Ensuring the safety of food and the quality and safety of medicines in a country is an important role of government, described by the World Health Organization (WHO) as an essential public health function. It is a technical and labor-intensive job, made more complicated by global manufacturing and international trade. Occasionally, product safety scares in the United States draw attention to the role of the U.S. Food and Drug and Administration (FDA), but for the most part, the regulation of food and medicines is taken for granted because it works well. The same cannot be said in most low- and middle-income countries. By recent estimates, unsafe food kills over 400,000 people a year, a third of them children under 5, mostly in low- and middle-income countries; every year poor quality medicines cause about 70,000 excess deaths from childhood pneumonia and roughly 8,500 to 20,000 malaria deaths in sub-Saharan Africa alone.
These and similar problems are of special concern to the FDA Office of Global Policy and Strategy2 as it is charged with improving capacity of the agency’s foreign counterpart offices and increasing understanding of the importance of regulatory systems for public health, development, and trade. This mission influenced the agency’s commission of the 2012 Institute of Medicine report on regulatory systems, Ensuring Safe Food and Medical Products Through Stronger Regulatory Systems Abroad. Among other things, the report outlines strategies to secure international supply chains,
1 References are not included in the report summary. Please view the body of the report for a full list of works cited.
2 Formerly called the Office of International Programs.
emphasizes capacity building and support for surveillance in low- and middle-income countries, and explores ways to facilitate work sharing among food and medical product regulatory agencies (hereafter, regulatory agencies).
Circumstances for regulators have evolved since 2012, as has the broader context of global health and development. With this in mind, the FDA Office of Global Policy and Strategy commissioned this study to clarify how such transitions affect the way regulators work, to promote understanding of the importance of regulatory systems, and to increase scientific robustness at regulatory agencies.
The committee recognizes the responsibility regulators have for the products in their market, while also emphasizing that these agencies do not operate in a vacuum. Therefore, the report gives considerable emphasis to actions at the global and national levels that foster the ability of a regulatory agency to function well. The report starts with analysis of global programs and trends, moving to increasingly narrow sub-divisions. As Table S-1 shows, recommendations start at the global level, then move to changes at the level of the national government. The last group of recommendations are made at the level of the regulatory agency, suggesting an agenda for regulatory agencies and cooperation among countries.
This report sets out a strategy to support good-quality, wholesome food and safe, effective medical products around the world. Its goal is to build on the momentum for strengthening regulatory systems and to set a course for sustainability and continued progress.
REGULATORY SYSTEMS, GLOBAL HEALTH, AND DEVELOPMENT
Health in low- and middle-income countries has improved over the last two decades. Child mortality and infectious disease prevalence have fallen; nutrition has improved. While bilateral, multilateral, and private donors deserve credit for this progress, it is also a function of increasing global prosperity and national investments in health systems and other social programs. By 2020, about half the world will live in a middle-class household. This change has implications for governments, as members of the middle class are better able to demand safe food and health services. But public services in most of the world are not keeping pace with that change. Safe food and good-quality medicines are a precondition to successful development, since a growing demand for these products is a consequence of progress.
Strengthening regulatory systems is important for continued global prosperity and progress in health. It also requires a common understanding of the regulatory process. Risk-based decision making, including the continuous and iterative assessment of risk, is the cornerstone of this process.
