// May 28, 2020

Limited drug sources pose risks to patient safety


The spread of COVID-19 has been a wake-up call to the world about dangers posed by over-reliance on single-country sources in the global medicine supply chain.

In the last two decades, pharmaceutical manufacturing has become a globalized enterprise. Today, more than 70% of manufacturing facilities making active pharmaceutical ingredients to supply the U.S. market are overseas. Drug products and their ingredients travel along complex supply, packaging and distribution chains before reaching patients. As complexity increases, so do the risks that medicine quality may be compromised anywhere along the supply chain, leading to potential threats to patient safety.

A watershed moment

The heparin crisis of 2007-2008 became a watershed moment for global drug quality and patient safety. At that time, the source material for heparin production was deliberately adulterated with a lower cost ingredient. The hundreds of patients that suffered adverse reactions to the adulterant (including over 80 deaths in the US), prompted a concerted response to the crisis. The U.S. Food and Drug Administration (FDA) intensified efforts to strengthen its global product oversight.  The U.S. Pharmacopeia (USP) worked with FDA, the scientific community, industry and others to revise the quality standard for heparin through USP’s open, transparent process. The response to the crisis underscored the importance of quality standards in protecting global drug supplies, especially in the event of an emergency.

Heparin is an anticoagulant with extensive clinical applications ranging from surgery and kidney dialysis to treating heart attacks and strokes. It can be derived from multiple animal sources, but for more than 20 years, the U.S. has only used porcine heparin due to concerns over the potential risk of Bovine Spongiform Encephalopathy, commonly known as mad cow disease. Given this limitation, the US is largely dependent on China for its heparin because nearly half of the global pig supply is in China. The latest threat to the pig supply in China is a highly contagious virus with no known cure and a near-zero survival rate for infected animals.

Protecting quality while mitigating risk

To proactively mitigate the possibility of shortages that would result from disruptions in the global porcine heparin supply, the FDA has encouraged the reintroduction of heparin derived from other sources. The existing quality standard for porcine heparin can be used to help detect and test for impurities in bovine-derived heparin. This would expedite the manufacture of bovine heparin in the event of an immediate need for alternative heparin sources. Additional research is underway to determine if other tests and acceptance criteria defined in the porcine heparin standard are also applicable to heparin from other sources.

In response to the changing landscape of the drug supply chain, USP has expanded its global footprint with programs to advance medicine quality around the world. In collaboration with key government and foreign regulatory organizations, other pharmacopeias, industry and other stakeholders, USP works to identify and address challenges and opportunities to secure the global drug supply. USP standards and related programs are trusted across the supply chain to help ensure the consistency and quality of medicine ingredients and finished products to protect patients and improve public health.

For details about the studies conducted to evaluate the applicability of the USP porcine heparin standard for impurities to bovine heparin, read this article published earlier this year. To learn more about USP’s work to improve global health, please visit the USP web site.