USP, Report of the Council of the Convention on Resolutions by Mr.Jack

Report of the Council of the Convention on Resolutions

Memorandum from the Council of the Convention TO:

USP Convention Members

FROM: Jesse Goodman, M.D.

President, USP Convention

Chair, 2015–2020 Council of the Convention

DATE: March 3, 2020 RE:

Report of the Council of the Convention on Resolutions

Presenting the Report of the Council of the Convention on Resolutions Resolutions are a long-established cornerstone of USP’s governance. They provide a mechanism for the membership of the USP Convention—which includes over 475 organizations that represent a wide crosssection of the health and science communities—to shape USP’s priorities for the coming five-year cycle. Proposed Resolutions are developed by the Council of the Convention (CoC), a committee comprising representatives from the Convention Membership. In developing the Resolutions, the CoC considered both the strategy for the next cycle, approved by the Board of Trustees, and Resolution proposals submitted through the Call for Resolutions that launched in March 2019 and concluded in August 2019. This work resulted in the 15 proposed Resolutions contained in this report. At the 2020 Convention Meeting, these proposals will be presented to the Convention Membership, discussed in an open forum where amendments will be considered, and voted on by Delegates.

Process of Soliciting Proposals and Developing the Proposed Resolutions In March 2019, USP issued a broad and public request for proposals to inform the Resolutions process. The CoC asked that submissions include consideration of the USP 2025 strategy as approved by the USP Board of Trustees. The strategy includes three “pillars” which, when working together, amplify USP’s impact on public health, patient safety, innovation, and access to quality medicines. These include the development of science-based public quality standards; training and education efforts to build the capabilities of stakeholders to fully leverage USP standards; and advocacy to raise awareness and create a sense of shared purpose and urgency for quality. In addition, the strategy recognizes organizational pillars that are essential for USP’s success: USP’s people, including volunteers and staff; digital capabilities; sustainability; and a culture of excellence. After review of the Board-approved USP 2025 strategy, the CoC developed 12 “Resolution concepts” that were posted on the USP Resolutions portal for Convention Member and stakeholder consideration, comment, and endorsement. These concepts received 198 endorsements from 29 participants. In addition, the CoC was gratified to receive 42 Resolution proposal submissions from 24 participants. By comparison, USP received 13 submissions from 8 participants prior to the 2015 Convention Meeting.

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Report of the Council of the Convention on Resolutions The CoC acknowledges the contributions of the organizations and individuals who submitted Resolution proposals; Resolution proposal submissions are available for review as a digital supplement to this report. Following careful review of all submissions and endorsement of Resolution concepts, USP staff identified and grouped those with similar aims into the final 15 proposed Resolutions. Please note that the order of the proposed Resolutions does not indicate level of priority; the CoC puts forward all proposed Resolutions as important recommendations for USP. The USP Board and Council of Experts considered each proposed Resolution and developed a corresponding Resource Assessment, describing the resources that currently exist at USP or additional resources that would be necessary to fulfill the Resolution if adopted. With the 15 proposed Resolutions identified, the CoC collaborated with USP staff to refine the language of each proposal. Additionally, with input from the CoC, USP staff developed white papers for each proposed Resolution to provide background information and descriptions of ongoing or planned activities at USP that are relevant to the proposed Resolution. The white papers include a section about how the proposed Resolution aligns with USPâ&#x20AC;&#x2122;s mission, as well as the Resource Assessments developed by the Board and Council of Experts. The 15 white papers are available as a digital supplement to this report.

Recommended Action Prior to the 2020 Convention Meeting The CoC encourages all Convention Members to review the proposed Resolutions and the white papers prior to the Convention Meeting. We look forward to a robust discussion on the proposed Resolutions, as well as any additional proposals from the floor. The Resolutions adopted at the Convention Meeting in May 2020 will set the direction for the first cycle of USPâ&#x20AC;&#x2122;s third century of impact.

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Report of the Council of the Convention on Resolutions

Members of the Council of the Convention Chair

Jesse L. Goodman, M.D., MPH President, USP Convention

Members

Lynette Bradley-Baker, Ph.D., R.Ph., American Association of Colleges of Pharmacy Amy B. Cadwallader, Ph.D., American Medical Association Glen Fine, M.S., M.B.A, C.A.E., Clinical and Laboratory Standards Institute David R. Gaugh, R.Ph., Association for Accessible Medicine Thomas E. Menighan, R.Ph., M.B.A., F.A.Ph.A., American Pharmacists Association Pallavi Nithyanandan, Ph.D., U.S. Food and Drug Administration Elizabeth Scott Russell, R.Ph., National Association of Boards of Pharmacy Maria Ines Santoro, Ph.D., University of SĂŁo Paulo School of Pharmacy Kasey Thompson, Pharm.D., M.S., M.B.A., American Society of Health-System Pharmacists

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Report of the Council of the Convention on Resolutions Proposed Resolution 1

Collaboration with FDA and Other Stakeholders on Health Priorities

Proposed Resolution 2

Efficiency in Standards Development and Revision

Proposed Resolution 3

Quality Standards

USP will be a definitive source and a recognized leader in quality standards to help protect patient and consumer safety and to meet the needs of regulators, policy makers, healthcare practitioners, and industry working in evolving global regulatory environments. In doing so, USP will work to identify emerging trends, align with technological advances, and develop innovative and agile approaches to address the future needs of industry, regulators, practitioner, and patient needs.

Proposed Resolution 4

Access to Biologics

USP will develop standards and other solutions to support innovation in the efficient development and manufacturing of quality biologics and advanced therapies to increase patient and health system access to these medicines.

Proposed Resolution 5

Innovation

USP will explore the development of quality standards and other fit-for-purpose solutions to help stakeholders safeguard the quality of promising healthcare innovations that address patient and public health needs.

Proposed Resolution 6

Digital Transformation of Standards

USP will create interoperable core digital solutions that leverage USP data and standards to improve public health through global access to quality medicines.

Proposed Resolution 7

Education and Training for Industry and Healthcare Practitioners

USP will build and strengthen capabilities fundamental for industry and healthcare practitioners to utilize USP standards through efficient, effective, and measurable training and education programs.

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Report of the Council of the Convention on Resolutions Proposed Resolution 8

Regulatory Systems Strengthening

USP will collaborate with global regulators and other partners to strengthen regulatory systems.

Proposed Resolution 9

Compounding

Proposed Resolution 10

Cannabis

Proposed Resolution 11

Pharmacopeial Cooperation and Convergence

USP will lead efforts to advance convergence around robust science-based standards across pharmacopeias. USP will focus efforts on those standards where convergence will have the most impact on global access to quality medicines.

Proposed Resolution 12

Evidence Generation to Inform Policy

USP will generate and disseminate evidence upon which informed choices can be made for investment in regulatory and quality systems, and reforms to regulatory paradigms that advance quality, patient safety and public health.

Proposed Resolution 13

Coalition Building

USP will lead and power a stakeholder movement for quality to advance public health and patient safety.

Proposed Resolution 14

Culture of Excellence

USP will model operational excellence, continuous improvement, stakeholder responsiveness, and transparency.

Proposed Resolution 15

Impact Expansion

USP will expand its public health impact by reaching more people in more geographies with USP standards, capability building, and advocacy.

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Report of the Council of the Convention on Resolutions

Bylaws Relevant to Resolutions Excerpts from 2015â&#x20AC;&#x201C;2020 USP Bylaws Article II. Purposes The purposes for which the Convention is formed are as set forth in the Articles of Incorporation and include developing and disseminating public standards for medicines and other articles, and engaging in related public health programs. The Convention may also set forth by resolution or in separate documents a more detailed mission statement. Article IX. Council of the Convention Section 1. Duties. There shall be a Council of the Convention which shall have the following general duties: d. Developing resolutions that advance the purposes of the Convention set forth in Article II for the Voting Members to consider based on input from the Membership, the Board and, where appropriate, the Council of Experts. The proposed resolutions shall be submitted to the Board and Council of Experts for a resource assessment and provided to the Membership along with the findings of the Board and Council of Experts by electronic mail or by a link to the USP website not later than sixty (60) days prior to the Regular Membership Meeting. For the full text of Article IX, please access via the following link: https://www.usp.org/sites/default/files/usp/document/ about/convention-membership/article9.pdf

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Proposed Resolution

Collaboration with FDA and Other Stakeholders on Health Priorities Resolution white paper developed by USP staff, with input from the Council of the Convention

Resolution white paper developed by USP staff

Proposed Resolution 1

Collaboration with FDA and Other Stakeholders on Health Priorities

USP will continue its commitment to collaboration with the U.S. Food and Drug Administration (FDA), industry, and other stakeholders by identifying shared priorities and leveraging USPâ&#x20AC;&#x2122;s capabilities to help advance patient safety, public health, innovation, and access to quality medicines. Summary Over the course of its 200-year history, USP as an organization, and the public quality standards developed by USP expert volunteers, have been an integral part of the public health framework safeguarding patients from poor-quality medicines, dietary supplements, and foods. As an independent, nongovernmental, and nonprofit organization, USP has and continues to work with a broad spectrum of stakeholders, including regulatory authorities in the United States and around the world, to leverage its standards-setting capabilities and education and training platforms to help advance national health priorities, as they align with USPâ&#x20AC;&#x2122;s mission. Going

forward, USP can also further leverage its global convening capabilities to bring stakeholders together on health priorities and advocate for the investment and policy reform that may be needed to address them. By adopting this Resolution, USP will seek new opportunities to make important contributions to help address national health priorities when they align with USPâ&#x20AC;&#x2122;s mission and capabilities and, in doing so, will expand on its legacy of partnering with stakeholders from government and industry to work together to build a healthy future for people everywhere.

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Resolution white paper developed by USP staff

Background Over the course of its history, USP has built a legacy of contributing to solutions to help address some of the most urgent public health crisis priorities of the United States and other governments and to advance their health priorities. Examples include contributions to help enable the mass production of penicillin during World War II, standards to address the contamination of milk products with melamine, and initiatives to help address the 2008 crisis of adulterated heparin. USP also has launched research initiatives to generate additional data on the link between poor-quality antimicrobials and the rise of antimicrobial resistance (AMR). Additionally, USP has advocated in global and regional forums for investment and regulatory focus to ensure the quality of antimicrobials as one component of comprehensive efforts to combat AMR, which is a top health priority of the World Health Organization (WHO) and many national governments. Partnering with government, physicians and pharmacists, and industry to address public health needs fits squarely within the public health mission of USP. The organization’s governance and operating model involves stakeholder organizations from the USP Convention that shape its work over a five-year period and volunteer experts who establish science-based standards in a public process. While USP is a part of the public health safety net of the United States as the legally recognized

organization that establishes public quality standards for the medicines that Americans rely on, USP also has a powerful capability to convene stakeholders, leverage its scientific network, deploy its global resources, and advocate to help make progress on the health priorities identified by policy makers and regulators. The following are three examples of USP leveraging its resources in the 2015–2020 cycle to help advance national health priorities that align with USP’s public health mission.

Prioritizing Off-Patent Medicines Lacking Competition to Increase Access to Quality Medicines The U.S. Food and Drug Administration (FDA) and many other public sector stakeholders agree that the price of prescription medicines in the United States is unsustainable. Since the enactment of the Hatch– Waxman Act in 1984, generic medicines have helped to significantly reduce the cost of medicines and have saved an estimated $1.5 trillion dollars over the past 10 years.1 While much progress has been made, there are still hundreds of off-patent medications that have few or no generic options. To help address this, FDA developed the Drug Competition Action Plan (DCAP), which outlines key steps that FDA is taking to help address this market

Stakeholder Collaboration to Improve Access to Safe, Quality Medicines Prioritizing OffPatent Medicines for New Standards: USP’s Generics Access Plan will help increase patient access to medicines by facilitating generics competition through new and revised standards, training and education, and collaborations with FDA, industry representatives, and others.

Strengthening the Global Supply Chain: USP coproduced the Supply Chain Security Toolkit for Medical Products, including best practices to improve the quality and security of global pharmaceutical supply chains. USP has also launched education and training initiatives through the USP– APEC Center of Excellence on Supply Chain Medical Product Quality.

Addressing Poor-Quality Antimicrobials to Address AMR: USP is helping to address this top priority of WHO and national governments by generating additional data, advocating for investment and regulatory focus, and working to strengthen regulatory systems to prevent, detect, and respond when poor-quality antimicrobials are found.

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Resolution white paper developed by USP staff failure, including the identification of medicines that lack competition. While there are many factors that account for this dynamic, one factor that can help foster a multi-manufacturer environment for a medicine is the existence of a USP public quality standard. A recent study found a correlation between the presence of a quality standard for a medicine and the availability of generic versions of that product. According to the study results, on average, medicines with a USP public quality standard had approximately 50 percent more generic manufacturers than medicines without such a standard. Availability of generic medicines led to a cost savings of $11 billion across the two years of the study (2015–2016), thereby allowing more patients to access the medicines they need.2 With this in mind, USP is working to support FDA’s DCAP,3 by prioritizing the development or revision of public monographs for the off-patent medicines lacking competition, as prioritized by FDA. The work is a core element of USP’s Generics Access Plan, which helps increase patient access to medicines by facilitating generics competition through new and revised standards, training and education, and collaborations with FDA, industry representatives, and others.4

Strengthening the Global Supply Chain The increasingly globalized medical marketplace has enabled communities around the world improved access to quality medicines and healthcare. However, globalization has also brought the rise of substandard and falsified medical products, and urgent needs for ensuring quality and security of medical products no matter where medicines are made and sold. The complexity of globalized manufacturing, distribution, and sale of medical products demands better coordination and collaboration across the healthcare landscape. To help address the challenges of safeguarding the global supply chain, the Asia–Pacific Economic Cooperation (APEC)—a trade platform for 21 economies across Asia, Oceania, and the Americas— established the Roadmap to Promote Global Medical Product Quality and Supply Chain Security.5 This is a multiyear, multistakeholder effort led by FDA in collaboration with other regulatory bodies, industry stakeholders, nongovernmental organizations, international organizations, and academics from across the globe. The group was tasked with curating evidence of global practices known to better ensure medical product quality and supply chain security, culminating in the

APEC Supply Chain Security Toolkit for Medical Products. Intended to cover the entire supply chain and lifecycle of medicines, the toolkit focuses on existing practices, guidances, procedures, and tools that can be adopted by regulators and industries to better secure medicines quality and supply chain security. USP has been a key partner with FDA and other stakeholders in the development and dissemination of this toolkit. During the toolkit development phase, USP contributed expertise and knowledge critical to the curation of best practices. Following completion of the toolkit in 2017, USP cocreated with FDA and global partners across industries, international regulatory bodies, and academic partners, the first APEC pilot program to disseminate learnings from the toolkit. In 2018, with FDA endorsement, APEC officially recognized USP as an APEC Regulatory Center of Excellence on Supply Chain Medical Product Quality, enabling USP to co-deliver trainings with FDA and other partners. As a standing member of the FDA-led Supply Chain workstream, USP advises new Centers of Excellence, contributes to supply chain toolkit updates, and provides feedback from trainings on regional challenges and developments that affect global supply chains. Since 2018, the USP–APEC Center of Excellence program has trained more than 400 regulators and industry participants across four continents. From this history of work, USP has been encouraged within APEC to bring the quality lens to emerging issues, such as advanced cell therapy products and future collaborations with regulatory bodies outside the United States.

Addressing Poor-Quality Antimicrobials to Address Antimicrobial Resistance Global health research estimates that, if not addressed, antimicrobial resistance (AMR) could cause 10 million deaths annually by 2050.6 AMR is considered a global health security priority because resistant pathogens travel across national borders in a today’s globalized world. One under-recognized driver of AMR is poorquality medicines—also referred to as substandard and falsified medicines—which can lead to treatment failure as well as escalate AMR. Substandard medicines are those that fail to meet standards or specifications of quality, while falsified medicines deliberately or even fraudulently misrepresent their identity, composition, or source.7 A comprehensive analysis conducted in 2018 found that more than 12 percent of antibiotics circulating in low- and middle-income countries are substandard and falsified medicines, which can also travel across borders in under-regulated markets.8

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Resolution white paper developed by USP staff USP has co-convened with the United States and other governments several critical dialogues in multilateral forums such as the World Health Assembly and the United Nations (UN) General Assembly to highlight the need to focus on medicines quality in the AMR response. These discussions have engaged high-level officials from FDA and the U.S. Agency for International Development, as well as experts from around the world, resulting in increased donor investments that will help to generate evidence about the scope and scale of substandard antibiotics and strengthen capacity for post-marketing surveillance of antimicrobials. Critical government agencies have subsequently incorporated this as a priority in global frameworks such as the UN Interagency Coordinating Group recommendations and resolution EB144.R11 on antimicrobial resistance adopted at the World Health Assembly in 2019.9 These global frameworks provide normative guidance on critical components of the AMR response to national governments. USP has committed to the AMR Challenge of the U.S. Centers for Disease Control and Prevention, a call for broad-based support to combat AMR in the United States and globally.10 Through its policy analysis and evidence generation functions, USP is also working to document and disseminate good practices that incorporate medicines quality assurance

into AMR National Action Plans worldwide, building on the “Prevent, Detect, Respond” framework promoted by WHO. While the focus is on AMR, such actions strengthen medicines quality oversight for all therapeutic classes, thereby improving health outcomes across the board.

Alignment with USP Mission USP’s science-based public quality standards help to protect patient safety and advance public health, innovation, and access to quality medicines. Over the course of USP’s history, standards, training, and advocacy have been deployed by USP to help address the health priorities of the U.S. government and other governments around the world. As the medicines supply chain and economy further globalize and biomedical advances create new challenges and health priorities, USP can expand and multiply its mission impact by seeking and partnering with governments to support their objectives when they are in alignment with the USP mission.

Resource Assessment Resources currently in place. Staff capabilities have been built for robust engagement with stakeholders, including industry and FDA, to discuss shared patient safety, public health access to quality medicines, and innovation priorities.

References and Notes 1 Association for Accessible Medicines. Generic drug access and savings in the U.S. Washington, DC: AAM; 2017. Available from: https:// accessiblemeds.org/sites/default/files/2017-06/2017-AAM-Access-Savings-Report-2017-web2.pdf. 2 Murimi-Worstell IB, Ballreich JM, Seamans MJ, Alexander GC. Association between US Pharmacopeia (USP) monograph standards, generic entry and prescription drug costs. PLoS ONE. 2019 Nov 12;14(11):e0225109. doi:10.1371/journal.pone.0225109. 3 U.S. Food and Drug Administration. FDA drug competition action plan. Silver Spring, MD: FDA; 2019 Dec 16. Available from: https://www.fda. gov/drugs/guidance-compliance-regulatory-information/fda-drug-competition-action-plan.

4 USP Generics Access Plan [Internet]. Rockville, MD: USP; c2020 [cited 2020 Jan 31]. Available from: https://www.usp.org/our-impact/generics. 5 Asia–Pacific Economic Cooperation. APEC roadmap to promote global medical product quality and supply chain security: supply chain security toolkit. Singapore: APEC; 2018 Jul 10. Available from: https://www.apec.org/-/media/Satellite/RHSC/PWA-roadmaps/Global-SupplyChain/APEC-Roadmap-for-Supply-Chain-Security--Core-Curriculum_190228.pdf. 6 O’Neill J. Antimicrobial resistance: tackling a crisis for the health and wealth of nations. Review on Antimicrobial Resistance; London: Wellcome Trust and UK Government; 2014 Dec. Available from: https://amr-review.org/sites/default/files/AMR%20Review%20Paper%20-%20Tackling%20 a%20crisis%20for%20the%20health%20and%20wealth%20of%20nations_1.pdf. 7 World Health Organization. Substandard and falsified medical products. Geneva: WHO; 2018 Jan 31. Available from: https://www.who.int/newsroom/fact-sheets/detail/substandard-and-falsified-medical-products.

8 Ozawa S, Evans DR, Bessias S, Haynie DG, Yemeke TT, Laing SK, Herrington JE. Prevalence and estimated economic burden of substandard and falsified medicines in low- and middle-income countries: a systematic review and meta-analysis. JAMA Netw Open. 2018 Aug 10;1(4):e181662. doi:10.1001/jamanetworkopen.2018.1662.

9 World Health Organization. Resolution: antimicrobial resistance. 72nd World Health Assembly. Agenda item 5.8. Geneva: WHO; 2019 Feb 1. Available from: https://apps.who.int/gb/ebwha/pdf_files/EB144/B144_R11-en.pdf. 10 Centers for Disease Control and Prevention. Antibiotic/antimicrobial resistance (AR/AMR): the AMR challenge. 2019 Oct 9. Available from: https://www.cdc.gov/drugresistance/intl-activities/amr-challenge.html.

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Proposed Resolution

Efficiency in Standards Development and Revision

Resolution white paper developed by USP staff, with input from the Council of the Convention

Resolution white paper developed by USP staff

Proposed Resolution 2

Efficiency in Standards Development and Revision

USP will proactively evaluate and enhance the process for developing and updating monographs to maintain and continuously optimize their impact. In doing so, USP will consider the perspectives and implications of process modifications from FDA, industry, and other stakeholders. A focus of this work will be to explore new approaches for the efficient sharing of information that is critical to standards development, along with the information needed for the evaluation of fit-for-purpose analytical methods and specifications, and the integration of scientific and manufacturing advances into USP standards. Summary For more than 100 years, USP has developed public quality standards in close collaboration with the U.S. Food and Drug Administration (FDA), industry, and other stakeholders to help ensure the quality of medicines used in the United States and around the world. As biomedical and technology advances led to an explosion of new drug approvals by FDA, the need for new USP standards for new medicines and modifications to existing monographs also grew exponentially. The

development of new and modernized monographs remains essential, not only to provide tools to help ensure the quality of medical products, but also to serve as an up-to-date resource for manufacturers to leverage to bring medicines to market, which helps to expand patient access to quality medicines. For these reasons, modernizing the U.S. Pharmacopeia and the National Formulary (USPâ&#x20AC;&#x201C;NF) compendia became the top priority of USP over its 2015â&#x20AC;&#x201C;2020 cycle.

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Resolution white paper developed by USP staff Beginning in 2015, USP embarked on an ambitious effort to eliminate the backlog of monographs in need of modernization. Throughout this process, USP Expert Committees—with representation from FDA liaisons as well as expert volunteers from global regulatory authorities, industry, the healthcare practitioner community, and academia—collaborated to accomplish a remarkable achievement. In the past five years, USP Expert Committees have brought more than 900 monographs up to date in the USP–NF and identified gaps that resulted in the establishment of 400 new monographs. Another 400 monographs were identified as no longer necessary and eliminated from USP–NF. USP remains committed to maintaining its monographs, and therefore, this Resolution proposes that USP enhance and strengthen its engagement with FDA and industry to identify new and more efficient ways to modernize monographs while continuing to evaluate and incorporate fit-for-purpose analytical methods and specifications as well as advances in scientific and manufacturing approaches. USP will explore new ways to gather stakeholder input critical to the standards-setting process from industry and regulators. Throughout the next cycle, USP will proactively evaluate its standards and update them as needed to maintain their relevance, with an understanding of the needs, resource constraints, and mission priorities of key stakeholders.

Background Pharmacopeias and their public quality standards are an important part of a larger regulatory ecosystem designed to help ensure the quality of medicines, dietary supplements, and foods. USP and FDA are longstanding collaborators in advancing public health and protecting patient safety, with a relationship that began with the enactment of the Pure Food and Drug Act of 1906. Effective collaboration is essential to ensure appropriate and up-to-date standards. FDA, USP, industry, and other stakeholders work together to identify areas for monograph or general chapter development where there is a need to address or advance quality issues. These interactions lead to a more efficient standardsdevelopment process and support the key stakeholders that value and depend upon quality products. USP sets public standards for the identity, strength, quality, and purity of medicines, dietary supplements, and food ingredients. USP also sets standards for healthcare quality and practice standards, such as drug labeling and compounding. All USP standards are developed through an open, transparent process that

has the flexibility to adjust standards to confront public health emergencies, adapt to new industry practices, and keep pace with the rapid, continuous advances in science and technology. USP Expert Committees and Expert Panels, which include more than 1,000 leading scientific experts who volunteer their time, are the groups that develop USP quality standards. These committees and panels benefit from the expertise, input, and participation of liaisons from FDA centers and offices. USP and FDA maintain official contact through several established channels. One of these channels is the participation of FDA delegates in the USP Convention. FDA delegates represent the Office of the Commissioner and five of its centers – the Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research, Center for Devices and Radiological Health, Center for Veterinary Medicine, and Center for Food Safety and Applied Nutrition. Another established channel is the participation of at least 100 FDA scientific staff as Government Liaisons on USP Expert Committees and Expert Panels. These liaisons have a critical function to provide FDA perspectives, contributing to the development of standards by providing expert input and regulatory context. A third established channel is that USP staff maintain executivelevel contacts with FDA leadership and participate in quarterly meetings with FDA’s scientific and compendial staff. Frequent interactions between USP and FDA lead to a more efficient standards-development process in support of quality medicines.

