A Milestone in our Partnership with Mexico on Food Safety

En Español

By: Michael R. Taylor

We know that food safety is more a journey than a destination, but there are times when we can point to a major milestone along the road. Today, we reached such a milestone in our long-standing relationship with Mexico by signing a statement of intent to establish a new produce safety partnership.

signing ceremony in Mexico

Left to right: Michael R. Taylor, FDA Deputy Commissioner for Foods and Veterinary Medicine; Enrique Sánchez Cruz, Executive Director, SENASICA, Margaret A. Hamburg, M.D., Commissioner of the U.S. Food and Drug Administration, and Mikel Arriola Peñalosa, Commissioner, COFEPRIS – at today’s signing ceremony.

Working with Mexico on food safety is a top priority. Mexico is one of the United States’ top trading partners, and much of the produce we eat is grown there, including produce that otherwise would be hard to find during the winter. And food safety modernization efforts are underway in both countries, providing an excellent opportunity for progress. In the U.S., we are implementing the Food Safety Modernization Act, and produce safety is a big part of that effort, while Mexico is implementing an amendment to its food safety laws that mandates standards for fresh produce, inspections, and surveillance and verification programs.

We have been working with the two food safety agencies in Mexico—SENASICA, the National Service for Agro-Alimentary Public Health, Safety and Quality, and COFEPRIS, the Federal Commission for the Protection from Sanitary Risks—for some time, and it has been a very rewarding relationship. Last fall, I had the pleasure of traveling to Mexico City to meet with Dr. Enrique Sanchez Cruz, director general of SENASICA, and Mikel Arriola, federal commissioner of COFEPRIS, who were both present for today’s signing ceremony. And in March of this year, I traveled to Tubac, Arizona, to meet with Mexican government officials and producers of fresh fruits and vegetables from both sides of the border to discuss how all of us—in both the public and private sectors—can do our part to meet high consumer expectations for food safety.

The statement of intent is just a two-page document, but it represents a strategy that is far-reaching and designed to achieve high rates of compliance with produce standards in each country. In the months and years to come, we will be working with Mexico to identify practices to prevent contamination during the growing, harvesting, packing, holding and transportation of fresh fruits and vegetables and verification measures to ensure these preventive practices are working. We will exchange information to better understand each other’s produce safety systems—and in fact, this sharing is already underway. We intend to develop culturally appropriate education and outreach materials to support industry compliance with produce safety standards, and we will work on enhancing our collaboration on laboratory activities and on outbreak response and traceback activities.  It’s an ambitious agenda, and that is the value of an inclusive partnership. We are engaging industry, commerce, agriculture, academia and consumers because everyone has a role in ensuring the safety of the food supply.

It is gratifying to see the progress we have made along the way—and even more gratifying to know that with the new produce safety partnership in place, fruits and vegetables will be safer for consumers on both sides of the border.

Michael R. Taylor is FDA’s Deputy Commissioner for Foods and Veterinary Medicine

On the road from Mexico: a model for regulatory cooperation

En Español

By: Margaret A. Hamburg, M.D.

Margaret Hamburg

FDA Commissioner Margaret A. Hamburg, M.D., meeting with Mexican public health and regulatory officials in Mexico City this week

This week I’m making my first visit to Mexico as FDA Commissioner and, while I am savoring the rich culture, warm people and delicious food, the trip is providing me with a vital first-hand perspective of the long-standing, productive and collaborative working relationship FDA maintains with our regulatory counterparts in this wonderful country. I’ve blogged many times about the importance of adapting to our rapidly changing world—one in which the medical products we use and the foods we eat are increasingly produced in countries other than our own. Perhaps nowhere is that dynamic more vivid than with our neighbors to the South. And nowhere provides a more profound example of how cooperation is essential to protect public health and realize the benefits of a vibrant trade relationship.

