Manager, Secondary Manufacturing at Cook Pharmica
PharmTech: Visual inspection in parental drug manufacturing is important to ensure product quality. Can you outline key issues/factors that should be part of a visual inspection process?
Galliher: The visual-inspection process begins with the inspection environment. The inspection environment should include booths that maintain the proper lighting, are constructed with black and white backgrounds, and are ergonomically comfortable. Once the environment is defined, the next key factor is inspector qualification. A robust inspector qualification process is critical to maintaining a quality visual-inspection program, automated or manual. The defect or qualification set used in the qualification process must be well defined and sufficiently challenge the inspectors. Ideally, the defect set would include defects from the actual process along with defects seeded with particles of certified size and material. A robust inspector qualification process should also challenge the inspector’s performance to inspection procedures as they pertain to container manipulation and pace. Once a robust inspection process is established, it can be used as a foundation for automated inspection qualification.
PharmTech: What are some recent technology advancements in visual-inspection systems?
Galliher: Somewhat recent advancements in automated inspection systems include changes in lighting and camera sensitivity that improve defect detection. Additionally, some original equipment manufacturers (OEMs) are using technologies other than vision technology for particle detection. Lastly, technological advancements have allowed for higher throughput by using oscillating inspection tables and redundant inspection stations. Higher throughput drives the need for use of the high-speed processors to manage and transfer data.
PharmTech: What are recent or pending changes to compendial and/or regulatory requirements with regard to visual inspection of parenterals or related to particulate testing?
Galliher: Pending changes include a new chapter in the US Pharmacopeia, USP General Chapter <790>, which provides guidance in regard to expectations for the manual visual-inspection environment. The guidance provides expectations for light intensity, booth construction, inspection pace, and container manipulation. The guidance will align with European Pharmacopoeia and World Health Organization expectations.
PharmTech: What are the relative advantages/disadvantages of automated versus manual inspection?
Galliher: Advantages of automated inspection include higher repeatability and reproducibility. Automated inspection machines will consistently inspect product per the criteria that they are programmed for. Higher throughput for the automated inspection process is also an advantage. For products that have large batch sizes and large annual volume requirements, automated inspection may be necessary to support demand. Process real-time feedback is another advantage of automated inspection. OEMs offer software packages that can establish reject limits and trend data real time, which can be an advantage, especially if the automated inspection machine operates in-line with the filling machine.
Disadvantages of automated inspection include higher costs. The initial investment in automated inspection capabilities can be quite costly. Additionally, there are costs associated with qualification. A robust qualification can require a significant quantity of components and product. Another disadvantage of automated inspection is that automated inspection machines will only inspect product per the criteria that they are programmed for. Depending on gaps in the initial recipe development or known machine limitations, there is a possibility of either a high false reject or accepting a defect. Lastly, because of high investment and qualification costs, automated inspection may not be for every product.
One advantage of manual inspection is the fact that inspectors can apply their judgment to the decision-making process. Manual inspectors can stop and involve the quality department when new or questionable defects are observed. Cost can be another advantage of manual inspection. The cost of establishing a manual inspection program and training operators is significantly less than costs associated with automated inspection.
Throughput is a disadvantage of manual inspection.Throughput is limited to the established pace and the number of qualified inspectors. The manual inspection process could require significant headcount and a large amount of floor space. Another disadvantage of the manual inspection process is the human impact on the inspection process. Factors, such as inspector fatigue and mood, can impact the performance of manual inspectors. Lastly, ergonomic considerations are a disadvantage of manual inspection. The process is repetitive by design and poses risk ergonomically if not set up properly.