Continuous manufacturing is influencing the wider adoption of processing strategies based on its proven quality and sustainable efficiency.
Continuous flow chemical synthesis has become increasingly mainstream in the pharmaceutical supply chain. The fine chemical industry is building in change to manufacturing based on this process in an effort to reliably supply error-free ingredients to drug manufacturers.
Competing chemical manufacturers are acutely aware that there is little room for inefficiency. One of the primary ways supply chain manufacturers are achieving operational excellence and cost contained efficient production has been their willingness to commercialize and institutionalize advanced manufacturing techniques.1
The primary manufacturing processes for fine chemicals, excipients, intermediates and other ingredients are shared by pharma and its suppliers. For oral solid dose (OSD) and active pharmaceutical ingredient (API) manufacturers, there are two primary methodologies available to produce their drug product: batch-to-batch processing or continuous-flow/continuous process manufacturing. Much of the OSD and API manufacturing capacity is still tied to dated, multi-step batch processing.1,2 However, some in the industry are migrating to advanced continuous synthesis. The automated continuous processing model is accelerating, aided by a growing body of solid decades-long experience and success from other manufacturing industries.3 With an increasing body of evidence, regulators in the quest for drug safety have embraced the concept as well.4
An Essential Quality
Representing mostly senior level excipient purchasers across the pharma manufacturing landscape, 541 respondents to Nice Insight’s 2017 Excipient Survey identified what drives their product and supplier selections.5 Reflecting a common theme, 70% of respondents agreed “quality” was the single most important driver for selecting an excipient manufacturer. Following closely were reliability, the ability to minimize risk, a strong regulatory track record and affordability. Competition for supply contracts is nevertheless quite strong, and even if there is a contract in place there are still factors that would prompt a switch. Survey respondents indicated that 56% would leave due to “better quality products promised by a competitor,” or an offer of a better price. Being able to offer a shorter timeline was also a consideration with 41% indicating this.
With commoditization and price competition shaving margins razorthin, the quest for manufacturing efficiency became paramount, along with a push to find it by integrating continuous processing concepts with advanced manufacturing automation and data managing technologies. According to DECHEMA’s Dr. Björn Mathes, it is only a matter of time before most all companies in the space, including drug processors, will have commercial-scale continuous manufacturing facilities.6 DECHEMA is the German Society for Chemical Engineering and Biotechnology which brings together experts from chemical engineering, process engineering and biotechnology (among others) to identify and evaluate emerging technological trends and facilitate the transfer of research results into industrial applications.
To attain the higher outputs needed, said Mathes, modularized plant systems, working with continuous manufacturing methods are a key enabler, and “allow reacting quickly on increasing or decreasing market demands and are very suitable for the chemical process industry.” The concept behind modular plant systems, he explained, is to use standardized modules in continuous manufacturing trains. Scalability from lab to scale is improved as well. “By using continuous manufacturing laboratory equipment with high similarity to the final process equipment, the detailed engineering of the final production facility can be realized with the chosen laboratory plant structure.”6
Chemical and ingredient suppliers are a natural extensions of the trend towards continuous, applying current good manufacturing practice in the context of the chemical processing industry, institutionalizing it to meet the requirements of the commercial spectrum. Continuous flow process is the future of pharma - and is the present as well.7 The pace of a technological migration of this caliber is usually glacial, but the move to continuous has been picking up real momentum, leaving a more fiscally sustainable landscape behind.
References
- https://www.pomsmeetings.org/confproceedings/043/fullpapers/fullpaper_ files/043-0248.pdf
- https://www.pharmasalmanac.com/articles/flow-chemistry-pathway-for-continuous-apimanufacturing
- https://www.zebra.com/content/dam/zebra_new_ia/en-us/solutions-verticals/verticalsolutions/ manufacturing/white-papers/2017-manufacturing-vision-study-en-emea.pdf
- https://www.fda.gov/downloads/aboutfda/centersoffices/ officeofmedicalproductsandtobacco/cder/ucm341197.pdf
- 2017 Nice Insight Pharmaceutical Excipients Survey
- http://www.chemanager-online.com/en/topics/production/future-production-conceptschemical-industry
- http://www.pharmtech.com/continuous-manufacturing-separating-hype-reality