Today, Mexico is a major player in the global marketplace and, of course, one of the United States’ most important trade partners. In the U.S., nearly one-third of the FDA-regulated food products we eat come from Mexico. On the medical products side, Mexico is the 2nd leading exporter of medical devices to the U.S.—the vast majority of which are lower risk devices such as surgical drapes, wheelchair components, and non-invasive tubing.

The foundation of successful cooperation is forging real relationships with our regulatory counterparts and our key stakeholders including the industries we regulate. FDA’s office in Mexico City—one of three in the Latin America region—has been a critical source of support for many of our collaborative activities since we opened its doors some four years ago. And this week my colleagues and I have had the opportunity to have fruitful meetings with the leaders of the Mexican Ministry of Health and the two regulatory agencies with whom work so closely: COFEPRIS (the Federal Commission for the Protection from Sanitary Risks) and SENASICA (the National Service for Agroalimentary Public Health, Safety and Quality).

We’ve discussed our respective strategies to address our nations’ most critical public health issues like obesity and nutrition, and the important ways in which we share information and align our regulatory approaches. For example, our partners in Mexico have such confidence in FDA’s premarket review system of medical products that COFEPRIS issues agreements with companies — agreements that recognize FDA approvals and grant drug and device companies “fast track” pathway to make their products available to patients dramatically more quickly.

Margaret Hamburg and Mike Taylor at mushroom farm

FDA Commissioner Margaret A. Hamburg, M.D. (foreground), and Michael R. Taylor, Deputy Commissioner for Foods and Veterinary Medicine (left), visit a mushroom farm in Mexico

We also held two interactive roundtable discussions with members of the medical products and food industries in which we had lively exchanges about key issues such as how quality manufacturing is not only good for public health, but good for business. And yesterday I got a close up view on that critical concept with a visit to the Monteblanco facility of Hongos de Mexico, S.A. de C.V., one of Mexico’s largest producer of mushrooms – located in the Toluca valley just a 90 minute drive from downtown Mexico City. Hongos de Mexico is a company that FDA has routinely visited and inspected given Monteblanco produces a staggering 60,000 pounds of mushrooms each day for consumption within Mexico and export to the U.S. and other countries. In addition to being an enlightening education on the process of growing and packing mushrooms, our visit to the Monteblanco facility was a living example of the critical role the private sector plays to ensure the safety of products for consumers in the U.S. and around the world.

Today is the final day of our jam-packed visit to Mexico and I’m thrilled that we will be signing a Produce Safety Partnership Statement of Intent, which is just the latest example of the successful collaboration to reduce the increased risk of foodborne illnesses that naturally comes with a more globalized market. The partnership will support our work to implement preventive practices and verification measures to ensure the safety of fresh and minimally produced fruits and vegetables.

At the end of the day, our trip to Mexico has shined a bright light on how important it is to continue to explore new ways to fulfill the mission that we share with our regulators around the world—to protect and promote public health. Our partnership with Mexico serves as a model not only as it relates to improving the health and well-being of consumers but also to promote innovation and economic growth.

Margaret A. Hamburg, M.D., is Commissioner of the U.S. Food and Drug Administration

Achieving an AIDS Free Generation – Highlights from the PEPFAR Annual Meeting in Durban, South Africa

By: Katherine Bond, Sc. D. and Jude Nwokike, MSc, MPH

The U.S. Global AIDS Coordinator, Ambassador Deborah Birx, recently described the President’s Emergency Plan for AIDS Relief (PEPFAR) as “one of the greatest expressions of American compassion, ingenuity, and shared humanity in our nation’s rich history.”

Kate Bond and Jude Nwokike

Katherine C. Bond, Director of FDA’s Office of Strategy, Partnerships and Analytics, Office of International Programs and Jude Nwokike, FDA’s PEPFAR Liaison, Office of Strategy and Partnerships, Office of International Programs.