Achieving “Up to Date”: Modernizing Monographs in USP–NF Since 2015, USP Expert Committees have worked to update the USP–NF by developing 400 new monographs, revising 900 modernized monographs, and eliminating 400 unnecessary monographs. After the adoption of a 2015 USP Convention Resolution proposed by FDA, USP worked with FDA to identify and prioritize monographs for creation or revision to align with modern regulatory, safety, and technological information, while also developing new methods for information sharing through a Cooperative Research and Development Agreement (CRADA) with FDA’s Office of Regulatory Affairs. Additionally, USP devoted a significant portion of its laboratory resources to develop some of the methods needed to update monographs and to verify data from sponsors, rather than relying solely on monograph donations from manufacturers.

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Resolution white paper developed by USP staff The enormity of the collective effort to modernize USP–NF cannot be overstated. Achieving “up to date” would not have been possible without extensive collaboration from FDA, which devoted significant internal resources to the effort. This included the assignment of many more FDA staff to USP Expert Committees through the Government Liaison Program than had previously occurred.

Improving the Government Liaison Program

Several learnings emerged from this tremendous undertaking, and USP is deploying internal initiatives to facilitate a consistent and efficient approach to keep standards current and address the needs of the future.

USP and FDA periodically share lessons learned about the Government Liaison Program. Based on these discussions, USP has already begun the work of identifying areas where it can enhance the communication process with FDA to ensure that the organizations’ collective work reflects the most pressing public health priorities. USP aims to better characterize each Expert Committee and its needs, as well as its primary objectives for the coming cycle and the corresponding workload so that the subject matter expertise of the selected Government Liaisons can be paired appropriately with Expert Committees’ responsibilities. USP and FDA also will collaborate on refining the roles and responsibilities of Government Liaisons so there is a better understanding of expectations in both organizations.

One such effort is Adapt. Transform. Progress. (ATP), a USP initiative designed to increase the efficiency and effectiveness of the standards-development process and systems. To learn more about ATP, please read the proposed Resolution white paper on Culture of Excellence. Another example is the Public Input Lifecycle and Impact Project (PILIP), which launched in 2019. Through PILIP, USP aims to enhance stakeholder engagement throughout the standards-setting process to ensure that stakeholder input and needs are reflected. For more information about PILIP, please read the proposed Resolution white paper on Quality Standards.

Creating more effective mechanisms to support and enrich the Government Liaison Program is one way to improve focused and strategic communication between USP and FDA.

Key Facts and Terms of Reference Up to Date: since 2015, USP–NF revisions have included: - 400 new monographs - 900 modernized monographs - 400 monographs eliminated

Adapt. Transform. Progress. (ATP) is an initiative designed to increase the efficiency and effectiveness of USP standards-setting processes and systems.

Pending Monograph Program (PMP) provides an efficient pathway for aligning the development of USP monographs with FDA approval of the associated applications.

Public Input Lifecycle and Impact Project (PILIP) aims to improve the engagement experience and help ensure that stakeholder input and priorities are reflected throughout standards-setting process.

Pharmacopeial Forum (PF) represents an important component of USP’s open and transparent standards-setting process, allowing anyone to comment on a proposed standard before it becomes official in the USP–NF.

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Resolution white paper developed by USP staff USP hopes to better support FDA by providing a more efficient process for identifying the anticipated outputs of the Expert Committee, thereby enabling successful inputs by an appropriate Government Liaison. Expert Committees and their work products benefit from engaging with FDA more effectively.

Evaluating the USP–NF Revision Process Proposed revisions to the USP–NF, including new or revised monographs and general chapters, are made public in Pharmacopeial Forum (PF). This free, bimonthly online journal published by USP provides a forum for public review and comment regarding new and revised monographs and general chapters and is open to receive commentary from all stakeholders, including, but not limited to, global industry, domestic and foreign regulatory bodies, patient organizations, and other standards-development bodies. PF represents an important component of USP’s open and transparent standards-setting process. While expert volunteers and FDA liaisons participate in the development of compendial standards in the USP Expert Committees, anyone is eligible to comment on a proposed standard through PF before the standard becomes official in USP–NF. The relevant Expert Committees review and consider comments from stakeholders and the public and incorporate changes if deemed appropriate. USP staff compile comments for discussion by the Expert Committees, which deliberate on their impact and determine whether the standard can move forward, with or without additional changes. If a proposal moves forward, the responses from the Expert Committees to comments submitted on those proposals are consolidated into a Commentary document that is published on USP’s website at the time the official text is published. USP also posts notices of proposals that are deferred or cancelled so stakeholders can track their development status. The high volume of proposals submitted through PF can create a significant burden on FDA and other stakeholders. To address this, USP is reviewing the USP–NF revision process, looking for opportunities to create improvements and introduce efficiencies. Specifically, USP is seeking ways to define and foster the appropriate degree of public engagement before standards are published in PF. That way, USP Expert Committees proactively can address stakeholder

perspectives or feedback that may not otherwise surface until the public comment period, reducing the likelihood of a standard needing to be published in PF multiple times, and saving time and other resource demands on Expert Committee participants as well as stakeholders.1 In the coming cycle, USP will explore new ways to ensure that new communication channels created through PILIP (see box on page 4 for more information) provide opportunities for deeper engagement and collaboration. USP plans more substantial engagement on cross-cutting and high-level initiatives that will lead to new efficiencies to the USP–NF revision process. This enhanced model has been tested with FDA in a proof-of-concept trial where logistical and technical issues were refined. USP will continue to review the process to identify additional opportunities for improved communication with FDA and other stakeholders.

Facilitating Efficient Development of Standards: USP’s Pending Monograph Process The Pending Monograph Process (PMP) provides an efficient pathway for aligning the development of a monograph with FDA approval of the associated application.2 The PMP is available in cases where a drug product monograph does not yet exist in the USP–NF, or where revisions to a monograph are required to align with a planned product approval from the FDA. Monographs generated through the PMP remain in an unofficial status until FDA approval of the drug product. Once FDA has approved the drug application, the PMP allows the new or revised monograph(s) to become official rapidly, often in only a few weeks. In cases where there is an existing monograph that needs to be updated, it is common for the application sponsor to donate analytical methodology and reference standard bulk material as necessary to revise the monograph promptly. Since 2015, more than 70 requests for monograph revisions have been processed through the PMP. In July 2019, FDA published a draft guidance, Harmonizing Compendial Standards With Drug Application Approval Using the USP Pending Monograph Process,3 which explains FDA-related aspects of the process. In the next cycle, USP will work to raise awareness to industry about the PMP pathway. Wider use of this program will facilitate more efficient standards development and thereby provide patients with more timely access to quality medicines.

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Resolution white paper developed by USP staff

Alignment with USP Mission As science and technology advance and approvals of new innovative medicines increase, it will be important for USP to engage with FDA and all stakeholders in ways that foster more effective communication and recognize the limited resources and other constraints bearing upon each organization and its key constituents. This Resolution reaffirms USP’s commitment to work collaboratively with FDA and other stakeholders to maintain a modernized USP–NF compendia through efficient processes to continually revise monographs, being cognizant of the priorities, constraints and needs of FDA and industry. At the same time, this Resolution also urges USP to work with FDA and industry to explore

new approaches for sharing the information needed for efficient standards setting, including evaluation of fitfor-purpose analytical methods and specifications and integration of scientific and manufacturing advances. Finding new ways to share information among USP, FDA, and industry, will enable a continually modern USP–NF that will advance access to quality medicines and help to safeguard patient safety.

Resource Assessment Resources currently in place. Aligns with USP process improvements already underway. Implementation will continue on these.

References and Notes 1 Adapted from a Resolution proposal submitted by Barbara Ferguson, New Jersey Pharmaceutical Quality Control Association. 2 USP-NF [Internet]. Rockville, MD: USP; c2020 [cited 2020 Jan 31]. Available from: https://www.uspnf.com/pending-monographs. 3 U.S. Food and Drug Administration. Harmonizing compendial standards with drug application approval using the USP pending monograph process: guidance for industry. Silver Spring, MD: FDA; 2019 Jul. Available from: https://www.fda.gov/media/128689/download.

200 years of building trust

Proposed Resolution

Quality Standards Resolution white paper developed by USP staff, with input from the Council of the Convention

Resolution white paper developed by USP staff

Proposed Resolution 3

Quality Standards

USP will be a definitive source and a recognized leader in quality standards to help protect patient and consumer safety and to meet the needs of regulators and policymakers, healthcare practitioners, and industry working in evolving global regulatory environments.

Summary The quality of medicines is fundamental to treating disease and maintaining health. Through its public quality standards, USP helps build a safety net across the industry and healthcare system to preserve the wellbeing of patients. Standards help ensure that medicines meet quality expectations from the time they are made until the moment they are taken by a patient. As scientific understanding evolves, so too must USP standards. This Resolution proposes that USP should evolve its approach to setting standards so it can continue to protect patient safety and public health in a way that reflects new and

emerging science, while understanding the impact of USP standards on regulators, policymakers, healthcare practitioners, industry, and patients. As a recognized leader and definitive source of high-quality, timely, fitfor-purpose standards that reflect the best expertise available from around the world, USP will maintain and even strengthen its cadre of expert volunteers, ensuring that this group of experts reflects the stakeholder community. USP will also work to maximize opportunities for volunteer engagement beyond the classic five-year fixed-term model. To ensure its standards are timely and

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Resolution white paper developed by USP staff

fit for purpose, USP will identify and implement ways to accelerate the standards-setting process while reflecting an understanding of the priorities of users and the impact of new or revised standards. Additionally, USP will disseminate relevant scientific findings in more flexible ways than it has in the past to allow earlier and broader access to valuable information, data, and methods. Finally, being a definitive source not only means that USP standards are of high quality, timely, and fit for purpose, but also that USP is creating the right standards. USP will prioritize standards that have the most relevance for stakeholders while simultaneously anticipating new technology and products. Engaging stakeholders will be essential to establishing priorities that reflect the needs of users while always keeping patient safety and public health top of mind.

Background USP’s core contribution to public health is the comprehensive set of well-established, broadly trusted public quality standards that USP establishes for medicines, dietary supplements, and foods. USP deploys a thorough, rigorous, and open process to develop its quality standards, leveraging the knowledge and expertise of leading scientific experts around the world. In this way, USP’s expert volunteers form the foundation of the quality standards. As part of the process, USP makes available several venues for the public to participate and provide input, including stakeholder forums, roundtables, and workshops. For example, the public is invited to review and comment on proposed standards through the Pharmacopeial Forum1 and the Food Chemicals Codex Forum.2 These opportunities allow stakeholders beyond those serving on USP’s Expert Committees to contribute their knowledge, ideas, or concerns to the process. By providing time for public review—and similarly by opening Expert Committee, Expert Panel, and other official meetings to the public—USP ensures that its process is robust, transparent, and collaborative. Since the 2015 Convention, USP has made strides toward increasingly modernized and up-to-date standards, launched new education and training programs to support users of USP standards, and increased efforts to connect with global stakeholders. USP made these efforts in response to rapidly evolving science, transformational advancements in healthcare, and the growing number of countries that are developing

or manufacturing medicines and making regulatory decisions for medical products. Expert volunteers and the scientific understanding they represent are the foundation of quality standards. In recognition of their valuable contribution to the mission of the organization, USP will adopt a new and nimbler approach in the next cycle that increases efficiencies and better reflects the needs and priorities of stakeholders while sharing scientific knowledge in flexible, innovative ways.3

The USP Expert Volunteer Model Expert volunteers are crucial for preserving public trust in USP standards. More than 1,000 scientific experts— representing the healthcare practitioner, industry, academic, public health, and regulatory communities— compose the committees that develop, refine, and approve USP standards. USP volunteers possess the critical expertise, state-of-the-science understanding, and ability to apply their knowledge in the standardssetting framework. Every five years, USP invites qualified candidates to apply for expert volunteer positions where they can serve as decision makers on its Council of Experts (CoE), Expert Committees, and Expert Panels. • Council of Experts: This body oversees USP’s scientific and standards-setting decisions. The USP Convention Membership elects CoE members every five years. Each member serves as the Chair of an Expert Committee for a five-year term. The Chairs, in turn, select the members of the Expert Committees. • Expert Committees: These committees develop and revise standards that constitute the USP compendia: USP–NF, USP Compounding Compendium, Herbal Medicines Compendium, Dietary Supplements Compendium, and Food Chemicals Codex. They also approve USP Reference Standards specified for use with the compendia. Each Expert Committee focuses on a different area of standards for medicines (including chemical medicines, biologic medicines, excipients, and compounded preparations), dietary supplements, and food ingredients. Expert Committees engage in scientific deliberation to develop proposed standards, solicit feedback on these proposals from the public, then review and consider the input received, adjusting the standards accordingly and adopting them by a majority vote. • Expert Panels: Expert Panels are formed to support the Expert Committees by providing additional expertise on a particular compendial topic. Each

200 years of building trust

Resolution white paper developed by USP staff Expert Panel has a specific charge (including scope of work, deliverables, and timeline for completion) and dissolves when its task is completed. Each Expert Panel advises one or more Expert Committees. Expert Panels are not decision-making bodies.

USP recognizes that the time commitment of serving on an Expert Committee or Expert Panel may prevent some experts from volunteering. To address this, USP is reimagining the volunteer model, seeking ways to appeal to scientists who have the requisite interest and expertise to participate in the standards-setting process, but who may not have the time or ability to commit to full Committee or Panel service These efforts will draw and retain experts who will help address current and future changes in healthcare and industry, including a complex global supply chain, the explosion of new medicine modalities, and innovative manufacturing technologies. USP envisions that a more flexible volunteer model will help attract a broader, more diverse group and increase volunteer engagement. To that end, USP will launch a volunteer model pilot project in which six Expert Committees will test a more agile and flexible model to engage and convene expert volunteers in a new role referred to as Expert Advisors. Participating committees will be encouraged to leverage the Expert Advisors, who

can share their expertise in a more ad hoc, flexible way without committing to a five-year cycle or being required to participate in mandatory balloting activities. USP will collect data throughout the pilot project to identify best practices and lessons learned. Ultimately, USP hopes the project outcome will be that potential volunteers view USP as the “go-to” scientific organization because it offers an engaging volunteer experience that makes the most of their time and expertise.

Timely and Fit-for-Purpose Standards USP will continue to fulfill its mission of creating timely and fit-for-purpose standards while simultaneously identifying ways to accelerate the standards-setting process, engage stakeholders in an effective and responsive fashion, and disseminate USP scientific findings in more flexible and agile ways. These approaches align with USP’s strategy of focusing on standards and building capabilities. USP will accelerate the standards-setting process, without sacrificing quality, in a way that reflects an understanding of the priorities and needs of users. Because USP creates standards with requirements that impact stakeholders, USP requests prompt stakeholder feedback to ensure that the organization can develop and, if necessary, revise the

USP Standards: Quality, Timely, and Fit for Purpose As a definitive source and recognized leader in high-quality, timely, and fitfor-purpose standards, USP is committed to ensuring that its standards are: Useful:

Recognized:

Comprehensive:

USP is focused on developing solutions that provide the most value to public health and to stakeholders. These solutions incorporate emerging and established science to ensure quality medicines and food ingredients.

USP staff and expert volunteers are scientific thought leaders; thus, the organization is a resource for quality standards recognized throughout the regulatory, industry, scientific, and healthcare communities.

USP data assets provide a critical mass of broadly applicable and definitive standards—including monographs and General Chapters—ensuring that the standards align with current, rigorous science and fully support the needs of stakeholders.

200 years of building trust

Resolution white paper developed by USP staff standards to closely reflect user needs and constraints and ultimately improve fit for purpose. In 2019, USP launched the Public Input Lifecycle and Impact Project (PILIP), which covers the lifecycle of a standard encompassing problem definition, solution development, identification of affected stakeholders, public notice and comment, and communication about outcomes. PILIP touches everything that goes through the Pharmacopeial Forum and Food Chemicals Codex Forum, including monographs, general chapters, and Stimuli articles. Implementing PILIP will help USP engage stakeholders in an effective and timely fashion. Through PILIP, USP staff will develop new, researchbased tools and comment mechanisms that integrate the public input processes/systems with the transformation of standards-development processes/systems to benefit everyone who uses USP standards. PILIP explores stakeholder engagement throughout the lifecycle of a standard and questions assumptions about policies and processes. Because USP standards have a broad stakeholder base, tailoring solutions to meet all needs while proactively engaging across a diverse group of stakeholders will be challenging but ultimately worthwhile. Currently, USP staff are implementing projects identified during the analysis phase of PILIP. These projects aim to enhance stakeholder engagement throughout the standards-setting process to ensure that stakeholder input and needs are reflected. Increased stakeholder engagement yields better standards, ultimately leading to improved patient safety and access to quality medicines. USP will disseminate its relevant scientific findings in more flexible ways to allow earlier and broader access to valuable information, data, and methods. USP conducts rigorous experiments and develops innovative scientific approaches (especially in new or emerging areas of science) that are shared through the traditional, peer-reviewed journal pathway. Additionally, internally developed and vetted white papers help explain USP positions on an array of related topics, such as advancing compounding quality or combating antimicrobial resistance. Future steps might entail growing USP’s presence in the digital realm, thereby increasing the visibility and flexibility of USP data as well as USP’s ability to quickly marshal resources to address risks and create solutions. In the next five-year cycle, USP will devote resources to increasing efficiency in publicly sharing the scientific expertise and knowledge developed by staff and committee-led activities in national and international

forums.4 Interactive workshops and trainings are another opportunity for USP to engage more directly with stakeholders who rely on USP standards, both to share the knowledge gained by staff and expert volunteers and to gather feedback that may inform revisions to USP standards. The goal is to increase access to the knowledge gained through USP’s scientific approaches as well as to stimulate the scientific community to engage with USP.

Developing the Right Standards Being a definitive source not only means that USP standards are of high quality, timely, and fit for purpose, but also that USP is creating the right standards. To this end, USP will prioritize standards that have the most relevance for stakeholders such as industry and regulators5 while anticipating new technology and products. USP recognizes that the key to this process is engaging stakeholders in different ways to identify priorities that reflect the needs of users while always keeping patient safety and public health top of mind. Developing the right standards does not mean creating standards for every product in an area. The approach should, and will, differ for different fields. New standards will be created where they can contribute the most value for patients. For most of its 200-year history, USP has focused primarily on end products. Going forward, the organization will reimagine what a standard can be—moving beyond monographs and reference standards—including how to better deliver them and connect to users. USP is seeking and finding innovative opportunities for quality standards to support the lifecycle of medical products beyond quality control testing. For example, to increase access to biologics, USP performance standards will support analytical testing throughout the product lifecycle. Following the 2015 Convention, USP embarked on an ambitious journey to ensure that all USP standards are up to date and reflect current scientific understanding. In that time, USP expert committees have created 400 new monographs, modernized 900 monographs, and eliminated 400 monographs. In the next five years, USP will address new and emerging therapeutic classes, including biologics and biosimilars, and others. More information on these approaches can be found in the proposed Resolution on Innovation. As a scientific organization, USP will begin any new approach by collecting data on what has been done already to identify a baseline, measure impact, and identify opportunities for improvement. To ensure that USP’s compendial

200 years of building trust

Resolution white paper developed by USP staff science work reflects the needs and resources of the industry and regulatory communities, the organization will adopt a more flexible, agile, and iterative approach to standards development and delivery that reflects the needs of industry and regulators as well as end users.6 For more information about PILIP, please read the proposed Resolution white paper on Quality Standards.

Alignment with USP Mission As standards are revised or created, USP must build stakeholders’ resolve to adopt and use those standards and support their capabilities to do so. USP has a strong foundation—200 years of deep expertise—that makes it uniquely qualified to collaborate with its stakeholders to create quality standards that ensure medicine and food ingredient quality, thereby boosting consumer confidence in medicines, foods, and dietary supplements. As USP embarks on the next five years,

an enhanced focus on capability building will help the organization to prioritize standards that are most needed and reflect the input of expert volunteers. Building on the open, transparent public process that has been the hallmark of USP standards, a reimagined expert volunteer model will catalyze a focus on creating the right standards and ensuring they are of high quality, timely, and fit for purpose.

Resource Assessment Additional resources required to supplement resources that are currently in place. Identification and development of standards that meet stakeholder needs is integrated into USP program unit planning. The current CoE Expert Committee structure and the proposed structure for the next cycle will support this work.

References and Notes 1 The Pharmacopeial Forum (PF) is a free bimonthly online journal in which USP publishes proposed revisions to USP–NF for public review and comment. A new issue is posted online every two months at the beginning of the month. The comment period lasts 90 days and ends on the last day of the month. 2 The Food Chemicals Codex Forum (FCCF) is a free online resource in which proposed revisions to the FCC compendium are published for public review and comment. All comments are made available to all interested parties to ensure a transparent and scientifically rigorous process.

3 To learn more about USP’s efforts to align with other national and international compendia, please review the proposed Resolution paper on Harmonization. 4 Adapted from a Resolution proposal submitted by Roger Clemens, University of Southern California School of Pharmacy. 5 Adapted from Resolution proposals submitted by Hany Demian, U.S. Food and Drug Administration, and Tina Morris, Parenteral Drug Association. 6 Adapted from Resolution proposals submitted by Hany Demian, U.S. Food and Drug Administration, and Priscilla Zawislak, DuPont Nutrition & Biosciences.

200 years of building trust

Proposed Resolution

Access to Biologics

Resolution white paper developed by USP staff, with input from the Council of the Convention

Resolution white paper developed by USP staff

Proposed Resolution 4

Access to Biologics

USP will develop standards, tools, and other solutions to support innovation in the efficient development and manufacturing of quality biologics and advanced therapies to increase patient and health system access to these medicines. Summary Public standards are an essential component of the framework that safeguards the quality of medicines, including biologics. USP standards establish and articulate expectations for quality biologics and biosimilars, thereby promoting access to quality medicines. Although USP standards for biologics have unique characteristics compared with those for chemical medicines, they provide the same value by establishing trust between manufacturers, physicians, and patients. USP is developing performance-based standards that support manufacturing and analytical testing throughout the product lifecycle for biologic medicines. These

performance-based standards help pharmaceutical companies solve some of the most challenging problems they face during production, thereby facilitating innovation. To ensure that this goal is met, USP proactively engages in discussions with key global stakeholders, including regulators, industry, and patient advocacy organizations. These ongoing discussions are intended to promote alignment among all stakeholders, which is important for achieving quality medicines. Over the past several decades, USP has demonstrated the ability to work effectively across a broad range of stakeholders to build standards to address drug purity,

200 years of building trust

Resolution white paper developed by USP staff activity, and stability, while simultaneously promoting the development of next-generation therapies.

Background Biologics are complex medical products derived from living organisms. These products either treat or prevent disease. Biologic medicines have long been used to prevent infectious diseases through vaccines; biologics also are effective treatments and solutions for cancers, autoimmune diseases, and rare diseases. The number of biological products—such as recombinant therapeutic proteins, blood components, and cell or gene therapies— continue to grow faster than any other segment of pharmaceuticals. Motivation for innovation is high because these medicines often dramatically transform the quality of life for patients and address significant unmet medical needs. These therapies are also among the most expensive, which can present challenges to healthcare systems and patient access. Standardizing validated test methods and requirements to safeguard and promote access to quality medicines, including biologics, is fundamental to USP’s mission as a public health organization. USP standards help developers and manufacturers ensure the quality—in terms of purity, potency, performance and reliability—of biological products for patient safety.

A Brief History of USP Standards-Setting for Biologics Since its founding in 1820, USP has been deeply committed to meeting its responsibility of setting public quality standards that help improve public health by safeguarding the quality of medicines as well as dietary supplements, and now foods. Over time, USP compendia were continually refined to reflect scientific advancements. By 1906, USP was recognized and codified into U.S. federal law with the passage of the Pure Food and Drug Act. In 1938, USP’s responsibilities were further amplified with the enactment of the Federal Food, Drug, and Cosmetic Act (FD&C Act). Today, through staff and committee-led activities, USP actively seeks expert input from a variety of stakeholders in an open and transparent process. This process establishes and continually refines a reliable repository of trusted information in the form of USP’s standards, including monographs, performance standards1 and general chapters, all published in the U.S. Pharmacopeia–National Formulary. These standards are foundational for the quality expectations of medicines, including biologics.

USP has set standards for biological medicines since the early 20th century, in some cases predating licensure of these medicines through any of the current approval pathways. The first USP standard for a biologic was introduced in 1906 to address the quality of diphtheria antitoxin. In 1941, USP first began developing public standards for insulin by introducing monographs for naturally derived insulin. Since then, USP has created a family of 16 monographs and two general chapters related to insulin that reflect advances in manufacturing technologies and development of modified forms and novel formulations while also providing purity and potency specifications for most insulins currently marketed in the United States. This allows for quality insulin and careful titration of each dose to promote consistent, reliable long-term diabetes management and patient safety. The benefit that USP’s public quality standards provide to Americans with diabetes is just one of multiple examples of the impact of USP biologics standards.

