INTEGRATED SOLUTIONS TO ENVIRONMENTAL-PROTECTION IN-PROCESS RESEARCH-AND-DEVELOPMENT

For the development of eco-efficient processes needed for the manufact uring of pharmaceutical drug substances, Chemical Development in forme r Sandoz Pharma (the described procedures were developed and establish ed in Sandoz Pharma, and they will have to be harmonized with the proc edures of former Ciba and will continue as redefined Novartis Pharma p ractice) has chosen a stepwise approach, whereby the solving of safety and ecological issues is synchronized with the total development proc ess, which includes clinical, pharmacological, and toxicological studi es over many years. At the start, when toxicological studies are the p rerequisites for any clinical program, and when only the research synt hesis is available for scaleup, the emphasis is on speed to deliver th e 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 sy nthesis routes, more cost-effective reaction conditions and reagents), including the elimination of 'criticals' (conditions and reagents whi ch are tolerable in smaller amounts but should be eliminated before th e final manufacturing process is to be established), are to be underta ken. Before any process step is carried out in the pilot plant, a tail or-made development risk analysis has to be performed where all aspect s 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 per iodically published by the Process R&D Group of Chemical Development a nd is circulated to all chemists of the Novartis Group worldwide. This has helped to raise the awareness of such potential problems and thei r avoidance already at the research level.