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With technology advances, continuous manufacturing shows steady progress to more widespread adoption.
Continuous manufacturing of pharmaceuticals is one of five manufacturing technology areas of emerging priority, according to an April 2016 report on advanced manufacturing issued by the National Science and Technology Council (NSTC), a government organization that sets national goals for federal science and technology investments (1).
FDA has been actively encouraging bio/pharmaceutical companies to adopt continuous manufacturing processes as part of efforts to update manufacturing facilities, improve quality and efficiencies, and ultimately, reduce drug shortages. The National Science Foundation (NSF), National Institutes of Health, National Institute of Standards and Technology, Department of Defense, and the Biomedical Advanced Research and Development Authority (BARDA) are also promoting the use of continuous manufacturing.
In addition, as FDA has accelerated approvals of breakthrough drugs, it has identified the need for earlier scale-up chemistry, manufacturing, and controls (CMC) work. To meet the development needs, FDA outlined a plan to develop an understanding these new technologies, in advance of the review process, in its draft guidance, Advancement of Emerging Technology Applications to Modernize the Pharmaceutical Manufacturing Base (2), published in December 2015.
Progress, but work to be done
There has been some progress in continuous manufacturing. In April 2016, FDA approved a continuous manufacturing line, which replaced an existing batch process, for the manufacture of PREZISTA (darunavir) 600 mg tablets by Janssen Supply Chain in Gurabo, Puerto Rico. The development of the continuous process that integrates all manufacturing steps (weighing, milling, blending, compression, and coating) into one single line is a result of a five-year partnership with Rutgers University and the University of Puerto Rico.
The Janssen Supply Chain conversion is a positive step forward in the move to continuous manufacturing. On the biologics drug manufacturing side, with more complex manufacturing processes, progress has been slower and incremental. At INTERPHEX 2016 in April, equipment manufacturers displayed systems that fit process development and scale-up continuum that could help drug companies move forward in these efforts. Several equipment manufacturers displayed systems that could work in a progressive chain, eliminating some batch process steps.
Single-use systems are key components of the adoption of continuous manufacturing. Complexity and scale, however, are two stumbling blocks to the implementation of single-use systems on the commercial manufacturing scale, according to participants in a panel discussion hosted by Pharmaceutical Technology and BioPharm International. The time needed to develop a process is often underestimated because the process is more involved than people expect. In addition, single use is not practical to use for very large volumes, such as 10,000 L; practical use of the system, versus volume, must be considered.
A continuous supply of consumables is vital to both batch and continuous manufacturing processes. At INTERPHEX, suppliers reported increased demand for custom formulations and packaging, and quality control reports. Several suppliers reported facility expansions to increase capacity and offer redundant operations to ensure a continuity of supply of vital materials in the event of manufacturing problems at another facility. Another trend is a shift toward in-line dilution and systems that provide access to large volumes of buffers without having to expand buffer storage areas.
With a goal to provide a continuous supply of quality drugs to patients, the bio/pharma industry is seeing some incremental progress. It is up to bio/pharma companies to see that this trend continues.
1. Executive Office of the President, National Science and Technology Council “Advanced Manufacturing: A Snapshot of Priority Technology Areas Across the Federal Government,” by the Subcommittee for Advanced Manufacturing of the National Science and Technology Council (April, 2016).2. FDA, Draft Guidance-Advancement of Emerging Technology Applications to Modernize the Pharmaceutical Manufacturing Base (Rockville, MD, December 2015).
Vol. 40, No. 6
When referring to this article, please cite as R. Peters, “Industry Moves Closer to Continuous Manufacturing," Pharmaceutical Technology 40 (6) 2016.