Nov. 21, 2019
WASHINGTON — Medicine regulatory authorities — including the U.S. Food and Drug Administration (FDA) — should strengthen cooperation with other countries’ regulators to ensure the quality, safety, and efficacy of medicines, says a new report from the National Academies of Sciences, Engineering, and Medicine. Regulating Medicines in a Globalized World: The Need for Increased Reliance Among Regulators contains recommendations to promote information sharing among RAs with the aim of protecting public health, ensuring faster access to critical medicines, and encouraging innovation in medicine and technology.
Today, drug development is increasingly global. An estimated 40 percent of medicines and 80 percent of active pharmaceutical ingredients used by Americans are made overseas. Different countries have different rules, regulations, and standards for the review and approval of new medicines. However, they are often unable to share inspection reports and other critical safety information with each other, because such reports are heavily redacted to protect trade secrets and other confidential information.
No regulator has all the human and technical resources it needs to meet all of its public health responsibilities, especially as their workloads increase due to the growing complexity of medicines; societal expectations for faster drug approvals; and the rising demand for inspections of manufacturing facilities overseas. Reliance and recognition arrangements enable regulators to share information and increase the transparency of each other’s activities; to optimize limited human and financial resources; to build expertise in specialized and emerging regulatory areas (such as gene therapies and biosimilars); and to mobilize resources in the event of a drug shortage or public health emergency.
Reliance is when a regulatory authority considers another’s work (such as inspection and scientific assessment reports) to inform its own regulatory decisions. Recognition — the highest level of which is a mutual recognition agreement (MRA) — is when a regulator not only relies on the work of another regulator, but also accepts and adopts the other regulator’s decisions. Smaller and under-resourced regulators often enter these arrangements with better-resourced countries to strengthen their capacity. However, it is up to the country’s regulatory authority to decide whether to approve a medicine. Entering one of these arrangements does not mean giving up decision-making responsibilities, the report says.
In order for regulatory authorities to build upon and enter new recognition and reliance arrangements, impediments to information sharing should be removed. Medicine regulatory authorities should consider sharing full, unredacted reports to help countries make better-informed, sovereign decisions about the approval of medicines, the report says. In addition, the FDA and Congress should re-evaluate such confidentiality restrictions and ensure that current redaction practices promote information sharing while protecting personal data.
The report identifies several potential public health benefits of reliance and recognition arrangements. These arrangements could allow for patients and consumers to gain faster access to quality medicines. For example, following the Zika outbreak of 2016, the World Health Organization (WHO) encouraged reliance as a way to expedite market access to tests, vaccines, and treatments for priority diseases. In the aftermath of Hurricane Maria in Puerto Rico — a pharmaceutical manufacturing hub — the use of reliance arrangements would have allowed regulators to share information to assess alternative manufacturing sites.
Greater cooperation between national regulators could help identify substandard or falsified medicines before they are approved or exported, says the report. It could also prevent duplicative activities, such as multiple RAs inspecting the same low-risk manufacturing site, which diverts time and resources from more urgent inspections as well as other regulatory priorities.
“Many industries — such as banking and telecommunication — operate seamlessly across national borders. Today’s medicines are global commodities, so the regulation of medicines should function just as seamlessly,” said Alastair Wood, emeritus professor of medicine and pharmacology at Vanderbilt University, who chaired the committee that wrote the report. “Regulatory authorities need to be able to use the best science, the best expertise, and the best resources to make informed decisions to protect the health of millions of people.”
Improve the Design of Mutual Recognition Agreements
The report outlines a stakeholder-driven strategy to improve cooperation and collaboration among regulators, which includes:
Respond to Evolving Science and Technology
Formal MRAs are not currently agile enough to respond to rapid changes in science and technology, or to public health emergencies. Regulatory authorities should consider potential areas for scope exploration of both formal recognition agreements such as MRAs and less formal reliance arrangements (e.g., collaborative activities) including: guidelines for reliable and high-quality laboratory data, guidance for studies involving human subjects, and guidance for the manufacturing, production, and distribution of medicines.
Expand the Scope of the European Union (EU)-U.S. MRA
Currently, the EU-U.S. MRA only applies to manufacturing site inspections. The EU-U.S. MRA should be expanded to include reliance in additional areas and for a broader range of medicine types, the report recommends. In addition, the provisions in the MRA for inspections that the FDA and European Medicines Agency conduct outside of the U.S. and EU (“third country” inspections) should be implemented immediately.
Formally Evaluate the Public Health Impacts of Reliance and Recognition Arrangements
Most reliance and recognition arrangements do not explicitly call for evaluation of public health benefits, and there is a lack of data on their successes and challenges. Regulatory authorities should create a results framework with clear indicators, metrics, and processes for monitoring and evaluating recognition and reliance arrangements, the report recommends. This would increase understanding of their public health benefits, and enable benefit-risk and cost-benefit analysis over time.
The study — undertaken by the Committee on Mutual Recognition Agreements and Reliance in the Regulation of Medicines — was sponsored by the U.S. Food and Drug Administration’s Office of Global Policy and Strategy.
The National Academies of Sciences, Engineering, and Medicine are private, nonprofit institutions that provide independent, objective analysis and advice to the nation to solve complex problems and inform public policy decisions related to science, technology, and medicine. They operate under an 1863 congressional charter to the National Academy of Sciences, signed by President Lincoln.
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