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In anticipation of CPHI Barcelona, the world's largest pharmaceutical event, often referred to as 'the heart of pharma,' the industry collectively focuses its attention on the manufacturing supply chain. In this context, CPHI expert Emil Ciurczak, from Doramaxx Consulting, sheds light on the often-underappreciated post-pandemic positives. Supply chain resilience, the competing aspects of Process Analytical Technology (PAT), cost reduction strategies, and Quality by Design (QbD) emerge as prominent themes for the 2500 companies in attendance. These topics also form the cornerstone of much of the content at this year's event, with over 50 sessions dedicated to exploring how the industry is poised to evolve in preparation for 2024.
For many thousands of companies and workers, the failure of the international supply chain was an unmitigated disaster. The Covid-19 epidemic was, of course, the major cause, but the manner in which each local addressed the problem didn’t help, either. For example, even after the major threat to mainland US was being controlled with the vaccines, many smaller countries were unable or unwilling to expend resources on purchasing them from the large Pharma companies (and, of course, the wealthier countries were gobbling up as many as could be made). Since most of the ship hands on freighters were from developing countries, many ships were barred from docking for fear of Covid-19 spreading. This, in effect, did as much to the supply chain that the actual epidemic did.
Shortages of raw materials (chemicals, auto and airplane parts, drug substances, etc.) shut down or greatly limited production in every industry. Why? Most companies had historically sought cost-cutting programs that largely entailed finding locales with lower labor costs, i.e., that translates into developing countries with large distances between source and production sites. This shortage has forced may industries to “on-shore” their sources after decades of “off-shoring” them. This is an inconvenience for most industries, but a major headache for Pharma.
Why? Well, simply stated, it is merely an engineering chore to reproduce, for example, an ink cartridge for a printer or a razor blade for a disposable razor. However, when the API or excipient sources for a dosage form change, it is a far different story. Aside for GMP considerations (paperwork, filings, Agency approval), there are the processing and health considerations to address. It is, for example, well-known that merely changing the source of magnesium stearate can affect the dissolution profile (and therefore the bioavailability) of the tablet.
In addition, the processability of any other excipient can vary from vendor to vendor. Under batch-type GMP production, proving equivalence or making process changes can take many months and require validation, validation, and more validation before the new supplier can be used for commercial production. If, however, the plant making the product is working under QbD or continuous manufacturing protocols, the time is drastically reduced.
This is simply because QbD is designed to accept that even a trusted supplier can (and, over time, will) have variations in the physical parameters of its excipients. QbD is a science-based technique that assures that the process can and will be (legally) adjusted to produce the pre-determined qualities of intermediates and final product. Under traditional GMP batch production, the MMF (master manufacturing formula) is blindly adhered to and, worse yet, under traditional GMP production, the assay and content uniformity are measured after the batch is completed. At that point the manufacturer can only sell or destroy the product with no chance of modifying the process to save the batch.
In my humble opinion, the “silver lining” in the supply-chain storm cloud is that it provided more impetus for manufacturers to move to adopt PAT, then QbD, and, when all goes well, possibly even continuous manufacturing. The result of coming into the 21st century would allow versatility in manufacturing: companies could still out-source purchasing and production to more “economically-friendly” countries (also known as “developing countries” with cheaper labor), but still have the capability to quickly turn to secondary and tertiary sources, should another supply-chain meltdown occur.
So, in a nutshell, supply chain problems could be the best impetus for the Pharma industry to adopt PAT, QbD, and CM protocols. Apparently, “merely” appealing to quality and product safety is not as compelling as squeezing the purses of the companies. Oh well, whatever gets the job done.
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