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The challenge of achieving zero visible defects (i.e., particulates) in parenteral drugs will require a coordinated effort at all stages of the supply chain, particularly in the production and filling of primary containers.
With attention from FDA and other regulatory agencies focused on visible particulates in parenteral drug products, the industry is actively working to find a solution. The problem is especially difficult to control because particulates can come from many sources, including external (people as well as secondary packaging), internal (primary packaging), and inherent (formed in the drug product solution) (1). The challenge of achieving zero visible defects (i.e., particulates) in parenteral drugs will require a coordinated effort at all stages of the supply chain, particularly in the production and filling of primary containers.
"Zero particulates will require a dramatic shift in how the industry operates," said Chris Sellards, general manager for Schott's glass packaging manufacturing, in a presentation at Schott's Forum for Ready-to-Use Solutions in Aseptic Manufacturing. "Lean, six-sigma, and Kaizen [continuous improvement activities] can't be only buzzwords, but must be how we do business every day." The goal of "engineering by design" (the component-suppliers' equivalent to a drug-product manufacturer's quality by design) is to first prevent problems, beginning with the glass tubing and extending through container conversion to fill/finish. Proper design requires understanding how the container will be used. "For example, with the use of camera inspection, the way the bottom of the container is formed is now more important than it was 10 years ago. We have tight control of the tooling to minimize dimensional defects for both the crown and the bottom of the container," noted Sellards.
West Pharmaceutical Services, which manufactures packaging components for injectable drugs, is working to decrease particulates by partnering with their suppliers and by adding automation wherever possible, explained Peggy Frandolig, director of technical customer support, Pharmaceutical Packaging Systems, North America, at West, in a presentation at the same conference. West's NovaPure product line of stoppers is supplied with both visible and subvisible particle specifications. Using a quality-by-design process, West chose the best of current materials and designs and added additional control strategies to meet the narrower specifications of this product line.
Another new technology that helps reduce particulates is nested vials, which prevents the glass-to-glass contact that occurs with traditional bulk processing. Although syringes (for prefilled syringes) are commonly supplied as ready to use in nested tubs, the deployment of ready-to-use, nested vials is just beginning. Schott developed nests for different sized vials, using the standard industry tub to allow use in existing equipment, explained Gregor Deutschle, product manager for Schott, at the conference. Schott's adaptiQ RTU vials will be available in nests by the end of 2015 for some sizes, with other sizes available in 2016. The vials can be lyophilized without being removed from the nest, as Benjamin Kammerich, product manager at GEA Lyophil, demonstrated in a case study at the conference. In addition, new, RayDyLyo push-fit, vial caps for RTU nested vials from A. Raymond offer advantages in the lyophilization closure process, including eliminating the crimping process, which can generate particles.