Moving to Single-Use Continuous Manufacturing
Everyone agrees on the value of reducing manufacturing costs, and the critical need to keep patients supplied with high quality drugs. Yet the biopharmaceutical industry--traditionally change-averse--has been slow in transitioning to modern technologies for achieving these goals. Currently, a paradigm shift in biopharmaceutical production is underway with the convergence of two complementary modern technologies, single-use systems and continuous production methods. Single-use technology has been gaining ground in bioprocessing for the past two decades. Single-use pre-sterilized and disposable polymer-based components eliminate cleaning, sterilization and associated validation steps, diminish contamination risks in product change-over, reduce manufacturing and energy costs, minimize plant footprints, and save time and labor. The environmental impact has been shown to be positive compared to reusable steel equipment. Continuous processing has been a longer road, despite FDA’s encouragement for continuous manufacturing as a more flexible and efficient means of ensuring a high-quality and safe drug supply. As an alternative to the batch processing methods practiced for decades, continuous manufacturing is inherently more efficient and safer because it integrates processing with fewer steps and requires little or no manual handling.
Continuous production moves the industry closer to the goal of continuous real-time monitoring for enhanced quality and process reliability. From the industry perspective, there appears to be a lot of risk with no assurance that a continuously manufactured drug product will be approved. Many of FDA's regulations are written for batch processes, and some in industry feel the agency should provide more guidance on how companies can actually develop an approvable continuous process. Investment in modern production methods has been an especially hard sell for producers of low-margin drugs. Yet, recent approvals of drugs using continuous manufacturing have set a precedent for continuous manufacturing adoption, helping to dissipate fears that the agency may not approve process changes or subject new drug approvals to prolonged review.
In July 2015, FDA approved Orkambi (lumacaftor/ivacaftor), the cystic fibrosis drug from Vertex Pharmaceuticals, produced using continuous manufacturing methods. Even more significant was FDA’s approval last April of Janssen Products, LP’s, HIV-1 medication Prezista (darunavir). This represents the first time the FDA has approved an actual change from batch to continuous manufacturing. As continuous processing gains a better footing, a new generation of single-use continuous manufacturing systems are being developed to fit within a continuous processing paradigm, pairing these complementary technologies. Early adoption of single-use continuous manufacturing will most likely emerge in small molecule drug product formulation and filling which is fairly easily configured to single-use continuous manufacturing method. New single-use continuous technologies are also coming on stream for biologics in areas such as bioreactor operations, cell separation and harvest fluid clarification, downstream buffer exchange and diafiltration processes, and chromatography operations. While batch methods are entrenched in some areas of biopharmaceutical processing and will take longer to change, companies moving to continuous manufacturing will find an encouraging partner in FDA. This should help accelerate faster adoption.
Learn More at Pharma EXPO At Pharma EXPO 2016 (McCormick Place, Chicago; Nov. 6-9), pharmaceutical manufacturers can find a number of educational resources on processing equipment to meet complex production. Pharma EXPO, co-located with PACK EXPO International, is co-produced by PMMI, The Association for Packaging and Packaging Technologies and ISPE. Learn more and register today!
By: Jerry Martin, Pharmaceutical and Life Sciences Consultant, PMMI, The Association of Packaging and Processing Technologies