Ensuring the Quality of Biologics The creation and advancement of biologic drugs has been staggering. Ensuring the quality of biologic drugs is a central component of increasing access to these medicines. Public standards contribute to establishing patient and provider trust in biologic medicines, including biosimilars. Whereas generic drugs are identical to the originator product (in terms of dosage form, safety, strength, route of administration, quality, and performance characteristics),2 biosimilars are not. Inherent variability in the manufacturing processes for biologics produces more variability than the manufacturing of chemical medicines. Because biosimilars must be manufactured using processes that are independently developed, the resulting complex molecule may not be identical to the reference product. For this reason, biosimilars are assessed to ensure that any differences are not clinically meaningful with regard to safety and efficacy. It is imperative to keep in mind that public quality standards for biologics do not indicate biosimilarity or interchangeability but can establish key quality parameters. Another challenge to ensuring biologics quality is the expanding global supply chain, which is increasingly fragmented and unevenly regulated. Since biologics and their ingredients (including excipients) come from a complex worldwide supply chain, before a biologic

200 years of building trust

Resolution white paper developed by USP staff medicine ever reaches the patient, multiple ingredient manufacturers, suppliers, and distributors may have participated in making, storing, and handling the product in locations across the world. Given the differences and complexity of biologic products, standards may be used to verify a specific product is not substandard or falsified. USP’s global presence and globally disseminated standards provide tools for manufacturers of biologics, including the key criteria needed to test quality at any point along the supply chain. In this way, USP standards help preserve the integrity and quality of biologics to better protect patient safety and public health.

Standards Promote Innovation Standards and innovation are linked and the relationship between the two is dynamic and continues to evolve. Sometimes a standard precedes innovation and establishes a baseline for design and performance. On other occasions, innovation becomes the foundation for new standards which takes shape as physical documentation of a proven and agreed-upon solution.

In its purest form, standardization can be a mechanism through which stakeholders disseminate technologies and knowledge that spur innovation.3 The impact of standards on innovation is nonetheless highly dependent on the level of uncertainty within an industry. Using standards in industries with very low levels of uncertainty, such as utilities, can impede innovation. 4,5,6,7 However, industries with high levels of technological uncertainty, such as pharmaceuticals (especially biologics), rely on standards for direction and a shared platform for further technological development and innovation.8 A lack of standards can also create economic barriers to production. As medical products become more complex, as with biologics, manufacturers must commit greater resources to developing them. Without public standards, the benefit–cost ratio can become dramatically imbalanced so that a manufacturer may find that it is no longer feasible to produce a specific product.9 As a result, companies may not develop biosimilar programs, which results in fewer products entering the market and ultimately fewer options for patients.

Terms of Reference Performance standards: These standards support biologics analytical testing throughout the product lifecycle, ensure and demonstrate methods and process performance, and broadly apply to product families or classes rather than specific drug substances or products. Biological products: Vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, and recombinant therapeutic proteins are all biological products; isolated from a variety of natural sources—human, animal, or microbial—they may be produced by cutting-edge technologies.

Biosimilars: These biological products are highly similar to and have no clinically meaningful differences from existing FDA-approved reference products.

Unit potency specifications: It is important to help ensure that a dose of a biologic medicine (e.g., insulin) is consistent from lot to lot and manufacturer to manufacturer.

Critical storage and distribution requirements: To help prevent medicine degradation, storage and distribution requirements must be met.

Safeguards for impurities: Manufacturers rely on these safeguards to control the presence of substances beyond acceptable thresholds, which can render a medicine ineffective or subject a patient to bacterial infection, toxicity, or with cumulative exposure, possible illnesses such as cancer.

200 years of building trust

Resolution white paper developed by USP staff USP recognizes that the complexity and variability of biologics present challenges for manufacturers. However, that complexity is the most persuasive argument for developing public standards for biologics: standards are needed to guide industry stakeholders in assessing risk. As increasing complexity makes decisions more difficult, standards allow the industry to coalesce around critical quality issues related to a productâ&#x20AC;&#x2122;s manufacturing process and to determine if it is fit for purpose.10 This aspect of public standards should not be underestimated given how pharmaceutical manufacturing is reliant on the quality of global supply chains.

Current USP Efforts in Biologics Biologic medicines offer lifesaving and life-sustaining treatments to patients, often for diseases where no effective conventional medications are available. To promote development of these important therapies, USP is developing standards that are broadly applicable across biological products and deliver solutions to address the quality of raw materials. USP is also developing performance standards that support manufacturing and analytical testing throughout the product lifecycle. Currently, there are more than 200 USP monographs and general chapters applicable to biologics.11 These standards address the quality of a wide swath of product classes, including peptides, bloodderived therapies, recombinant proteins, cell and tissue products, glycosaminoglycans and carbohydrates, and vaccines. As with all its standards-setting activities, USP helps advance the biologics field in a collaborative fashion with key stakeholders including academia, professional associations, and regulatory and industry representatives. This approach promotes alignment and clearly identifies appropriate use. These proactive discussions take into consideration the impact, relevance, approach, and implementation pathways for the standards being developed. Doing so may promote and facilitate innovation in product development. USP engages these stakeholders through its Expert Committees, a variety of educational workshops, roundtable meetings, and the Pharmacopeial Forum.12 These activities represent an essential component in advancing performance-based standards for biologic products. This collaborative approach allows USP to determine which biologic standards should be prioritized based on their potential for greatest usefulness and

impact. USP has stated publicly that it will not develop new product-specific monographs for biologics without the support of stakeholders, including industry and the U.S. Food and Drug Administration. In tandem, USP has been able to build staff expertise as well as a supporting laboratory network and key enabling collaborations with other standards-setting organizations globally to maximize impact by avoiding duplicate efforts and complementing existing efforts. In the next five years, USP will continue to devote resources to evaluate, modify, and create performance and other quality standards to help accelerate the burgeoning field of biologics, which encompasses cell and gene therapy, gene editing, and mRNA-based therapies, among other emerging approaches.13 For example, cell and gene therapies represent one area of advanced biologics where USP developed early and timely standards. To support this work, USP added the required expertise within its expert volunteer bodies, and the result of this focus has produced several general chapters with test procedures for cell and tissue-based products. As USP embarks on strategic planning for the next five years, the organization relies on its expert volunteers and scientific staff to continually develop and refine expertise relevant for an increasingly complex portfolio of standards.

Alignment with USP Mission USP standards are central to promoting patient safety, public health, access to quality medicines, and innovation. During the previous five-year cycle, USP prioritized modern, relevant standards that would broadly support the quality of medicines throughout the product lifecycle. Over the course of the next five years, USP will be committed to ensuring that its approach evolves with the science of biologics and the needs of stakeholders, including patients, practitioners, industry, and regulators. USP will continue to prioritize its portfolio of standards based on impact, technology, and regulatory considerations. This will provide a pathway for quality-assured medicines, and public health, by promoting broad access to biologics. USP standards provide the public with access to biologics in important ways. The general requirements delineated in the USP general chapters, as well as the existing monographs, provide the expectations for quality biologics, thereby allowing a manufacturer, regulator, or other interested party to test quality at any

200 years of building trust

Resolution white paper developed by USP staff point in the supply chain. Furthermore, USP performance standards are intended to support the development of analytical methods and new manufacturing methods, with a goal of facilitating the development of biologics as well as biosimilars as critical medicines needed to reduce the cost of these therapies. Lower costs promote broader access for patients with life-limiting or chronic diseases. The evolution of, availability of, and adherence to public and transparent quality standards will build patient and healthcare practitioner confidence in biologics.

Resource Assessment Additional resources required to supplement resources that are currently in place. Several biologics performance standards have been, or are, in the standards development process currently. To meet stakeholder need, additional investment is required to support product development and to help ensure quality in this exploding category of medicines.

References and Notes 1 USP. What are biologics performance standards. 2020 Jan. Available from: https://www.usp.org/biologics/performance-standards. 2 FDA. Generic drug facts. 2018 Jun. Available from: https://www.fda.gov/drugs/generic-drugs/generic-drug-facts. 3 Friedrich J. Making innovation happen: the role of standards and openness in an innovation friendly scosystem. In: 7th International Conference on Standardization and Innovation in Information Technology (SIIT). IEEE. 2011 Sep 28–30; Berlin, Germany. doi:10.1109/ SIIT.2011.6083609. 4 Blind K. Driving forces for standardization at standardization development organizations. Appl Econ 2002 Nov;34(16):1985–98. doi:10.1080/00036840110111158.

5 Blind K. The impact of standardization and standards on innovation. Manchester, UK: Manchester Institute of Innovation Research; 2013 Nov. Working Paper 13/15. Prepared for Compendium of Evidence on the Effectiveness of Innovation Policy Intervention Project, a project of Nesta. Available from: https://media.nesta.org.uk/documents/the_impact_of_standardization_and_standards_on_innovation.pdf.

6 Blind K, Jungmittag A, Mangelsdorf A. The economic benefits of standardization: an update of the study carried out by DIN in 2000. Berlin: Deutsches Institut für Normung e.V., the German Institute for Standardization; 2011 Jun. Available from: https://www.din.de/ blob/89552/68849fab0eeeaafb56c5a3ffee9959c5/economic-benefits-of-standardization-en-data.pdf 7 Blind K, Petersen SS, Riillo CAF. The impact of standards and regulation on innovation in uncertain markets. Res Policy 2017 Feb;46(1):249–64. doi:10.1016/j.respol.2016.11.003.

8 Dyer J, Furr N, Lefrandt C. The industries plagued by the most uncertainty. Harvard Business Review. 2014 Sep 11. Available from: https://hbr. org/2014/09/the-industries-plagued-by-the-most-uncertainty. 9 von Koeckritz K. Generic drug trends—what’s next? Pharmacy Times 2012 Apr 11;(1):53–55. Available from: https://www.pharmacytimes.com/ publications/issue/2012/april2012/generic-drug-trends-whats-next9 Allen RH, Sriram RD. The role of standards in innovation. Technol Forecast Soc 2000; 64(2–3):171–81. 10 Ibid. 11 Williams RL, Bristow AF, Hauck WW, Srinivasan VS, Morris T, Atouf F, Ambrose M, Surendranath KV, Chakrabarty R, Menon K. Role of public standards in the safety and efficacy of biologic medicines. AAPS J. 2014 May;16(3):516-521. doi:10.1208/s12248-014-9586-7.

12 Pharmacopeial Forum is a free bimonthly online journal in which USP publishes proposed revisions to USP–NF for public review and comment. New issues are posted online every two months at the beginning of the month.

13 Adapted from a Resolution proposal submitted by Joseph Laning, Astellas.

200 years of building trust

Proposed Resolution

Innovation

Resolution white paper developed by USP staff, with input from the Council of the Convention

Resolution white paper developed by USP staff

Proposed Resolution 5

Innovation

USP will explore the development of quality standards or other fit-for-purpose solutions to help stakeholders safeguard the quality of promising healthcare innovations that address patient and public health needs. Summary The biomedical innovations of today and tomorrow offer enormous promise for patient care. Given the accelerating pace of transformation in drug development and manufacturing, therapeutic modalities, and healthcare practicesâ&#x20AC;&#x201D;coupled with the increasing complexity of therapies being administered to patientsâ&#x20AC;&#x201D;USP has built a framework to explore and implement new and flexible approaches in standards development for emerging innovations. Recognizing that there are numerous organizations developing standards for innovative medicine modalities, USP is seeking to partner, when appropriate, to help fill gaps while leveraging its own capabilities to generate standards that support both product development and

quality assurance. Some of this work is accomplished through the USP Research & Innovation (R&I) function, which was formed as a result of a 2015 Resolution; R&I undertakes a careful vetting and incubation process to explore promising healthcare innovations relevant to USP capabilities. Additionally, USP staff within Program Unit Teams scan the innovation horizon in biologics, chemical medicines, excipients, foods, and healthcare quality. This Resolution proposes that USP continue to seek opportunities to leverage its expert volunteer and staff resources, along with its convening power, to build standards that support product development and build trust in these promising innovations.

200 years of building trust

Resolution white paper developed by USP staff

Background Across the 200 years of USP’s history, there have been significant therapeutic advancements in healthcare and drug development. In many of these, USP standards have played a role in fostering innovation and building trust. Today, medicines are becoming ever more complex, and their therapeutic effect is increasingly mediated by medical devices that deliver them or as enhancements to chemical therapeutics (e.g., to promote medicine adherence or to predict or avoid adverse effects). In addition, new manufacturing approaches are changing the way some medicines are produced, thereby changing the mechanisms by which their quality is assured and sometimes creating new product quality challenges. Finally, new approaches are changing how medicines are targeted and administered to specific patients through personalized medicine. Historically, USP has developed or adapted standards in response to changes in healthcare, drug development, or manufacturing. In 2015, the USP Convention Membership recognized the need to formalize this role by adopting a Resolution to “cultivate a robust research and innovation culture and operationalize a function within the organization to continuously assess new technologies and capabilities relevant to its standardssetting activities and to identify, prioritize, evaluate, and develop new opportunities that respond to the needs of USP’s stakeholders and further its mission.” This gave rise to USP’s Research & Innovation (R&I) function as well as to concerted efforts within all functional areas across the organization. Meanwhile, the foundation of USP’s work is to foster public trust in medicines, dietary supplements, and foods through standards that establish quality specifications, which are informed by scientific evidence. USP standards, both new and revised, help to build trust in medicines and can also facilitate innovation. In some cases, USP standards provide a useful starting point for new drug development. USP standards also help foster the development of new and generic medicines that promote widespread availability and access to generally more affordable quality medicines. Over time, new analytical technologies have arisen, and USP has embraced them to improve approaches for assessing the quality of medicines. As a standards-setting organization, USP is committed to working with stakeholders to build trust in healthcare

innovations by developing new standards and other fitfor-purpose solutions for these products as appropriate. For example, the rise of pharmacogenomics techniques in recent years has facilitated personalized medicine; early indications suggest that this could improve the quality and safety of medications prescribed to patients. To promote innovation and foster trust in these technologies, USP standards could inform the implementation of personalized medicine strategies such as pharmacogenomics. By extension, USP standards could establish trust in pharmacogenomics and thereby encourage greater use among key healthcare functions such as laboratory testing, drug information, and integration into electronic medical records.1

Creating a Culture of Innovation USP is committed to fostering an environment that continues to promote innovation. Looking forward, innovation is driving several emerging shifts affecting medicines and healthcare, requiring USP to evolve its thinking on standard setting. • Medicines are becoming increasingly complex: In multiple ways—including how medicines are produced; their degree of personalization to specific patient populations or individuals; and how they are combined with other therapies, medical devices, or software—the medicines of tomorrow are more complex and will require new approaches to help ensure their quality. • Healthcare is increasingly digitized: Every aspect of a medical product’s development, manufacturing, distribution, prescribing, administration, and pharmacovigilance is going through a rapid digital transformation. Like nearly every other industry, healthcare has a plethora of new digital tools that can be used to monitor, analyze, and react to events captured in ever-increasing data streams. Combined with the advent of purely digital solutions—such as digital therapeutics and the infiltration of artificial intelligence throughout many facets of healthcare— this may require entirely new types of standards to help ensure quality. • Supply chains are increasingly global: The supply chains for medicines have become tangled webs that cross numerous national borders. Ensuring the strength, integrity, and transparency of these complex supply chains will require new ways of thinking and collaborating around traceability for products and their ingredients.

200 years of building trust

Resolution white paper developed by USP staff • Paradigms are shifting in manufacturing: From the burgeoning interest in continuous manufacturing to the emergence of on-demand 3D-printed dosage forms, pharmaceutical manufacturing is evolving in ways that require USP to understand and adapt to these trends.

USP encourages a culture of innovation throughout the organization in all areas and activities, with distinct yet overlapping approaches. The USP Research & Innovation (R&I) function explores emerging trends and technologies and helps foster a culture of innovation by strengthening the supporting infrastructure across USP, thereby accelerating the generation of novel ideas including those proposed by staff and expert volunteers. Additionally, Program Unit Teams across USP pursue innovation in their respective disciplines. USP’s Research & Innovation Function The vast array of innovations in healthcare practices and technologies means that USP must prioritize its work across the biomedical innovation landscape. Research & Innovation (R&I) explores emerging technologies and trends likely to impact industry, particularly the use of USP’s quality standards, or the way USP develops them. R&I operates in two ways: first, it makes a set of tools available to the rest of USP to foster innovation and continuous improvement of standards-setting activities; second, R&I systematically investigates new scientific and technological opportunities. R&I has become vital to USP. In the past five years, this division has grown from a

concept on paper to a team of more than a dozen full-time staffers scanning for new ideas and shepherding them through the R&I project lifecycle (see box on page 4). R&I does not develop standards directly. Its approach is to conduct research on topics that may enter the regular USP public process for standards-setting, at a later point. R&I’s systematic process aims to uncover trends that will enable the development of quality standards or their utilization in new modalities for drug manufacturing or delivery. The overarching goal is to ensure quality outcomes for the next generation of medical products and technologies through internal research and early collaboration with external organizations. Aligned to the innovation-driven shifts described in the previous section, the R&I pipeline has a dynamic portfolio of projects designed to better understand and adapt to evolving trends in product quality assurance, analytical methods, production and distribution, and informatics. A few examples from this portfolio are described below: • Proof of Concept in Product Quality Assurance – Digital Therapeutics: Digital therapeutics is an evolving and rapidly growing industry. In recent years, the U.S. Food and Drug Administration (FDA) has approved several digital therapies to treat substance use disorders, type 2 diabetes, respiratory disease, schizophrenia, and other disorders. At the request of stakeholders from the digital therapeutics industry, R&I is exploring how USP may play a role in ensuring the quality of these new modalities

R&I Project Lifecycle Ideation: The first step is to identify, collect, or catalyze initial technology ideas and trends—using horizon scanning, crowdsourcing, and stakeholder outreach—that may impact USP or the industry.

Concept Note: The second step is to begin outlining key technologies and trends to assess the potential need and fit for a Proof of Concept.

Proof of Concept: The third step is to identify potential implications, risks, and opportunities (for industry and USP) and develop an incubation plan, as warranted.

Incubation: The fourth step is to dedicate time and personnel to test hypotheses, generate evidence, or prototype products relating to emerging technologies or trends (helping crystallize the case for incremental USP investment and adoption) and propose an operating model and scale-up plan. Organizational Adoption: The final step is to commit to and invest in select projects to build necessary capabilities and initiate the appropriate public standards-setting process.

200 years of building trust

Resolution white paper developed by USP staff of medicines and how USP’s definitions of quality and quality attributes may be applied to digital therapeutics. USP may develop quality standards that address digital therapeutic product design, manufacture, and verification. Such standards would inform product manufacturers, regulators, clinicians, and end users as they work to develop, evaluate, or deploy digital health technologies.2 Through its proof of concept project for digital therapeutics, R&I has worked with stakeholders to examine and understand how standards for digital solutions are currently developed, and how USP’s involvement could help meet patient and public health needs for medical products they can trust, regardless of the mode of delivery (e.g., chemical, digital).3 • Incubated Project in New Analytical Technologies – qNMR: Although nuclear magnetic resonance (NMR) has been used for many years, it has required expensive instruments and significant expertise. Recent advances in hardware and software have brought the cost down substantially and reduced the organizational burden of NMR instruments to levels that are comparable to other, more widely used analytical methodologies. This represents a significant opportunity because NMR is a primary technique that allows identification of known molecules as well as determination of the relative concentrations of known and unknown molecules in complex mixtures. Given the inherent advantages of NMR over other analytical methods, R&I is exploring whether quantitative NMR (qNMR) may enable the use of quality assurance tests that are faster and easier to perform. • Organizational Adoption in Production and Distribution – Continuous Manufacturing: Pharmaceutical manufacturing is typically done as a batch process, which involves multiple starts and stops during production. Work-in-progress materials may be stored for periods of time and may be shipped to other facilities for finishing. Eventually, the process concludes when the finished product is tested; the results determine whether the batch is released to the marketplace. Continuous manufacturing changes all of that. Medicines are produced in a single, continuous process that runs from beginning to end without interruption or intermediary steps. As the product is made, quality is assessed in-line using a validated process. FDA is developing regulations for continuous manufacturing, and industry is increasingly adopting the approach because of

its advantages. As this adoption accelerates, USP needs to ensure that its physical and documentary standards are ready and in place. As such, USP has made a significant investment in building a Continuous Manufacturing Team that collaborates with USP colleagues as well as academic, industry, and others involved in this space.

Innovation within USP Program Unit Teams In every area of the organization, innovative ideas are raised, fostered, and moved forward to help USP improve public health through standards and related solutions that ensure the quality and safety of medicines and foods. Examples of innovation from USP Program Unit Teams include the following: • Biologics: USP has launched standards-setting initiatives around components used in the manufacture of emerging therapies such as gene therapies and mRNA-based therapies. By providing tools to control the quality of ingredients and other components (e.g., enzymes, vectors) in these products, USP is helping to bring a new class of medicines to patients. USP Biologics also develops best practices and standards to control the level of trace elements in cell culture media, thereby supporting the streamlining of bioprocesses and enabling critical steps in a common component of biologics manufacturing. • Excipients: USP has developed standards for more than 150 excipients used in approved products; these quality standards are utilized by both regulators and industry, thereby supporting innovative drug development. To further facilitate drug innovation, USP also created a pathway to introduce novel excipients in the productdevelopment pipeline. Additionally, USP is creating standards for complex polymeric excipients used in controlled-released and parenteral dosage forms. This will help manufacturers in characterizing and selecting the right excipients for the intended use. • Foods: USP supports innovation by creating Identity Standards for complex and variable agricultural products such as honey and olive oil, as well as emerging ingredients such as plant-derived protein isolates. These standards will help ensure the integrity of the supply chain for products that are highly vulnerable to fraud and adulteration. • Healthcare Quality and Safety (HQS): USP has developed a mobile application called <800>

200 years of building trust

Resolution white paper developed by USP staff HazRx® that healthcare practitioners can use to identify a hazardous drug; the app also provides the safe handling guidance outlined in USP General Chapter <800>. This solution also is available as <800> HazRx® DataSet, which can be integrated into the electronic systems and workflows used by healthcare institutions (e.g., hospitals). HQS continues its commitment to patient and healthcare worker safety through innovation and development of standards and other fit-for-purpose solutions that can be integrated into healthcare digital environments.

Alignment with USP Mission For two centuries, USP has met its public health mission by leveraging its capabilities and standards setting across nearly every area of biomedical innovation. Given the abundance of opportunity for new medicine modalities and manufacturing advances, the opportunity

to develop standards to support product development and quality assurance is enormous and will also yield exponential advances to patient care and public health. Pursuing these opportunities is at the core of USP’s purpose.

Resource Assessment Additional resources required to supplement resources that are currently in place. A USP Research & Innovation (R&I) function was established in the current USP cycle. To keep pace with biomedical advances, we will continue to explore ways to meet stakeholder need for standards. Additional resources will be required as opportunities move from exploration, to incubation, to standards development, to utilization among stakeholders. This work is undertaken with close engagement of stakeholders, through resources that are in place across the USP organization.

References and Notes 1 Adapted from a Resolution proposal submitted by James Hoffman, St. Jude Children’s Research Hospital. 2 Adapted from a Resolution proposal submitted by Megan Coder, Digital Therapeutics Alliance. 3 Adapted from a Resolution proposal submitted by Megan Coder, Digital Therapeutics Alliance.

200 years of building trust

Proposed Resolution

Digital Transformation of Standards Resolution white paper developed by USP staff, with input from the Council of the Convention

Resolution white paper developed by USP staff

Proposed Resolution 6

Digital Transformation of Standards

USP will create interoperable digital solutions that leverage USP data and standards to improve public health through global access to quality medicines. Summary At its core, USP is a scientific organization that gathers, distills, and disseminates information to improve public health, support access to quality medicines, protect patient safety, and foster innovation. A critical goal has always been to ensure that the information gathered reflects the most robust and current science. The next step, distillation, requires analysis of the information gathered, which is traditionally accomplished through deliberative, transparent processes conducted by USPâ&#x20AC;&#x2122;s Expert Committees. Dissemination of information occurs primarily through publication of USP standards. It also occurs through training, scientific exchanges, advocacy, and capability building throughout the world. Although these approaches will continue, with this proposed Resolution USP aims to address the digital needs of its stakeholders. Increasingly, the environments in which USP

standards are used are becoming automated and digital. In addition, interactions between patients and providers, manufacturers and distributors, and other stakeholders with each other increasingly occur over digital platforms. To address this shift, this Resolution aims to advance the tradition of gathering, distilling, and disseminating highquality information by enabling USPâ&#x20AC;&#x2122;s content to be more seamlessly used in automated, digital environments. The Resolution proposes that during the next five years, USP will begin to augment and transform its existing compendia of standards with digital, interoperable components to support the people and systems that rely on the information in USPâ&#x20AC;&#x2122;s compendia. Although USP has always aimed to advance scientific knowledge through its standards, it must now also make that knowledge accessible to automated systems that are increasingly used in all aspects of life

200 years of building trust

Resolution white paper developed by USP staff sciences. Availability of machine-readable content and services will allow users to access USP content through digital platforms to help enhance drug development, quality assurance of medicines, formulary design, and even the preparation and use of compounded drug preparations.

