Drug Product Manufacturers and Packaging Suppliers Working Together to Enhance Drug Product Quality: Automated Vision Inspection for Parenteral Closures

The healthcare industry is challenged with meeting stringent quality requirements regarding the manufacturing of drug products. Packaging components are critical to this operation. Because of these requirements, each final container processed for parenteral preparation must be inspected thoroughly for the presence of visible particulates. According to USP 32-NF 27, “Each final container of all parenteral preparations shall be inspected to the extent possible for the presence of observable foreign and particulate matter in its contents. The inspection process shall be designed and qualified to ensure that every lot of all parenteral preparations is essentially free from visible particulates.” A survey regarding industry practice related to visual inspections of injectable products was generated in 2008. Twenty-one companies responded and the survey results identified particulate as the most common defect found in parenteral finished products. Due to USP 35NF30 <1> requirements and the occurrence of particles at low frequencies and randomness, each finished injectable drug must be inspected. Additional challenges facing the healthcare industry include reducing product and process variation, meeting Japanese defect-free quality expectations and minimising product rejects. According to Good Manufacturing Practices (GMP), “sterilized container/closures must be sterile as to not alter the purity of the drug product” 211.67 and 211.113. Further direction regarding the manufacturing of sterile drug products, provided in Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing, recommends excluding particulate matter and container closure defects. Additionally, packaging suppliers can contribute to reducing particulate matter in finished drug products by supplying components virtually free of embedded and adhered particles. This practice will assist in reducing the risk of rejecting drug products caused by visible particulates. An attempt to proactively address these challenges in the healthcare industry would require all packaging components to be inspected for defects prior to shipment. This procedure would expedite the pharmaceutical industry process, while maintaining more stringent safety standards. This article will examine the use of vision inspection systems to mitigate the risk for particulates and defects associated with container closure systems. Vision inspection systems used by elastomer closure suppliers are automated, program-controlled devices that inspect all sides of elastomeric stoppers and pistons. Vision inspection allows suppliers to develop standardised procedures for improving the component manufacturing process upstream. The ultimate goal is for suppliers to work with pharmaceutical companies to provide a finished product that meets the needs of the healthcare industry. A quality drug product has been defined by Janet Woodcock of the FDA as a drug product free of contamination that delivers the therapeutic benefit promised in the label to the consumer. Particulate matter in finished drug products is a concern, since a product’s quality can be affected by the presence of various degradation materials, including particulate. The foreign particulate matter in parenterals comes from a combination of intrinsic and extrinsic sources. Extrinsic sources may include hair, cellulose, polyester, etc. Intrinsic sources are derived from processes and container contact surfaces such as rubber, silicone or glass. This article will explore regulatory expectations and methods for inspection of finished drug products. It will also examine the use of vision inspection systems to mitigate the risk for particulate and defects associated with container closure systems. Visual Inspection of Foreign Particulate in Finished Drug Product The particulate matter burden of an injectable product has been taken by some healthcare practitioners, academic investigators and regulatory personnel as an indicator of the overall finished drug product’s quality. Several regulatory guidance documents exist to inspect and control particulate in finished drug product. The manufacturing of sterile drug product requires visual inspection of the final drug product in filled, sealed containers. The inspection is intended to ensure the quality of the packaged drug product by rejecting any container that is defective or contains particulate. Filled containers of parenteral products should be inspected individually for extraneous contamination or other defects. Inspection for visible particulate may take place when inspecting for other critical defects, including cracked or defective containers or seals. An inspection system can identify, isolate, trend and address particulate and other critical defects of container closure components, thus augmenting the quality expectations for sterile drug products. This type of preventative action will not only avoid nonconformance, but also will identify areas for improvement in component manufacturing, which results in higher