The Potential of Continuous Sterile Manufacturing

Sterile manufacturing may be the next aspect of pharmaceutical manufacturing to consider in the continous process paradigm.
Sep 02, 2008

Much of the attention given to continuous processing has centered on soliddosage and small-molecule manufacturing. Similar advantages of reduced process variability and potentially lower manufacturing costs, however, may be achieved with continuous sterile manufacturing. Pharmaceutical Technology Senior Editor Patricia Van Arnum discusses the potential of continuous sterile manufacturing with Fred Watson, executive vice-president and cofounder of Neovex (Northbrook, IL), a provider of technology and equipment for continuous sterile processing for pharmaceutical production.

PharmTech: When was Neovex founded, what are your core competencies, and when and why did the company begin offering continuous processing systems for sterile manufacturing?

Watson: Neovex was founded in 1993 with the specific purpose of designing and fabricating fully integrated intravenous (IV) and renal solutions production systems scaled to meet local or regional demand. The company designs and integrates all the subsystems necessary to produce IV and renal solutions: water-for-injection (WFI) production, blending, packaging, and terminal sterilization. In part, the genesis of Neovex was Baxter Healthcare's desire to mate a continuous solution production system with the continuous form–fill–seal system that it had developed. One of Baxter's goals was to set up distributed solutions manufacturing. Much like the beer industry's move from centralized to regional brewing to reduced transportation expense, Baxter did a strategic assessment of manufacturing technologies to produce IV solutions regionally. Although Baxter never moved beyond small-scale production prototypes, Neovex enhanced the basic concept by incorporating continuous production techniques and technology in common use in the petrochemical industry and applied them to the pharmaceutical industry.

As with other technology-based companies, Neovex's core competencies are derived from professionals that founded the company and the talent pool available to it in northern Illinois, corporate home to Baxter, Abbott Laboratories, G.D. Searle [now part of Pfizer], and others. Continuous production design and engineering knowledge initially came from engineers that had worked for the leading automated pilot-plant company in the US. They were particularly knowledgeable in state-of-the-art continuous process manufacturing and control technologies across a broad range of industries: refining, chemicals, and petrochemicals. Neovex complemented their engineering skills with expertise in pharmaceutical sterilization techniques and procedures, operational pharmaceutical quality assurance/quality control (QA/QC), and regulatory experience with the US Food and Drug Administration. Additionally, Neovex has drawn on the expertise of its technology vendors in in-line measurement, instrumentation testing, and computer process control. Neovex has also attracted design and project management talent from leading pharmaceutical engineering consulting and engineering firms.

Admittedly, Neovex was ahead of its time with regard to offering a continuous IV production system. The advantages and technology for safely producing IV solutions have been available for more than 15 years. The greatest barriers to adopting the economic and quality benefits of continuous process technologies in the pharmaceutical industry have been the innate conservatism of the pharmaceutical industry and FDA along with a high degree of comfort with batch processing. That said, the benefits of continuous production technology are very compelling. Batch protocols don't guarantee quality. Quality is 'tested into' batch products. You know they are good only after laboratory testing. In contrast, quality is 'designed into' continuous systems. They can be designed with 'fail-safe' processes that do not allow the production of off-spec product. If the solution doesn't meet specifications at each and every step, it can move no further in the process. Continuous production eliminates human contact and contact with the surrounding work environment.

In addition, automated continuous production can increase a facility's output by 100–400% while reducing its footprint and cutting all costs, including capital-equipment costs, facility costs (including cleanroom costs), and out-of-pocket costs for labor, laboratory analysis, maintenance, and utilities.

PharmTech: Can you explain how systems for continuous processing for in-blending and WFI operate and how these differ from what is typically performed in a batch environment?

Watson: Continuous production can be achieved with a number of different process designs. There is not one best design. A continuous system can be designed to be highly flexible to accommodate multiple products or to be very specialized to produce a single product at the absolute lowest cost. They can be designed to use liquid or powdered ingredients or a combination.