Background Digital transformation is a pervasive global trend that is impacting virtually all industries and sectors, including the pharmaceutical industry and healthcare. For example, manufacturing of many products, including pharmaceuticals, is undergoing a shift known as Industry 4.0, which is characterized by the presence of sensors and automated systems that generate and consume massive amounts of data about the equipment and products on the line to manage quality and efficiency. Similarly, digital transformation across healthcare has led to innovations such as electronic medical records (EMRs), telemedicine, and digital therapeutics. Many of these innovations create, utilize, or exchange vast amounts of data involving multiple computer systems, providers, or even patients. In addition, health-related data are now generated outside the clinical environment on a daily basis—for example, via apps, wearable devices, and medications with sensors—and this information is reported back to patients, providers, pharmacists, and others. These data can include sensitive or private information at the individual level, such as genetic profile, medications, lab reports, vital signs, and social determinants of health. Taken together, these data can inform individual diagnosis or treatment, reveal population health trends, provide clinical insights, and signal safety and quality concerns. Given the vast volume of data spanning multiple categories, USP standards should be integrated into the healthcare ecosystem to promote the quality and delivery of medicine as well as patient safety. Developing and translating standards to be machine readable will require consideration of a continuum of options ranging from digital versions of previously printed materials to innovations such as applications that can derive and communicate new insights from accumulated data. To have a positive impact on public health, the information within this ecosystem needs to present USP content clearly, reflect the most up-to-date science and technology, provide interoperability across platforms, and consistently be of high quality.

Digitizing Standards Meaningful engagement in informatics and digital transformation will enable USP to positively influence the data ecosystem. By leveraging its scientific knowledge and technical skills, USP can facilitate quality-enhancing developments by expert volunteers, USP staff, and others.

Doing so will maximize the public health impact of USP standards. USP’s approach to the digitization of standards will transform its existing compendia of standards into digital, interoperable components that support the people and systems that rely on information contained therein. As part of this commitment, USP is creating a Health IT Expert Committee for the 2020–2025 cycle. The specialized knowledge and experience of USP expert volunteers will be essential in the creation of interoperable, digital standards that can be used across health IT implementations. Digitizing USP standards includes creating digital versions of existing print resources, such as general chapters, monographs, and other data assets. Much of this work has already begun, and in some cases, it is finished. An example is the complete, successful transition from print to digital for the U.S. Pharmacopeia–National Formulary (USP–NF), which houses USP general chapters and monographs. The creation of digital versions is only one part of the work involved in digitizing USP standards. Also involved is the standardization of format (syntax) and meaning (semantics) to allow computer systems to communicate with one another effectively and unambiguously. In addition, standardization includes the creation of conceptual domains and correct contexts (e.g., “mobile phase,” or “Baclofen Compounded Oral Suspension”) that can be uniquely identified by machines via databases or uniform resource locators (URLs) on the internet. For example, digital versions of USP monographs could be made available to vendors for integration with their instruments to help customers execute USP-described assays. In other words, a USP end-user’s instrument, in industry or a regulatory agency, could verify that the scientist is utilizing the right equipment and procedure to conduct a specific quality assay.

USP Digital Solutions To support the transformation of USP data assets into digital forms, USP’s Informatics and Digital Solutions Development (i-DSD) framework provides the healthcare community with translational products to advance health and healthcare. The i-DSD framework aims to provide machine-readable services and solutions for healthcare practitioners and pharmaceutical manufacturers. It also aims to build services around USP and United States Adopted Names (USAN) nomenclature; these services are needed throughout the lifecycle of drug manufacturing, labeling, prescribing, dispensing, and post-marketing surveillance. To date, USP has developed several solutions in digital environments and systems that manage drug information, clinical decision support, and formulary design. USP Digital

200 years of building trust

Resolution white paper developed by USP staff Solutions are typically derived from the standards-setting activities advanced by its Expert Committees. Examples include the following: • USP Compendial Nomenclature Dataset: This cumulative dataset of USP nomenclature for active pharmaceutical ingredients (APIs) and excipients is integrated into the RxNorm vocabulary (see below). • USP <800> HazRx® Drug Classification: Institutions and organizations can use this dataset to identify hazardous drugs and provide handling instructions to their personnel per established standards such as USP <800>. • USP <800> HazRx® Mobile App: Individual healthcare workers can use this app to identify hazardous drugs and access handling instructions per established standards such as USP <800>. • USP DC Alignment File: This tool allows formulary managers to map and compare disparate formulary submissions to the USP Drug Classification. • USP MMG Alignment File: Regulators and formulary managers can use this tool to map Medicare Part D sponsor plans to a minimum baseline of drugs in the USP Medicare Model Guidelines.

To further the efforts toward interoperability enhancement across the drug supply chain, USP has joined the Allotrope Foundation, a consortium of pharmaceutical manufacturers, lab instrumentation vendors, and software solution providers focused on development of standards

that can be used to represent lab instrumentation data such as results from high-performance liquid chromatography, mass spectrometry, and other techniques. The Allotrope Foundation’s focus on scientific reproducibility, digital integration, and data integrity complement and align with USP’s efforts to digitize standards that can integrate into laboratory information management systems (LIMS), electronic lab notebooks (ELNs), chromatography data systems, and other digital systems used in pharmaceutical manufacturing.

Nomenclature Alignment USP’s critical role in establishing drug nomenclature was formalized with the passage of the Federal Food, Drug, and Cosmetic (FD&C) Act of 1938. In the United States, unless the U.S. food and Drug Administration (FDA) has designated an official nonproprietary name for a drug by notice and comment rulemaking under FD&C Act section 508, the compendial (i.e., USP) name will apply. Per the FD&C Act, any drug with a name recognized in USP–NF must comply with compendial identity standards or be deemed adulterated, misbranded, or both. The USP Nomenclature Expert Committee approves the titles for USP drug product and drug substance monographs each month, and these names become the required nomenclature to be used on drug labels. One of the challenges with digitization of standards across the multitude of systems is the variation in the way that data are organized and understood. Differences between humans and machines in how they interpret the same

Nomenclature Standards ASAP: American Society for Automation in

HL7 FHIR: A standard designed by Health Level

Pharmacy (ASAP) standards are used to report drugs dispensed to prescription drug monitoring programs.

7 (HL7), Fast Healthcare Interoperability Resources (FHIR) aims to provide interoperable exchange of healthcare-related information across the continuum of care.

RxNorm: A resource from the National Library of Medicine (NLM), RxNorm provides normalized names for clinical drugs and links its names to many of the drug vocabularies commonly used in pharmacy management and drug interaction software.

SNOMED CT: A systematically organized,

NCPDP Script: A standard created by the National Council for Prescription Drug Programs (NCPDP), NCPDP Script facilitates the transfer of prescription data among pharmacies, prescribers, intermediaries, facilities, and payers.

computer processable collection of medical terms, SNOMED CT provides codes, terms, synonyms, and definitions used in clinical documentation and reporting.

200 years of building trust

Resolution white paper developed by USP staff data could result in patient harm. USP is exploring the creation of standards, models, and reference data that aim to mitiga te the public health risk and patient safety issues caused by missing or non-standardized data or architecture.1 USP will seek to align these standards with existing vocabulary and messaging standards in use today, such as ASAP,2 RxNorm,3 SNOMED CT,4 HL7 FHIR,5 and NCPDP Script6 (see box on page 4). Recently, USP collaborated with the National Library of Medicine (NLM) to integrate USP Compendial Nomenclature into RxNorm. This resource provides normalized names for clinical drugs and links drug names to many of the drug vocabularies commonly used in pharmacy management and drug interaction software. NLM is the central coordinating body for clinical terminology standards within the Department of Health and Human Services (HHS). The inclusion of USP Compendial Nomenclature in RxNorm will help ensure that compendial drug names used on manufacturer labels are preserved when used in digital environments. Apart from the need for consistent nomenclature for FDA-approved drugs in electronic systems, there are other areas where standardizing nomenclature is critical for patient safety. For example, consistency in the way drug allergies and intolerances are documented and transferred among different EMR vendors may help reduce the risk of patients being prescribed a drug that they cannot tolerate.7 In addition, standardized nomenclature for compounded drug preparations is essential for vulnerable populations such as pediatric patients who may not be able to tolerate a commercially available FDA-approved drug product. As we look to the future, standardized reporting of genetic testing results for how a patient metabolizes a drug (i.e., pharmacogenomics) at the point of care may help prevent a supratherapeutic or subtherapeutic dosing error.8

Alignment with USP Mission Enhanced focus on and commitment to the rapidly evolving and increasingly meaningful digital realm is an existential step for USP. The organization seeks to positively impact public health goals associated with enhanced interoperability across the healthcare continuum to safely and securely connect patients, providers, manufacturers, distributors, and others across digital platforms. Transforming standards into interoperable, digital components of the healthcare ecosystem is essential to promote patient safety through the delivery of quality medicine. Through resources such as the Informatics and Digital Solutions Development (i-DSD) framework, USP helps build capabilities with translational products to advance health and healthcare. Adopting this Resolution will inevitably result in standards and related data-centric services that will be new to USP stakeholders. To deliver upon the scope of the Resolution, USP must ensure the standards-setting process can accommodate the rapidly evolving world computational informatics. USP must also develop or otherwise support data services that meet stakeholder needs across USP nomenclature, pharmaceutical, and healthcare informatics platforms that align and complement USP standards.

Resource Assessment Additional resources required to supplement resources that are currently in place. Several efforts are currently underway, many of which will move forward through by the Health IT Expert Committee that will be established within the 2020–2025 expert committee structure.

References and Notes 1 Adapted from a Resolution proposal submitted by Tiffany Chan, USP. 2 asapnet.org [Internet]. Blue Bell, PA: American Society for Automation in Pharmacy; c2010 [cited 2020 Jan 31]. Available from: https://www.asapnet.org/. 3 Unified Medical Language System® [Internet]. Bethesda, MD: National Library of Medicine; c2019 [cited 2020 Jan 31]. Available from: https://www.nlm.nih. gov/research/umls/rxnorm/index.html. 4 snomed.org [Internet]. London: SNOMED International; c2020 [cited 2020 Jan 31]. Available from: https://www.snomed.org. 5 Fast Healthcare Interoperability Resources [Internet]. Ann Arbor, MI: Health Level 7; c2019 [cited 2020 Jan 31]. Available from: https://www.hl7.org/fhir/ overview.html. 6 National Council for Prescription Drug Programs [Internet]. Scottsdale, AZ: NCPDP; c2009–2018 [cited 2020 Jan 31. Available from: https://ncpdp.org/ Standards-Development/Standards-Information.

7 Adapted from a Resolution proposal submitted by Shelly Spiro, Pharmacy HIT Collaborative. 8 Adapted from a Resolution proposal submitted by James Hoffman, St. Jude Children’s Research Hospital.

200 years of building trust

Proposed Resolution

Education and Training for Industry and Healthcare Practitioners Resolution white paper developed by USP staff, with input from the Council of the Convention

Resolution white paper developed by USP staff

Proposed Resolution 7

Education and Training for Industry and Healthcare Practitioners

USP will build and strengthen capabilities fundamental for industry and healthcare practitioners to utilize USP standards through efficient, effective, and measurable education and training programs. Summary USP’s mission is to improve global health through public standards and related programs that help ensure the quality, safety, and benefit of medicines, dietary supplements, and foods. To fulfill this mission, USP engages with stakeholders—including industry and healthcare practitioners—through educational outreach that helps them learn, integrate, and leverage USP standards into their practices correctly and consistently. USP offers education and training programs through a variety of formats, including in-person and online attendance, as well as a variety of venues, such as universities, USP sites, and stakeholder sites. This Resolution proposes that USP update and expand offerings as needed and in a timely manner. As part

of this Resolution, USP will develop a prospective measurement plan to continually assess registration for and evaluation of its programs. Based on these data, USP will adapt existing programs or create new programs that reflect the evolving needs of industry and healthcare practitioners. To meet these goals, USP already has expanded its pool of instructors, increased the number of trainings available, established modulebased courses so they can be tailored to attendee needs, and expanded the ways in which trainings are delivered, such as embedded in university curricula. This proposed Resolution aligns with USP’s ambitions to expand impact by providing scalable tools to support capability building across a broader audience than is currently reached.

200 years of building trust

Resolution white paper developed by USP staff These efforts will help ensure the intended impact of USP standards through their correct adoption and consistent use. Furthermore, USP education and training provides an opportunity to engage the next generation of stakeholders and volunteers earlier in their careers through university curricula.

Background The development and production of quality medicines, dietary supplements, and food ingredients depend upon a relentless pursuit of characteristics, systems, and requirements necessary for attaining quality. Standards provide guidelines for consistently reaching these requirements and characteristics through the use of appropriate systems. In other words, standards are the foundation of quality assurance. In todayâ&#x20AC;&#x2122;s rapidly evolving, global medicines supply chain, effective quality assurance requires education and training for current and future professionals in the pharmaceutical industry and healthcare arena. Industry personnel and healthcare practitioners, such as manufacturers and pharmacists, continually need ways to acquire new knowledge and skills in quality assessment. The knowledge and skills are necessary to comply with evolving regulatory standards and align with quality assurance across the medicines supply chain. By doing so, industry and healthcare practitioners are positioned to deliver the quality medicines and care to patients. Furthermore, new scientific approaches and medical products also lead to new training requirements. For example, industries that have traditionally manufactured solid oral dosage forms are moving toward complex generics such as injectables and drugâ&#x20AC;&#x201C; device combination products. This, too, requires industry and healthcare practitioners to develop new skills in quality assurance. USP has provided continuing education and training for industry and healthcare practitioners since 2000. Over the past twenty years, more than 63,000 trainees have attended trainings on the effective use of USP standards. In 2019 alone, USP Education offered 155 courses to more than 6,700 trainees. The content of USP education and training curricula covers a wide range of topics, including pharmaceutical products and active pharmaceutical ingredients, biologics, healthcare quality and safety, dietary supplements and herbal medicines, excipients, current good manufacturing practices, regulatory systems strengthening, and USPâ&#x20AC;&#x2122;s General Notices.

Developing and Delivering Education and Training in Quality USP Education provides courses and training programs year-round about how to effectively interpret and apply USP quality standards. The scientists and other experts who help develop USP standards that are used worldwide also help create the course curricula and materials offered through USP Education. Courses are presented by approved instructors with practical, first-hand knowledge of the subject area and related standards. The insights shared in the courses not only facilitate implementation and use of USP standards, but also connect trainees to an independent, nonprofit scientific body with the goal of creating a strong foundation for a healthier world. USP is continually evolving and expanding its training to new sites, new formats, and new topic areas. Courses are presented in classrooms and laboratories at USP sites in the United States, Brazil, China, Ghana, and India, as well as in person at customer sites in more than 37 countries. USP works with manufacturers (including local suppliers) throughout the world, as well as academia and other stakeholders, to increase access to training and education related to medicines quality. To demonstrate its commitment to support manufacturers in building capabilities to achieve international quality standards and excellence in manufacturing, USP launched the USP Training Institute in Hyderabad, India, in 2018. The Training Institute has offered intensive, application-driven, hands-on training in quality control, quality assurance, and research and development for new pharmaceutical professionals and recent graduates. Additional courses for pharmaceutical professionals across functional disciplines will be offered over time. As with all USP Education offerings, students at the Hyderabad institute have access to world-class faculty and state-of-the-art facilities and instrumentation. Courses are developed by USP scientists and are based on modern techniques used in industry and their applications, interspersed with current, relevant case studies. The content is delivered using a sophisticated platform to enhance engagement and retention. This platform has pre- and post-class components designed for use on smartphones to expand learning opportunities beyond the classroom.

200 years of building trust

Resolution white paper developed by USP staff Beyond the physical classroom at sites around the world, USP Education offers trainings online via webcasts, webinars, and other forms of eLearning. Participants have access to live online programs, such as “Performance Verification Test: Apparatus 1 and Apparatus 2” and “USP Certificate of Pharmacopeial Quality Assessment.” Self-paced online education is available as well, and includes courses on biologics, chemical medicines, dietary supplements and herbal medicines, dietary supplement verification, excipients, food ingredients, regulatory systems strengthening, and healthcare quality standards (HQS). In the area of HQS eLearning, self-paced courses are offered on handling hazardous drugs and compounding. Role-specific modules are developed for entire hospitals, minimizing staff time away from their duties and allowing training participants to receive training specific to their responsibilities. Existing modules have been designed to meet the needs of institution leaders, compounding professionals, clinical licensed personnel, and general healthcare personnel. USP Education assesses course content and the delivery of trainings to ascertain the course’s effectiveness and make improvements as needed. USP gathers student feedback after each course and tracks scores for courses and instructors. Overall, students express high rates of

satisfaction with training content and instructors. USP Education will seek ways to capture additional data on the utility and value of its trainings, including whether trainees have implemented what they learned. These findings will guide USP in refining or expanding courses.

Scaling Up Sustainably and Economically Efforts to expand education and training for industry and healthcare practitioners align with USP’s overall strategy to broaden its impact worldwide. USP will focus on programs that are efficient, effective, and measurable. Expanding its education and training offerings through digital platforms will allow USP to reach many more students with the same investment or a limited increase (e.g., webcasting could triple the reach of courses USP already hosts). USP’s experience in developing and deploying educational content and training will be leveraged across the quality continuum wherever there is a need for capability building and USP can convene the requisite expertise. Three imperatives support a vision of USP as a world leader in creating and delivering education and training related to the quality of medicines, dietary supplements, and foods within the context of a globalized supply chain. The strategic imperatives are:

Terms of Reference

USP Education Facts

Curricula Expansion: The enhancement

2000: USP Education launched

of curricula or course offerings supports customers who are looking to comply with a wide range of practices that improve quality. 2000–2019: 63,000 trainees

Content Licensing: The distribution of educational assets to or through a third party enables wider reach.

University Curricula Integration: This refers to the uniting or meshing of discrete USP courses or modules into a larger university program.

2019: 155 courses; more than 6,700 trainees

2025 Goal: 60,000 trainees per year through a scalable, sustainable, global model

200 years of building trust

Resolution white paper developed by USP staff • To support standards that impact stakeholders most significantly, • To expand curricula to encompass a wider range of quality practices and requirements, and • To integrate content licensing and university curricula. Support Standards That Impact Stakeholders Most Significantly The impact of a new or revised standard on stakeholders can vary greatly. USP’s support of standards that have far-reaching consequences will enable the effective adoption of the most critical and complex USP standards and engage potential contributors to future standards development. Education is a powerful tool for those adopting new ways of working. Because USP standards have a significant impact on industry and healthcare providers, educational materials should be developed or revised in conjunction with new or revised standards. Updates of standards for compounding, packaging, reference standards labeling, and residual solvents have already prompted action toward new or revised courseware. Education can also support USP efforts in new areas where public health can be protected through public standards. Innovative learning techniques (e.g., process animation, focused community learning, instructor-led online courses, and blends of live and online formats) appear promising in the effort to support adoption of consequential standards—those standards that can impact many stakeholders or patients, may require significant changes or investment to adopt, or are high profile for various reasons (e.g., regulatory action, litigation, media reports). Expand Curricula to Encompass a Wider Range of Practices and Requirements That Promote Quality Expanding curricula will support USP stakeholders who are looking to comply with a wide range of practices that improve quality, including good manufacturing practices (GMP), pharmaceutical continuous manufacturing, and quality by design. This will also help support USP’s existing work in activities to sustainably strengthen medical product quality assurance systems in low- and middle-income countries. Online and blended delivery can dramatically expand reach at a lower cost to participants. Certificate programs in new or foundational areas can meet the needs of growing cohorts of professionals looking to

differentiate themselves. For example, USP recently made available its Certificate of Pharmacopeial Quality Assessment as a comprehensive, online training. The content includes the key USP standards necessary for quality assurance and the knowledge and skills necessary to comply with U.S. regulatory standards and align with GMP. This program was designed and taught by the experts who help establish USP standards. USP currently has one global education catalog rather than custom courses created at each site. This centralized-portfolio approach allows USP to 1) develop a pool of global instructors able to deliver the full set of courses, 2) ensure that students get the same learning from USP regardless of where they are taught, 3) reduce the expense of course creation by limiting “wheel rebuilding” and by reusing modules across courses, and 4) make it easier for potential students to understand what USP offers by having a consistent curricula, regardless of location. When this expansion requires development of new curricula, USP will recruit consultants with the required expertise to develop and teach new content and to build internal USP capabilities over time. Integrate Content Licensing and University Curricula Content licensing and university curricula integration will positively influence those learners who will work toward pharmaceutical quality in the future. Content licensing is the distribution of media assets and intellectual property to any third party. University curricula integration will involve incorporating discrete elements or features of USP Education courses or modules into existing or new academic course curricula, where USP retains the ownership of the intellectual property.1 These activities aim to prepare incoming professionals for industry expectations. Many universities are eager to incorporate USP education and training content, as they see the potential for collaborations to expand impact. Already, Northeastern University has hosted USP content for four semesters, and the Massachusetts College of Pharmacy and Health Sciences has licensed USP course content for two semesters. In addition, the University of Maryland, Duquesne University, Chapman University, and the University of Toledo have expressed interest in USP’s education content. Enabling in-classroom broadcasts may be one way to fulfill these unmet needs. Meanwhile, industry learning and development departments represent an as-yet unrealized opportunity for growth and expansion of USP Education.

200 years of building trust

Resolution white paper developed by USP staff Creating on-demand content, which is increasing in use on a global scale, is another way to efficiently leverage subject matter experts’ impact via smaller live interactions. These approaches can help expand the reach and impact of USP’s education program through universities and other third parties. Expanding access to USP education and training by leveraging technology (such as webcasting and on-demand services) to enable scalability will widen the use of quality practices by a greater number of industry and healthcare professionals, helping to benefit patients nationally and internationally. To create on-demand content, however, USP will need to develop a sustainable model for delivery. Tailoring training should be balanced by not overly customizing the content, which will allow a broad model to be rolled out. Reaching the global market necessitates expanding the faculty pool and communicating in a variety of languages; quality will be maintained through careful master course file management practices. Enabling new delivery models at all sites is an innovative way to achieve scale sustainably. Building online delivery capability will expand the reach of live events and enable self-service training. These capabilities also allow USP to provide translated courses for priority languages and support efforts to grow regional instructor pools.

Alignment with USP Mission By 2025, USP is striving to become the world leader in education and training delivery related to quality

of medicines, dietary supplements, and foods. By offering a wide range of education and training options in a variety of settings, USP aims to promote greater engagement of stakeholders directly affected by USP standards.2 USP aspires to reach at least 60,000 students per year through a scalable and sustainable model that is applicable around the globe, leveraging state-ofthe-art technology to enable delivery of each training opportunity to a far wider audience. This Resolution will help support standards by enabling the correct adoption of standards and engaging potential contributors to participate in future standards development as USP Volunteers. The Resolution will support advocacy by promoting the value of capacity and demonstrating the value of both USP Education and USP standards. The curricula expansion, content licensing/university curricula integration, and global expansion strategic imperatives all align with USP’s strategy to build capability among stakeholders—one of multiple approaches to improve global health.

Resource Assessment Additional resources required to supplement resources that are currently in place. This work will build upon the existing USP Education framework but expand to meet the additional needs of stakeholders, through modern training mechanisms, in more regions.

References and Notes 1 Pearson ML, Hubball HT. Curricular integration in pharmacy education. Am J Pharm Educ. 2012 Dec 12;76(10):204. doi: 10.5688/ajpe7610204. PMID: 23275669; PMCID: PMC3530066.

2 Ibid.

200 years of building trust

Proposed Resolution

Regulatory Systems Strengthening Resolution white paper developed by USP staff, with input from the Council of the Convention

Resolution white paper developed by USP staff

Proposed Resolution 8

Regulatory Systems Strengthening

USP will collaborate with global regulators and other partners to strengthen regulatory systems.

Summary The strengthening of regulatory systems will sustainably empower key government institutions to ensure the safety, efficacy, and quality of medical products for the global community. These efforts are most urgently needed to build the capabilities of regulatory systems in low- and middle-income countries (LMICs) where medicines quality is vulnerable due to constrained resources, weak governance, or ineffective regulatory and enforcement practices. USP is committed to continue and expand its efforts to work with regulators around the world to combat substandard and falsified medicines and thereby help to secure the global supply of life-saving medicines. This proposed Resolution

aligns with efforts to achieve regional convergence by supporting the adoption of international standards and work-sharing platforms as well as the use of information and data to improve evidence-based decision making and risk-based resource allocation. Through collaboration and advocacy across key sectors, USP will work to strengthen the local and regional workforce in LMICs through a variety of capability-building interventions. Working with national medicines regulatory authorities (NMRAs), USP will help strengthen the building blocks of effective regulatory systems in support of its mission to improve public health with broad access to qualityassured medicines.

