Standards respond to public health crises
Concerns about drug shortages and vulnerabilities or disruptions to the global medicine supply chain didn’t begin with COVID-19. While the pandemic has put unprecedented strain on an already fragile system, the U.S. has experienced a rapid increase in the frequency of drug shortages during at least the last decade, according to the FDA.
Throughout the years, governments, manufacturers and health professionals have relied on USP quality standards as a foundational tool enabling a strong supply chain so that medical products are reliable, safe and work as they should for the many patients who depend on them.
More than 7,000 science-based standards set the bar for development, manufacture, distribution and administration of medicines and other health products. Governments and manufacturers rely on them to increase the availability of safe, quality medicines and to build patient and health provider trust in the global supply of medicine. USP standards are used on a daily basis to prevent shortages that result from quality errors. They are also critical response tools when public health emergencies arise. Read on to learn how our standards were used to confront adverse effects from heparin, discover the effects of impurities such as nitrosamines and, most recently, respond to the hand sanitizer shortage, among many others.
In 2007 and 2008, nearly 150 patients died and hundreds more suffered serious adverse reactions after being treated with the blood-thinning drug heparin. The culprit—over-sulfated chondroitin sulfate (OSCS)—was discovered to have been substituted for some actual heparin. OSCS costs far less and was able to deceive existing quality tests by mimicking heparin’s blood thinning characteristics. The U.S. FDA, USP, and heparin manufacturers quickly converged to update the existing standard to include a new OSCS detection test.
Given the widespread sourcing, manufacture, and use of heparin worldwide, input from industry scientists in different countries and regions was critical for updating the standard to address the crisis. USP also developed physical reference standards for manufacturers to verify that their heparin products met new test requirements. This work yielded much more than a checklist for manufacturers to ensure regulatory compliance. To better ensure that bad actors could not easily mimic heparin again in the future, a more stringent verification test of true heparin was implemented through the USP standard. However, FDA and USP recognized that it would take time for all heparin manufacturers to be able to meet the new requirements as newer technology was required.
Thus, a phased approach was used to deploy and enforce more rigorous testing requirements to avoid unintended heparin shortages. The result—improved quality overall in the world’s global supply of this critical medicine.
USP, FDA and the pharmaceutical industry continue to strengthen the quality of medicines like heparin through ongoing, collaborative development of robust scientific standards.
Since 2018, high levels of nitrosamine impurities – a probable carcinogen -- have been found in commonly prescribed blood pressure medicines, antacids, diabetes drugs, and smoking cessation medicines. Not only did the impurities pose a risk of harm, but the ensuing recalls left millions of patients without treatments they depended on. Nitrosamines can be introduced in numerous ways along the pharmaceutical supply chain – from raw materials to manufacturing processes and to packaging, and storage.
USP consulted with its own scientific experts as well as experts from industry, regulatory agencies, and academia to examine and evaluate challenges manufacturers face regarding nitrosamine impurities, and developed new standards, technical training, and other resources to help support effective mitigation plans for controlling nitrosamine impurities. Our documentary standards include test methods for detecting and measuring nitrosamine levels and for developing control strategies.
Our reference standards are highly purified physical samples of different kinds of nitrosamines that can be used by manufacturers to test against their own materials. We also offer training and educational resources to help ensure the standards are being used correctly. These are important solutions to maintain medicine quality and head off the potential for more drug recalls and shortages.
In early 2020, the rapidly evolving COVID-19 pandemic caused an expected shortage of alcohol-based hand sanitizers. Pandemic-related supply chain pressures created global shortages that led to new manufacturers, materials, and production pathways to meet demand.
These fast-paced changes caused an emergence of quality incidents both regionally and globally. When dangerous hand-sanitizer products entered the markets, USP quickly responded to update the alcohol standards to detect the toxic substance, methanol. Since USP standards are referenced in the laws of over 50 countries, and used in over 100 more, this update helped improve the quality of alcohol throughout the entire global supply chain and protected consumers around the world.
To support the manufacturers and protect the public, USP worked closely with U.S. FDA to provide three new formulations for hand sanitizer using different forms of alcohol and new test methods to detect dangerous impurities, including methanol. Additionally, USP developed an online toolkit with guidelines from major public health organizations on compounding alcohol-based hand sanitizers and the preparation of hand sanitizers by manufacturers, pharmacies, and other facilities. The toolkit was developed to help organizations meet the demand for these products, in light of ongoing shortages of commercially manufactured sanitizers.