Almac continues biocatalysis business growth with a further $4m R&D investment
The need for green, economic, robust and scaleable processes for the synthesis of chiral APIs and intermediates prompted Almac (CPHI Booth 4F32) to build and fully integrate a biocatalysis group into its service portfolio. Last year Almac launched carbonyl reductase, transaminase, hydrolase, nitrilase, and nitrile hydratase enzyme screening kits and is continuing to both advance the biocatalysis business – and to broaden application of its biocatalysis expertise with a further $4m R&D investment.
The investment will be used primarily to focus around discovery of new biocatalytic platforms that can be rapidly implemented and scaled delivering cost effective processes to chiral intermediates. Other areas of research will investigate hyper-activation of biocatalysts reducing enzyme loadings, as well as development of efficient and robust drivers for cofactor recycle and problems with equilibriums.
As anticipated, the business has advanced from the sale of enzyme screening kits, then to screening and optimising custom transformations, and finally to the supply of 10s then 100s of kgs of chiral intermediates.
For example, preliminary screening was carried out to demonstrate that a carbonyl reductase (CRED) bioreduction could replace a resolution for the preparation of a chiral alcohol. Having identified a CRED at small scale, Almac prepared a hundred grams of the chiral alcohol and integrated it into the API process development programme.
The next step was to manufacture 30 kgs for incorporation into the GMP API manufacture for Phase I clinical trials.
The rapid scale-up from biocatalyst screening has been the critical success factor for the recent paradigm shift to bioprocessing acceptance for the synthesis of APIs and fine chemicals.
“The biocatalyst is now Almac’s first choice for scale-up chemistry involving chirality as it provides efficient, clean and robust processes. The $4m R&D investment demonstrates Almac’s continued commitment to biocatalysis, supporting further growth in our expertise and capabilities in biotechnology”. notes Head of Biocatalysis Dr. Tom Moody.
The latest addition to the application of Almac biocatalysis expertise is for the “clean-up” of chemical reactions (Moody, T. Pharma Chem, April/May edition, 36-38, 2010). Impurities produced in multi-step processes are often difficult to remove, particularly if they are similar in structure to the desired product. When crystallisation or partition does not provide sufficient purity, Almac has used a biocatalytic process to selectively modify impurities. The impurities are then sufficiently different in physical properties from the desired product that they can be removed using conventional separation techniques.
“Biocatalysis provides a mild, regio & chemoselective process to modify impurities, thus altering their physical properties to facilitate their removal” says Tom Moody.