Most biopharmaceutical products are dried before they are shipped from the manufacturing site. Lyophilization, or freeze drying, is a common way of preparing drugs for distribution as it stabilizes them and protects them against heat-relate degradation.
But while effective, freeze frying is costly and not particularly suited to intensified production methods, including continuous manufacturing, says Ashutosh Sharma, a PhD scholar from the pharmaceutical and molecular biology research center at the Waterford Institute of Technology in Ireland.
“Conventional freeze drying is a batch process. Typically, a biopharmaceutical freeze-drying process involves the filling of glass vials with the desired volume of the formulated drug substance. The vials are then partially stoppered with a rubber stopper and placed inside a drying chamber wherein the process of sublimation occurs. Post processing, each vial is completely stoppered and sealed,” explains Sharma.
“This type of drying can be categorized as a ‘single dose’ drying technology. While this is a widely accepted process, long cycle times, high capital costs, reduced efficiency, inability to produce free-flowing powder and bulk dried product etc., are some of the drawbacks.”
Freeze drying alternatives
With this in mind Sharma and colleagues assessed potential alternatives in a study in the International Journal of Pharmaceutics and found that industry has multiple options to suit a range of potential needs.
“Technologies such as spin freeze drying, spray-drying, lynfinity offer a paradigm shift towards continuous manufacturing, whereas PRINT Technology and microglassification allow controlled dry particle characteristics,” states the study.
“Some of these drying technologies can be easily scaled-up with reduced requirement for different validation processes. The inclusion of Process Analytical Technology (PAT) and offline characterization techniques in tandem can provide additional information on the Critical Process Parameters (CPPs) and Critical Quality Attributes (CQAs) during biopharmaceutical processing.”
Sharma says PATs like NIR-CI, NIR-FMS, TDLAS, raman spectroscopy, and mass spectrometry would work best in combination with the alternative drying methods because they “can be employed for individual doses or bulk product in real time.”
Whether biopharmaceutical companies switch from lyophilization to alternative drying methods en masse remains to be seen. However, Sharma says the potential benefits of doing so outweigh the risks and challenges, particularly for firms commercializing new products.
“In terms of scaleup, packaging and validation some of these technologies offer a greater advantage. The requirement for the qualification and validation of multiple unit operations is eliminated for some of the described bulk drying technologies,” he tells GEN.
Moreover, these technologies also minimize the complexities associated with the regulatory filing and qualification of an end-to-end fill finish process. To enable successful scaleup and technology transfer, drying processes require a QbD approach where the process boundaries are well defined.
“Although moving a commercial product from a batch freeze-drying process to an alternative process is regarded as a major regulatory change, the most viable route to introduce alternative drying processes may very well be on the back of the development and industrialization of new biopharmaceutical products,” notes Sharma.