|Level of Action||Topic||Actors||Recommendation|
|Global||Food safety||FAO and WHO||Recommendation 2-1: The Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO) should convene biennial meetings for food safety regulators similar to the International Conference of Drug Regulatory Authorities.|
|Medical products||WHO||Recommendation 3-2: The World Health Organization should expand prequalification to include treatments for cancer, diabetes, and other diseases with a high global burden.|
|Global health and development||Donor organizations working in health and development||Recommendation 3-1: Development partners, including multilateral and bilateral donors and private philanthropic organizations, should encourage countries’ participation in regulatory benchmarking assessments, the development of institutional development plans, and reports on progress against those plans. To this end, assistance should be targeted to priorities identified in benchmarking assessments and the related institutional development plans.|
|Recommendation 3-3: Development partners, including multilateral and bilateral donors and private philanthropic organizations, should support countries and regional organization in pursuing greater collaboration for regulating food and medical products. This collaboration can include harmonization and mutual recognition of data or standards, equivalence agreements, and regulatory reliance.|
|Recommendation 3-4: Development finance institutions such as the United States International Development Finance Corporation, the International Finance Corporation (IFC), the UK CDC Group, and the European development finance banks should create vehicles to finance producers, distributors, and retailers in low- and middle-income countries interested in meeting regulatory standards. This would involve advisory services and, when appropriate, concessional financing.|
|Recommendation 3-5: The United States International Development Finance Corporation, the International Finance Corporation (IFC), the UK CDC Group, and the European development finance banks should provide advisory services and concessional financing to manufacturers of quality and safety screening technologies to optimize manufacturing and create stronger distribution systems in low- and middle-income countries.|
|NIH, FDA, and USAID||Recommendation 3-6: The National Institutes of Health, in collaboration with the U.S. Food and Drug Administration and the U.S. Agency for International Development, should develop a network of Global Centers of Excellence in Regulatory Science for research and capacity building to address the challenges of food and drug safety in low- and middle-income countries.|
TABLE S-1 Continued
|Level of Action||Topic||Actors||Recommendation|
|National||Government and financing||National governments, their leaders||Recommendation 4-1: National governments should guarantee in legislation that national regulatory agencies be independent and financially viable, with statutes that encourage cooperation with other agencies and require a scientific basis for decision making.|
|Agency||Risk-based regulation, communication, and information||Food and drug regulatory agencies||
Recommendation 5-1: National regulatory authorities should take a risk-based approach to the regulation of food and medicines. This includes:
|Informal markets||Recommendation 5-2: National regulatory agencies should use evidence to guide strategies to reduce the risk posed by informal markets. Strategies to consider include accreditation or licensing to formalize sellers, consumer education, and increasing competition from regulated products.|
|Management and collaboration||Recommendation 5-3: National regulatory authorities should take advantage of global tools to support regulatory actions. Resources from United Nations agencies, including World Health Organization prequalification and Codex standards, are examples of such tools, as are the third-party standards increasingly used in food and agriculture.|
|Recommendation 5-4: National regulatory authorities should determine which functions are most effectively and efficiently carried out directly by the agency and which can be delegated to state or local authorities; collaboration and data sharing among domestic agencies should be part of any delegation plan.|
Data from and public consultation with a range of stakeholders, both domestically and internationally, are also crucial. International agreement on technical guidelines, requirements for registration, and the approach to inspections can control the regulatory burden on industry; it also reduces repetitive work. International collaboration has therefore been cited as a minimum function of the regulatory agency. There are many international venues for such collaboration; some are initiated by industry, others are the product of trade or bilateral relationships. A recent 2-year mapping exercise by the International Coalition of Medicines Regulatory Authorities led to comments on the overlapping objectives and confusing array of similar initiatives.
There is no comparable, international mapping of food safety programs, partly because there is no analogous international coalition of food regulators. This is unfortunate, as the modern food safety landscape is so complex that even people with the best knowledge of the system see only parts of it. It is also symptomatic of a larger problem, the absence of a standing international venue for food regulators to interact with their counterparts around the world. Such a convention is an investment in the efficiency of the various regional cooperatives and technical groups working in the field. Convening food regulators also supports emergency response, building relationships that regulators can draw on during a crisis.
Recommendation 2-1: The Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO) should convene biennial meetings for food safety regulators similar to the International Conference of Drug Regulatory Authorities.
The increasing complexity of regulatory work and the interconnected nature of the food supply chain make it necessary for food regulators to have a standing, formal venue for exchange and cooperation. As the United Nations (UN) agencies responsible for global health and food security, the FAO and the WHO are the best choices to convene the meeting suggested.
