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Indeed, such apprehensions are now codified in arbitrary batch size ratios beyond which regulatory constraints to process change apply. Process Development 45 Often enough scale-up is done much too tentatively, inserting intermediate scales that are not needed. , fast liquid phase reactions with known kinetics and thermochemistry). All that is required is that the issues be understood and the proper parameters reproduced or improved at the large scale, using adjusted process conditions, as it is the set of the defining parameters what needs to be reproduced, not necessarily each process condition.

A. Bench development of the route (or routes) of choice is pursued aggressively, ideally by both synthesis chemists and chemical engineers, with the former elucidating reaction pathways and byproducts, seeking superior reaction conditions (solvents, catalysts, auxiliary chemicals, temperature, pressure, concentrations, reactant ratios, and approximate kinetics) as well as probing work-up and isolation methods. ). Such bench development by both disciplines is what transforms a synthesis route into a process candidate for scale-up and eventual manufacture.

Timely to present the full spectrum of the bulk drug development disciplines and all the activities that they carry out, including those shared with others in the corporation or with outsources, as shown in Fig. 12. 3. The Consolidation Stage Although it is not infrequent for a significant bulk process ‘‘loose end’’ to remain tenaciously loose until late in the cycle, by and large the development cycle reaches a stage at which the more difficult development work has been done. To wit: a. The chemical synthesis route is fully defined, albeit sources and specifications of starting materials may still be under negotiation or definition.