200 years of building trust

Resolution white paper developed by USP staff

Background In many parts of the world, governments lack sufficient resources to ensure quality medicines. Weak governance and inefficient practices have left health systems vulnerable to corruption and mismanagement, with detrimental effects on health budgets, patient health and well-being, and trust in public institutions. Other challenges have included unjustified regulatory measures, lack of transparency in the regulatory process, and slow procedures, which can become obstacles to medicines access. Because of these circumstances, the supply chains for medicines and their ingredients are not secure in many parts of the world. In other words, the healthcare and regulatory systems that should work together to keep poor-quality medicines away from patients do not exist or are not effective in some countries or regions. While substandard and falsified products have always existed, poor-quality medicines are a growing problem.1 According to World Health Organization (WHO) estimates, at least 10 percent of medicines in LMICs are substandard or falsified.2 Risks from substandard and falsified medicines could include medical products that do not contain the correct substance or dose to effectively treat a disease or health condition, or harmful substances intentionally added to drugs. Misuse or overuse of some medicines, such as antibiotics or antimalarials, can make these products ineffective over time, reducing the ability to fight simple infections in the future. Considerable progress has been made to strengthen regulatory systems throughout the world, but gaps remain. Current challenges to medicines quality in LMICs include difficulties in implementing value-added regulatory practices that best utilize available resources; lack of timely access to new, quality medical products; limited evidence to support post-marketing regulatory actions; and inadequate resources to undertake postmarketing surveillance effectively. Regulatory decisions can also affect drug prices, as certain regulations may require manufacturers to generate additional data that demonstrate the safety of a product or to further invest in manufacturing facilities to reach necessary standards for production practices, thereby increasing costs. Increased costs generally reduce access to medicine. A functioning regulatory system is a prerequisite for ensuring the quality, safety, and efficacy of products on the market. National governments are responsible for

establishing national or regional regulatory authorities that have a clear mission, sound legal basis, realistic objectives, appropriate organizational structure, adequate number of qualified staff, sustainable financing, access to evidence-based technical literature, access to the appropriate equipment, and the capacity to exert effective market control. Decision-making processes should be transparent, and regulatory authorities must be accountable to both the government and the public.

Medicines Regulation in a Globalized Framework Following breakthrough progress in the sciences, especially chemistry, physiology, and pharmacology, the modern era of drug research and development began in the 20th century and flourished following the second World War. Yet regulations for the development, distribution, and use of these medicines were inconsistent or lacking. Several public health crises prompted advancements in regulatory approaches for medicines. For example, in 1937, the deaths of more than 100 people in the United States from diethylene glycol poisoning following ingestion of elixir sulfanilamide resulted in the Federal Food, Drug and Cosmetic Act in 1938, requiring premarket notification for new drugs. Between 1958 and 1960, thalidomide, a sedative and hypnotic drug, was introduced in 46 countries. Used primarily by pregnant women, thalidomide caused phocomelia and other deformities in an estimated 10,000 babies worldwide. As a result, the U.S. Congress passed the Drug Amendments Act of 1962, which required the U.S. Food and Drug Administration (FDA) to review all new drug applications and approve those with adequate evidence that a new drug was safe and effective. FDA was also given the authority to require compliance with current good manufacturing practices, to ofďŹ cially register pharmacies, and to implement other requirements. While unfortunate, these public health tragedies ultimately led to the development of a more secure supply of medicines for patients in the United States. However, even today and in well-resourced settings with strong regulations, exceptions can occur, and substandard or falsified medicines can reach patients. Additionally, because todayâ&#x20AC;&#x2122;s medicine ingredients are sourced and manufactured in countries around the world, the ability of NMRAs to ensure product safety for their respective countries is increasingly linked to collaboration with and reliance on counterpart agencies.

200 years of building trust

Resolution white paper developed by USP staff

Recent Approaches to Regulatory Systems Strengthening

authorities in health systems, and it urged WHO member states to strengthen national regulatory systems by:

Strengthening medical product regulatory systems is critical to expanding global access to quality medicines, which in turn is vital for improving health and saving lives. Global health organizations have conducted comprehensive analyses of what is needed among regulators to ensure medicines quality.

• Undergoing self-evaluations (with technical support, as needed) as a step toward planning for future strengthening

In 2012, FDA commissioned a study of regulatory systems in LMICs, conducted by the Institute of Medicine (now the National Academy of Medicine). The committee’s report described the core elements of effective regulatory systems: a rulemaking process that allows for stakeholder comment, a protocol for agency collaboration, and a mechanism to identify when regulatory action is necessary. To address the gaps in existing regulatory systems, the committee recommended that LMICs develop a strategy that emphasizes public health, market incentives, risk-based investments, and international coordination.3 In 2014, in response to a WHO Secretariat report on regulatory systems strengthening,4 the 67th World Health Assembly issued Resolution 67.20, Regulatory System Strengthening for Medical Products.5 This was the first ever WHO resolution addressing the role of regulatory

WHA Resolution 67.20 Regulatory Systems Strengthening for Medical Products: Key Messages Regulatory systems are an essential component of health systems strengthening and contributes to public health outcomes. Regulators are an essential part of the health workforce. Inefficient regulatory systems themselves can be a barrier to access to safe, effective, and qualityassured medical products.

• Collecting data on regulatory system performance for benchmarking and improvement • Developing strong legal foundations and political leadership • Identifying and developing core regulatory functions • Developing needed technical competencies and encouraging the development of the regulatory field as a profession • Facilitating the use of science-based guidance and outputs • Developing and implementing strategies to address the increasing complexities of supply chains Most recently, in 2019, the National Academies of Sciences, Engineering, and Medicine convened a consensus committee that determined that recognition and reliance arrangements are a 21st century “best practice” for global regulators.6 Key areas that are part of

Core Elements of Effective Regulatory Systems A rulemaking process that allows for stakeholder comment A protocol for agency collaboration

A mechanism to identify when regulatory action is necessary A strategy that emphasizes public health, market incentives, risk-based investments, and international coordination

200 years of building trust

Resolution white paper developed by USP staff this best practice include improving the design of mutual recognition agreements and expanding them to include more regulatory activities, greater sharing of information, and more evaluation of the public health impacts of reliance and recognition arrangements for medicines. In today’s globalized world, maximizing reliance and cooperation efforts with other trusted regulators is key to ensuring the quality, safety, and efficacy of medicines.

process, which will facilitate accelerated registration of quality-assured medicines in Pakistan. In Ethiopia, PQM supported the development and implementation of standard operating procedures to improve the quality management systems of the Ethiopian Food, Medicine and Healthcare Administration and Control Authority’s inspection functions and processes.

For more than 25 years, USP has collaborated with organizations such as the U.S Agency for International Development (USAID) and the Asia-Pacific Economic Cooperation (APEC) Life Sciences Innovation Forum (LSIF), as well as WHO and FDA, to help strengthen regulatory systems and protect public health.

The PQM approach reflected a holistic view of medicines quality assurance—seeking to address quality-related aspects of medicine production, patient use, and everything in between—to strengthen and improve the systems, structures, and processes that promote product quality. This approach recognized the dynamic and cross-cutting relationships among different components of the health system, and therefore aimed to address product quality issues in a sustainable manner using systems-based thinking and solutions.

Promoting the Quality of Medicines (PQM) Program

Promoting the Quality of Medicines Plus (PQM+) Program

As the implementing partner for the Promoting the Quality of Medicines (PQM) program, USP worked with a multitude of stakeholders to advance quality assurance systems. From 2009 to 2019, the PQM program worked with:

The Promoting the Quality of Medicines Plus (PQM+) program, also funded by USAID, will continue efforts to sustainably strengthen medical product quality assurance systems and improve national and regional regulatory systems in LMICs. Awarded in 2019, the objectives of PQM+ are to:

USP Programs and Collaborations for Regulatory Systems Strengthening

• National and regional regulatory authorities to strengthen quality assurance systems. • Quality control laboratories to improve the ability of countries to test the quality of products on the markets. • Academic and training institutions to ensure new graduates in pharmacy and regulatory sciences are ready to tackle quality assurance challenges. • Manufacturers in LMICs to elevate production practices to be in line with international standards. • Research organizations to conduct rigorous bioequivalence studies that help more generic products reach patients. • Larger global pharmaceutical companies to facilitate technology transfer for essential medical products to smaller, local manufacturers. Through PQM, USP supported the development or revision of 22 pharmaceutical laws, policies, and regulations in 12 countries. Recent successes through PQM’s technical assistance and advocacy efforts include the Drug Regulatory Authority of Pakistan’s endorsement in 2019 of a procedure to register product dossiers in accordance with the WHO Collaborative Registration Procedure

• Improve governance for medical product quality assurance systems • Improve country and regional regulatory systems to assure the quality of medical products in the public and private sectors • Optimize and increase financial resources for medical product quality assurance • Increase supply of quality-assured essential medical products of public health importance • Advance global medical products quality assurance learning and operational agenda USP has assembled a consortium of internationally recognized leaders that complement USP core strengths, technical knowledge, and geographic reach to address the most critical quality assurance challenges. Led by USP, each PQM+ partner brings specialized expertise to bear on achieving PQM+ objectives. Additionally, USP partners with local leaders and experts with focused capabilities. Through PQM+, local partners will advance to become direct providers of technical assistance. By working with local stakeholders, PQM+ will align and

200 years of building trust

Resolution white paper developed by USP staff leverage funding provided through various mechanisms and donors to support existing or strengthen new coordination mechanisms. Furthermore, PQM+ will participate on the committees and working groups of Ministry of Health, pharmaceutical departments, and other groups involved in the development and implementation of national strategies or institutional development plans. PQM+ considers quality-related issues that occur across a complex, globalized supply chain, including the marketbased factors that affect the availability of qualityassured medical products as well as the variability of regulatory capacity across country and regional contexts. USP–APEC Center of Excellence USP also collaborates with the APEC LSIF, a government and industry platform for 21 economies around the Pacific, to disseminate best practices, standards, and guidance for improving the quality and security of global pharmaceutical supply chains. Through a fiveyear agreement with LSIF and FDA, USP is hosting the USP–APEC Center of Excellence to disseminate APEC supply chain quality approaches. USP is committed to building regulatory workforce capacity and regulatory convergence through its trainings, discussion forums, and related activities based on the APEC supply chain toolkit. Since being formally endorsed in August 2017, the USP– APEC Center of Excellence has delivered trainings to more than 400 participants from industry and regulators around Asia and the Pacific region, and is considering additional collaborations with WHO to respond to other needs in other regions, as identified by regulators and industry.

Alignment with USP Mission By adopting this Resolution, USP will continue to work with key stakeholders, including national regulatory authorities, national quality control laboratories, academic institutions, and international organizations to strengthen regulatory systems.7 This Resolution proposes that USP continue its efforts to advocate for the use of science-based public quality standards, promote application of risk-based approaches, and advance reliance models and the use of work-sharing platforms to ensure greater efficiencies and faster approval of medical products. These efforts will complement donorfunded systems strengthening initiatives implemented by USP using a wide range of USP capabilities. By promoting collaboration and engagement across key sectors, USP can build capabilities among NMRAs to help ensure medicines quality while expanding patient access to essential medicines in countries around the world.

Resource Assessment Additional resources required to supplement resources that are currently in place. USP is beginning to implement the PQM+ program, supported by USAID through a cooperative agreement, to strengthen regulatory systems in low- and middle-income countries. Other ongoing initiatives include the USP–APEC Center of Excellence for Quality Assurance across the supply chain. This strong foundation will be supplemented to further expand impact and support regulators in ensuring the quality of medicines in their countries.

References and Notes 1 Mackey, TK, Liang BA, York P, Kubic T. Counterfeit drug penetration into global legitimate medicine supply chains: a global assessment. Am J Trop Med Hyg. 2015 Jun 3;92(Sup6):59–67. doi:10.4269/ajtmh.14-0389. 2 WHO. WHO Global Surveillance and Monitoring System for substandard and falsified medical products. Geneva: World Health Organization; 2017. License: CC BY-NC-SA 3.0 IGO. 3 Institute of Medicine Committee on Strengthening Core Elements of Food and Drug Regulatory Systems in Developing Countries, Board on Global Health and the Board on Health Science Policy. Ensuring safe foods and medical products through stronger regulatory systems abroad. Washington, DC: National Academies Press; 2012. Available from: http://nationalacademies.org/hmd/Reports/2012/Ensuring-Safe-Foods-andMedical-Products-Through-Stronger-Regulatory-Systems-Abroad.aspx. 4 World Health Organization. Regulatory system strengthening: report by the Secretariat. 67th World Health Assembly, Provisional agenda item 15.6. Geneva: WHO; 2014 Mar 14. Available from: https://apps.who.int/gb/ebwha/pdf_files/WHA67/A67_32-en.pdf. 5 World Health Organization. Regulatory system strengthening for medical products. 67th World Health Assembly, Agenda item 15.6. Geneva: WHO; 2014 May 24. Available from: https://apps.who.int/medicinedocs/documents/s21456en/s21456en.pdf.

6 National Academies of Sciences, Engineering, Medicine. Regulating medicines in a globalized world: need for increased reliance among regulators. Washington, DC: NAS; 2019 Nov. Available from: https://www.nap.edu/resource/25594/regulating-medicines-highlights.pdf. 7 Adapted from a Resolution proposal submitted by Tina Morris, Parenteral Drug Association.

200 years of building trust

Proposed Resolution

Compounding

Resolution white paper developed by USP staff, with input from the Council of the Convention

Resolution white paper developed by USP staff

Proposed Resolution 9

Compounding

USP will continue to collaborate with stakeholders on standards to help ensure the quality of compounded drug preparations. New and revised standards will be developed utilizing data, scientific evidence, and input from recognized healthcare professionals. Summary USP defines the practice of compounding involves combining, admixing, diluting, pooling, or otherwise altering a drug product or drug substance to create therapies tailored to meet the unique or specific needs of individual patients. Compounding remains an important and necessary practice that provides specialized formulations for individual patients when commercially available medicines may not be appropriate. In the United States, compounding is regulated by federal and state laws and regulations. USP provides public standards to help ensure the quality of compounded drug preparations, including monographs for bulk drug

substances and other ingredients, monographs for compounded preparations, and general chapters to aid in the preparation of compounded medicines and the handling of hazardous drugs in healthcare settings. USP monographs and general chapters are part of the U.S. Pharmacopeiaâ&#x20AC;&#x201C;National Formulary (USPâ&#x20AC;&#x201C;NF). This Resolution proposes that USP will strengthen its collaboration with practitioners, academia, industry, and regulators to ensure that its standards for the quality of compounded preparations reflect best practices and current science while preserving patient access.

200 years of building trust

Resolution white paper developed by USP staff

Background USP has a long history of setting standards for compounding, starting in 1820 with the first edition of the United States Pharmacopeia, which contained 217 formulas for making medicines. Today, compounding continues to play an important role by providing medications tailored to individual patients’ needs. Millions of prescriptions are compounded by pharmacists, nurses, and doctors each year in the United States to meet the unique needs of patients. All stakeholders and personnel involved in compounding should have a clear understanding of the risks inherent in compounding. In addition, incorporation of established USP standards into everyday practice is essential for patient safety. USP considers that compounding is accomplished by combining, admixing, diluting, pooling, or otherwise altering a drug product or bulk drug substance to create therapies tailored to the unique or specific needs of patients. Compounding plays a critical role in situations where the strength or dosage of a medicine needs to be customized. Another important function of compounding is reformulating a drug to exclude an unwanted, nonessential ingredient (e.g., lactose or a dye to which the patient is allergic). In still other cases, compounding is used to alter the physical form or route of administration of the medication for patients with certain limitations or disabilities, such as those who have difficulty swallowing oral medication.

USP sets standards for compounding that include general chapters, compounded preparation monographs, and monographs for components that may be used in compounded preparations (see box on page 3). General chapters include those such as <795> and <797> for nonsterile and sterile compounding, or <825> for compounding of radiopharmaceuticals. USP has more than 200 compounded preparation monographs that were developed based on the following criteria:1 • Medications with the highest public health impact (i.e., those that affect major population groups, disease states, and access needs) • Medications essential for treating pediatric and geriatric patients where there are unmet needs • Medications that need to be formulated to avoid allergic reactions and to be suitable for patients with specific genetic anomalies • Medications for currently unmet clinical and therapeutic needs

Quality Framework for Compounded Medicines USP standards are recognized in various provisions of the Federal Food, Drug, and Cosmetic (FD&C) Act and in state laws, regulations, and policies. Specific to human drug compounding, USP standards are recognized in Section 503A of the FD&C Act, as added by the Food

USP Standards for Compounding Monographs for Bulk Drug Substances and Other Ingredients:

Compounded Preparation Monographs:

These provide standards for the identity, quality, purity, strength, packaging, and labeling of bulk substances and other ingredients that may be used in compounded preparations.

These contain formulations and quality standards for specific preparations. Compounded preparation monographs assist practitioners in compounding formulations for which there is no suitable commercially available product and provide standards to ensure the quality of these medicines.

General Chapters: These serve as overviews and outline information, procedures, or analytical methods that apply across multiple products or settings (e.g., compounding). General chapters aid in the preparation of compounded medicines and the handling of hazardous drugs in healthcare settings.

200 years of building trust

Resolution white paper developed by USP staff and Drug Administration Modernization Act of 1997, which states that, among other things, to qualify for the exemptions under section 503A, a compounder using bulk drug substances must comply with the standards of an applicable USPâ&#x20AC;&#x201C;NF monograph, if a monograph exists, and the USP chapter(s) on pharmacy compounding. In 2013, Congress enacted the Drug Quality and Security Act (DQSA) to clarify FDAâ&#x20AC;&#x2122;s authority over human drug compounding and to reaffirm that USP standards for compounded medicines apply under Section 503A. Following enactment of the DQSA, FDA provided further clarification of its views on the application of USP standards to pharmacy compounding through an FDA Guidance: Pharmacy Compounding of Human Drug Products Under Section 503A of the Federal Food, Drug, and Cosmetic Act.2,3 This guidance states that compounded preparations made by a licensed pharmacist or physician can qualify for exemptions from new drug approval requirements, current good manufacturing practice requirements, and the requirement to label drug products with adequate directions for use, if, among other things, they are compounded in compliance with the USP chapters on pharmacy compounding and, if bulk drug substances are used, such substances and ingredients comply with the standards of an applicable USPâ&#x20AC;&#x201C;NF monograph, if one exists. State pharmacy regulatory bodies generally are responsible for the day-to-day oversight of the practice of pharmacy. FDA may conduct oversight in certain instances. Almost all states have laws, regulations, or policies specific to compounding.4 Although it has no role in enforcement, USP is committed to continuing to work with stakeholders and state and federal regulators to encourage the use of public standards to help ensure the quality of compounded drug preparations.

USP Efforts to Ensure Quality in Compounding USP supports collaborative efforts to advance safe compounding. These efforts include discussions among stakeholders, including state and federal policymakers, to support quality compounding. USP compounding standards describe widely acknowledged, scientifically based procedures and practices and facilitate consistency and quality in the

medicines prepared for patients. New and revised standards represent many years of deliberation and stakeholder engagement in the form of public comments and their review, roundtables, workshops, public face-toface meetings, and open, public microphone sessions. USP actively seeks diverse input and participation from pharmacists, practitioners, representatives of healthcare organizations, academicians, industry, patients, federal and state regulators, and many others. USP develops standards based on public health needs. Such needs can be identified by any stakeholder and are evaluated by the relevant Expert Committees who consider risks to patient safety and access in determining whether a quality standard is warranted. For example, through stakeholder engagement, USP has learned of the request for standards specific to veterinary practitioners, who treat a range of species and practice in varied settings and environments.5 USP has also received public input requesting development of resources for assigning and extending beyond-use dates for compounded preparations.6 Based on stakeholder input, USP experts expanded provisions in USP <795> and <797> to develop a public standard aimed at minimizing the potential risk of exposure to hazardous drugs. The result of these efforts is USP <800>, a general chapter that applies to hazardous drug handling during nonsterile and sterile compounding, and that contains principles that stakeholders may choose to apply across healthcare settings more generally. With evolving work practices and new technologies, USP will consider public input on safe practices and monitoring tools to ensure safety. As a sciencebased, solution-oriented organization, USP is uniquely positioned to convene stakeholders and is committed to increase engagement with a diverse group of stakeholders to ensure the multifaceted issues relative to compounded drug preparation are well understood and addressed to the extent possible. Additionally, revised monographs and general chapters reflect advancements in science and clinical practice, rephrasing and reorganization to promote clarity, and input from the public.7 In the next USP cycle, the relevant Expert Committees will evaluate all stakeholder input and determine whether standards, tools, and other resources may be able to address these public health needs. USP will continue to support the implementation of new or revised standards, using education programs, practical tools, and innovative solutions.

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Resolution white paper developed by USP staff

Alignment with USP Mission USP is working to ensure continued rigor in the development of quality standards for compounding while maintaining patient access to medicines. USP engages with stakeholders to advance compounding quality, promote patient safety, and respond to evolving public health needs. Key elements of USPâ&#x20AC;&#x2122;s strategy support efforts to build awareness and encourage use of compounding quality standards. Through its education and training programs as well as domestic stakeholder engagement activities, USP can help strengthen practitioner awareness of appropriate circumstances and

settings for compounded drug preparations, including how to consistently follow procedures that promote patient safety.8 Additionally, USP will monitor relevant advancements in science as well as patient safety issues related to compounding to inform the development and revision of standards.9

Resource Assessment Refocus of resources currently in place. Significant staff efforts from across the USP organization are underway and will continue in this area.

References and Notes 1 USP. Compounded Preparation Monographs (CPMs). Available from: https://www.usp.org/compounding/compounded-preparationmonographs. 2 FDA. Pharmacy Compounding of Human Drug Products Under Section 503A of the Federal Food, Drug, and Cosmetic Act Guidance. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/pharmacy-compounding-human-drug-products-undersection-503a-federal-food-drug-and-cosmetic-act.

3 USP. Recognition of USP Compounding Standards. Available from: https://www.usp.org/compounding/legal-considerations. 4 U.S. Government Accountability Office. Drug Compounding: FDA Has Taken Steps to Implement Compounding Law, but Some States and Stakeholders Reported Challenges; Report to Congressional Committees, GAO-17-64; 2016 Nov 17. Available from: https://www.gao.gov/ assets/690/681096.pdf. 5 Adapted from a Resolution proposal submitted by Dharati Szymanski, American Veterinary Medical Association. 6 Adapted from Resolution proposals submitted by Ronna Hauser, National Community Pharmacists Association, and Michael Ganio, American Society of Health-System Pharmacists. 7 Adapted from a Resolution proposal submitted by Mark Neuenshwander, THRIV Coalition for IV Accuracy. 8 Pew Charitable Trusts. Best practices for state oversight of drug compounding. Washington, DC: 2016 Mar. Available from: http://www. pewtrusts.org/~/media/assets/2016/02/best_practices_for-state_oversight_of_drug_compounding.pdf.

9 Kienle P, Federico F. Pharmacy impact on quality and outcomes: new era for measuring value. Paper presented at 15th Annual ASHP Conference for Leaders in Health-System Pharmacy; Chicago, IL: 2010 Oct 17â&#x20AC;&#x201C;18.

200 years of building trust

Proposed Resolution

Cannabis

Resolution white paper developed by USP staff, with input from the Council of the Convention

Resolution white paper developed by USP staff

Proposed Resolution 10

Cannabis

USP will leverage its scientific expertise and convening power to collaborate with stakeholders and develop fit-for-purpose scientific resources and solutions that will help address quality and patient safety concerns and advocate for additional scientific research on cannabis, cannabis-derived products, and cannabis-related compounds. Summary USP has observed a critical and growing need for scientific articulation of quality attributes for cannabisderived products to help protect patients and consumers from harm. Access to broadly sourced products is increasing as many U.S. states and jurisdictions outside the United States, have enacted initiatives that permit the use of cannabis and cannabis derivatives for medical purposes. This increased availability raises risks for patients and consumers of exposure to contaminated, adulterated, substandard, or super-potent products. USPâ&#x20AC;&#x2122;s long history and cumulative experience in establishing quality standards for medicines and other

products provides a strong foundation upon which to develop fit-for-purpose scientific solutions for cannabisderived products. Already, USP has made significant progress to define suitable quality specifications for this plant material; a peer-reviewed scientific paper is forthcoming in 2020. This Resolution proposes that USP continue its tradition of providing scientific and technical information and resources to develop quality attributes for products and their ingredients that help to protect patient safety and public health. In so doing, USP will monitor and evaluate policy, regulatory, and public health developments related to cannabis and

200 years of building trust

Resolution white paper developed by USP staff publish scientifically relevant information at appropriate times, utilizing appropriate mediums. Additionally, USP will provide technical advice to stakeholders, including U.S. states, national and state regulatory agencies, academic research centers, as well as other research or science organizations. These approaches align with the strategic ambition for the next five-year cycle to make USP scientific understanding available in more flexible formats than only USP standards in the compendia.

