The importance of robust drug containment and inspection solutions cannot be overstated. These processes are essential for maintaining the integrity and safety of drug products throughout their life cycle, from development to delivery to patients.
As drugs evolve, so too do their containment and inspection needs. Fortunately, as technology advances, the methods and equipment used in these processes are continuously evolving, providing enhanced accuracy and safety.
To better understand the issue, Pharma Manufacturing recently sat down with Alessandro Morandotti, Daniel Martinez and Federico Scattolin from Stevanato Group to discuss the latest advancements in containment and inspection technologies.
Q: What are the recent growth trends in pharma?
Alessandro Morandotti: We’re seeing significant growth in biologics and biosimilars, the fastest-growing segments in the industry. Additionally, there’s substantial growth in vaccinations, which are now expanding their technology from Europe and the United States to emerging countries. Prefillable syringes are increasingly important for delivering new drugs and therapies.
Three areas are particularly noteworthy: GLP-1 treatments for weight management, biologics, and mRNA treatments, which have surged since the pandemic. These are all driving growth in the biopharma market and creating specific requirements for drug-containing solutions.
Q: How are GLP-1 formulation advancements influencing container design and production?
Daniel Martinez: GLP-1s aren’t new. Recently, we’ve seen advancements in formulations for weight management for type 2 diabetes treatment. The design and production of these containers must ensure compatibility and performance when integrated into devices. GLP-1s, being smaller and less complex than biologics, are less sensitive, yet they demand high-volume production — hundreds of millions of containers. This requires high-capacity, high-speed processing not just for the containers but for the machines handling them.
Developers of GLP-1s target various suppliers, requiring different containers. It’s crucial to handle fill and finish capacities efficiently to maximize production and distribution. To minimize breakages, line issues, or high rejection rates during inspection, a high-quality container is necessary. For Stevanato Group, this means using Nexa syringes or cartridges, which provide mechanical robustness and cosmetic quality to reduce false rejects during inspection.
AM: I see similarities between GLP-1s and vaccines, particularly in terms of volume and the need for flexibility in container solutions. Globally, vaccines are delivered using diverse drug containment methods. We’re witnessing a trend toward pre-fillable syringes and a significant role for vials.
Specifically, there’s growing interest in ready-to-fill vials, which offer the pharma industry more flexibility and finishing options. For us, both bulk and ready-to-fill vials remain crucial, especially as the latter allow vaccine manufacturers to utilize contract manufacturers for these containers.
Q: What specific container challenges do biologics face?
DM: Biologics are sensitive to substances like silicone, tungsten oxide residues, and even the glass of the container itself. This necessitates a distinct approach to container design, including mechanical resistance and additional measures to ensure stability before application.
These containers must meet high cosmetic standards to prevent rejects, but also accommodate lower batch sizes typical of new monoclonal antibodies, usually between 3 to 6 million units, unlike the larger batches of blockbuster biologics. This smaller scale necessitates greater flexibility and careful inspection of each container. For example, in our Alba syringes, we use a cross-linked silicone coating to prevent silicone from interacting with and destabilizing the drug. We also work to minimize tungsten residues in syringes to reduce harmful interactions.
Q: How have vaccine container trends evolved after the pandemic?
DM: For mRNA vaccines, the primary concern during the pandemic was managing the extremely cold storage conditions required for dry ice shipments at -80 degrees Celsius. Our containers are robust enough to manage these conditions, ensuring no loss of container closure integrity. The shift has been towards using syringes for mRNA, reflecting a broader trend in vaccine delivery.
The major challenge for mRNA stability, aside from storage temperature, is its sensitivity to silicone particulates from standard silicone oil used in syringes, which can destabilize the drug during freeze-thaw cycles. Our Alba syringes effectively reduce the release of particulates, enhancing the stability of the drug product through several freeze-thaw cycles.
Q: How can inspection processes be enhanced?
Federico Scattolin: A key aspect of flexibility is having a robust set of inspection stations, so you can utilize various lighting options, cameras and viewpoints, potentially integrating them. For instance our Mavis inspection platform, which exemplifies this nicely. Another significant aspect of flexibility is the ability to handle products in a human-like manner, which we’ve achieved with our VRU unit.
Q: How do higher drug concentrations and viscosities impact visual inspection?
FS: Managing this issue often involves controlling how the product is spun and the speed of the spin. We have multiple techniques at our disposal for this. Additionally, in our product portfolio, we have machines like the VRU, which I mentioned earlier, that offer more flexibility. Other machines like the CVT and Mavis also facilitate this by allowing the product to be spun in various ways, preparing it for the final inspection. Dealing with this is a daily occurrence for us.
AM: Another key point to discuss is the ability to perform human-like inspections on drug containment solutions — especially when dealing with very expensive products. The challenge of false rejections commonly associated with automatic visual inspections is significant. In this context, integrating artificial intelligence around the vision inspection machine can enhance inspection quality, increase productivity and minimize the waste of expensive drugs.
Q: How can AI be leveraged to improve visual inspection systems?
FS: At Stevanato Group, we’ve integrated AI into our operations for over five years. Our machines are equipped with AI, using neural networks to improve defect detection and ensure more accurate defect classification. This enhances process understanding and helps eliminate errors like bubbles or protein agglomerates that shouldn’t cause rejections.
We utilize pre-trained networks to reduce the need for sample quantities, boosting efficiency. Additionally, our inspection digital twin technology supports the offline development and testing of inspection recipes, allowing uninterrupted production. This process includes collecting images, developing, testing and validating the inspection recipe while production continues.
Q: Does Stevanato Group offer solutions tailored to these market needs?
DM: Sure, our drug containment offering includes a wide portfolio to answer each specific market need. Including our Alba and Nexa glass platforms we have mentioned earlier, and NexaFlex, our COP and COC pre-fillable polymer syringes that help us provide customers with the broadest choice for PFS.