Integrated Solutions to Environmental Protection in Process R&D

Abstract

For the development of eco-efficient processes needed for the manufacturing of pharmaceutical drug substances, Chemical Development in former Sandoz Pharma (the described procedures were developed and established in Sandoz Pharma, and they will have to be harmonized with the procedures of former Ciba and will continue as redefined Novartis Pharma practice) has chosen a stepwise approach, whereby the solving of safety and ecological issues is synchronized with the total development process, which includes clinical, pharmacological, and toxicological studies over many years. At the start, when toxicological studies are the prerequisites for any clinical program, and when only the research synthesis is available for scaleup, the emphasis is on speed to deliver the required amount of drug substance for such time-critical activities. Consequently, only the 'unacceptables' (conditions or reagents which pose threats to the environment (safety, ecology, industrial hygiene)) are to be eliminated at this stage. Further down in development time scale, other improvements of the processes (short cuts, alternative synthesis routes, more cost-effective reaction conditions and reagents), including the elimination of 'criticals' (conditions and reagents which are tolerable in smaller amounts but should be eliminated before the final manufacturing process is to be established), are to be undertaken. Before any process step is carried out in the pilot plant, a tailor-made development risk analysis has to be performed where all aspects of safety and ecological considerations are analyzed and resolved. A Safety & Ecology Newsletter, a collection of such 'unacceptables' and 'criticals', as well as proven solutions/alternatives for them is periodically published by the Process R&D Group of Chemical Development and is circulated to all chemists of the Novartis Group worldwide. This has helped to raise the awareness of such potential problems and their avoidance already at the research level.