GLOBAL EFFORTS TO STRENGTHEN REGULATORY SYSTEMS
Recent reports on falsified and substandard medicines and foodborne disease in low- and middle-income countries have drawn attention to the consequences of regulatory failures. Yet, much of the immediate reaction to such news has emphasized local solutions, from the need for consumers to demand food safety from their governments to the responsibility of governments to enforce regulations. While no one could deny the importance of the consumer, regulator, or political leader in solving these problems,
their actions are of limited value if the global environment does not foster product safety. Part of this report discusses how circumstances beyond the policy of any country influence food and medical product systems.
The Role of Aid
Global health and development organizations have considerable power to influence policy in ways that encourage functional regulatory systems. Development aid is one important tool to this end. Since the 1990s, there has been concern that the manner in which aid is given can do unintentional harm to recipient countries. In an effort to avoid this harm, the Organisation for Economic Co-operation and Development (OECD) has set out principles of aid effectiveness, two of which are especially relevant to the discussion of building regulatory systems. One is the untying of aid, meaning the removal of conditions that require recipient countries to procure goods and services through the donor country. The other is institution building, meaning spending in ways that support organizations and capacity in the recipient country. Attention to regulatory systems advances both goals, building the institutions that protect product safety, thereby increasing options for local procurement.
A valid benchmarking tool can put clear parameters on the concept of building regulatory institutions, thereby making it more concrete, measurable, and attractive to donor investment. The WHO Global Benchmarking Tool is an assessment for agencies that regulate medical products. Benchmarking assessment involves independent evaluation on nine functions; results inform a 5-year institutional development plan, which in turn informs a strategy to improve on identified weaknesses. Benchmarking food systems is more complicated. Food safety involves a variety of different fields, and there are various benchmarking tools for plant and animal health, as well as a more comprehensive food system assessment from the WHO and the FAO.
The institutional development plans developed out of benchmarking assessments help translate the sometimes vague job of institution building into concrete measurable steps. This is not a benefit that can be realized if countries do not participate in the benchmarking assessment, however, making an incentive to participate especially valuable. Global health and development organizations, including UN agencies, development banks, bilateral donors, and private philanthropy (described increasingly as “development partners”) all have a role to play in providing such incentive.
Recommendation 3-1: Development partners, including multilateral and bilateral donors and private philanthropic organizations, should encourage countries’ participation in regulatory benchmarking
assessments, the development of institutional development plans, and reports on progress against those plans. To this end, assistance should be targeted to priorities identified in benchmarking assessments and the related institutional development plans.
The move toward universal health coverage means that countries are now responsible for the purchase of more and varied types of medicines. This puts a strain on health budgets, even more so in those middle-income countries transitioning away from donor procurement. An increased demand for medical products draws attention to the essential procurement question of value for money, something that can be difficult to judge, especially when products are imported.
The WHO Prequalification Program provides regulatory assessment, inspection, and ongoing quality control for certain medical products procured through UN agencies or other large donors. Though the WHO does not act as a supra-national regulator, prequalification can act as a proxy regulatory approval that helps manage the combination of limited regulatory capacity and foreign procurement. It also has an important capacity building element for both manufacturers and regulators. Regulators from advanced agencies and from agencies in the countries where prequalified products will be used work together on prequalification teams; the program has also shown positive spillover effects on manufacturing.
Recommendation 3-2: The World Health Organization should expand prequalification to include treatments for cancer, diabetes, and other diseases with a high global burden.
In its recent 5-year plan to build regulatory capacity, the WHO cited prequalification as a strategic priority. The committee commends this plan and encourages the WHO to look beyond those products associated with HIV, tuberculosis, and malaria in its expansion. The choice of products and the order in which they are added to the prequalification list are topics for further discussion. There is clear demand for any product where a third or more of the total market by volume is subject to global procurement. Review of the Global Burden of Disease data will also be important to this discussion, as will considerations for products with small but important markets. Biologic medicines present a particular challenge to regulators because of the complexity of manufacturing. Biologic treatments would also be good candidates as would anti-infectives since the risk of drug resistance makes the quality of these products a global public good.
