Natural product source material use in the pharmaceutical industry: the Glaxo experience.

Glaxo PLC has had a significant involvement with Natural Product Source Materials for all of its commercial history and, most recently, has pursued this interest by use of such materials as templates for new lead discovery. Through the expertise and facilities in its Natural Products Discovery Department, Glaxo extracts relatively small quantities of plant material (typically 200-250 g dry weight) and cultures microorganisms from environmental samples (typically 10-50 g). Extracts and fermentation broths are screened in order to detect bioactive principles (BPs). If the potency, selectivity and specificity of the BP is acceptable, isolation, purification and structural elucidation follows. It is most unlikely, in our experience, that the BP itself will become a drug; it is much more likely that we shall need to initiate a medicinal chemistry synthesis program in order to try to produce a molecule that has both the essential biological and desirable chemical properties to become a drug development candidate. This synthetic process is often a long one and our confidence that such a process is worth undertaking is greatly improved if the BP is novel. An essential component of any medicinal chemistry strategy is that it allows us to obtain secure intellectual property rights through patents. Acquisition of product claim protection, the strongest form of patent protection, is of great importance. Safety testing and clinical development of the candidate drug can take 7-10 years, and often more, during which patent protection is constantly eroding. Recognizing that acquisition of Natural Products Source Materials is an issue of growing concern, Glaxo Research and Development Ltd. (GRD), in the early part of 1992, implemented a policy for plant supply. This policy was subsequently modified to embrace source materials such as environmental, soil and marine samples from which fungi, micro- and microorganisms may be obtained. As a direct consequence of this policy, Natural Product Source Materials supply agreements are only concluded with national and international organizations who possess the expertise to identify and collect the samples. It is equally important that our suppliers have the authority, which must be provided to GRD in writing, to collect such materials and to provide them to GRD for extraction and screening purposes. Such materials must be from sustainable and accessible sources. We will not seek to collect any endangered species. Though ethnomedical information can be helpful, it is not essential. Plants must be taxonomically classified. We reimburse the supplying institute for their efforts and their expertise, and recognize an obligation to offer a royalty to the institute in the event that drug discovery, with subsequent commercialization, owes its origin, however indirectly, to a material that it provided. In discussions with the institute, we insist that "a fair proportion' (>40%) of that royalty be used for the direct benefit of the people in the collection source area. In this context, GRD recognizes the importance of local training and education.