The Global Supply Chain: Risky Business for Pharmaceutical IngredientsPost by: RJ Lee Group News
- 1:17PM Apr 15, 2013
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By Crystal Morrison, Ph.D.
Diversity within the global supply chain may provide competitive benefits for industry, but its complicated nature may also mask risk and liability. Recent headlines regarding adulterated pharmaceuticals have provided a sobering reminder of the importance of supply chain security and quality control. While regulatory agencies are doing what they can to keep up with economically motivated adulteration, ingredient substitution, and altered potency, there are still gray areas that pose a threat to manufacturers and consumers alike. The U.S. Food and Drug Administration (FDA) has, at times, been forced to respond to quality breakdowns rather than acting to prevent them, but new efforts such as the Food Safety Modernization Act and proactive warnings to industry show promise for the future of supply chain safety and security. One recent warning to industry, concerning the potential for adulterated glycerin, provides an example of the FDA’s proactive shift and why product manufacturers must also take extra steps to ensure product safety when faced with new risks associated with the global supply chain.
In July 2012, the FDA notified industry that, “oils, glycerin, and proteins commonly used in the production of human and animal food, medical products, cosmetics, and other FDA-regulated products may contain toxins if they are derived from the Jatropha plant.” Jatropha plants, primarily grown in tropical areas, have become an attractive energy crop for biodiesel production because of their high oil content. Jatropha contains highly toxic phorbol ester compounds known to intensify cancer cell growth and tumor formation. While no cases of Jatropha adulteration have been reported, the plant’s toxic compounds can transfer into biodiesel byproducts like glycerin and become an immediate concern for product safety. Distributors could intentionally or unintentionally substitute their stock with glycerin contaminated with Jatropha-derived toxins. This adulterated glycerin could be sold to manufacturers. If these manufacturers rely on distributor certification and do not perform their own quality testing they may unknowingly incorporate toxic glycerin into their final products.
With a ramp up in production of biofuels and the need for additional feedstocks, Jatropha poses a serious threat to manufacturers who include glycerin in their products. Between 2004 and 2008 the amount of crude glycerin derived from biofuel production increased by over one million tons. As use of Jatropha becomes more prevalent, the likelihood increases that glycerin contaminated with Jatropha toxins could make its way into the supply chain.
Adulteration of glycerin is not a new problem. Over the past 20 years, glycerin adulterated with diethylene glycol (DEG) has been linked to hundreds of deaths worldwide. Despite FDA warnings and increased awareness of the food and drug supply chain, adulteration remains a serious threat especially within pharmaceutical excipients. Excipients are inactive ingredients used to make drug components such as binders, capsules, or coatings. Glycerin serves as a common type of excipient. Unfortunately, excipients rest within a gray area that is unregulated by the FDA. While the FDA provides guidelines for excipient quality, they are not laws, and legal burdens associated with the supply chain rest on the manufacturers of the final product. This situation means it is up to whoever is at the end of the supply chain to ensure all testing has been performed and all materials and final products are safe for use or consumption. In 2010, GlaxoSmithKlein agreed to pay $750 million due to allegations of adulterated drugs manufactured at a now closed plant in Puerto Rico. Although this example is not glycerin-specific, it demonstrates how manufacturers have been held financially responsible for suspect adulterated products, and it draws attention to the need to follow preventive practices.
The FDA and many industry groups provide recommendations on how to monitor and prevent supply chain liabilities. In the case of Jatropha-adulterated glycerin, the FDA suggests following these steps:
- Know, monitor, and audit supply chains that include naturally-derived ingredients.
- Conduct comprehensive risk assessments for naturally-derived ingredients, unless the composition has already been verified and it does not pose a risk.
- Confirm the composition of naturally-derived ingredients and conduct appropriate testing of those ingredients.
By following these steps, manufacturers will be protecting the integrity of their final products and driving quality expectations at the distributor level.
The global supply chain will only expand due to competition and the search for new raw material applications. All those involved in product manufacturing, from quality assurance departments to company decision makers, should take a proactive role by setting up programs to confirm the quality of materials received by distributors. Change may eventually come in the form of tighter regulation for raw material distributors, but until that time, it is the responsibility of those at the end of the line to be the gatekeepers of quality materials and to ensure product safety.