Expansion of prequalification puts a financial burden on the WHO, and an increased demand for expertise from advanced regulatory agencies. The products included in prequalification to date are those procured by
international agencies. Treatments for noncommunicable diseases are subject to national procurement, which cannot command the same negotiating power. Nevertheless, there is growing interest in helping countries respond to the challenge of noncommunicable disease, and expanded prequalification might make consolidated regional or global procurement an option.
When resources are scarce, the imperative to make good use of what is available increases. There is room to improve product safety and quality by making better use, where appropriate, of information already collected in the routine operations of government, business, and nonprofits. For regulatory agencies this means collecting, managing, and sharing data with their counterpart agencies abroad and with other interested parties. Donor funding could help minimize the technical obstacles and expense associated with this process, helping to tip the balance of tradeoffs in favor of greater openness.
Recommendation 3-3: Development partners, including multilateral and bilateral donors and private philanthropic organizations, should support countries and regional organizations in pursuing greater collaboration for regulating food and medical products. This collaboration can include harmonization and mutual recognition of data or standards, equivalence agreements, and regulatory reliance.
Data sharing produces a global public good; the information generated can inform public policy and risk analysis and can be used to answer valuable research questions. The technical cost of data sharing is an obstacle, and one that donors could help overcome. Providing data standards and a common platform could also help build trust among regulators and advance the long-term goal of regulatory harmonization.
The Role of Commerce
Regulatory enforcement can improve the products in a market, but the regulator’s power to change manufacturing is limited if industry is not investing in quality. Investing in quality can grow business and improve efficiency, but such benefits are not always clear to people in a position to change business practices. Even when they are, if the capital available comes at too high a price, the manufacturer’s calculations will not favor improvement. Development banks and bilateral development finance organizations can adjust this calculation, both with advisory services and with concessional financing (meaning loans with more generous terms than the market would offer).
Recommendation 3-4: Development finance institutions such as the United States International Development Finance Corporation, the
International Finance Corporation (IFC), the UK CDC Group, and the European development finance banks should create vehicles to finance producers, distributors, and retailers in low-and middle-income countries interested in meeting regulatory standards. This would involve advisory services and, when appropriate, concessional financing.
There are also global companies that are active in quality testing, but not necessarily expanding in low- and middle-income countries. Their products can be used in manufacturing, and are often helpful in downstream product monitoring, testing for authenticity or contamination at point of use, or at point of entry to a country. While such testing is not a substitute for regulatory checks or full quality assurance in manufacturing, it is important to the system.
There is a need for inexpensive, field-ready screening tools to detect product contamination or fraud in low- and middle-income countries. There is also a need to decrease the cost associated with existing technologies. When the market for such products is small the companies that make them do not have good reason to invest in manufacturing or build their distribution systems. The lack of both optimal manufacturing and distribution creates a vicious cycle where small markets lead to weak incentives to invest, which keep the market small.
Recommendation 3-5: The United States International Development Finance Corporation, the International Finance Corporation (IFC), the UK CDC Group, and the European development finance banks should provide advisory services and concessional financing to manufacturers of quality and safety screening technologies to optimize manufacturing and create stronger distribution systems in low- and middle-income countries.
Expanding the Evidence Base for Regulatory Policy
Regulatory science is not well studied, and the evidence base to support regulatory policy is lean, especially in small countries, regional consortia, and low- and middle-income countries. Advanced agencies have ways to collaborate with academia to advance the science they need; the FDA Centers of Excellence in Regulatory Science is a good example of such collaboration. These centers research priorities in the FDA’s strategic plan; they are evaluated on how well the information they produce informs the agency’s work and advances public health. This model of dedicated research centers run in collaboration with universities could be adapted globally.
Recommendation 3-6: The National Institutes of Health, in collaboration with the U.S. Food and Drug Administration and the U.S. Agency for International Development, should develop a network of Global Centers of Excellence in Regulatory Science for research and capacity building to identify and address the challenges of ensuring food and drug safety in low- and middle-income countries.
The proposed Centers of Excellence would be primarily research centers, distinguishing them from the similarly named Regional Centers of Regulatory Excellence in Africa, which are mainly concerned with training. In order to ensure that the research generated is useful and tailored to questions of local priority, the proposed centers would involve regulators in setting a research agenda. This type of demand-drive research would promote the implementation and uptake of research findings.