Background Public standards for product quality are essential to reduce the risks of harm to patients and consumers. Documentary standards that set out specifications as series of tests with validated analytical procedures and suitable acceptance criteria are fundamental for good agricultural and collection practices (GACPs) and good manufacturing practices (GMPs). Reference standards are key in determining that quality control methods are fit-for-purpose, accurate, and reproducible. Application of these standards and practices provides federal and state regulatory agencies as well as the regulated industries methods to help ensure the identity and content of components of the marketed products. In the case of complex articles such as cannabis and its extracts, this includes laboratory verification of identity, including any distinctions from hemp ; quantitative composition of phytocannabinoids and other relevant constituents; and tests to help assure minimal exposure to contaminants such as microorganisms, elemental impurities, mycotoxins, residual solvents, and pesticide residues. Many biologically active chemical compounds can be derived from the cannabis plant. Of these, the two most well-known are cannabidiol (CBD) and tetrahydrocannabinol (THC). THC produces the psychoactive intoxicating or euphoric symptoms commonly associated with cannabis recreational use; purified CBD, does not. However, countless CBD products are available on the market today; it is not known whether any of these contain amounts of THC that are beyond the 0.3 percent limit established by federal statute. Even at small amounts, THC can cause adverse effects, such as increased heart rate, coordination problems, dry mouth, red eyes, slower reaction times, and memory loss. Although the U.S. Food and Drug Administration (FDA) has issued general guidelines for botanical drugs and laboratory controls, currently, there are no specific standards upon which to base GACP

and GMP for extracting the chemical compounds from the cannabis plant. These are needed to limit consumer exposure to toxic substances, microorganisms, and adulterants in cannabis and cannabis-derived products. Increasingly common perceptions about cannabis and cannabis-derived compounds, such as CBD, include potential benefits for patients such as relief from symptoms associated with a wide variety of conditions. These include inflammation, pain, psychosis and other mental disorders such as depression and anxiety, inflammatory bowel disease, nausea, and migraines. While many cannabis-derived consumer products make claims about their supposed health benefits, generally those claims have not been scientifically demonstrated nor reviewed or approved by regulatory authorities, including FDA. To date, FDA has approved only one cannabis-derived and two cannabis-related drug products containing dronabinol as active pharmaceutical ingredient. All three cannabis-related products are available to patients only with a prescription from a licensed healthcare provider. Any other cannabis derived or cannabis related product making drug claims in the United States would be considered misbranded as per federal statute and related regulations. CBD is no longer classified as a Schedule I drug; it was moved to Schedule V after FDA approval of a CBD product in 2018. Specifically, the federal Controlled Substances Act classifies cannabis containing more than 0.3 percent of THC as a Schedule I drug (termed in Controlled Substances Act as “Marihuana” or “Marijuana”), which means that it has “no currently accepted medical use in the United States, a lack of accepted safety for use under medical supervision, and a high potential for abuse.” In light of the current federal regulatory status, USP has committed not to publish quality standards for cannabis in official compendia. This federal regulatory status precludes the publication of USP quality standards for cannabis. USP may, however, provide scientific resources and other solutions to help address discrepancies in quality and concerns about patient safety. Despite the status of cannabis under federal law, 33 U.S. states and the District of Columbia have passed various forms of legislation permitting the use of cannabis for medical purposes including laws relating to the cultivation, distribution, and sale of cannabis for medical purposes. Outside the United States, nearly 20 countries have addressed the use of cannabis for medical

200 years of building trust

Resolution white paper developed by USP staff purposes by instituting legislation that allows patients to access cannabis products for medical conditions. As of time of writing, Canada and 18 European countries have approved drug products containing as the active pharmaceutical ingredient a mixture of natural cannabinoids extracted from cannabis, mainly THC and CBD. Navigating the dynamic and variable legal and regulatory landscape, especially given the plethora of cannabis-derived products on the market, will require careful evaluation by USP, which will engage for the express purpose of helping to ensure patient safety by setting quality standards. This risks of harm from poor-quality products for patients establishes a clear imperative for USP to create and distribute fit-forpurpose scientific resources.

USP Solutions for Cannabis-Derived Substances Given the wide use of cannabis and cannabis-derived products, and the general lack of standards in this space, quality standards can serve as a resource to help protect patients from harm. In addition, there is a pressing need for rigorous clinical research on the benefits and harms of cannabis-derived products. Public quality standards help provide a consistent scientific basis for identity and consistent quality attributes for substances used in clinical research and guidance for cannabis testing in laboratories.

Hempseed, which is rich in oil, protein, and other nutrients, is a potentially valuable food product from cannabis. While cannabis seeds are not believed to produce cannabinoids, hempseed can become contaminated with THC, CBD, and other cannabinoids during harvesting and processing. Standards for hempseed safety and quality are needed to facilitate trade and to protect consumers from inadvertent exposure to cannabinoids through food. Preventing Harm Recalls and reports of harm to consumers and patients due to contamination, variable composition, and incorrect labeling in jurisdictions where cannabis is sold legally, such as in Canada and some U.S. states, highlight the pressing need for quality control and scientific guidance. In U.S. states where cannabis or derived products have been legalized for medical use, and where state agencies collect data, reports of cannabis-related visits to hospital emergency departments (ED) have increased.1 The most common symptoms associated with these ED visits include gastrointestinal discomfort, (cannabinoid hyperemesis syndrome), intoxication, and psychiatric symptoms such as acute anxiety, depression, or psychosis. It is challenging to determine what products cause adverse events since most of what is known about adverse effects come from aggregate

Terms of Reference Cannabis inflorescence:

Cannabis sativa L. (family Cannabaceae) is of botanic origin; the term “inflorescence” indicates a substance derived from the complete flower head.

CBD: Cannabidiol is one of the biologically active chemical compounds derived from the cannabis plant. CBD does not contain the psychoactive intoxicating properties associated with THC.

THC: Tetrahydrocannabinol is the second of two most commonly known derivatives of cannabis. In sufficient quantities, THC produces adverse effects such as increased heart rate, coordination problems, dry mouth, red eyes, slower reaction times, and memory loss; psychoactive intoxicating properties associated with THC.

Marijuana:

This refers to consumer products containing more than 0.3% THC, also known as “adult use” (federally illegal in the United States). Proposals by USP to develop scientific resources for cannabis-derived products do not pertain to marijuana or recreational cannabis.

200 years of building trust

Resolution white paper developed by USP staff

reports, where all products (i.e., cannabis with and without THC) and routes of exposure to cannabis (i.e., topical, edible, inhaled) are grouped together. Rigorous Research and Laboratory Testing Public standards provide an essential resource for the conduct of safe, reproducible research by facilitating the use of well-characterized or standardized materials. Despite significant changes in the legal landscape across the United States at the state level and internationally, and relatively high rates of cannabis and derived product use, evidence about potential therapeutic and adverse effects remains scant. The study of cannabis and cannabis-derived compounds in clinical trial settings is needed to assess the safety of these substances to inform policy and clinical practice. To study these substances appropriately, researchers require precise characterization of clinical trial materials in terms of identity, content of components, and the absence of contaminants, to achieve reproducibility of the laboratory, preclinical, and clinical research. In other words, standards are needed for risk assessments that regulators, clinicians, and the public rely upon to make informed decisions about cannabis use. Ensuring the quality of cannabis requires appropriate analytical test methods and acceptance criteria to define the identity, constituents, and limits of contaminants. USP scientific resources can provide scientifically validated tests to ensure the identity and content of components, as well as limit contaminants in a product. Non-contaminated, non-adulterated products reduce patient and consumer exposure to toxic substances, pathogenic microorganisms, and adulterants, such as synthetic compounds that mimic the effects of phytocannabinoids on receptors. Furthermore, the absence of finalized federal guidance for cannabis testing and harmonized laboratory testing protocols raises concerns about differences in results obtained by different laboratories. Important considerations for cannabis testing are the development and adoption of validated analytical methods to help address the challenges faced by state lab directors such as inter-laboratory variability and the ability of cannabis producers and consumers to have confidence in the composition and safety of cannabis products.

Leveraging USPâ&#x20AC;&#x2122;s Scientific Expertise and Convening Power Over its entire 200-year history, USP has convened a diverse and relevant group of experts to assess the need for new standards and develop or revise the criteria within those standards when warranted. One of USPâ&#x20AC;&#x2122;s areas of expertise is the development of standards for articles of botanical origin, including analytical procedures and acceptance criteria to help ensure identity and content of components of botanical articles. In the absence of monographs or General Chapters in the official compendia, USP also provides scientific guidance in a variety of other forms. In September 2016, the USP formed a Cannabis Expert Panel with representation from several states and Canada that included members of academia, industry, and regulators with the charge to develop quality standards for cannabis used for medical purposes. The USP Cannabis Expert Panel has recommended specifications for fit-for-purpose analytic methods and to limit the content of contaminants such as toxic elemental impurities, pesticides, microorganisms, and fungal toxins. Multiple tests are included to complement each other to provide an appropriate quality characterization. The Expert Committee also highlighted the importance of naming, definition, use of reference materials, and packaging/storage conditions. In the next five-year cycle, the USP will collaborate with stakeholders to develop, strengthen, revise, and promote adoption of scientific resources that address quality of cannabis-derived products.2 USP will focus on three broad groupings of cannabis, which have been identified as relevant for labeling expectations.

Alignment with USP Mission Based on interactions with various stakeholders throughout the past several years, USP has observed a need for public quality standards for cannabis-derived substances to protect consumers and healthcare practitioners from harm, while improving patient safety and public health by facilitating rigorous research and innovation. This proposed Resolution asks USP to continue the tradition of providing scientific and technical guidance for products used by consumers

200 years of building trust

Resolution white paper developed by USP staff to protect patient safety and public health. The USP Expert Panel has made significant progress to define suitable quality specifications, prepared for publication as a peer-reviewed scientific article. This work aligns with USPâ&#x20AC;&#x2122;s ambition for the next five years of making scientific findings more readily accessible and in formats other than monographs or General Chapters found in the official compendia. It also builds capabilities among stakeholders; USP will provide technical advice, upon request, to U.S. states, national and state regulatory agencies, academic research centers, as well as other research or science organizations.

Resource Assessment Resources currently in place. Scientific work underway and stakeholder engagement expanding. USP is working to support efforts of stakeholders to identify and utilize science-based parameters for the quality of cannabis products to reduce risks to consumers/patients. We anticipate need in this area will continue to expand. The current CoE Expert Committee structure and the proposed structure for the next cycle will support this effort.

References and Notes 1 Monte AA, Shelton SK, Mills E, Saben J, Hopkinson A, Sonn B, Devivo M, Chang T, Fox J, Brevik C, Williamson K, Abbott D. Acute illness associated with cannabis use, by route of exposure. Ann Intern Med. 2019 Apr 16;170(8):531â&#x20AC;&#x201C;37. doi:10.7326/M18-2809. PMID: 30909297. PMCID: PMC6788289. 2 Adapted from a Resolution proposal submitted by Greg Amidon, University of Michigan.

200 years of building trust

Proposed Resolution

Pharmacopeial Cooperation and Convergence Resolution white paper developed by USP staff, with input from the Council of the Convention

Resolution white paper developed by USP staff

Proposed Resolution 11

Pharmacopeial Cooperation and Convergence

USP will lead efforts to advance convergence around robust, science-based standards across pharmacopeias. USP will focus efforts on those standards where convergence will have the most impact on global access to quality medicines.

Summary Today, medicines are increasingly the products of a global supply chain and are obtained from a global marketplace. Within this context, pharmacopeial convergence aims to achieve voluntary alignment of public standards with well-established, robust pharmacopeias toward a shared goal of advancing patient safety and public health. Harmonization, on the other hand, requires uniformity across standards. The process of harmonization across pharmacopeias is complex for many reasons that are often beyond the control of the pharmacopeias, such as the increasing

diversity of sources for medicines. Specifically, efforts to harmonize standards are challenged by multiple factors, including 1) differences in the products approved, approval specifications, and the timing of approvals by the regulatory authorities that grant market authorization in their countries; 2) the rapid evolution of biopharmaceutical science; 3) advances in manufacturing and analytical technology; and sometimes 4) variations in the scientific evidence required by various pharmacopeias for standards development and revision.

200 years of building trust

Resolution white paper developed by USP staff At the same time, USP has increasingly focused its efforts on convergence around standards that will achieve the greatest public health impact. These are often standards utilized across products and product categories to eliminate redundancy in testing and reduce the regulatory burden of compliance with multiple divergent standards that may impact numerous individual finished drug products. During the next five years, USP will lead efforts to align the most critical quality standards across robust, science-based pharmacopeias to optimize the impact of convergence on access to quality medicines. In the course of executing this resolution, USP will continue and expand its engagement with the World Health Organization (WHO), the International Conference on Harmonization (ICH), the Pharmacopeial Discussion Group (PDG), and individual pharmacopeias as well as other stakeholders such as industry and regulatory agencies to determine optimal ways to advance and sustain globally aligned standards.1 USP also will advocate that all pharmacopeias recognize and adopt the following essential elements of the standards-setting process: 1) transparency throughout the process, 2) science-based and unbiased decision making, 3) genuine and robust opportunities for industry and other stakeholders to provide input, and 4) prioritization of access to quality medicines, patient safety, and innovation. Widespread adoption of these elements will help foster convergence among national pharmacopeias.

Background The research, development, manufacture, and distribution of medicines, including active pharmaceutical ingredients (APIs) and excipients, have become increasingly globalized. On one hand, a global supply chain may mean improved access to essential ingredients, other raw materials, and finished medical products, but on the other, it creates additional challenges in ensuring that the medicines patients rely on are quality-assured to be safe and effective. These circumstances present pharmacopeias with challenges that are similar to, and in some ways even more complex than, those faced by national regulatory authorities. The main responsibility of regulators is to ensure that medical products approved for marketing and use in their jurisdictions meet appropriate standards for quality, safety, and efficacy throughout the product

lifecycle. Importantly, each regulator is ultimately responsible for its decisions. Because of their first responsibilities within their own countryâ&#x20AC;&#x2122;s regulatory and legal framework, regulatory authorities have recognized that international harmonization is a complex and difficult task and not always a realistic goal. Regulatory authorities increasingly recognize that none of them alone has the resources needed to meet its public health responsibilities in a globalized medicines supply chain.2 Reliance and recognition, therefore, help regulators to meet the demand for regulatory review and oversight, and this approach has become a best practice for global regulatory cooperation. Reliance occurs when one regulatory authority, in the course of making its own decision (e.g., to approve a product for marketing), may consider the information gathered or analysis performed by another regulatory authority. Recognition indicates that meeting the regulatory requirements of one country sufficiently meets the regulatory requirements of another country.3 Likewise, pharmacopeias, as part of a larger ecosystem designed to ensure the safety and quality of medicines, may benefit from some of the reliance approaches increasingly deployed by regulatory authorities. Already, reliance arrangements among pharmacopeias exist and range from informal activities, such as information sharing and visiting scientist programs, to more formal efforts, such as the Pharmacopeial Discussion Group (PDG). These efforts are described in greater detail below. Whereas harmonization aims to achieve uniformity of standards in multiple pharmacopeias, the goal of pharmacopeial convergence is to achieve alignment of public standards with trusted pharmacopeias representative of robust science and transparent and trusted standards development processes, toward a shared public health goal. The benefits of harmonization, in an ideal state, include increased efficiency because eliminating redundant testing allows industry to serve multiple markets with the same processes and products and broader patient access to quality-assured medicines. Given the global supply chain for medicines and their APIs and other components (e.g., excipients), harmonized standards can provide a vital resource to ensure quality medicines. However, harmonization efforts present multiple, significant, and often extremely timeconsuming challenges and must be balanced with the need to ensure timely, robust, and scientifically sound standards to stakeholders. The goal of convergence applies scientific principles yet recognizes the legal and practical impediments to technical harmonization.

200 years of building trust

Resolution white paper developed by USP staff Broad harmonization across public standards-setting organizations is constrained by dependence on regulatory approvals and regulatory processes which vary across regulatory authorities. For example, one medicine that is approved by regulators in multiple countries may have different impurity profiles in the different countries. This situation can make harmonizing a specific standard challenging for pharmacopeias. In addition, differences in how pharmacopeias operate in their respective regulatory structures also hamper efforts to harmonize standards. Understanding why harmonization is challenging requires an appreciation of these limitations. The nature of harmonization is resource intensive for USP as well as other pharmacopeias, involving both staff time and volunteer hours. The harmonization process also leads to “revision reticence” because it is so arduous; once harmonization is achieved on a standard, there is reluctance to make revisions, even in the face of compelling science and evolving manufacturing technologies. A Brief History of Pharmacopeial Harmonization The first recorded “pharmacopeia” (translated from the Greek as “drug making”), De Materia Medica, included the names and preparation methods of herbal remedies commonly used in ancient Greece and Rome. Since that time, more than 40 pharmacopeias have been established around the world to provide guidelines

and reference standards for medicines, with a focus on the needs of patients within their respective countries. The earliest pharmacopeias used recipes that aimed to establish common approaches by which pharmacists and medical practitioners could bring consistency to the treatments they made for their patients. Today’s robust, science-based pharmacopeias describe for the public the quality attributes of drug products and ingredients to ensure their identity, strength, purity and performance along with other characteristics. USP is one of the earliest examples of an effort to harmonize disparate approaches to the making of medicines into a single pharmacopeia. In 1820, a group of physicians gathered in the U.S. Capitol in Washington, DC, to establish a harmonized pharmacopeia for the 23 states of the time. By the end of that year, the first USP compendium was published. The preface to the first edition of the USP emphasized the importance of uniformity for pharmacopeial standards: “In the United States the evil of irregularity and uncertainty in the preparation of medicines has been felt with peculiar weight… (A) number of Pharmacopeias have been produced in different parts of the Union… (A) National Pharmacopoeia…should be established and adopted…being evidently the only mode by which a uniform system could be introduced at once into all parts of the American territory.”

Terms of Reference Prospective Harmonization: Dialogue among two or more pharmacopoeias in advance of finalizing a standard helps to create harmonized monographs.

Adopt Agreements: These allow other pharmacopeias or regulatory authorities to directly incorporate USP standards into their own compendia to promote convergence among pharmacopeias.

WHO Good Pharmacopeial Practices (GPhP): GPhP provide high-level guidance for the development of pharmacopeial standards by the WHO’s International Meeting of World Pharmacopoeias (IMWP); the WHO Expert Committee on Specifications for Pharmaceutical Preparations oversees the work of IMWP and the GPhP.

USP Exchange Programs: Global organizations involved in standards setting and effective use of standards can share scientific knowledge via USP Exchange Programs. USP’s Visiting Scientist Program and Executive Exchange Program (VSP and EEP) promote exchanges of scientific staff and information with collaborators and organizations committed to pharmacopeial advancement.

200 years of building trust

Resolution white paper developed by USP staff

Following the example set by USP, in 1858 the British Pharmacopoeia (BP) unified the three existing pharmacopeias of Great Britain at the time, which were from London, Edinburgh, and Dublin. In 1951, WHO first published its International Pharmacopoeia. Since 1979, The International Pharmacopoeia has focused primarily on the needs of developing countries and includes specifications for the identification, purity, and content of the WHO List of Essential Medicines. USP and BP provided approximately 80 percent of the 200 drug monographs in the International Pharmacopoeia. Most recently, the European Pharmacopoeia provided an example of successful harmonization across national pharmacopeias, done within the context of the modern era of pharmaceutical development, manufacturing, and regulatory review. Today, harmonization efforts are fraught with the challenges presented by the global supply chain for medicines; as well as the rapidly evolving biomedical and manufacturing science; variations in the approval of medicines; the timing of approvals and approval specifications across national regulatory agencies; inconsistencies in regulatory approaches for approvals of new products; and at times, the absence of a sound scientific basis for compendial decision making. Current USP Efforts Toward Convergence and Harmonization USP engages with international counterparts through the Pharmacopeial Discussion Group (PDG), prospective harmonization and bilateral agreements, adopt agreements, the WHO International Meeting of World Pharmacopeias (IMWP), and USP exchange programs (see box on page 4). USP staff and expert volunteers also provide topic-specific input into the standardssetting activities of the WHO expert groups and working groups on medicines quality topics within the ICH. Each engagement effort is further described below. Together with the European and Japanese Pharmacopoeias, USP formed the PDG in 1989 to harmonize pharmacopeial standards. WHO also participates in PDG as an observer. PDG is established as an informal body for pharmacopeial harmonization, but it operates through a formalized, stepwise process. PDG meets twice a year to carry out retrospective

harmonization of excipient monographs and selected general chapters to help manufacturers satisfy pharmacopeial requirements across these regions. PDG states: “A pharmacopeial general chapter or other pharmacopeial document is harmonized when a pharmaceutical substance or product tested by the document's harmonized procedure as published in the EP, JP and USP yields the same results and the same accept/reject decision is reached.” USP participates as an observer to the ICH Assembly4 and currently has observer-experts appointed to five expert working groups and two informal discussion groups on quality topics. ICH was founded in 1990 by representatives of the regulatory agencies and industry associations of the United States, Europe, and Japan, which corresponds to the regions that participate in pharmacopeial harmonization through PDG. In recent years, ICH has evolved and expanded to include more regulatory authorities in response to increased globalization of drug development. While USP works directly with many national pharmacopeias who are not members of PDG, USP believes that the structure and approach to harmonization and convergence must include additional national pharmacopeias to reflect supply chain globalization.5 Finally, the WHO IMWP is a convening group for all national and regional pharmacopoeias. Its initial focus was developing the guidance document on good pharmacopeial practices, described in the box on page 4. The future direction of the group has yet to be determined; USP has participated in collective efforts to develop a white paper on the Value of Pharmacopeial Standards under this group’s umbrella of activities.

Alignment with USP Mission USP’s efforts towards pharmacopeial cooperation and convergence align with and support USP’s mission. Beginning in 2020, USP will expand dialog to bring its scientific expertise on standards-setting into critical forums such as WHO and ICH, in addition to fostering alignment of the pharmacopeias from more countries and leveraging its relationships with key regulatory bodies and pharmacopeias. Through scientific exchange and training programs, USP remains committed to pursuing convergence with other national

200 years of building trust

Resolution white paper developed by USP staff pharmacopeias to build capabilities among emerging pharmacopeias while advocating for robust, sciencebased standards to improve patient safety and public health. For this work to be successful, it will be important for industry and regulators to continue their support by working with USP to identify and advance more efficient mechanisms and approaches for achieving convergence.

Resource Assessment Resources currently in place. USP is a core participant in the Pharmacopeial Discussion Group and an observer in the International Council on Harmonization. The current Council of Experts (CoE) Expert Committee structure and the proposed structure for the next cycle will support this effort.

References and Notes 1 Adapted from Resolution proposals submitted by Tina Morris, Parenteral Drug Association, and Barbara Ferguson, New Jersey Pharmaceutical Quality Control Association. 2 National Academies of Sciences, Engineering, and Medicine. Regulating medicines in a globalized world: the need for increased reliance among regulators. Washington, DC: National Academies Press; 2019. https://doi.org/10.17226/25594. 3 World Health Organization. Good regulatory practices: guidelines for national regulatory authorities for medical products. Working document QAS 16.686. Geneva: WHO; 2016. Available from: https://www.who.int/medicines/areas/quality_safety/quality_assurance/GoodRegulatory_ PracticesPublicConsult.pdf 4 The mission of ICH is to â&#x20AC;&#x153;achieve greater harmonization worldwide to ensure that safe, effective, and high-quality medicines are developed and registered in the most resource-efficient manner.â&#x20AC;? There are more than 60 ICH Guidelines, which help reduce duplication of clinical trials, minimize animal testing, and simplify submission of new drug applications to multiple regulatory agencies. They also create a common regulatory language that helps to streamline regulatory review and monitoring processes. 5 Adapted from a Resolution proposal submitted by Barbara Ferguson, New Jersey Pharmaceutical Quality Control Association.

200 years of building trust

Proposed Resolution

Evidence Generation to Inform Policy

Resolution white paper developed by USP staff, with input from the Council of the Convention

Resolution white paper developed by USP staff

Proposed Resolution 12

Evidence Generation to Inform Policy

USP will generate and disseminate evidence upon which informed choices can be made for investment in regulatory and quality systems and reforms to regulatory paradigms that advance quality, patient safety, and public health.

Summary Evidence is an essential component of sound public and regulatory policy and is also an important foundation that informs prudent resource investments. A lack of robust evidence can lead to underappreciation of an important public health issue, such as the problem of poor-quality medicines. This issue is critical to public health outcomes, yet the prevalence and impact of poor-quality medicines is still under prioritized during policy formation. In addition, there is sometimes a lack of strong evidence regarding the best regulatory and policy practices and the most costâ&#x20AC;&#x201C;effective strategies for ensuring quality. USP has a demonstrated

commitment to building a robust evidence base that will facilitate sound, science-based decisions. These decisions will help increase the availability of quality medicines around the world and will catalyze action when poor-quality medicines are found in the market. USP has led, collaborated on, or sponsored research that generates evidence on the impact of poor-quality medicines on health threats; regulatory paradigms; and the impact of adherence to public quality standards on public health, patient safety, innovation, and access. At USP, these questions are researched by internal staff and volunteer experts, as well as through independent

200 years of building trust

Resolution white paper developed by USP staff research conducted by outside entities and investigators. This Resolution proposes that USP expand its efforts to generate and disseminate evidence that will help inform both public policy and regulatory policy to safeguard the quality of medicines and their ingredients with a goal of expanding access to quality medicines and protecting patient safety.