We recently attended the PEPFAR 2014 Annual Meeting in Durban, South Africa. Since its inception in 2003, PEPFAR, the U.S. Government’s initiative to help save the lives of those living with HIV/AIDS around the world, is supporting 6.7 million people on anti-retroviral treatment (ART) and has resulted in one million babies born HIV-free. In FY 2013 alone, PEPFAR supported 12.8 million pregnant women for HIV testing and counseling and as of September 30, 2013 will have supported voluntary medical male circumcisions for 4.2 million men in east and southern Africa.

The focus of this year’s conference was on delivering a sustainable AIDS Free Generation. We were privileged to represent FDA at the meeting, along with other Health and Human Services operating divisions –including the Centers for Disease Control, the National Institutes of Health, the Health Resources and Services Administration, and the Substance Abuse and Mental Health Services Administration.

FDA has played a critical role in the PEPFAR program. As of March 2014, the Agency had approved or tentatively approved 170 antiretroviral drugs for use by PEPFAR, including 80 fixed dose combinations (FDCs), 24 of which are triple FDCs. Triple FDCs are significant because they have simplified ART from up to 20 pills a day to one pill daily — improving adherence to treatment, reducing the risk of developing resistance, and simplifying the supply chain.

We saw the direct impact of the program during a visit to the KwaMashu Community Health Centre, north of Durban in South Africa’s KwaZulu-Natal Province. Formerly a sugar plantation, the area saw a mass resettlement of poor people in the early 1960’s. It was often the site of political violence during the Apartheid era, and is now characterized by inadequate housing, poor infrastructure, high unemployment and crime, and among the highest rates of HIV in the world.

In 2012, the prevalence of HIV in antenatal women in KwaZulu-Natal Province was 37.4%. With the support of PEPFAR, in 2014 over 12,000 adults and nearly 800 children are receiving anti-retroviral therapy at KwaMashu, extending life expectancy, and giving hope for a better future. This hope was especially apparent in two girls, ages 12 and 14, each living with HIV/AIDS, who spoke eloquently to us about being cared for by grandmothers and a dedicated cadre of area doctors, nurses, pharmacists and community workers.  One girl dreams of becoming a medical researcher and the other aspires to be a lawyer.

At the conference we learned that thirteen low- and middle-income countries (LMICs) are at the tipping point of overcoming the HIV/AIDS epidemic, with the number of those starting therapy exceeding the number of newly infected. This makes the goal of an AIDS Free Generation plausible. PEPFAR is supporting HIV/AIDS response in more than 100 LMICs. Also, promising comprehensive prevention strategies present great opportunities to stem the epidemic’s tide. But, even with PEPFAR’s numerous achievements, challenges still exist. In 2012 alone, there were 1.6 million deaths, 2.3 million new infections, and 260,000 babies born infected with HIV.

Scaling up treatment and effective preventive interventions, and sustaining support and access to care are critical to achieving an AIDS Free Generation.  Essential to sustainability is ensuring product availability, quality, and safety of medical products used in the PEPFAR program.  Several PEPFAR country representatives described challenges in supply chains attributable to weak regulatory infrastructure (for example, limited sources for Tenofovir-containing FDCs used as first line regimen); lack of capacity of PEPFAR country regulators to assure quality of rapid diagnostic kits; seizure of products at border posts because products are not registered or approved in a country; few national standards for diagnostics and medical devices; and limited capacity of local regulators for regulating medical devices. Representatives of several countries called for strong pharmacovigilance and post marketing surveillance.

Despite these challenges, there are promising developments that are likely to bring benefits to regulators in PEPFAR countries, and ultimately, the PEPFAR program’s beneficiaries. In May 2014, African nations voiced unified support for a World Health Assembly resolution on strengthening regulatory systems; reductions in time to register medicines has been reported by the African Medicines Registration Harmonization Initiative; and the WHO global surveillance and monitoring system for substandard, falsified and counterfeit medical products is receiving reports from, and issuing drug alerts based on vigilant reporting by, African regulators.

We held a special session on strengthening regulatory systems with our colleagues from a number of PEPFAR countries and identified several possible areas for future collaboration. Strengthening regulatory systems will be a key component in defining a sustainable path forward.

