It is not uncommon for people to sometimes take important things for granted, such as the quality of the medicines they rely on for their health. While not usually top-of-mind, standards and other quality-focused solutions developed by the U.S. Pharmacopeia (USP) help manufacturers, regulators, healthcare providers and others ensure quality throughout the pharmaceutical product lifecycle – from development through distribution – to support public trust in quality medicines. Looking ahead, USP quality-related focus areas with the greatest potential impact include USP’s ongoing efforts with global stakeholders to address medicines supply chain vulnerabilities, combat substandard and falsified medicines, support newer treatment modalities, and facilitate the digitization of standards.
Quality: A public interest
Poor quality medicines can pose a major threat to global health while reducing the effectiveness of authentic treatments, wasting resources, and contributing to antimicrobial resistance. To address this threat, adherence to USP public quality standards helps ensure medicines are safe, work as intended, and are available when needed. More specifically, standards enable industry, regulators and others to identify and limit dangerous impurities, and they articulate requirements for a medicine’s potency and performance in the human body.
USP’s approach to standards development relies on multi-stakeholder collaboration and contributions of hundreds of independent, expert volunteers leveraging rigorous science and real-world experience. The results facilitate availability of medicines with consistent quality, no matter the company producing them or where they are made. In fact, USP documentary standards are recognized in U.S. law and in 50+ other countries, while USP physical Reference Standards for comparison purposes are used in 150+ nations. While drug makers rely on USP standards for the clarity they provide on product quality specifications, regulators also look for manufacturer adherence to USP standards to indicate no additional validation of quality testing methods may be needed. This enables efficient regulatory processes, timely product reviews, and faster market access.
Quality across the product lifecycle
The role of standards goes far beyond the drug manufacturing process – from the sourcing of raw materials to packaging, labeling, distribution, and point-of-care administration – to help ensure quality across the pharmaceutical product lifecycle. Examples include standards for both active and inactive pharmaceutical ingredients (excipients), distribution standards covering temperature excursions, and labeling standards that support health literacy. Such standards help reduce health disparities, ensure health equity, and bolster supply chain resilience around the world.
USP’s mission of improving global health through public standards and related programs is further enhanced through its role as a convenor of diverse stakeholders. Beyond the standards-setting process, this includes offering training and education on use of USP standards, and work with overseas regulators in low- and middle-income countries to facilitate capability building and policies that support quality in countries around the world. This year, it also includes USP’s work with FDA to assemble regulators from the 21 Asia-Pacific Economic Cooperation (APEC) economies in April for a dialogue on supply chain resilience.
Supply chain vulnerabilities
A resilient supply chain withstands disruptions so that quality medicines can be supplied to patients in adequate quantities when they are needed. To address supply chain vulnerabilities including potential quality issues that can lead to drug shortages, USP is leveraging insights from data on USP standards distribution and usage at more than 22,000 locations worldwide and 40 external data sets to provide an early-warning capability for supply chain disruptions. Launched in 2021 and composed of more than 250 million data points spanning 92% of generic medicines approved in the U.S., USP’s Medicine Supply Map enhances visibility into the upstream supply chain to help stakeholders identify vulnerabilities, guide risk mitigation strategies and reduce the frequency and duration of potential drug shortages.
USP also supports supply chain resilience by developing quality-focused solutions to address barriers to adoption of advanced manufacturing technologies including pharmaceutical continuous manufacturing. While traditional batch manufacturing will remain an essential pillar of global manufacturing strength, continuous manufacturing can facilitate efficiencies to help make more medicines in more places and reduce the over-reliance on sourcing from a few countries that can lead to supply chain disruptions.
Substandard and falsified medicines
In recent years, multiple recalls due to nitrosamine impurities found in medicines have made headlines due to the potential cancer risks of exposure to nitrosamines at certain levels. The complexity of the threat stems in part from the fact that pharmaceutical impurities can potentially form in a variety of ways during the lifecycle of a drug’s development, manufacture, distribution, and storage. Related product recalls can lead to shortages and undermine patient trust in medicines. To address this threat, USP has developed standards and solutions to help regulators, manufacturers and other stakeholders better understand nitrosamine impurities, how to control them and how to mitigate the risks. USP’s latest such tool – the Nitrosamines Analytical Hub housed within USP’s Nitrosamines Exchange online community for sharing knowledge and solutions – is a public, web-based repository of downloadable analytical procedures to test for nitrosamine impurities in pharmaceuticals.
Beyond impurities, increased proliferation of substandard and falsified medicines can stem from drug shortages and pandemics like COVID-19 through high demand for scarce supplies and economic incentives for fake medicines to enter the market. USP’s quality-focused solutions include tools with practical strategies to help detect substandard and falsified medicines and ensure quality. Recently, following identification of substandard medicines in The Gambia, Indonesia and Uzbekistan, USP developed a toolkit to address potential diethylene glycol contamination associated with certain allergy, cold, and cough medicines.
Biopharmaceutical innovation
The evolution of medicines and treatment modalities is ongoing and has been fueled in part by the emergence of those produced using biological systems. Perhaps most noticeably during the COVID-19 pandemic, this included approval or authorization of an unprecedented number of novel vaccines that help save lives. The increased focus on biologics includes the first messenger ribonucleic acid (mRNA) vaccines, protein-based therapeutics like advanced monoclonal antibody (mAb) treatments and their biosimilar versions, as well as personalized medicines like cell and gene therapies. Biosimilars, which are biological products highly similar to brand-name biologics that may offer more affordable treatment options for a range of conditions, hold great promise to help increase availability of quality medicines. We also see complex generics that can have a complex active ingredient, formulation, route of delivery or device component. For these and other new modalities to reach their full potential, the development of appropriate guidelines, best practices, and standards helps set expectations for quality, speed approvals, and support public trust.
USP has led development of new mRNA vaccine quality guidelines, for example, for use by manufacturers to further support adoption of the technology and help prepare for future public health emergencies. In recent years, USP has launched mAb analytical standards to support assessment of multiple test methods used to evaluate mAb quality. USP also offers a range of quality standards supporting complex generics, though there remain opportunities for future standards development to facilitate market access. Such quality-focused solutions allow manufacturers and regulators to focus more of their time on evaluating efficacy and safety, and on bringing more quality-assured therapies to market faster.
Digitization of standards
In a rapidly evolving, increasingly digital and interconnected world, USP is also working to transform quality standards into interoperable digital components of the healthcare ecosystem to help meet stakeholders’ evolving needs. For example, to facilitate the manufacturing modernization and digitization trend known as “Pharma 4.0,” USP is working to make standards easier to integrate into stakeholders’ digital environments. As artificial intelligence, automation, and advanced computing increasingly challenge traditional manufacturing approaches, we want to make sure stakeholders can leverage related tools as a seamless part of the quality process using structured content. This includes leveraging technology, such as natural language processing, to curate standards and scientific content as machine-readable, structured data, and to publish it directly through laboratory IT systems used in the quality analysis of medicinal products.
USP is also exploring how we can leverage artificial intelligence to boost our ability to manage and analyze complex data from diverse sources, with the related potential to enhance standards development, increase our ability to understand and meet evolving industry and regulatory needs, and improve customers’ experience.
As we have for more than 200 years, USP will continue to evaluate and address opportunities to meet evolving stakeholder needs and emerging public health priorities, through standards and other quality-focused solutions that expand supplies of quality medicines for the benefit of people around the world.