Background Quality healthcare is often discussed—in peer-reviewed literature, policy dialogue, and media reports—with little or no mention, and in fact the assumption, of quality medicines as an integral component of a quality healthcare system. Yet quality healthcare cannot exist without quality medicines, and the quality of medicines cannot be assumed; it must be assured. USP defines medicines quality as a balanced, riskbased set of prespecified characteristics, systems, and requirements that consistently ensure a medicine’s delivery of stated and implied clinical outcomes for patients. This definition encompasses all aspects of a medical product’s lifecycle, including its design, manufacture, supply chain, storage and distribution, and in some cases, falsification. Quality can be designed into a product and then improved and reinforced all along the medicine lifecycle, from initial research and development through dispensing to the patient. Interventions to improve quality assurance systems may vary by cost, feasibility, and outcomes for different products, product classes, and geographies. Assessing which interventions are most actionable and potentially effective is of critical importance to promote judicious policies and investment aimed at promoting medicines quality. Ensuring quality medicines requires planned investments, meticulous execution, and rigorous and relentless monitoring—of manufacturing, transportation, storage, distribution, and use—from the national level to community-based clinics and pharmacies. Pharmaceutical products are varied, dynamic, and sensitive in their quality assurance requirements, but they universally require rigorous, science-based pharmacopeial standards. Different types of evidence are often necessary to drive policy changes, regulatory reform, and resource investments. To address broad public health policy issues, we need evidence of the prevalence of poorquality medicines and their links to negative health

outcomes. To strengthen regulatory pathways and systems, evidence showing which approaches are effective in quality assurance and regulatory systems strengthening is needed; this evidence will inform riskbased investments in systems. USP draws on policy, scientific, technical, and global health expertise from internal and external subject matter experts. Through these strategic alliances and investments in independent research, USP has demonstrated its commitment to build a robust evidence base that facilitates decision making and increases the availability of quality medicines everywhere. Although these efforts are still in their early stages, they represent a commitment to 1) contribute to the broader policy environment supporting medicines quality; 2) build a community of global experts in medicines quality research; and 3) foster a generation of investigators who will lead medicines quality research into the future.

Moving from Evidence to Policy and Practice: Poor-Quality Medicines and Antimicrobial Resistance Antimicrobial drug resistance is a serious problem because increasingly more strains of bacteria are becoming resistant to multiple antibiotics and evolve into “superbugs” that are untreatable creating a potentially devastating impact on the entire world. Unless there is an immediate, collaborative response at the global level, antimicrobial resistance (AMR) could lead to 10 million deaths a year by 2050.1 Globally, AMR represents a major threat to patients and the public health, yet until recently, product quality has not been recognized as a driver of AMR due to only limited evidence on the prevalence of poor-quality antimicrobials and their link to resistance, and the lack of advocacy efforts to raise awareness of the issue. Poor-quality medicines—also referred to as substandard and falsified (SF) medicines—can lead to treatment failure and can also escalate AMR. Substandard medicines are those that fail to meet standards or specifications of quality, while falsified medicines have been deliberately or even fraudulently misrepresented in terms of their identity, composition, or source.2 A comprehensive analysis conducted in 2018 found that more than 12 percent of antibiotics circulating in lowand middle-income countries (LMICs) are SF medicines.3 The World Health Organization (WHO) has estimated that nearly 1 in 10 medicines circulating in LMICs are substandard or falsified.4 Antibiotics and antimalarials

200 years of building trust

Resolution white paper developed by USP staff combined constitute 40 percent of SF medicines, making up the largest proportion reported to the WHO Global Surveillance and Monitoring System.5 Poor-quality medicines can result from degradation due to improper storage or distribution, or from poor manufacturing practices that are used either inadvertently or intentionally. The presence of poorquality medicines drives AMR primarily through subtherapeutic dosing. When a patient takes a substandard antibiotic, bacteria are usually exposed to just enough of the active ingredient in the drug to kill weaker strains but strengthen pre-existing resistant strains and give rise to new ones.6 The same phenomenon is observed when patients do not adhere to the full treatment regimen. Resistant strains can grow and spread from human to human, leading to more virulent and deadlier infections. In this manner, SF medicines can contribute to or accelerate AMR. To increase policy attention on this critical issue, the USP Quality Institute supported a study to understand the impact of poor-quality antimicrobial medicines on

the emergence and spread of AMR. Through research collaborations between USP and leading academic partners, the study is exploring historical patterns of antimalarial drug resistance in southeast Asia. It aims to help inform policy choices about treatment strategies in settings where it is known that there are SF medicines. This work demonstrates that poor-quality medicines, like poor adherence, lead to adverse treatment outcomes. The Quality Institute also supports research that builds on evidence related to other pathogens. A low-quality version of rifampin, a broad-spectrum antibiotic often used as a first-line treatment against tuberculosis, can contribute greatly to the development of drug-resistant infections.7 USP supports a study that is exploring mechanisms of resistance to antibiotics. Early findings appear to confirm prior assumptions that, when pathogens are exposed to subtherapeutic doses of SF medicines in vitro, their resistance can increaseâ&#x20AC;&#x201D;which could then give rise to the next deadly superbug. The stakes are even higher because pathogens exposed to SF antibiotics may not only become resistant to that one drug but to multiple other antibiotics as well. This specter

USP Quality Institute Investigational Themes Independent academic researchers and their mentors conduct research sponsored by the USP Quality Institute. Research questions are framed to address evidence gaps around the following problem statements: Antimicrobial Resistance: A global public health threat, AMR is due, in part, to the widespread prevalence of substandard and falsified medicines.

Quality of Excipients:

Procuring for Quality:

The diversity and variability of excipients, the lack of a harmonized regulatory framework, and the fragmented supply chain for products used as excipients allow for potential and unknown risks to quality.

Procurement practices and purchasing negotiations for medicines may be driving behavior that puts quality at risk and leads to an increased prevalence of substandard and falsified medicines. At the same time, implementing certain practices in procurement can ensure patient access to quality medicines and promote â&#x20AC;&#x153;value for moneyâ&#x20AC;? by purchasing quality medicines that are safe for patients and have their intended effect on patient care.

200 years of building trust

Resolution white paper developed by USP staff of â&#x20AC;&#x153;pan-resistanceâ&#x20AC;? points to a greater need for tools to screen for poor quality as or even before clinicians screen patients for resistance. These projects and other research conducted through the USP Quality Institute will generate a rigorous evidence base to inform open discussion, public policy, and regulatory reforms that advance medicines quality. Established in 2017, the Quality Institute partners with leading academic institutions to establish fellowships where independent researchers and their academic mentors address relevant questions in a series of investigational themes related to the quality of medicines (see box on page 4). The research conducted is independent by design to protect the validity of the results. Ultimately, the Quality Institute research helps support the rationale for investments in quality medicines and sheds light on issues such as what investments are needed, where they are needed most, and why they are critical to achieving global public health goals.

Informing Regulatory Paradigms: The Case of Quality Excipients The diversity and variability of excipients, the lack of a harmonized global regulatory framework for excipients, and the fragmented supply chain for products used as excipients pose risks to the quality of these materials and the medicines in which they are used. Excipients are intentionally added ingredients that serve many purposes, such as improving the delivery and bioavailability of the active pharmaceutical ingredient (API). In general, excipients are not intended to have a therapeutic effect; however, they are not necessarily inert. Most excipients are commodity products sold to diverse industries. In fact, only small fractions of these materials are used in medicines. Worldwide, regulation of excipients varies by country and region. Through policy and stakeholder dialogues, regulators have raised concerns regarding the quality of excipients in the global supply chain and their impact on patient safety. At the same time, industry stakeholders have raised concerns over the challenges they experience in the way that excipients are reviewed by the U.S. Food and Drug Administration (FDA) only in the context of a drug application. FDA reviews excipients used in a drug product as part of an investigational new drug application (IND) or a marketing application to determine whether they are safe for use in human pharmaceuticals. Historically, FDA has not reviewed the safety of novel excipients outside

the context of an IND, a new drug application (NDA), or a biologics license application (BLA) describing a finished product to which the excipient has been added. Stakeholders in industry have expressed concerns that the use of novel excipients elevates the risk that safety issues would be raised by FDA during the drug application review, putting tremendous burden on the drug company, including delays or even non-approval. Yet certain novel excipients may provide public health benefits, such as improved drug delivery or utility in certain formulations. Stakeholders have stated that one solution to this challenge could be to create an independent regulatory review of a novel excipient outside of the drug development application to provide FDA with a baseline of safety and toxicological data for consideration in the drug application process. USP surveyed industry stakeholders who formulate medicines to determine the significance of the perceived need for a novel excipient regulatory pathway. The majority of respondents indicated that drug development has been limited, at least some of the time, due to the excipients currently available for use in approved drugs. A smaller proportion of respondents reported having to reformulate a drug product because of excipients limitations. The most common reason related to the current excipient not being used in the selected dosage form. Nearly one-third had experienced a discontinuation of drug development as a result of excipients limitations. Since USP completed and shared publicly the results of this research, FDA has issued a Federal Register Notice to call for public comment on a pilot program for an independent toxicological and quality evaluation of novel excipients intended for use in human drugs.

Making the Economic Case: Quality Standards Facilitate Generic Product Development Research is also needed to address barriers to quality as they relate to cost. Examples point to efficiencies brought about by public standards in increasing access to generic medicines, or economic modeling of return on investments in strengthening specific regulatory and medicines procurement practices. In 2018, USP conducted a blinded online survey of finished-dosage generic drug manufacturing organizations in the United States and India to understand the perceived benefits of pharmacopeial standards in generic research and development (R&D). The survey included both qualitative and quantitative

200 years of building trust

Resolution white paper developed by USP staff measures and narrowed its focus to manufacturers of generic pharmaceutical products seeking FDA approval for the manufacturing and sale of their products in the United States. USP scientists and coauthors wrote a commentary piece reviewing the findings from the survey, published in the Journal of Pharmaceutical Sciences (October 2019).8 The survey sought to explore whether specific types of pharmacopeial monographs bring efficiencies to product development and reduce risks in applications for generics. Most respondents agreed that the use of documentary standards accelerated the development of a generic product and that standards reduce the risk that the ANDA would be rejected by FDA. Garnering this type of evidence from manufacturers can further guide USP’s prioritization of monographs to facilitate access to generic medicines though the product pipeline.

Alignment with USP Mission While historically, USP has emphasized the science in standards-setting, in the last few years, USP has laid a foundation for evidence that informs capability building and policy advocacy. USP has also explored various mechanisms for generating evidence, from

undertaking inquiries directly with stakeholders, such as opinion surveys and qualitative stakeholder dialogue and analysis, to commissioned studies and collaborative research conducted under the Quality Institute. Engaging with other institutions and individuals committed to advancing knowledge in the field of medicines quality, including forming an “evidence curation working group” under the Medicines We Can Trust campaign, is contributing to a growing community of research and practice in medicines quality. Building on these foundations, and through these relationships, USP will continue to work with others to communicate the significance of research findings to policy and public awareness.

Resource Assessment Modest incremental investments required to supplement resources currently in place. The USP Quality Institute has been established and has undertaken several evidence-generating projects, along with additional efforts from across the organization. The staff and framework are in place. Modest incremental funding is planned for additional research.

References and Notes 1 United Nations Interagency Coordination Group on Antimicrobial Resistance. No time to wait: securing the future from drug-resistant infections. 2019 Apr. Available from: https://www.who.int/antimicrobial-resistance/interagency-coordination-group/final-report/en/. 2 World Health Organization. WHO global surveillance and monitoring system for substandard and falsified medical products: reports and executive summary. 2017 Nov. Available from: https://www.who.int/medicines/regulation/ssffc/publications/gsms-report-sf/en/. 3 Ozawa S, Evans DR, Bessias S, Haynie DG, Yemeke TT, Laing SK, Herrington JE. Prevalence and estimated economic burden of substandard and falsified medicines in low- and middle-income countries: a systematic review and meta-analysis. JAMA Netw Open. 2018 Aug;1(4):e181662. doi: https://doi.org/10.1001/jamanetworkopen.2018.1662. 4 World Health Organization. A study on the public health and socioeconomic impact of substandard and falsified medical products. 2017 Nov. Available from: https://www.who.int/medicines/regulation/ssffc/publications/se-study-sf/en/.

5 World Health Organization. WHO global surveillance and monitoring system for substandard and falsified medical products: reports and executive summary. 2017 Nov. Available from: https://www.who.int/medicines/regulation/ssffc/publications/gsms-report-sf/en/. 6 Andersson DI, Hughes D. Microbiological effects of sublethal levels of antibiotics. Nat Rev Microbiol. 2014 Jul;12(7):465–78. doi: 10.1038/ nrmicro3270. 7 Weinstein ZB, Zaman MH. Evolution of rifampin resistance in Escherichia coli and Mycobacterium smegmatis due to substandard drugs. Antimicrob Agents Chemother. 2018 Dec;63:e01243-18. doi: https://doi.org/10.1128/AAC.01243-18.

8 Warthin IK, Berik J, Podolsky D, Raghavendran V, Reddy R, Chang J, Porter N, Gartio N. Commentary on the benefits of US Pharmacopeial

standards: a generic pharmaceutical industry survey. J Pharm Sci. 2020 Feb;109(2):944–49. doi: https://doi.org/10.1016/j.xphs.2019.10.008.

200 years of building trust

Proposed Resolution

Coalition Building Resolution white paper developed by USP staff, with input from the Council of the Convention

Resolution white paper developed by USP staff

Proposed Resolution 13

Coalition Building

USP will lead and power a stakeholder movement for quality to advance public health and patient safety.

Summary In most parts of the world, the political will to make health policy reforms and investments arises from a combination of factors, but almost all involve a coalition of stakeholders, including patients, practitioners, scientists, public health leaders, and others. USP, through its structure of organizations in the USP Convention and its network of expert volunteers is itself a powerful coalition that for two centuries has come together to advance policy on medicines quality. Yet, in our increasingly complex healthcare ecosystem, it takes a broad, diverse set of voices to elevate medicines quality as an important priority for policymakers. Coalitions of

quality champions help transform evidence-based policy imperatives into action. This Resolution proposes that USP lead or engage in multi-stakeholder coalitions that build upon the reach of the USP Convention and other stakeholders to expand and amplify awareness, urgency, and will to improve and ensure the quality of medicines and supplements and thereby advance public health and patient safety. Leveraging its scientific expertise in setting public standards for quality medicines, USP must seek the support and influence of diverse stakeholders, including the public policy, patient, and practitioner communities, and must cultivate an alliance

200 years of building trust

Resolution white paper developed by USP staff

for combined action to address existing or emerging challenges to quality. Over the 2015â&#x20AC;&#x201C;2020 USP cycle, USP has established, led, and participated in a variety of coalitions to advance quality. Examples of this work include the Medicines We Can Trust campaign (https:// medswecantrust.org), founded by USP in collaboration with other influential organizations; the National Coordinating Council for Medication Error Reporting and Prevention (https://www.nccmerp.org), which comprises 27 organizations devoted to patient safety regarding medication use; and the Dietary Supplements Quality Collaborative (https://www.dsqcollaborative.org) a group consumers, patients, caregivers, and manufacturers working together to improve the quality and safety of dietary supplements in the United States.

Background In 1820, a group of concerned physicians gathered to take action to protect patients from poor-quality medicines. Their alliance led to the formation of the U.S. Pharmacopeia (USP). Now, 200 years later, USP is a global leader in building trust in medicines, foods, and supplements. Such trust relies upon complex healthcare, regulatory, and quality assurance systems designed to keep poor-quality products away from the market and out of the hands of patients, and also relies on patients and practitioners understanding the risks and being vigilant in identifying and reporting problems. Building this trust at the national level involves implicit challenges due to the dynamic and sensitive nature of medical products. Today, ensuring medicines quality and maintaining public trust have become increasingly challenging as medicines and their components come from many countries around the world. Global demand means that medicines made in one country may be delivered to patients in many others. Throughout its history, USP has focused on establishing standards to promote quality of medicines and supplements in the United States. U.S. regulatory and enforcement mechanisms rely on these standards as central components of the quality assurance system. Over the past several decades, USP has increasingly spread its reach and impact beyond the United States, an effort that recognizes the interconnected and globalized nature of the supply chain and market for medicines. To fulfill its mission today, USP must work across geographic boundaries and with a multitude of stakeholder groups, including regulators and policymakers protecting public health in countries

around the world as well as industry, healthcare practitioners, and public health organizations. Engaging with and strengthening a scientific community to actively promote and prioritize quality in medicines requires deliberate and focused attention. Yet trust in medicines does not rely on science alone. USP is committed to building broader coalitions to ensure quality, and in the next five years will embark on an expansive vision that includes leading or participating in coalitions to help protect a global community of patients from substandard and falsified medicines and dietary supplements.

Substandard and Falsified Medicines Pose Risks to Patients Globally Substandard and falsified medicines are a growing problem worldwide,1 especially in poorly controlled supply chains or in the absence of stringent regulatory systems. Substandard medicines fail to meet standards or specifications of quality, whereas falsified medicines have been misrepresented in terms of their identity, composition, or source.2 According to estimates of the World Customs Organization, the market for substandard and falsified medicines has risen by 90 percent in the past five years, with estimated worldwide annual sales now nearing $200 billion.3 The high prevalence of poor-quality medicines in the global marketplace poses a grave threat to patient safety and public health. Risks from substandard and falsified medicines include medical products that do not contain the correct substance or dose to effectively treat a disease or health condition, or harmful substances intentionally added to drugs. Misuse or overuse of some medicines, such as antibiotics, can lead to antimicrobial resistance and renders these products ineffective over time, reducing the ability to fight even simple infections in the future. USP recognizes that quality medicines cannot be realized without the political will to act in ways that prevent substandard or falsified medicines from reaching patients. Cultivating this resolve among a diverse and global network of actors cannot be accomplished by any one organization. Coalitions of institutions working together toward a common goal are necessary to achieve meaningful and lasting results. Coalitions are necessary to raise awareness of the problem of substandard and falsified medicines, elevating the issue for practitioners, patients, and policymakers through outreach campaigns about risks and possible responses.

200 years of building trust

Resolution white paper developed by USP staff

USP’s Approach to Coalition Building Coalitions are likely to be effective for medicines quality because the issue is broad enough to attract diverse support and specific enough to motivate action and impart urgency. Furthermore, USP is a natural leader for coalitions on medicines quality given its scientific and technical expertise. The scientific and technical aspects of medicines quality can make this issue challenging for broad public policy discussions and right for USP leadership. USP can convene and organize groups of traditional and nontraditional allies and experts on pharmaceutical ingredient quality and integrity, including and beyond its Convention Membership, and can develop messages appropriate for each audience, whether policymakers, regulators, or the public. In doing this, USP will be better positioned to achieve its mission impact. Typically designed with specific goals in mind, coalitions take different forms and approaches. While there are some common principles that USP applies to each coalition it forms (i.e., focused goal, strategic approach including a call to action, and measurable outcomes), there also are unique characteristics that result from careful consideration each time a coalition is formed

or adapted for a new purpose. These unique features result from a deliberate process of identifying the right partners to join the coalition, generating a sense of shared ownership, agreeing on a singular or focused set of goals, determining the geographic scope and the relevance of coalition, and determining the appropriate cadence of activities and outputs in order to draw and sustain engagement among all collaborators as well as achieve the intended outcomes. Once a coalition has achieved its goal, USP and its partners will need to collectively consider and decide what happens next. The coalition could be redirected to a new goal, preserved but on a reduced scale to help ensure continuity of its outcomes, or dissolved because the new challenges require a different group or approach. In any case, USP will move forward recognizing that coalitions must be organic and dynamic, and success is determined by continuing commitment from USP to maintain and catalyze its partners and policymakers to action. Examples of USP-Led Coalitions USP leads or engages in multiple coalitions to advance quality in the context of a globalized supply chain and market for medicines. Examples of coalitions that are

Theory of Change Coalitions are one component of a broader USP strategy to achieve its mission. USP has undertaken a comprehensive “theory of change” analysis of the core public health problem that it aims to address: People lack access to safe, quality medicines and dietary supplements. The theory of change framework shows the interdependencies of USP’s efforts: How one intervention contributes to multiple outcomes,

Why partnerships could prove fruitful in tackling complex or unique problems, and

Where USP could provide leadership.

A theory of change includes a comprehensive strategy to obtain the desired change and the metrics to measure the success of specific actions that are hypothesized to lead to the desired change. This analysis has led to an understanding of how coalitions will support USP in pursuing its mission of advancing medicines quality. 200 years of building trust

Resolution white paper developed by USP staff

underway include broad and standing groups such as the Medicines We Can Trust campaign, the National Coordinating Council for Medication Error Reporting and Prevention, and the Dietary Supplements Quality Collaborative. • Medicines We Can Trust: Through a globally distributed network of more than 300 partners, USP has catalyzed the Medicines We Can Trust campaign to raise awareness about the importance of medicines quality. Launched in 2018, the campaign is a global movement to ensure that decision makers in government and the public understand the scope and impact of poor-quality medicines. Beyond simply conveying information, the campaign aims to inspire collective action by illustrating effective solutions, showcasing personal stories about people affected by and working to address poorquality medicines, and providing a platform for advocates to access resources and mobilize policy change. Partners include representatives from civil society organizations, government entities, philanthropic foundations, and others committed to medicines quality. The campaign is led by a steering committee of activists, researchers, regulators, and global health leaders, and USP leads the committee in its strategic discussions and direction setting for the campaign. • National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP): In 1995, USP led the effort to form NCC MERP, with the goal that no patient will ever be harmed by a medication error. Today, NCC MERP comprises 27 national organizations committed to patient safety regarding medication use. Participating organizations meet, collaborate, and cooperate to address the interdisciplinary causes of medication errors and to promote the safe use of medications. Through their participation in NCC MERP, USP and collaborating organizations aim to stimulate the development and use of reporting and evaluation systems by individual healthcare organizations, and to report to a national system for review, analysis, and development of recommendations to reduce and prevent medication errors. By evaluating the causes of medication errors and increasing awareness of how to prevent them, NCC MERP organizations come together to recommend strategies for system modifications, practice standards and guidelines, and changes in

packaging and labeling. USP is the Secretariat for NCC MERP. • Dietary Supplements Quality Collaborative: Many consumers in the United States take one or more dietary supplements4 either occasionally or daily, and they expect these supplements to be safe, quality products that are accurately labeled for their contents. Over the past 25 years, the dietary supplement industry has grown from $4 billion with 4,000 products to $40 billion with more than 50,000 diﬀerent products. As demand for supplements has increased, some unethical individuals and companies have engaged in the manufacture and distribution of intentionally adulterated or misbranded products labeled as supplements, which have generated significant threats to consumer health and safety. Recognizing the need to advance the quality and safety of dietary supplements, USP convened the Dietary Supplements Quality Collaborative (DSQC) in 2016. This group includes more than 20 consumer, patient, caregiver, and public health organizations as well as dietary supplement ingredient and finished product manufacturers. United by its guiding principles, the DSQC works cooperatively to advance consensus-based solutions to improve public health with respect to dietary supplements. Examples of specific accomplishments include development of a set of consensus principles intended to modernize and strengthen policies to advance the safety and quality of products marketed as dietary supplements, an educational infographic related to the topic of tainted products and accompanying communication plans.

Alignment with USP Mission USP has recognized that to optimize impact and grow a demand for quality medicines globally, the organization must actively work to develop evidence and awareness about the issues, develop coalitions of motivated stakeholders, and through these, work to create a sense of urgency and political will toward policies and investments in quality. As demonstrated by the examples above, USP has a strong foundation upon which to expand the scale and help drive a sense of urgency to act. These efforts will require ongoing investment and commitment, from both USP and its partners. Through coalitions, USP will activate its partners in medicines quality to have broad geographic

200 years of building trust

Resolution white paper developed by USP staff and political reach. Either as a leader or participant in coalitions, USP can elevate national and global health policy discussions by deploying assets where needed to influence policy outcomes and directing debate over key issues. Coalitions will position USP and its allies to take on new issues as they arise and create a balanced public narrative as well as support capabilities among policymakers. This nimble approach will allow USP to provide scientific input on relevant policy issues and deepen its role in the public conversation around medicines safety and quality.

Resource Assessment Resources currently in place. USP’s Global External Affairs function established in the 2015–2020 cycle and the organization achieved official and formal recognition of in global forums including WHO, Pan American Health Organization (PAHO), International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), Asia–Pacific Economic Cooperation (APEC), and others. Proof-of-concept successful with the development of both international and U.S.-focused coalitions.

References and Notes 1 Mackey, TK, Liang BA, York P, Kubic T. Counterfeit drug penetration into global legitimate medicine supply chains: a global assessment. Am J Trop Med Hyg. 2015;92(6):59–67. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4455087. 2 World Health Organization. WHO global surveillance and monitoring system for substandard and falsified medical products. 2017. Available from: https://www.who.int/medicines/regulation/ssffc/publications/%20gsms-report-sf/en. 3 Reuters. Customs group to fight $200 billion bogus drug industry. 2010. Available from: https://www.reuters.com/article/us-customs-drugs/ customs-group-to-fight-200-bln-bogus-drug-industry-idUSTRE65961U20100610. 4 U.S. law defines a “dietary supplement” as a product that contains a “dietary ingredient” intended to add further nutritional value to (supplement) the diet.

200 years of building trust

Proposed Resolution

Culture of Excellence

Resolution white paper developed by USP staff, with input from the Council of the Convention

Resolution white paper developed by USP staff

Proposed Resolution 14

Culture of Excellence

USP will model operational excellence, continuous improvement, stakeholder responsiveness, and transparency.

