In the 1980s, British health and agricultural officials started receiving reports of cows with symptoms of neurological disease. This disease erupted into an epidemic (in Britain) of bovine spongiform encephalitis (BSE), and the scourge of “Mad Cow Disease” was born. The disease, caused by a prion, crossed over to humans to become new variant Creutzfeld Jacob Disease. The diseases, which were often fatal to cows and rarely fatal to humans, were caused by a mis-folded prion protein fragment, and spread by ingestion of contaminated tissue from a cow’s nervous system. More than 450,000 animals entered the food chain before measures were taken to halt the use of BSE-infected cows.
Even after the disease was made public, and the FDA and other agencies issued warnings about using materials from countries that had BSE, a number of pharmaceutical manufacturers continued to make vaccines and other drugs with materials from those countries. One issue was that the FDA wasn’t clear, and that it was too difficult to keep up with the accelerating number of countries on the “BSE infected” list. The other issue revealed the need for manufacturers to ensure the quality of their materials.
The discovery of mad cow disease and the risk of transmission to humans highlighted the need for greater controls over the sourcing of animal derived material for use in the pharmaceutical industry.
The discovery also spotlighted the increased difficulties in ensuring supply quality in a global pharmaceutical supply chain. This globalization has increased the use of manufacturing materials from emerging countries like India and China (which, incidentally, have never reported a case of BSE or vCJD), as well as from “BSE” risk countries like Britain, France (and now, the United States and Canada).
But the responsibility for ensuring the quality of manufacturing materials is entirely on the shoulders of the pharmaceutical manufacturer, according to GMP regulations.
In the wake of BSE/CJD and supply chain globalization, there’s been increasing debate about creating a drug pedigree, one that could verify the authenticity of every drug product that’s part of the pharmaceutical supply chain. A great deal of this debate focuses on recent increases in counterfeit pharmaceutical products, which pose a significant risk to consumers, patients and manufacturers. These counterfeit products could also carry any number of pathogens, perhaps including BSE.
No matter if the imported supply is an active substance or excipient, pharmaceutical companies absolutely must:
• Know where all manufacturing materials are from and how they were made, including whether any product was animal-derived.
• Identify the country of origin of starting material for animal derived products, and confirm that the country of origin is considered low risk.
• Understand the controls that the animal-derived material supplier has in place to minimize the risk of introducing pathogens and other agents into the supply chain.
• Demand a transmissible spongiform encephalopathy (TSE) and BSE statement from every supplier of animal-derived materials; this document will demonstrate that the supplier is committed to ensuring their materials are free from disease-causing organisms.
• Monitor suppliers of animal-derived products, knowing that the risk of such diseases as BSE/TSE can never be eliminated.
At Synergy Bioscience, we have many years of experience in conducting GMP/GLP audits, including those making sure that you can successfully understand and control the sources and safety of all the materials in your manufacturing supply chain. In today’s manufacturing world of multiple supply chains extending over the globe, your controls can be complex. We can help you answer the questions you need to maintain GMP compliance and minimize the risk of harboring adventitious agents in your products. We also can help develop the processes needed to determine the sources of your entire supply chain, and document your compliance for regulatory review.
Does your company have supply chain concerns today? How well have you prepared for changes in suppliers? Tell us what you’re doing in this area—we’d love to hear from you. And we’re always available for a deeper conversation about your auditing, compliance and quality control concerns.