Process Chemistry News
Today Quality by Design (QbD) is implemented primarily for economic considerations, and less because of possible regulatory flexibility that could be gained. The value added by QbD methodology has two components:
(i) very low cost of poor quality, and
(ii) systematically generated process understanding
(as Dr. Thien from Merck recently commented about the role of chemical process R&D: "...we make material ....and we make knowledge...").
Dr Trevor Laird (Scientific Update) talked about appearing and disappearing polymorphs and other solid forms in process development, during the '2nd Winter Process Chemistry' Conference in December. This involved a number of case studies including axitinib, Pfizer's anti-cancer drug, has 5 anhydrous forms and over 70 different solvates known to date and requires a complex crystallisation wash procedure to obtain the correct form. In another example from Merck-Schering Plough batches from one reactor train started to fail because of a yellow colouration. Product from an older reactor train did not have this problem. Temperature and humidity, particularly during drying were found to be critical. During drying a new anhydrate was being formed which then formed a new hydrate when exposed to moist air. The new hydrate is unstable forming the yellow impurity. The problem was solved by a modified wash and drying sequence.
Professor Nick Turner (University of Manchester) was the keynote speaker on the topic of biocatalysis, which was the special topic for the conference. The presentation covered a variety of new developments in the area of biocatalysis as well as highlighting the improvements that have taken place over the last 10-15 years. The final part of the talk covered biocatalytic cascade reactions where two or more enzymes are used in conjunction for example taking a 1,4-diketone and reacting it with an –transaminase and a monoamine oxidase and NH3:BH3, to produce enantiomerically pure pyrrolidines as shown below: