FDA Presentation: American Public Health Association's 2020 Virtual Annual Meeting October 26, 2020

Speech | Virtual

• Speech by: Bruce Ross ; Director - Office of Global Operations

• To: American Public Health Association

Department of Health and Human Services’ Global Health Workforce – On the Front Lines of Health Diplomacy During the Time of COVID-19

Hello, and thanks Matt for that introduction - it’s an honor to join today’s panel with my other HHS colleagues to talk about our foreign offices and the impact of COVID-19 on operations. I’m Bruce Ross, director of FDA’s Office of Global Operations in the Office of Global Policy and Strategy within the Office of the Commissioner.

The FDA regulates human and veterinary drugs; biologics, including vaccines; the broad category of medical devices, which include everything from ventilators, and in-vitro diagnostic tests to medical imaging equipment and certain personal protective equipment (PPE) both human and animal food; cosmetics and tobacco.

Many of these products rely on complex supply chains. In fact, FDA-regulated products originate from more than 150 countries and from approximately 135,000 FDA-registered foreign facilities. Given this landscape, the FDA must maintain a dedicated global focus to fulfill our mission of protecting and promoting the public health of Americans.

Multiple offices within the FDA support these global efforts. The Office of Regulatory Affairs inspects regulated products and manufacturers, conducts sample analyses and reviews imported products for entry into the U.S. to ensure that the FDA-regulated products produced overseas meet the same regulatory requirements as those produced domestically. The FDA’s product centers (e.g., CDER, CDRH, CFSAN, etc.) provide scientific and technological positions on commodity-specific global policy and outreach.

Finally, our Office of Global Policy and Strategy, or OGPS, serves as the focal point for the FDA’s global engagements, institutional linkages, trade negotiations, bilateral and multilateral partnerships. OGPS uses diplomacy to leverage the resources of FDA partners on significant scientific issues, where appropriate, to expand our reach and foster alignment. In OGPS we consistently advocate for regulatory frameworks that are predictable, efficient, modern, and underpinned by decision-making that relies on data and sound science.

OGPS also oversees the work of the FDA’s foreign offices, located in strategic locations around the world. That’s my responsibility. The first of these offices was established in 2008 in the wake of public health tragedies from contaminated heparin and melamine-laced pet food, both from China. Today we have offices in Belgium, Chile, China, Costa Rica, India and Mexico and an employee seconded to the European Medicines Agency in the Netherlands. Our foreign offices serve as the eyes, ears and voice of FDA abroad. They respond to disruptions caused by disasters, outbreaks or other events; engage with local and regional stakeholders to strengthen host country regulatory frameworks and increase industry’s compliance with FDA’s safety, quality and efficacy standards; collect data; conduct foreign inspections and provide FDA with in-country information regarding manufacturing and other key factors that might influence public health.

Products manufactured overseas must meet the same statutory and regulatory requirements as those produced in the U.S. Our staff conducts surveillance inspections, prioritized by risk, to ensure that facilities making FDA-regulated products for sale in the U.S. are in compliance with the FDA’s current good manufacturing practice requirements that address such topics as quality management systems, operating procedures, use of raw materials, product quality deviations, and testing laboratories. In addition, our staff may be called upon to conduct for-cause inspections based on complaints or adverse event reports.

Having investigators located overseas allows the agency to conduct more timely inspections with greater flexibility. Consider the instrumental role that our India Office played in the initial investigation of the presence of cancer-causing nitrosamines in medications. Nitrosamines were first encountered in 2018 in blood pressure drugs known as angiotensin II receptor blockers or ARBs. As you might expect, the India Office inspected active pharmaceutical ingredient (API) manufacturers and rapidly mobilized to collect product samples that were urgently needed due to resolve initially discrepant test results. But they also were aware of an in-country manufacturing trend, sharing the emergent practice of using recovery plants in India as a cost-effective measure to “recycle” solvents previously used in drug manufacturing processes. This knowledge led to for-cause inspections of these recovery plants and the discovery of nitrosamines in those solvents being used to make APIs for ARB drugs.

Our foreign-office based staff typically accomplish between 175 – 200 inspections across all commodities a year. In responding to the COVID-19 outbreak, FDA’s ability to conduct foreign inspections has been severely limited by worldwide and in-country travel restrictions and by the desire to protect the health and safety of our own staff and those in the facilities producing FDA-regulated products. Thus, there was a shift by the agency to only do “mission-critical” inspections where/when travel was possible. When one country went into lockdown and shut down internal travel, one of our investigators was left stranded, away from her home and direct Embassy support for over 5 weeks, while conducting a mission-critical inspection of a firm producing an API for a drug in shortage!  Without the ability to travel in-country, or having been evacuated to the U.S., most of our investigators shifted to help out on “remote regulatory assessments” of firms of interest. Other investigators contributed to a one-USG mode of operations helping in the repatriation efforts in many countries, triaging phone calls from U.S. citizens seeking to return home; or in those contact-tracing efforts within their Embassy community.

While navigating local COVID-19 restrictions where they live and work, FDA personnel in China, India, and Latin America have been on the front lines leading bilateral exchanges of information. Our staff has assisted in Embassy-led supply chain taskforces, advising Country Teams about FDA-regulated commodity sources in-country that could meet the shortages of PPE or to identifying alternate suppliers by reviewing documents and manufacturing records available to support various U.S.-based procurement initiatives.

FDA’s China Office staff were evacuated to the United States from Beijing at the onset of the pandemic. Nevertheless, they have worked hand-in-hand with our Center for Devices and Radiological Health to help support various U.S.-based procurement initiatives seeking to identify sources of PPE from China that would meet FDA’s requirements, and then facilitate its export to the United States. They’ve also contributed to import alerts placed on Chinese manufacturing facilities that have tried to export substandard PPE products and to identify, follow-up, and research fraudulent COVID-19 claims related to FDA-regulated products.

Our India Office staff has worked throughout the year to mitigate the export restrictions that India placed on 28 different APIs and drug formulations related to COVID-19. We also deepened our ties with India’s Ministry of Health and Family Welfare by entering into a Memorandum of Understanding (MOU) that has the objective of promoting access to high-quality, safe, effective and affordable medications for Indian and American consumers. Thanks to this bilateral arrangement, we’ve been able to prevent the marketing of some unapproved products that fraudulently claim to mitigate, prevent, treat, diagnose or cure COVID-19 in both of our countries.

Our Latin America Office staff, which has the responsibility of covering 44 different countries with varying levels of regulatory sophistication, has worked tirelessly to share important information about FDA’s Emergency Use Authorizations (EUA) with our regulatory and industry counterparts on items like ventilators and test kits, as well as best practices for responding to product shortages.

Certainly, one of the FDA’s most robust regulatory relationships, developed over a period of many years, is with the European Medicines Agency (EMA). Since the pandemic began, we’ve shared information, data, and our current thinking with the EMA about products as diverse as antiviral drugs, serology testing kits, and respirators. Much of this work takes place within the specialized scientific working groups we established more than a decade ago, allowing for unprecedented scientific collaborations as the scope of the COVID-19 pandemic has expanded. Thus, our antiviral experts exchanged information about the disease and discussed shared approaches to sound design of clinical trials; our epidemiologists collaborated on how to use real world data to understand the benefits and risks of already marketed products being used to treat the disease; and our pediatric experts considered standards for studying COVID-19 pediatric protocols. In many cases, experts from other mature regulatory counterparts, including Canada and Japan, have participated in these working groups.

Our efforts with European and other trusted international partners have been further magnified by bringing pandemic-related issues to larger forums, including the International Coalition of Medicines Regulatory Authorities (ICMRA), which the EMA currently leads. In March of this year, the FDA’s Europe Office staff worked with the EMA to organize and co-chair the first ICMRA global regulators meeting to discuss regulatory strategies to facilitate the development of vaccines for the novel coronavirus, work that had first begun between the FDA and the EMA. Through the ICMRA forum we have established a common understanding regarding preclinical data requirements, allowing regulatory agencies to support first-in-human clinical trials for COVID vaccines. Later, ICMRA worked to prioritize, and provide guidance for, the conduct of clinical trials for COVID-19 vaccines and therapeutics.

FDA has also been in close contact with global regulators through the International Medical Device Regulators Forum (IMDRF). Early in the pandemic, the FDA participated in regular teleconferences with regulators to exchange information under confidentiality commitments on a range of device-related issues such as emergency procedures enabling availability of critical devices, supply chain disruptions due to export restrictions, and potentially fraudulent products.

During this difficult time, it’s been important that the FDA not abandon its non-COVID related public health initiatives such as the work we do to protect the food supply from unsafe imported food. Our foreign office staff in India and Latin America collaborated to provide virtual workshops and trainings on key aspects of the landmark Food Safety and Modernization Act (FSMA) that has successfully shifted our public health focus from responding to foodborne illness outbreaks to preventing them. The Latin America office staff renewed its produce-focused activities into a broader expanded Food Safety Partnership with Mexican regulatory authorities, and both our Europe and Latin America Office staff are engaged in separate collaborations to apply whole genome sequencing technology for use in outbreak detection.

We’re also continuing our efforts to ensure the safety and effectiveness of imported medical products. Our medical product experts in India and China collaborated with experts at FDA headquarters to lead “Midnight Madness,” a real-time outreach event targeting Asia on a range of pharmaceutical quality issues covering manufacturing assessment, quality expectations, and surveillance findings. Finally, our close working relationship with Europe has led to the mutually-beneficial Pharmaceutical Annex to the US/EU Mutual Recognition Agreement (MRA), which allows us to recognize one another’s drug inspections and to rely upon that information for possible enforcement actions. Exchanging these inspectional reports increased as we both sought to respond to the travel limitations imposed during the pandemic. This means FDA can devote its inspectional resources to higher-risk facilities while reducing repeat inspections for industry.

While I’ve touched on a lot of activities, we believe that FDA’s global outreach and the efforts of our FDA staff in strategic global locations is fulfilling our mission critical work at a time of intense public health need.

These individuals are literally the eyes and ears of the agency, helping to ensure the safety, quality, and effectiveness of medical products and food produced for export to the United States.