Summary Excellence and quality underpin USPâ&#x20AC;&#x2122;s foundational pursuit: to build trust in the quality of medicines, dietary supplements, and foods through its public standards. As a global leader in establishing public standards for quality, USP works to ensure that its products, services, and personnel exceed the expectations of stakeholders and the needs of patients around the world. Through its Quality Assurance department, USP continually evaluates and refines internal work processes to increase efficiency and improve consistency. This Resolution proposes that USP maintain and strengthen its commitment to implementing a fully integrated,

global approach to operational excellence and monitor its progress to achieve continuous improvement as codified by clearly defined metrics and objectives.1 USP will model a culture of excellence across all sites and divisions, including a robust quality management system (QMS), as the foundation for an environment where USP scientists and other staff can do their best work and from whom stakeholders can reliably expect responsiveness and transparency. Furthermore, USP will continuously strive for excellence in its quality systems to ensure that proposed standards,

200 years of building trust

Resolution white paper developed by USP staff whether new or revised, capture and respond to the perspectives of stakeholders. This will be accomplished before proposed revisions to USP–NF are made public in Pharmacopeial Forum (PF; the free bimonthly online journal in which USP publishes proposed revisions to USP–NF), thereby increasing efficiency and transparency in the standards-setting process.2 This proposed Resolution defines what USP means by a “culture of excellence” and how that culture serves to enable and support effective standards, evidence-based advocacy, and efficient capability building.

Background Excellence and quality together form the foundation for USP’s greatest strength and core mission: developing public quality standards to build stakeholder trust in medicines, dietary supplements, and food. As USP standards define quality for the products made or used by stakeholders, quality also defines the culture within which USP staff and expert volunteers establish those standards. In a culture of excellence, a set of values guides the way that everyday practices and outputs are assessed and improved. USP leadership inspires all staff to foster excellence in every action undertaken and every decision made. USP staff have access to a dynamic portfolio of tools and learning opportunities, including a wide range of continuing education courses. In addition to a rigorous onboarding process for new hires, staff are regularly required to complete training to stay current with best practices, knowledge, and skills relative to the organization and important for individual responsibilities. Additionally, USP encourages collaboration and information-sharing among teams, across divisions, and with external stakeholders as appropriate. USP leadership urges staff across the organization to raise concerns about quality whenever they arise. At USP, a “culture of excellence” means everyone shares the responsibility of ensuring the quality of USP standards.

USP’s Quality Policy and ISO Accreditation USP cultivates excellence in its processes and performance, using approaches that are both internationally recognized and organizationally unique. As a global leader in setting public standards, USP demonstrates the importance of abiding by quality standards through the implementation and execution of its own robust QMS. This defined QMS comprises a set of policies, processes, and procedures that guide the ways that USP manages and delivers its core business,

i.e., setting quality standards for medicines, dietary supplements, and food. USP’s QMS also helps ensure that the organization models operational excellence and maintains an environment conducive to continuous improvement. Because USP relies on the elements of an effective QMS and an established culture of excellence, the organization’s processes are clearly defined, information is readily accessible, and decisions are made on the basis of sound science. Ultimately, USP’s culture of excellence honors its quality commitment, which makes USP’s work more effective and efficient, both internally and externally. On a daily basis, USP staff are required to comply with the USP Quality Policy as well as international quality standards that apply to USP’s operations. The USP Quality Policy defines the way the organization works, letting its customers and stakeholders know about USP’s values, intentions, and principles. The Quality Policy is defined and driven by specific organizational principles, and USP achieves its public health mission through its ongoing commitment to these principles: • USP relies on robust public input and independent, scientific decision making to develop and deliver standards, programs, and services that are timely and effective and meet or exceed users’ needs and expectations. • USP builds mutually beneficial relationships with customers, stakeholders, and volunteers to advance shared public health goals. • USP drives continual improvement based on applicable requirements, a rigorous QMS, welldefined measurements, best practices, and user feedback. • USP engages in proactive risk management across its functions. Generally, a QMS must demonstrate an organization’s ability to consistently provide products and services that meet customer needs as well as applicable statutory and regulatory requirements. A QMS must also aim to enhance customer satisfaction through the effective application of the system, including processes for improvement and assurance of conformity with applicable requirements.3 For USP, the QMS is a formalized system that documents processes, procedures, and responsibilities for achieving quality policies, objectives, and process excellence. It helps coordinate and direct activities to meet customer

200 years of building trust

Resolution white paper developed by USP staff and regulatory requirements and improve effectiveness and efficiency on a continuous basis.4 USP actively pursues compliance with relevant ISO standards. USP has partnered globally with other recognized leaders in the certification and accreditation of the QMS to provide objective, third-party evaluations of its systems. USP’s partners include BSI Management Systems for ISO 9001 certification and ANSI–ASQ National Accreditation Board (ANAB) for ISO 17025 accreditation. • ISO 9001:2015 “Quality Management Systems”: This global certification demonstrates that USP’s QMS provides effective management of internal processes to meet international quality requirements. The certification ensures that USP’s global locations in the United States, Europe, Brazil, China, Ghana, and India all adhere to, and demonstrate, the same QMS practices and procedures. • ISO 17025:2017 “General Requirements for the Competence of Testing and Calibration Laboratories”: This an international standard demonstrating that testing and calibration laboratories operate a quality system, are technically competent, and generate technically valid results. The standard covers every aspect of laboratory management. ISO 17025 accreditation of the USP laboratories resulted from an extensive review of USP’s laboratory practices and was achieved at each USP site: USP–U.S., USP–Brazil, USP–China, USP–Ghana, and USP–India.

Cultivating Operational Excellence During the next five years, USP will focus on developing a norm of operational excellence that will guide the organization’s work and enhance its quality culture. This way of working will be embodied by staff across all USP sites and divisions; it will be organization wide and codified by specific metrics. This will mean that everyone at USP is held accountable for work products, is expected to look continuously for ways to improve processes, and is empowered to own and manage those improvements. USP has identified three areas that, if handled effectively, will result in the enhanced quality culture that USP wants to achieve. These areas are 1) building and establishing a continuous improvement mindset, 2) developing robust knowledge management capabilities, and 3) applying a strategic lens to decision making to ensure that staff use reliable, valid data and information to drive decisions. • Continuous Improvement Mindset: Guided by USP’s “right the first time” mindset, USP will leverage industry best practices to enhance continuous improvement throughout the organization and establish enabling behaviors that reduce variability and increase efficiency. Continuous improvement means building behaviors that increase consistency by controlling variability, setting risk mitigation and governance strategies, increasing transparency, continuously improving data quality for building products and services, and supporting self-reinforcing processes for organizational enhancements. Continuous improvement and

Terms of Reference7 Continuous improvement: This

Stakeholder responsiveness:

refers to the ongoing improvement of products, services, or processes through incremental and breakthrough improvements. These efforts can seek “incremental” improvement over time or "breakthrough” improvement all at once.

Responding to stakeholder needs in a timely fashion includes having the capability to respond to stakeholder demands.

Operational excellence: This relates to an organizational state in which people, processes, and systems are optimized in support of organizational goals, leading to a consistent output and consistently meeting customer requirements.

Transparency: This attribute is

characterized by visibility or accessibility of information, especially concerning business practices.

200 years of building trust

Resolution white paper developed by USP staff continuing to put quality at the center of everything USP does will result in even greater quality and efficiency, foundations for measuring success, and an improved reputation as a standards-setter. It will also provide a vehicle for refining and refreshing processes, as well as lead to a more rewarding experience for staff and volunteers. USP will build off the momentum from the current cycle and continue to transform programs aimed at redesigning processes; develop systems, tools, metrics; and bring staff along to drive a continuous improvement environment. • Robust Knowledge Management: Knowledge management is an accelerant of both quality and productivity at USP. The intellectual capital developed by USP will be managed and shared across the organization and, where appropriate, with its external stakeholders. Knowledge will be leveraged to create new and better outcomes and will be kept current and retrievable. Reinforcing the importance of knowledge management will help ensure that USP retains the intellectual capital of its staff, builds new and better deliverables based on cross-functional learnings, collaborates across silos to create stronger and more innovative products, and enables better cycles of continuous improvement. A commitment to retaining, sharing, and building USP’s institutional knowledge will ensure that knowledge management accelerates existing processes, enhances decision making through a well-organized and easy-to-use structure, enables a global workforce, supports USP’s mission of developing and advancing scientific knowledge, and ensures consistency with USP’s standards-setting process of open collaboration and transparency. USP will enhance and upgrade its knowledge management systems and processes by establishing a knowledge management center of excellence and a five-year organizational strategy. • Strategic Decision Making: Data-driven decision making is a guiding principle at USP. This means a strategic lens is applied to decision making; hypotheses and forward-looking assumptions are tested based on measurable data to make informed long-term choices. This way of working values high-quality data, considers diverse viewpoints, promotes transparency, standardizes and trusts internal data sources and measured processes, uses measurable key performance indicators to inform high-level decision making and planning. Data-driven organizations function with agility by detecting new opportunities and responding to

changes in a timely manner. This approach elevates measurable methods to test hypotheses, thereby supporting investments in people and sustainability with data, as well as leveraging learnings and fostering innovation.

USP’s new Adapt.Transform.Progress (ATP) program brings together these three bulleted areas described above by establishing a consistent and efficient casebased approach to standards development. ATP will leverage technology, organizational knowledge, and USP’s talented staff and expert volunteers. Furthermore, through ATP, USP will institute a new way of working that will improve quality, better align its products with customer needs, establish more predictable product delivery, and generally enable more effective pursuit of USP’s mission. These enhancements will allow USP to meet the growing needs of users and stakeholders by optimizing key systems and processes. By focusing on these areas, USP can continue to invest in science, deliver consistent quality, and respond to global health needs in a digital age. Several additional activities that will be addressed in the 2020–2025 cycle are considered foundational for supporting USP’s culture of excellence: • Enterprise Content Management via Desktop Tools: These tools will provide a user-friendly way to develop and collaborate on content, both internal and external, and to structure, store, and retrieve information. This is foundational to a valueadded knowledge management platform, which is critical to empowering a robust environment for identifying, capturing, sharing, and learning information for staff and volunteers. • Customer Relationship Management Tools: Given that one of USP’s key strengths is the trust of its stakeholders, USP will utilize customer relationship management tools that help the organization value its customers, enhance customer experience, improve transparency, and ensure that USP’s culture of quality results in a positive impact on health. USP recognizes that stakeholder responsiveness is essential to earning trust, and this means responding to stakeholders, not only quickly but also effectively and meaningfully. USP commits to timelier stakeholder dialogue and to expanding its communication and outreach about proposed changes. USP will ensure that the quality of the commentary is consistently reflective of the revision input received.5

200 years of building trust

Resolution white paper developed by USP staff Part of enhancing USP’s quality systems is ensuring appropriate communication and transparency; USP recognizes that public review and publication processes and communication are essential to reviewing and resolving feedback from stakeholders and publishing correct information.6 The Public Input Lifecycle and Impact Project (PILIP) at USP, which covers the lifecycle of a standard, encompasses development, identification of affected stakeholders, public notice and comment, and communication about outcomes; PILIP is an example of a key improvement effort in this area. Through PILIP, USP staff will develop new, research-based PF tools and comment mechanisms that integrate the public input processes and systems with transforming standards development processes and systems. For more information about PILIP, please read the proposed Resolution white paper on Quality Standards.

Alignment with USP Mission A culture of excellence at USP means people, processes, and systems are aligned and working optimally in pursuit

of the organization’s mission. An effective foundation of rigorous process and data management with continuous improvement will enhance decision making as well as the way that USP interacts and shares information with its stakeholders. By focusing on improving effective and reliable procedures and systems, USP will be better positioned to expand access to quality medicines, facilitate innovation for quality medicines, and improve public health.

Resource Assessment Resources currently in place. The USP Quality Department works across the organization to ensure compliance to ISO 9001 and also to identify further areas to advance excellence in operations. Additionally, several standards development and organizational process effectiveness initiatives were developed in this cycle. These provide the foundation to implement the culture of excellence ambition in the 2020–2025 cycle.

References and Notes 1 Adapted from a Resolution proposal submitted by Tina Morris, Parenteral Drug Association. 2 Adapted from a Resolution proposal submitted by Barbara Ferguson, New Jersey Pharmaceutical Quality Control Association. 3 International Organization for Standard (ISO). ISO 9001:2015 Quality management systems–requirements. 2015 Sep. Available from: https:// www.iso.org/standard/62085.html. 4 USP. Quality management systems training course. 2017 Jan. Available from: https://www.usp.org/sites/default/files/usp/document/workshops/ cepat-courses/qms-training-may-2018.pdf. 5 Adapted from a Resolution proposal submitted by Tina Morris, Parenteral Drug Association. 6 Adapted from a Resolution proposal submitted by Barbara Ferguson, New Jersey Pharmaceutical Quality Control Association. 7 TOR definitions adapted from https://asq.org/quality-resources/continuous-improvement; https://digitalcommons.usu.edu/cgi/viewcontent. cgi?article=1367&context=manage_facpub; and https://www.benchmarksixsigma.com.

200 years of building trust

Proposed Resolution

Impact Expansion Resolution white paper developed by USP staff, with input from the Council of the Convention

Resolution white paper developed by USP staff

Proposed Resolution 15

Impact Expansion

USP will expand its public health impact by reaching more people in more geographies with USP standards, capability building, and advocacy.

Summary When USP was founded, and throughout much of its early history, the organization focused primarily on medicines quality in the United States. Today, the increasingly global nature of medicines development and production, economic development, and expanding health systems around the world has created numerous opportunities to help advance patient safety, public health, and access to quality medicines in nearly every part of the world. One of USPâ&#x20AC;&#x2122;s greatest impact opportunities is to further harness and leverage its 200 years of commitment to, and investment in, robust, science-based quality standards for the benefit of people

wherever they live, whether in the United States or elsewhere in North America, Latin America, Asia, Africa, or Europe. This Resolution proposes that USP apply its capabilities proactively, intensively, and in collaboration with public agencies and stakeholders, to help advance patient safety and public health worldwide.

Background At its founding 200 years ago, USPâ&#x20AC;&#x2122;s mission was to help ensure that safe, quality-assured medical products were available in the United States. Over time, and increasingly for the past 10 years, USP has invited

200 years of building trust

Resolution white paper developed by USP staff

dozens of government, industry, practitioner, and consumer groups from outside the United States into the USP Convention. In addition, the composition of USP’s standards-setting Expert Committees has become more global. Through this combination, USP has made important strides forward in integrating the global healthcare community into the framework of USP’s governance and standards-setting mechanisms. Today, as part of a global community, USP has broadened its mission to encompass improving global health through public standards and related programs that help ensure the quality of medicines. This expanded mission will be accomplished through USP standards, capability building, and advocacy. USP’s achievements include modernized quality standards for medicines that benefit patients around the world. As part of its modernization efforts, USP relied on research that examined the World Health Organization (WHO) Model List of Essential Medicines and identified those medicines lacking public quality standards.1 Informed by these data, USP-NF includes greater coverage of medicines on the WHO list, and the organization has established a mechanism by which to prioritize monograph revision or development for highburden medicines. Additionally, USP has developed and deployed education and training programs to expand the capability of regulators, industry, and others to optimize the impact of USP standards. USP has invested in both laboratory capacity and collaborative efforts with government and industry in countries on every continent; more than 30 percent of USP staff are based in locations outside the United States. In addition, USP has implemented U.S. Agency for International Development (USAID)-funded programs, including the Promoting the Quality of Medicines (PQM) program. Through these programs USP has worked with regulators and industry in nearly 40 countries over a 26-year period. USP has also launched research initiatives to help inform public policy and regulatory policy making, and USP forms coalitions of stakeholders to raise awareness and increase urgency and political will to invest in regulatory systems and policy reforms to help ensure the quality of medicines. These steps have positioned the organization to build global perspectives and insights as well as incorporate global expertise into its work, which allows USP to expand its impact significantly around the world.

A Brief History of USP’s Impact Expansion USP’s presence as a key actor in the global health community is not new. International demand for USP’s reference and documentary standards increased dramatically at the end of the 20th century. In 1969, USP standards were recognized in 27 countries, serving as the sole standard in Costa Rica, El Salvador, and Panama. By 1990, the list of countries officially recognizing the U.S. Pharmacopeia–National Formulary (USP–NF) had risen to 46. From 1995 to 2000, the Convention also reached agreements with the pharmacopeias of Argentina, Brazil, and Mexico to adopt and adapt USP standards. These initiatives served to build relationships with other agencies and enhanced awareness of USP as a global leader in quality standards. Since 2000, USP has expanded its impact by creating its global sites, establishing modern translations of USP–NF, developing and formalizing multiple alliances with collaborator organizations, and launching a globally accessible digital platform for USP–NF, among other activities. • Modern Translations of USP–NF: Almost a century after the first USP Spanish translation, USP resumed its translation efforts and began publishing an official, annual USP–NF Spanish Edition in 2005. In 2009, a Russian edition of USP 29–NF 24 was published. While not official or intended for regulatory compliance, the translation is a useful reference for the growing Russian pharmaceutical industry. A new effort has just begun to translate a more recent version of the USP–NF into Russian and keep it current. USP has also started working on Chinese translations of the USP–NF. • Alliances: Throughout its history, USP has had strong relationships with international bodies, pharmacopoeias, and regulatory authorities in many countries (for more information about these relationships and USP efforts, review the white paper on the proposed Resolution, Pharmacopeial Cooperation and Convergence). USP has advanced these relationships by jointly hosting annual science meetings and symposia in various parts of the world. These meetings facilitate the exchange of scientific information and strengthen collaborative relationships. Since 2000, USP has partnered with organizations to host meetings and stakeholder forums in India, China, Latin

200 years of building trust

Resolution white paper developed by USP staff counterfeit medicines, and support global efforts to improve public health. PQM supports the prevention of substandard and counterfeit medicines by developing monographs, providing collaborative testing, and offering technical assistance in the form of reference standards, documentary standards, and training. PQM has helped communities in more than 35 countries in Africa, Asia, Eastern Europe, and Latin America.

America, the Middle East, and North Africa. Formal agreements signed with standards-setting groups, government agencies, and industry organizations in 2008 and 2009 have solidified these partnerships, fostering collaboration in the development of standards, verification activities, training, and visiting scientist programs. • Investing in Laboratory Infrastructure: In 2000, USP implemented the USAID-sponsored Drug Quality and Information (DQI) program, focused on improving the quality of medicines and their appropriate use in resource-limited countries. It concentrated on malaria, HIV/AIDS, and tuberculosis in Latin America, Africa, and Asia, working with national governments and global agencies to combat counterfeit medicines. The first Official Medicines Control Laboratory (OMCL) Network—the External Quality Control Programs (EQCP) network—was created in 2001 through the collaboration of USP, the Pan American Health Organization (PAHO), and OMCLs from Latin American and Caribbean countries.

Expanding Impact USP’s efforts have grown consistently in response to increasing complexities and risks in global health. USP now has in place an infrastructure that allows the organization to work with both local stakeholders and global entities to leverage its capabilities to help protect patient safety and public health around the world. These capabilities include:

• Promoting the Quality of Medicines (PQM) Program: In 2009, USP was awarded a five-year $35 million USAID grant to support a new expanded program that transitioned DQI efforts and resources into the PQM program. PQM’s focus was to strengthen medicines quality assurance systems, combat substandard and

• Formation of a matrixed leadership structure using the best of both a global, centralized approach to function and a decentralized, regional leadership for collaboration and execution; • Recruitment of locally based staff to engage with regulators, practitioners, and industry concerning local needs and public health priorities; • Establishment of USP as an officially recognized nongovernmental organization in multilateral forums including the Asia-Pacific Economic Cooperation

USP 2025 Impact Strategies Standards:

Capability Building:

Advocacy:

USP will continue to be a definitive source of medicines quality standards using several new strategies

USP will be a leading provider of services that are essential to improving patient access to quality medicines

USP will be a global institutional leader advancing medicines quality

• Remain up-to-date

• Collaborate with regulators

• Generate and disseminate evidence

• Adopt a more flexible, agile, and iterative approach to standards development and delivery

• Provide training for industry

• Build trust in USP standards

• Engage practitioners

• Integrate USP standards into frameworks for biomedical innovations and emerging areas of medicine

• Address new and emerging therapeutic classes, including biologics and biosimilars.

• Facilitate adoption of new technologies

200 years of building trust

Resolution white paper developed by USP staff

(APEC), New Partnership for Africaâ&#x20AC;&#x2122;s Development (NEPAD), PAHO, WHO, and as well as collaborations through Memorandums of Understanding with most of the major pharmacopeias and regulatory agencies in the world;

â&#x20AC;˘ Geographically expanded training and education platforms to reach stakeholders on every continent; â&#x20AC;˘ Implementation of the Promoting the Quality of Medicines Plus (PQM+) program funded by USAID, which will expand the capabilities of governments and manufacturers in low- and middle- income countries around the world. USP Will Be a Definitive Source of Quality Standards USP will expand its impact by continuing to work with regulators, sharing its legacy of scientific expertise to support local regulatory efforts and build confidence in USP standards among regulators (to learn more, please read the papers on Efficiency in Standards Development and Revision and Collaboration with FDA and Other Stakeholders on Health Priorities). Additionally, USP will work toward greater convergence in public quality standards (to learn more, please read the paper on Pharmacopeial Cooperation and Convergence). USP will also prioritize new or revised standards that meet stakeholder needs or address medicines quality issues where people are most at risk; these may include performance standards for biologics or standards for antibiotics and vaccines, among others (to learn more, please read the paper on Access to Biologics). Finally, USP will strive to ensure that its standards remain up-to-date and will encourage and support the use of innovative technologies such as new analytical methods for improving the quality of medicines (to learn more, please read the papers on Innovation and Digital Transformation of Standards). USP will develop and revise standards in a manner consistent with the best scientific knowledge available through increasingly global and flexible networks of expertise (for more information, please read the paper on Quality Standards). By taking a more flexible, agile, and iterative approach to standards development and delivery, USP can deliver standards that are fit-for-purpose in more geographies, in an efficient manner, and responsive to the needs of USP stakeholders (to learn more, please read the paper on Culture of Excellence).

USP Will Be a Leading Provider of Services That Are Essential to Improving Access to Quality Medicines Another way USP can impact more people is as a leading provider of services that are essential to improving medicines quality. This involves collaborating with regulators, providing training for industry, engaging practitioners, and facilitating the adoption of new technologies. USP offers unique and tailored education and training programs to students as well as stakeholders in industry and regulatory agencies worldwide (to learn more, please read the paper on Education and Training for Industry and Healthcare Practitioners). Trainings are available in person and through multimedia digital platforms. USP also provides direct support to governments in countries around the world to build regulatory and quality assurance systems. For example, USP works with governments and regulators in low- and middle-income countries through APEC and the USP Center of Excellence for Securing Medicines Quality Across the Supply Chain (to learn more, please read the paper on Regulatory Systems Strengthening). USP Will Be a Global Institutional Leader Advancing Medicines Quality As a global organization focused solely on advancing patient safety, public health, innovation, and access to quality medicines through science-based standards, USP is uniquely positioned to lead and convene stakeholders around medicines quality. In doing so, we support stakeholders around the world by helping make the broader community mindful that the quality of medicines is foundational to healthcare and requires focused financial and human resource investments and prioritization among policy initiatives. USP brings together stakeholders in coalitions to advocate for policies that will ensure patient access to quality medicines in the United States and around the world (to learn more, please read the paper on Coalition Building). In addition, as a science-based and mission-driven organization, USP generates evidence that can help policy makers and regulators worldwide make informed decisions about investments and policy reform (to learn more, please read the paper on Evidence Generation to Inform Policy). Finally, by leveraging digital media and other innovative forums, USP can build awareness and create a sense of urgency about quality in the interests of patient safety and public health.

200 years of building trust

Resolution white paper developed by USP staff

Alignment with USP Mission The complexities of our interconnected world impact patient safety and public health, both in the United States and abroad. The medicines supply chain for all countries is global, making adherence to science-based standards more important than ever. Patients, regardless of where they live, remain vulnerable to the safety risks of poor-quality medicines. With globalization has come shared societal public health risks that can accompany medicines quality challenges. An urgent example is antimicrobial resistance, driven partly by poor-quality antimicrobials. USP begins its third century ready to make a greater impact on public health than ever before. USP will accomplish this by leveraging its capabilities in collaboration with partners around the world, along with an expanded commitment to advance access to quality medicines. USP has the greatest impact on medicines quality when it brings together USP standards, advocacy,

and capability building. By cultivating critical success factors that focus on people, continuous improvement, digital optimization, and investment and sustainability, USP will fulfill its mission and expand its impact to reach more people in more areas around the world.

Resource Assessment Modest incremental investments required to supplement resources currently in place. In the second half of the 2015–2020 cycle, USP invested in externally facing functions and staff on five continents, worked with stakeholders to identify needs, and has begun to implement programs to leverage USP’s 200 years of investment and expertise in collaboration with, and in support of, stakeholders around the world. We will optimize this foundational investment to support medicines quality across the global supply chain for the benefit of patients and consumers around the world.

References and Notes 1 Roth L, Adler M, Jain T, Bempong D. Monographs for medicines on WHO’s Model List of Essential Medicines. Bulletin of the World Health Organization 2018;96:378–385. doi:http://dx.doi.org/10.2471/BLT.17.205807.

200 years of building trust