For medicine regulators, reliance is a global imperative

It’s never been more challenging to make sure that medicines meet standards for quality, safety, and effectiveness. Rapidly evolving technologies, advances in medical therapies, and increasingly complex supply chains are stressing medicine regulators around the globe.

Great gains can be made when countries’ medicine regulators work together and share resources to ensure that their citizens have timely access to high-quality, safe, and effective medicines — an important role of government and an essential public health function.

Regulatory authorities that share information or that rely on each other’s work have expedited the approval of essential vaccines and medicines, prevented the distribution of substandard and fake medicines, and quickly mobilized resources during drug shortages and public health emergencies.

Still, medicine regulators in some countries do not collaborate with their counterparts in other countries to the extent they could, or should. That increases their workload, limits their access to essential decision-making data, and creates redundant and duplicative work when their time could be better spent addressing more urgent public health priorities.

Entering into a recognition or reliance arrangement — the process by which one agency recognizes or relies upon another’s work as equivalent to its own — allows medicine regulators to make use of shared information while retaining their decision-making power. When relying on the work of other regulators, national regulators are responsible for interpreting information and making decisions based on the context of their own nation’s health care system, population, and public health goals. For example, regulators working in countries with intense sunlight and high rates of skin cancers, such as Australia and New Zealand, might come to different decisions regarding the approval of certain dermatological medicines than those working in more temperate climates. This underscores that it is ultimately a national decision as to whether to approve a medicine.

Clinical assessments, manufacturing site inspections, and post-market safety data are just a few examples of information that regulators can share with each other throughout the life cycle of medicines. While the presence of trade secret information in inspection reports can be a barrier to information sharing, there are strategies to address this barrier, including confidentiality arrangements. Full inspection and assessment reports that omit personal privacy information should be made available to other medicine regulators — especially those that are lower-resourced — to promote transparency and provide a clear picture of a drug’s risks and benefits.

We served on a committee assembled by the U.S. National Academies of Sciences, Engineering, and Medicine to explore how countries work together to oversee the regulation of medicines. Our report, “Regulating Medicines in a Globalized World,” shows how regulatory authorities can work together and avoid duplication by designing and implementing reliance arrangements. Strategic evaluation of such arrangements must go beyond economic and trade motivations and center on the public health benefits to patients and consumers.

Reliance, the essential component of these agreements, has two main types: reciprocal and unidirectional.

Reciprocal reliance typically occurs between well-resourced authorities with the same level of technical standards and resources. It can take the form of work sharing, as in the case of the Australia, Canada, Switzerland, Singapore Consortium. This consortium is exploring opportunities for work sharing in areas such as generic medicines registration, assessment reports for new prescription medicines, and investigations into post-market medicine safety. Other reciprocal alliance arrangements include pilot studies, which can provide a safe space in which both regulators can learn from each other and establish trust before entering a more formal agreement.

Unidirectional reliance typically occurs when a lower-resourced authority relies on the work of a well-resourced authority. Under unidirectional arrangements, participating authorities do not need to have the same level of staffing, technical standards and capabilities, or legal authority. Mexico’s regulatory authority, the Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), for example, has relied on decisions made by other regulatory authorities — including the FDA, Health Canada, European Medicines Agency, and Swissmedic — to expedite the approval and entry of new medicines into the Mexican market. In this case, recognizing the decisions of trusted authorities helped COFEPRIS alleviate Mexico’s drug shortages, while allowing the agency to devote more time to other activities where reliance couldn’t be used.

Countries with fewer resources for regulating medicines face multiple challenges that include staff shortages, lack of technical capability, limited access to data, and more. These can lead to backlogs of products that require review. Unidirectional reliance arrangements can help these countries improve access to safe and effective medicines and avoid using limited resources on redundant inspections and assessments.

Unidirectional arrangements come with added responsibilities for medicine regulators in the the better-resourced nation. It must be mindful of the ramifications its decisions could have for the global health system.

Technical arrangements and concrete agreements help regulators uphold their public health mission. Trust, albeit intangible, is fundamental to the lasting success of these arrangements. It’s no surprise that trust is highest among agencies that have similar standards for inspections and assessments, similar cultures and languages, and shared understanding of the environmental, health, and social context in their jurisdictions. Trust is further enhanced by participating in crafting and implementing international standards, such as those from the International Council for Regulatory Harmonization of Technical Requirements for Pharmaceuticals for Human Use.

As the development of new therapies and the manufacturing and sale of medicines become increasingly global and complex, it is in tandem becoming more difficult for countries to implement effective regulations without international partners. Policymakers, regulatory authorities, and other stakeholders all have roles to play in promoting recognition and reliance activities. Industry needs to work with regulators to achieve more transparency in regulatory processes. Policy makers must engage patient and consumer groups so reliance arrangements are established and evaluated with their needs in mind.

Governments and regulatory authorities should not view producing and sharing regulatory information as a burden, but as a provision of public good.

Katherine C. Bond, Sc.D., is the founder and principal of Network Strategies for Health, LLC. Gavin Huntley-Fenner, Ph.D., is a human factors and safety consultant at Huntley-Fenner Advisors. Lembit Rägo, Ph.D., is the secretary-general of the Council for International Organizations of Medical Sciences. The authors are members of the National Academies of Sciences, Engineering, and Medicine’s Committee on Mutual Recognition Agreements and Reliance in the Regulation of Medicines.