THE ROLE OF THE NATIONAL GOVERNMENT
Regulatory quality is one of the six aggregate measures of good governance the World Bank uses to assess the institutions in a country. Like other features of good governance, the capacity of the regulatory system is partly determined by the willingness of the national government to support it. Much of the regulatory agency’s effectiveness, efficiency, and independence is determined by a country’s political leaders, who are ultimately responsible for creating an environment conducive to product safety.
Providing the legal framework for product safety may be the most fundamental step national political leaders can take to protect food and medical products in their countries. Legal provisions define which institutions are part of the regulatory system, the ways they are involved, and their ability to enforce rules. The process of drafting food and drug laws is complicated; it may be eased by consulting model legislation, though model laws often require significant modifications to the local context. In any case, the legal mandate for regulatory systems should give special attention to their independence, sustainable financing, and provisions for cooperation.
A lack of political interference in an agency’s decisions and in the hiring and firing of technical staff is necessary for consumer confidence in the system. It also allows industry to function with confidence that the rules affecting their products will be applied in a predictable way. A regulatory agency’s independence in partly dependent on a stable and diversified revenue stream, something that is difficult to ensure in low- and middle-income countries. Broadly speaking, governments have a short list of revenue
sources from which to fund regulatory agencies: taxes, fees on industry, earmarks, or some combination thereof. There are administrative and economic tradeoffs associated with all options, and the appropriate balance of revenue should be revisited periodically.
Sustainable financing is important because all agencies are facing the limits of their resources. Sharing work with foreign agencies can allow countries to work more efficiently. International cooperation is so central to modern food and medical product regulation that the WHO and the FAO assess it in their regulatory benchmarking evaluations. Government support for this cooperation is essential, and the drafting or revision of national food and drug laws is an important time to ensure legislative provisions are in place.
Supporting the regulatory agency is part of government’s responsibility to its citizens. Political leaders can take a meaningful step toward meeting that responsibility through attention to the laws that protect it.
Recommendation 4-1: National governments should guarantee in legislation that national regulatory agencies be independent and financially viable, with statutes that encourage cooperation with other agencies and require a scientific basis for decision making.
Regulatory resources should be allocated with an eye to those jobs that add the maximum value for effort. Political leaders should give regulators clear authority for international coordination and guidance on how to resolve any tension between national and shared international responsibilities.
THE ROLE OF THE REGULATORY AGENCY
Decision makers at the regulatory agency have the most direct, proximal control over the actions taken to mitigate product safety risks. Attention to risk and work sharing could increase the scientific rigor at regulatory agencies and ensure their resources are deployed efficiently.
Strategies for Controlling Risk
Decisions about how to reduce risks facing the regulatory agency are, even at the most advanced agencies, often made in the face of uncertainty. Therefore, an over-emphasis on the ideal quantitative risk analysis could be a barrier to progress in low- and middle-income countries. While acknowledging that the public sector is often limited in its data and analytic capacity, regulators can still use risk-based approaches to make use of the information they have. A risk-based framework, even when applied to imperfect data, draws attention to the relative vulnerabilities in a system.
A risk-based regulatory system protects health; it also has positive spillovers for the economy, but quantifying these effects is challenging. There is a time lag between a regulatory policy going into effect and measurable changes taking place. Cost-to-benefit analysis and analysis of the causal pathway between regulatory policy and health and welfare gains are useful in estimating the value of the agency’s work. Such analyses depend on technical skills that are not always available, however. The proposed Centers of Excellence in Regulatory Science could undertake these assessments when necessary. Regulators can facilitate evaluation by clearly stating the goals of regulatory policies, the data that would be evaluated in an assessment, and sources for these data.
Regulatory work is highly technical and complicated and, when done properly, invisible to the consumer. This poses a barrier to public appreciation for the regulatory agency, but one that can be overcome with effective communication, data about the risks facing the consumer, and steps the agency is taking to mitigate them.
