The active pharmaceutical ingredient (API) is the foundation of a final drug product and is a crucial consideration when choosing a Contract Development and Manufacturing Organisation (CDMO) or Contract Research (in House) Development and Manufacturing Organisation (CRDMO). As we well know APIs production is a complex and highly specialized activity, requiring the expert intertwining of chemistry, biology and engineering. Outsourcing to CDMOs can also provide companies with access to a flexible workforce comprised of highly-specialized experts. Recently, increased outsourcing to CDMOs has been observed for drug owners from biopharma to pharma companies, from small to large firms, and for early to late stage development projects.
The quality of APIs has a significant effect on the efficacy (producing the result desired) and the safety of medications.Choosing a CDMO/CRDMO that can provide the right API at the required strength, quality and purity is, therefore, a critical decision for drug development companies.
NEW OPPORTUNITIES IN THE CDMO/CRDMO MARKET
In order to satisfy the growing demand for outsourced Drug Substances & Drug Products manufacturing services, CDMOs have been continuing to heavily invest capital in expanding capacity to support growth, especially in areas of the market where there are capacity bottlenecks. CDMOs looking to enhance their growth generally have two strategic options: they can either integrate vertically by offering new services for existing Dosage Forms (DFs) or Active Pharmaceutical Ingredients (APIs) production or integrate horizontally by offering existing services for new dosage forms. This is beginning to change however, as more mergers and acquisitions (M&A) take place across the CDMO sector, with significant consolidation expected in the next few years. This is in line with the preferences of many pharmaceutical companies; more and more customers are choosing to outsource to one full-service CDMO rather than several niche providers, as this simplifies the supply chain and can reduce time to market.
GO FLOW IN ASYMMETRIC SYNTHESIS: AN EXAMPLE AND A NEW OPPORTUNITY
Since discovery of the proline-catalyzed direct asymmetric intermolecular aldol and Mannich reactions in the early 2000s, the asymmetric organocatalysis is remained unexplored research area with very few industrial contributions in API process chemistry landscape, majorly due to the diffi culty of organocatalyst recycling – critical economic and environmental factor to successfully scale up of a catalytic process in a chemical-pharmaceutical industrialization context. The recent rapid and exciting progresses in the field of catalyst immobilization techniques and micro-reactor technology (MRT) have recently witnessed a renaissance on research area of chemo-catalysis. The revival of this field arose from the possibility of combining the strengths of micro-reactors with that of chemo-catalysts to achieve enantioselective synthetic routes more industrial friendly than current ones. Improved heat/mass transfer, faster reactions, process intensification, easier scale-up & TT, R&D cost saving, and reduction drug development to-market timeframe are just some of the benefits of continuous-flow enantioselective processes (3). In terms of challenging chemotypes, the catalytic chiral key reactions to build up asymmetry in the API syntheses comprised only a limited type of enantioselective transformations, such as various conjugate additions, aldol reactions, aminations, esterifications, reductions and oxidations.
Today, continuous_flow enantioselective catalysis is opening new opportunities to exploring novel process windows, filling a current gap in Pharma R&D between medicinal chemistry and process chemistry. “To responding to the rising number of chiral APIs that require ever more specialized and niche chemistry, the research in this field is focusing on design and synthesis of novel catalytic complex and also on application of non-conventional technology platforms (such e.g. photo-organocatalysis, electrochemical activation of chiral catalyst-bound substrates, just to name few examples) for broadening of the toolbox of asymmetric reactions.” commented Carlo Lusso, Custom Synthesis Manager of Angelini Fine Chemicals (Angelini Pharma S.p.A.(. Under the shared objective of entering the CRDMO business in the pharmaceutical field, particularly for small-molecular drugs, Angelini Fine Chemical began working in 2015 on the joint development of a flow synthesis method mainly targeting the production of small-molecules, APIs, and intermediates. By combining Angelini Fine Chemical’s flow synthesis technology, small-molecules drug manufacturing technology, and Good Manufacturing Practice (GMP) management know-how in order to produce powered by advanced measurement and control technologies, our company have developed an industry solution that integrates the continuous flow synthesis method with in-line measurement, making it possible to carry out non-destructive measurements in real-time with a high level of precision.
Custom Synthesis Manager, Chemical Development and Manufacturing, Angelini Pharma S.p.A. | Fine Chemicals Business Unit, Italy