Ronald Piervincenzi

The COVID-19 pandemic made the last year both an extraordinary and challenging time to work in health care. Development, distribution and administration of new vaccines, treatments and preventatives moved at a pace never before experienced. Pharmacists and other health care practitioners were called to the front lines of a mass vaccination effort, working to balance safety, speed and a plethora of daily demands in caring for patients and working to save countless lives. Manufacturers, regulators, pharmacists and other care providers demonstrated how cross-sector collaboration could rapidly transform cutting-edge innovation into the new standard of care, including an expanding scope of practice for many pharmacists.

Supply chains continue to be challenged, and while medicine supply chains proved more resilient than those of many other products, the pandemic made obvious long-standing weak spots that must be addressed. Much of the work now taking center stage is focused on applying lessons learned from the pandemic to bolster resilience in the medicine supply chain, prepare for future public health crises, and help ensure the quality and benefit of emerging innovations.

The organization I’ve been proud to lead since 2014 — the U.S. Pharmacopeia (USP) — plays a role in almost every stage of the medicines supply chain, in collaboration with our scientific expert volunteers and other stakeholders. Through our public quality standards and related programs, we help governments, manufacturers and health care practitioners increase the availability of safe, quality medicines that support public trust throughout the world. In fact, quality standards are a big reason why patients can get a prescription filled at their neighborhood pharmacy and trust that the medicine received will be safe and work as it should. Together with stakeholders across the health care ecosystem, USP works to support trust in medicines to improve global health. We believe the areas of focus with the greatest impact include our shared efforts to support biopharmaceutical innovation, foster adoption of advanced manufacturing technologies, and strengthen supply chain resilience to expand the supply of quality medicines worldwide.

Biopharmaceutical innovation

The emergence of new medicines is a hallmark of a robust and innovative pharmaceutical industry. Today, we see an increased focus on biologics — including the first messenger ribonucleic acid (mRNA) vaccines, protein-based therapeutics like advanced monoclonal antibody (mAb) treatments, personalized medicines like cell and gene therapies, and biosimilars — as well as complex generics that combine devices with drug delivery and products that supplement conventional medicines with software to facilitate care. 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, reduce potential risks, speed approval and support public trust. In turn, this will 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.

Just within the past year, we’ve seen the first-ever marketed mRNA vaccines. Thanks to more than a decade of public and private sector investment, mRNA vaccine technology had its breakthrough on the global stage. The technology helped shorten the time needed to create life-saving vaccines for COVID-19 to less than a year. As with other recent innovations, there was and remains much to be learned. That’s one of the reasons USP created a COVID-19 vaccine handling tool kit to help pharmacists and other health care practitioners address operational efficiency gaps in vaccine administration. Building on existing standards, USP also developed tool kits for vaccine quality assessments. USP is now leading development of new mRNA vaccine quality standards for use by manufacturers to further support adoption of the technology and help prepare for future public health emergencies.

Recent biopharmaceutical innovations have also included market authorization for the first mAb treatments for COVID-19. In recent years, USP has launched mAb performance standards to support assessment of multiple analytical methods used to evaluate mAb quality.

Unlike the case with small-molecule medicines, for which there is deep experience in characterizing and defining quality attributes, experts have less experience with biologics — including cell and gene therapies — as large molecule drugs are manufactured using relatively complex processes. From a manufacturing standpoint, increasingly complex and sophisticated therapies and treatment modalities can have the potential to require different ways to think about quality and how it is measured. Traditional measures — such as identity, strength and purity — are being redefined in some cases to establish consistent and appropriate expectations for quality.

Other modalities becoming increasingly predominant in the drug pipeline include complex generics that can have a complex active ingredient, formulation, route of delivery or device component. USP offers a range of quality standards supporting complex generics, though there remain opportunities for future standards development to facilitate market access.