It can be difficult for regulators to advocate the importance of their work when things are going well. For this reason, agencies need a plan for crisis communication. The reason some crises undermine the agency and others cause people to rally behind it is not clear, but effective communication plays a role. Regulators should be prepared to communicate clearly and honestly during a crisis, because the tragedy of a product safety failure is only compounded if the agency fails to use the spotlight as an impetus for change.
Recommendation 5-1: National regulatory authorities should take a risk-based approach to the regulation of food and medicines. This includes:
- Developing effective data systems to systematically identify areas of greatest risk;
- Participating in research, data sharing, technology adoption, and training activities with international partners;
- Growing capacity to assess the health and economic impacts of regulation, and using this information to inform actions to protect public health;
- Communicating about risks, including the uncertainty around them, especially during a crisis; and
- Communicating the ways regulation improves quality, safety, and access, using different strategies to convey this information to government leaders, regulated industry, and the public.
The tools available to make regulators’ work more efficient are best deployed to deal with the formal operations of known producers and
distributors, but in low- and middle-income countries food and medical products are often sold outside these channels. In such circumstances, regulators may need to give more attention to strategies that drive consumer preference to the best feasible option and increase the reach of safe products.
Informal food markets account for an estimated 80 percent of food sold in low- and middle-income countries and are especially prominent sources of nutrient-dense, animal-source foods. Though storage and handling conditions are poor, shutting down informal markets is not usually logistically feasible and would have disastrous consequences for food security and livelihoods. Educational campaigns to help consumers mitigate the risks facing them can help, as can intervention at aggregating points on the supply chain (e.g., the slaughterhouse, dairy plant, or wholesale market).
Regulatory agencies may be more likely to consider aggressive enforcement as a way to combat the informal medicines market, though enforcement alone is unlikely to put informal sellers out of business. In low- and middle-income countries, the informal market is a response to a demand for medicines that exceeds the supply. Accreditation is one tool with promise to improve the reach of good-quality medical products; consumer education and mobile technology can also be effective.
Recommendation 5-2: National regulatory agencies should use evidence to guide strategies to reduce the risk posed by informal markets. Strategies to consider include accreditation or licensing to formalize sellers, consumer education, and increasing competition from regulated products.
Steps taken to mitigate the risks of informal markets can be expected to have disproportionate returns for the regulatory agency because they depend on local knowledge. The question remains as to how to manage work in a way that allows regulators to devote more time to these value-added activities. Jobs that do not pay off in terms of better understanding or control of local risks are best approached with an eye to making use of the work of other trusted authorities.
Cooperation and Delegation
Regulatory collaboration can result in more opportunities for training and exchange and a more predictable business environment. It also allows for more opportunities for networking with other experts, and can thereby improve the scientific rigor of regulatory decisions. Regional networks are one venue for regulatory cooperation, but regulators can also make unilateral decisions to rely on certain authorities’ decisions. UN agencies
also provide valuable tools; some private organizations produce useful technical guidelines. To serve the goal of maximizing staff time and effort, regulators should look for ways to make use of publicly available resources.
Recommendation 5-3: National regulatory authorities should take advantage of global tools to support regulatory actions. Resources from United Nations agencies, including World Health Organization prequalification and Codex standards, are examples of such tools, as are the third-party standards increasingly used in food and agriculture.
Realizing the benefits of work sharing requires identifying those tasks best shared among countries, as well as those best devolved to sub-national authorities. There is no universal blueprint to guide the coordination of multiple levels of government. Developing technical capacity at the local level and governance capacity (the skills that allow levels to work together) at all levels is important for effective delegation.
Recommendation 5-4: National regulatory authorities should determine which functions are most effectively and efficiently carried out directly by the agency and which can be delegated to state or local authorities; collaboration and data sharing among domestic agencies should be part of any delegation plan.
Efficient division of work, collaboration, and information sharing are tools that can help regulators manage the increasing challenge of protecting the safety of food and the quality of medical products in their countries. National governments and development partners also have roles to play to advance this goal. This report sets out a strategy for building regulatory systems in low- and middle-income countries; progress toward this end can be measured with regular benchmarking assessments.