drugs. This covers such issues as toxicity, heterogeneity and analysis in relation to quality. When considering the significance of any issue for the regulation of a biological product it must be in relation to the type of product (e.g. homogeneous or heterogeneous) its clinical use (e.g. single or multiple dose form, life-threatening disease or not) and efficacy (e.g. complete cure, palliation or treatment adjunct) as each of these impinges on the scientific appropriateness of any control decision.