Barrier materials

Cyclo olefin polymer (COP), a material relatively new to pharmaceutical packaging, is capturing companies' interest because it it is less brittle and more moldable than a related resin, cyclic olefin copolymer, which is used to make syringes. COP can also be used to make vials, bottles, and push-through blister packaging. COP exhibits high transparency, low interaction from protein adsorption, low water-vapor transmission rate, and low residual-metals content. Diluent in COP containers is less likely to experience a pH shift than is diluent in glass and other materials. COP also is compatible with steam, ethylene oxide, and gamma sterilization ("Zeonex" COP, Zeon Chemicals, Louisville, KY).

"Zeonex" cyclo olefin polymer resin from Zeon Chemicals is suitable for syringes and other types of pharmaceutical packaging.

Expanded capacity for polychlorotrifluoroethylene film helps meet growing demand from pharmaceutical packagers for barrier film. The clear film supports compliance initiatives because it shows whether a dose has been taken ("Aclar" film, Honeywell Specialty Films, Morristown, NJ). To help design optimum blister structures, enhanced analysis software helps compute the total cost of candidate materials. Software also can help fine tune designs and line speeds to minimize material consumption and maximize line output (thermoformed packaging analysis, Honeywell).

Quality control

Quality control begins with package design, and it can be difficult to manually track all the changes that occur between concept and printing. A web-based artwork-management system, used by Merck & Co. (Whitehouse Station, NJ) in Europe and Mylan Pharmaceuticals (Morgantown, WV), automates this process for generic pharmaceuticals. The system complies with 21 CFR Part 11, provides a complete record of changes, and prevents errors. The software gives drugmakers control over the artwork at all times and provides access to authorized parties such as printers and contract packagers. Because sign-off occurs online, the system is particularly suitable for multisite operations and eliminates the expense and time involved in sending documents by courier ("GL-AMS Global Artwork Management System," Precise Data, Dublin, Ireland).

Another full-range system combines software and vision technology to automate proofreading, prepress doublechecks, color matching and counterfeit detection. Applications include regulatory affairs, clinical-trial labeling, packaging development, document development and prepress, customer and vendor proofing, print-plate inspection, production-document inspection and incoming inspection. Text-verification software identifies deviations between combinations of electronic files and physical output, including proofs, bluelines, plates, inserts, and labels. The personal computer-based system locates, marks, ranks, and tabulates disparities greater than a specified size and contrast. Because the operator only has to check deviations instead of performing a complete visual inspection, efficiency increases nearly 100% ("Avia Proofreading," "Avia Prepress," "Avia Color Matching," and "Avia Private Eye" anticounterfeiting modules, Mnemonics, Mt. Laurel, NJ).

The European Union requires Braille writing on pharmaceutical packaging, and quality-control companies are working on automated contact and noncontact methods to verify the presence and correctness of these codes. Because dot height is critical to legibility, the law requires dots to be 0.02 mm high. One system that uses a contact method to check dot presence, location, and accuracy relies on a pen-like micrometer to measure and verify dot height. The system complies with 21 CFR Part 11 and includes a validation package that features installation-qualification, operational-qualification, and performance-qualification documentation ("Braille Suite," including "Digital-Page" with "Scan-TVS," "Docu-Proof," and "BraillePoint" modules, Global Vision, Montréal).

A nondestructive leak detector for empty or full vials and syringes reportedly exceeds the performance of the standard dye microbial-ingress test because it pinpoints multiple flaws smaller than 1 μm. To identify integrity problems, the vacuum-based system detects vapor or gas release at levels as low as 0.1 μL. The tester currently checks one syringe in a 10-s cycle, but a model that can handle multiple syringes is being built ("VeriPac 325/LV" leak tester, Packaging Technologies and Inspection, Tuckahoe, NY).