As we have studied qualitatively, quality standards facilitate a multi-manufacturer environment that increases availability of trusted medicines. A study by researchers from Johns Hopkins University found that drugs with a USP monograph standard had 50% more manufacturers than drugs without one. Looking ahead, USP will continue to lead the way in developing guidelines, best practices and standards to support quality, regulatory predictability and manufacturing capability for emerging modalities — as we are doing for mRNA vaccines, mAbs and complex generics — to facilitate access and public trust. Multi-stakeholder collaboration will remain essential to ensure our standards are appropriately flexible, agile and iterative, so that they may continue to facilitate innovation.

Advanced manufacturing technologies

Advanced manufacturing technologies are also emerging to facilitate efficiency; shorten production and scale-up times; and enhance preparedness for global health care emergencies. As seen with new types of medicines, advanced manufacturing technologies like pharmaceutical continuous manufacturing (PCM) and 3D printing raise new questions and require new thinking about establishing appropriate guidelines, best practices and standards.

Alongside traditional batch manufacturing, which will stay an essential pillar of global medicine manufacturing strength, PCM is one way to increase domestic production of critical drugs and active pharmaceutical ingredients in the U.S. and other countries to help guard against overreliance on over-concentrated sources and the related potential for supply chain disruptions. Unlike batch manufacturing, where finished medicines are made in intermittent steps, PCM allows each element of the manufacturing process to take place in a single facility to help increase efficiency, lower costs, reduce dependence on foreign suppliers, and accelerate production and scale-up in response to emergencies.

FDA has offered resources for manufacturers interested in pursuing PCM, including draft guidance on PCM quality considerations. The Biden administration has proposed increased funding of PCM to help shore up the pharmaceutical supply chain. At USP, we’re collaborating with stakeholders to address knowledge gaps and explore where there is a need and opportunity to develop new standards. We are also working with partners to certify and validate related manufacturing processes.

Meanwhile, 3D printing technology has the potential to enable production of smaller batches of medicines with tailored dosages, shapes, sizes and release characteristics to facilitate personalized medicine. One can even imagine a future where pharmacies are 3D printing custom medicines for their patients. USP conducts research and holds workshops on 3D printing with stakeholders to further explore state-of-the-industry quality considerations, regulatory perspectives, current guidelines and new opportunities.

Health crisis preparedness

Support for advanced manufacturing technologies and new types of medicines will help us prepare for future public health emergencies. Recent USP stakeholder outreach suggests most health care practitioners are concerned that the global medicine supply chain may not be reliable in a time of crisis, and most physicians feel that the responsibility for maintaining and ensuring supply chain resilience lies with every stakeholder, including global governments, manufacturers, distributors, payors, the World Health Organization and standards-setting organizations.

Standards-setting organizations are an important contributor to the solution in part because standards help address quality issues that can lead to drug shortages. A 2019 Food and Drug Administration report found 62% of drug shortages occur because of quality issues in manufacturing. Standards can also offer low- and middle-income countries new opportunities to rapidly build manufacturing capacity that can bolster health crisis preparedness as well as economic development. We know this to be critical, particularly as we look to curb new COVID-19 variants globally.

Newer stakeholders in the supply chain such as data technology companies are also poised to play a role in bolstering resilience by generating data and analytics. These insights into the supply chain can help identify vulnerabilities upstream so they can be addressed before shortages occur. At USP, we’re developing a digital data tool to do just that. We’re using de-identified insights from approximately 22,000 locations in 150 countries where USP standards are used to develop an early-warning capability for potential disruptions in the upstream medicines supply chain.

As COVID-19 continues to challenge us all in ways we never could have imagined, it’s clear global collaboration among all stakeholders remains essential to ensuring a focus on quality that substantively increases supply chain resilience and facilitates advances in therapies and technologies. Pharmacists are poised to face both increasing opportunities and heightened challenges through these innovations, and as customized medicines become more accessible. To meet the challenges of today and maximize opportunities that better prepare us for the future, USP remains committed to developing public quality standards; strengthening the capabilities of industry, health care practitioners and governments; and advocating for solutions to support public trust in medicines.

Ronald Piervincenzi is chief executive officer of U.S. Pharmacopeia.