Katherine C. Bond is Director of FDA’s Office of Strategy, Partnerships and Analytics, Office of International Programs

Jude Nwokike is FDA’s PEPFAR Liaison, Office of Strategy and Partnerships, Office of International Programs

For more information please visit:

PEPFAR BLUEPRINT: Creating an AIDS-free Generation

Approved and Tentatively Approved Antiretrovirals in Association with the President’s Emergency Plan

Finding the Cause of Thrombosis in Some Immunoglobulin Treatments

By: Mikhail Ovanesov, Ph.D.

The Food and Drug Administration’s Office of Blood Research and Review (OBRR) has a broad mission to ensure the safety and efficacy of products it regulates. It also does mission-related research, some of which can be described as problem-solving.

Mikhail OvanesovOne of the problems on which OBRR focused recently was a serious adverse effect linked to some treatments with immune globulin intravenous (IGIV), a product that contains pooled immunoglobulin (antibody) extracted from the plasma of thousands of donors. Licensed IGIV uses include the treatment of immune deficiencies and autoimmune disorders.

These immunoglobulin treatments are generally safe, although they can cause mild to moderate adverse effects during and after infusion, such as headache, malaise and nausea. Less common but potentially fatal complications are the formation of blood clots.  These thrombotic events (TEs), as they are known, can block large arteries or veins, causing heart attack, stroke, deep venous thrombosis and pulmonary embolism. That’s why, since October 2003, FDA has recommended precautionary labeling for IGIV products that includes the risk of thrombotic events. But while the new labeling helped raise awareness of this risk, the causes of TE remained unclear. In fact, since many patients receiving IGIV are already considered at risk for thrombosis, the causes were often attributed to the patient’s medical condition. The fact that TEs only rarely occurred in clusters linked to a single lot of IGIV from a particular manufacturer also made it difficult to pin down a specific cause for these adverse effects.

That all changed in May 2010 when TEs — stroke and myocardial infarction in several patients — linked to two lots from one manufacturer prompted the company to put a hold on the release of these lots. My laboratory responded by launching a series of tests to find out what caused the TEs. We studied the ability of four different lots of IGIV to generate the blood protein thrombin, which triggers clotting. Specifically, we compared two lots which caused stroke or myocardial infarction in several patients with those that did not. Our work showed that the lots linked to TEs induced faster and higher generation of thrombin. We then confirmed these results by recording blood clot formation under a specially designed video microscope. The lots associated with TEs again demonstrated higher rates of clotting. Additional tests confirmed that the thrombin generation test reliably identifies lots that are potentially thrombogenic.

In early August 2010, OBRR shared its data with the company, which confirmed the results and established product evaluation methods using similar coagulation assays. After the company voluntarily withdrew 31 IGIV lots from the United States market, there were many more international reports of TEs. By the end of September, all product lots were voluntarily removed from the U.S. market.

But we still didn’t know what was triggering the rapid rise in thrombin. So we continued our studies and identified a blood protein called coagulation factor XIa as an impurity in IGIV products causing thrombosis. This enabled us to develop a Factor XIa assay that could determine if an IGIV lot contained this thrombogenic impurity. We then tested other lots of licensed and investigational IGIV products, which prompted testing and manufacturing changes by industry to improve the safety of several other products.

OBRR has since then been working with the World Health Organization and other laboratories to ensure that tests for factor XIa done anywhere in the world will work the same way and give reliable results.

This work has also contributed to the ongoing development in CBER of a new lot release assay for immunoglobulin products.

These important contributions by OBRR illustrate the leading role the FDA plays in ensuring the safety and efficacy of the products it regulates. As FDA Commissioner Margaret Hamburg, M.D., put it when discussing the role of the agency: “The bottom line is that if FDA does not do its job, there is no backstop. Ours is a unique role, and it is critical that we do it well.”

