Standardization of complex natural substances--official goals and their realization

Abstract

The mostly very complex composition of biogen drugs and particularly of combination drug products forces to compromises in the evaluation of their quality and efficacy. These necessary compromises are compatible with the current guidelines of the European Union, provided their reasonable interpretation. The problems occuring on the standardization of complex natural products of vegetable and animal origin do less result from insufficient knowledge of their composition at present, but rather mostly from ignorance of the contribution of their single components to the therapeutically wanted actions in qualitatively and particularly in quantitatively respect. Reasons are frequently methodical deficiencies in older experimental pharmacological and also clinical studies including an insufficient standardization of the tested products, but partly also the fact that due to the multiple ingredients their quantification or even their isolation and their single assay is impossible with justifiable efforts. The necessity of compromises with regard to the standardization of natural drug products results from the exclusive purpose of the quality assurance consisting in the guarantee of constant efficacy and safety of the product with consideration of the respective therapeutical claim as well as from the scientific state of knowledge, which is mostly lower of natural products in comparison to synthetic products. Therefore the requirements on product standardization must not orientate to their principal scientific feasibility, but have to consider the need of safety in the actual case and moreover the therapeutical relevance of the chemical components of the respective natural product. Conclusion for the quality control is that complex mixtures of natural origin with highly active components have to be standardized with defined and close content limits by chemical analytical or biological assays, whereas for natural products with mild active components - and this concerns the majority of them - broader tolerances or only lower limits for the content of the specified components with consideration of the natural fluctuations should be sufficient. Therefore the qualified quality evaluation of complex natural drug products besides a high scientific expertise and the knowledge of the obligative regulations also requires the ability and readiness adequately to interprete these regulations in the sense of a justified claim of safety in the concrete case considering product specific particularities and from an interdisciplinary synopsis.