August 24, 2021 PAO-08-21-CL-05
Like all drug products, parenteral products must be manufactured and packaged at the highest possible quality to ensure both efficacy and patient safety. For parenteral drug products, visual inspection of packaging containers — from glass vials to blow–fill–seal (BFS) systems to infusion bags — can be quite challenging. Issues ranging from container defects to the presence of visible and subvisible particles or container closure failures can have significant impacts on final product quality, requiring comprehensive inspection and quality control.
For products filled in glass vials, proper inspection ensures that there are no cracks in the glass, the fill level is correct, no particles are present in the solution within the filled vials, the container closure is appropriate and sufficiently sealed (stopper properly positioned and cap properly crimped), and the serialization code for track and trace activities is correctly applied.
Bags designed for intravenous drug delivery, meanwhile, have seams where the sides of the container are connected to one another and where ports are inserted to allow access to the bags for filling and delivery of the drug. These seams (or welds) must be positioned correctly and closed completely. Each bag must also be the correct size and shape, and any printing on the label must be verified. For containers produced using BFS technology, similar requirements must be met in terms of container closure, capping, contour deformations, spots, and particles.
Traditionally, visual inspection of parenteral products has been a manual process often performed at the end of the production line following fill/finish. Many pharmaceutical companies continue to rely on manual inspection operations, even though it is typically costly and less effective than automated visual inspection (AVI).
Meanwhile, many drug manufacturers have transitioned to end-of-line automated systems. While these systems typically deliver excellent inspection results, they suffer from the major limitation that — because issues are not identified until after the fill/finish process is completed — if they do occur, the product generally must be disposed of, which can be very costly in terms of both materials and time lost. With this approach, it is also not really possible to identify performance trends to anticipate future quality issues and take proactive steps to avoid them.
Inline AVI at multiple points throughout the fill/finish process increase the efficiency of inspections. Rather than identify problems hours or days later, after a large quantity of failed product has been produced, failures are caught as close as possible to the moment when they occur, allowing for their immediate correction. In addition, inline AVI generates data that can be used to identify trends in equipment performance that can signify the need for maintenance or replacement, which can prevent failures from occurring and proactively, rather than reactively, ensure higher quality. The overall result is fewer failures and increased product yield. Of course, inline AVI complies with regulatory requirements.
Inline AVI of glass vial filling using Vitronic’s solutions starts with inspection of the empty vials before entering the filling line. Here, the vial is inspected for particles, cracks, and other defects before filling. Directly after filling, the fill level is controlled. After the stopper is placed, its positioning is checked for correct placement and defects. After crimping of the aluminum cap, the whole cap and crimping is inspected for the presence of defects or color mix-ups. Finally, after coding the vial, it is verified via optical character verification (OCV). At each inspection step, containers with identified defects are immediately ejected from further processing.
Using this approach, each step in the process is quality checked directly after it has been conducted. In addition, data are analyzed to identify trends in equipment performance. If a certain threshold or level of performance degradation is reached, the system notifies the manufacturer of the developing issue. This direct feedback allows immediate action to improve the process.
Inline AVI of fill/finish processes of parenterals requires advanced hardware and software. The hardware must be fit for purpose, such as an appropriate high-resolution camera for identifying particles down to one hundred micrometers in a product solution or minute cracks in glass vials. The software must also be fit for purpose and intuitive, with an easy-to-use operator interface.
Expertise in the installation of that equipment, such as positioning and illumination (e.g., polarization and color filtration, sides and angles) is also essential to ensure that any defects are identified. Integration of the software, as appropriate for each fill\/finish operation and facility systems, is also important.
Using artificial intelligence as part of the inspection strategy can provide great benefits, especially when it comes to difficult inspection tasks like particles. Indeed, recent studies have shown that leveraging artificial intelligence in concert with traditional image processing can lead to better failure detection combined with low false rejects.
All of the individual inspection tools must also be leveraged to ensure an effective overall inspection plan. The overarching strategy must, in turn, enable successful completion of each individual inspection task. There must also be good synergy between the hardware and the software. Especially when working with very high-resolution sensors, the acquired data must be handled very rapidly to match the requirements of the process speed. High-performance industrial computers and specialized data processing software are critical to success.
With the need to ensure quality as the driver for the use of AVI systems, building trust with the inspection system supplier is fundamental to establishing a successful relationship. Drug manufacturers need to be assured of the capabilities of the inspection system provider and trust that the supplier will be a reliable partner, not only in terms of the provision of consistently high-performing, efficient, cost-effective inspection systems, but for excellent and timely technical field support.
Vitronic focuses on the inspection of fill/finish processes of parenterals, with a particular emphasis on the filling of vials, infusion bags and BFS containers. Our solutions are standardized where possible, can be used in different applications, and are customized to specific project and customer needs. The solution for crimp quality inspection, for instance, can be easily installed on various lines and with different crimping machines.
In addition, drug manufacturers are increasingly seeking greater flexibility in their AVI systems. As batches are trending toward smaller volumes, product or format changeovers become more frequent. With this comes a growing demand for inspection systems that support more rapid product changeovers, ideally without the need for intervention by the inspection system supplier. Vitronic has focused on addressing this need with solutions designed using advanced tools with excellent graphical user interfaces.
Participation in many different industrial sectors for more than 35 years has also enabled Vitronic to develop more advanced solutions for our pharmaceutical customers. Having operated and supported the pharmaceutical industry, Vitronic is a reliable partner for parenteral drug manufacturers. We are also a global service organization with a network of offices and experts located on every continent. Many of our customers have been with Vitronic for over 25 years, a testament to our ability to meet their demanding and evolving needs.
The enormous amount of data generated by automated inline inspection systems has value beyond the initial inspection result. Stored data are correlated to specific batch runs, and, if a problem is identified sometime after a batch is completed, the stored data can be used to help identify the root cause.
In addition, the data are also available for trending analyses. Such analyses can be used to identify potential problems as they are developing so they can be addressed before failures actually occur. They can also be used to generate predictive maintenance tools that help minimize costs. When process changes are made, rapid data analysis can provide near-real-time feedback on the impacts of those changes.
Access to the data can be achieved in different ways, depending on the equipment and facility systems in place. Individual user interfaces can be provided for machine operators on the plant floor so they can directly view the machine status. In facilities with centralized control rooms, it is also possible to send the data to the control room. Vitronic provides the appropriate equipment, switches, and tools to enable the inspection system to communicate with the specific manufacturing execution system of each filling machine at each customer site.
Florian joined VITRONIC’s healthcare division in 2018. He is responsible for automated visual inspection solutions for pharmaceuticals and medical devices. The main focus of his work as a Product Manager is the identification of process requirements in difficult to inspect products and translating into new standardized solutions. Before joining VITRONIC Florian gained experience in medical device, hygiene and environmental technology industries. He holds an MBA and an engineering degree in Technical Health Care.