Pharmaceutical manufacturing is both exceptionally process-driven and heavily regulated. A single misstep in manufacturing can be costly in the best-case scenario or even endanger lives in the worst case, particularly if a product has already reached consumers.
The industry is required to comply with an array of guidelines outlined by the Food & Drug Administration (FDA), for example, the Current Good Manufacturing Practices (cGMP) requirements.
Product quality is central to cGMP, which has been developed to ensure the appropriate design, monitoring, and management of manufacturing processes and facilities.
cGMP also offers useful guidance on acquiring good-quality raw materials, as well as recommendations around the ideal management processes and systems for maintaining optimal laboratory testing procedures. All these factors play key roles in pharmaceutical products’ success and safety.
Compliance with cGMP is a necessity for manufacturers, and while safety and quality are significant concerns in the pharmaceutical industry, these guidelines do increase the number and scope of challenges throughout the manufacturing process.
Accelerating Processes and Outputs Without Compromise
The presence of even a minimal amount of contaminant can adversely affect results considerably, and the broad range of active pharmaceutical ingredients (APIs) in use means that verifying raw materials is a fundamental part of the production process.
Samples are typically sent to labs outside the manufacturing floor when verifying materials. These materials will be analyzed by a team of highly trained professionals, potentially leading to bottlenecks and frequent stoppages in production despite being highly accurate.
Regulations requiring the sampling of a statistical number of containers for a delivered material (sqrt n+1) can lead to challenges, but the industry is moving towards verifying every single container of a delivered material (100 % material verification).
This is a trusted method, but it is important to consider the size of delivery when using 100 % material verification to improve production safety.
Facilities could be required to verify one drum or 1000 drums per day when adopting this approach, meaning that the collection of test batches will become increasingly labor-intensive and time-consuming, potentially intensifying the bottleneck issue and causing a further obstacle later in the production line.
Solvent drying is the partial or complete removal of a solvent or solvents from an intermediate or API. Solvent drying occurs in a wide range of process vessels, including tray dryers, vacuum dryers, and rotary dryers.
Historically, testing the success of solvent drying could only be done when the process was complete, again requiring the outsourcing of sample testing to a separate or external lab.
The product had to re-enter the drying process if a test failed, resulting in slow production times and the potentiality of over-drying the solvent and potentially a lost batch.
Assigning the testing of drying samples and raw materials to separate or external laboratories is no longer feasible due to the sheer number of test batches. Pharmaceutical manufacturers are now investigating the use of new tools with the capacity to accelerate the verification process without compromising results’ accuracy.
Technologies Meeting the Challenge
Technological progress is currently being made in bringing the accuracy and power of the lab to the manufacturing floor. For instance, new spectroscopy technology is facilitating raw material ID and other analyses, eliminating the need for wet chemistry testing, and allowing testing to take place on the warehouse floor.
Staff responsible for accepting shipments and handling raw material inventory can now rapidly test a sample using a portable, user-friendly device designed for the verification of materials like ionic salts, including sodium chloride and potassium chloride, which are extensively used in buffers, injectables, and biologics.
Analysis of the material in its original packaging also means that these tools reduce the risk of cross-contamination and remove the need to transport the materials via several different locations.
Process mass spectrometers can precisely measure individual solvent concentrations in multiple dryer vents, allowing the drying process to be monitored at different stages of the production line.
This provides manufacturers with an advanced understanding of the emissions from APIs on the drying tray, allowing them to make rapid amendments to heating and temperature durations where required.
Appropriately used process mass spectrometers limit the risk of product loss that may result from over-drying, accelerating the production process while reducing dependence on time-consuming offline testing methods such as Loss on Drying (LOD).
This online technique significantly reduces interruptions to the process, improves batch-to-batch quality, and shortens drying times.
Accelerating Innovation Through Simplification
Like many other industries, technological progress is making the pharmaceutical industry a safer and more productive setting.
Manufacturers are now able to improve innovation and speed up production times with uncomplicated testing and analysis while simultaneously freeing up highly technical staff to focus on R&D and reducing the dependency on lab testing.
Factory floor workers’ time can also be better spent while maintaining compliance with cGMP and other key regulations.
Acknowledgments
Produced from materials originally authored by O. Dean Stuart and Daniel Merriman from Thermo Fisher Scientific.
This information has been sourced, reviewed, and adapted from materials provided by Thermo Fisher Scientific – Environmental and Process Monitoring Instruments.
For more information on this source, please visit Thermo Fisher Scientific – Environmental and Process Monitoring Instruments.