Loui April W
Genentech, Inc., Hillsboro, OR.
PDA J Pharm Sci Technol. 2011 Jul-Aug;65(4):380-91. doi: 10.5731/pdajpst.2011.00677.
The pharmaceutical and biotechnology industries have long been challenged with setting appropriate cosmetic defect size acceptance criteria on glass vials. Limits are rarely data-driven and scarce information is available on defect survivability through shipping and handling downstream of final product visual inspection. This study was undertaken to quantitatively understand cosmetic defect dynamics on glass vials and their impact on patient safety. Scratch and bruise defects were artificially manufactured on product or placebo-filled, inspected, and glass defect-free tubing vials. The vials were processed and filled using commercial filling operations (i.e., vial washing, heat tunnel, conveyors, lyophilization, etc.). The defects were quantitatively characterized, subjected to automated packaging simulations, manually packaged in the approved commercial configurations, and subjected to ASTM Level I (highest intensity) shipping simulations in both pallet and small package configurations. The defects showed no statistically significant or applicable level of propagation, post-packaging and shipping simulation. Additionally, all test vials were subjected to dye leak testing, post-shipping simulation. All vials, except for one, met acceptance criteria for dye leak testing. Data-driven cosmetic defect dimensions for scratches and bruises were established based on this study.
When delivering life saving medicines from the manufacturing plant to the patient, it is of great importance that the medicines arrive without damage that might harm the patient. In the case of medicines filled into glass vials, it is paramount that manufacturers understand whether minor cosmetic defects in the glass (such as small scratches and bruises) may weaken the vial enough to cause damage that might allow contamination of the contents. This study was performed to determine if scratches and bruises on the glass vials might propagate during operations that occur downstream of the manufacturer's final vial inspection. The study vials were filled with product or placebo on the commercial filling lines to fully simulate environmental factors in a typical run. Scratches and bruises were then artificially created on the vials. Each defect was measured microscopically and labeled. The study population was then manually packaged into the approved configurations and subjected to the highest level intensity shipping simulations (ASTM Level 1). Upon completion of the simulations, the vials were unpackaged and defects re-measured microscopically. The defects showed no statistically significant or applicable level of propagation. Additionally, all test vials were subjected to dye leak testing, post-shipping simulation. All vials, except for one, met acceptance criteria. Data-driven cosmetic defect dimensions for scratches and bruises were established based on this study.
长期以来，制药和生物技术行业在设定玻璃小瓶合适的外观缺陷尺寸验收标准方面面临挑战。这些限制很少是由数据驱动的，而且在最终产品目视检查下游的运输和搬运过程中，关于缺陷可存活性的信息也很匮乏。开展这项研究是为了定量了解玻璃小瓶上的外观缺陷动态及其对患者安全的影响。在装有产品或安慰剂、经过检查且无玻璃缺陷的西林瓶上人工制造划痕和擦伤缺陷。这些小瓶使用商业灌装操作（即小瓶清洗、热隧道、传送带、冻干等）进行处理和灌装。对缺陷进行定量表征，进行自动包装模拟，以批准的商业配置进行手动包装，并在托盘和小包装配置下进行ASTM I级（最高强度）运输模拟。在包装和运输模拟后，缺陷没有显示出统计学上显著的或可适用的扩展水平。此外，所有测试小瓶在运输模拟后都进行了染料泄漏测试。除了一个小瓶外，所有小瓶都符合染料泄漏测试的验收标准。基于这项研究，确定了划痕和擦伤的数据驱动型外观缺陷尺寸。
当将救命药物从生产工厂运送到患者手中时，药物完好无损地送达至关重要，因为任何损坏都可能伤害患者。对于灌装在玻璃小瓶中的药物而言，制造商了解玻璃上的微小外观缺陷（如小划痕和擦伤）是否会使小瓶足够脆弱，从而导致损坏并可能使内容物受到污染至关重要。进行这项研究是为了确定玻璃小瓶上的划痕和擦伤在制造商最终小瓶检查下游的操作过程中是否会扩展。研究小瓶在商业灌装线上灌装产品或安慰剂，以充分模拟典型生产过程中的环境因素。然后在小瓶上人工制造划痕和擦伤。对每个缺陷进行显微镜测量并标记。然后将研究样本手动包装成批准的配置，并进行最高强度的运输模拟（ASTM 1级）。模拟完成后，打开包装并对缺陷进行显微镜重新测量。缺陷没有显示出统计学上显著的或可适用的扩展水平。此外，所有测试小瓶在运输模拟后都进行了染料泄漏测试。除了一个小瓶外，所有小瓶都符合验收标准。基于这项研究，确定了划痕和擦伤的数据驱动型外观缺陷尺寸。