Mikhail Ovanesov, Ph.D., is a visiting scientist in the Laboratory of Hematology in the Office of Blood Research and Review at CBER

Global Partnerships Advance the Regulatory Science That Protects Public Health

By: William Slikker, Jr., Ph.D.

In work, as in life, your success often comes down to the strength of your relationships. And as the director of FDA’s National Center for Toxicological Research (NCTR), among the most pre-eminent regulatory science centers in the world, I have found that this axiom, often so apt in daily life, is also true on a grander scale in the world of research.

William SlikkerNCTR scientists develop innovative tools and strategies to advance FDA’s mission to protect and promote public health. Our center sits on 500 acres in Jefferson, Arkansas, far from agency headquarters in the Washington, D. C., metropolitan area.

But the power of the safety assessment work done at NCTR has global reach, and it is leveraged by the global nature of partnerships we have developed across FDA and with research centers in other countries. Late this summer, Aug. 21-22, I will travel to Montreal for the Global Summit on Regulatory Science, where government, industry and academic scientists from all over the world will assess how to address emerging technologies and implement innovative ways to use them to determine the safety and effectiveness of FDA-regulated products when used in real-world applications.

If you imagine our scientific collaborations as a family tree of sorts, our international activities are one limb. In addition to the annual summit, we provide opportunities for scientists from other countries to work with experienced FDA researchers in all facets of safety assessment. NCTR also has outreach partnerships with the World Health Organization, the European Food Safety Authority and other international organizations such as the International Union of Toxicology (IUTOX).

Our internal partnerships are another limb to the science of public health. Of 200 active research projects ongoing at NCTR, over 100 are done in collaboration with scientists from other FDA centers and the Office of Regulatory Affairs (ORA). For example, we work with the Center for Drug Evaluation and Research in assessing the danger, or toxicology, of certain drugs on the most vulnerable populations— pregnant women and children.

We are partners with the ORA in the Nanotechnology Core Facility on our campus that supports the study of nanomaterials, so small that they can’t be seen with a regular light microscope, yet their effects can be profound on the increasing number of drugs, foods and cosmetics in which they are found. NCTR also works with state partners in this research.

In fact, this particular effort and other partnerships have put NCTR at the forefront of research on nanotechnology. The safety and effectiveness of nanotechnology is a focus of a Memorandum of Understanding signed by the FDA Commissioner in 2011 with the State of Arkansas that enables NCTR to collaborate with five major research institutions in the state, including the University of Arkansas for Medical Sciences.

Our state partnerships within Arkansas are invaluable as they add both laboratory and investigator expertise not normally available to FDA. In addition to work with nanomaterials, our projects with Arkansas researchers include research on the effects of anesthesia on the developing brains of young animals to emulate the possible effects in children, and the development of novel bioinformatic approaches to collect, analyze and visualize massive pharmacogenomics (the genetic response to drugs) or imaging data sets.

Our federal partners, including the National Institute of Environmental Health Sciences and the National Toxicology Program (NTP), both of which share our mission to keep you safe from chemical and environmental hazards, combine with NCTR to produce a world powerhouse for safety assessment.

This 20-year partnership between NCTR/FDA and NTP has produced numerous sets of safety data that provide the scientific foundation for FDA regulators and others around the world to establish guidance and set standards to control food contaminants and assess drugs. For example, NCTR’s work on a naturally-occurring fungal contaminant (fumonisin FB1) in the nation’s corn crop produced data for FDA’s Center of Food Safety and Applied Nutrition to provide new recommended limits for fumonisin, an action that reached across the world.

NCTR also engages in public-private partnerships to foster the development of innovative products. For example, we are working with the International Anesthesia Research Society to improve the safe use of anesthetics in children. FDA has many such partnerships to leverage the expertise and resources of industry, government, and non-profit organizations in developing tools that drive innovation.

The crux of regulatory science is this: Just as an art critic must be an expert in art, a scientist at FDA must be an expert in the science that he or she is evaluating. “It takes a village” has become almost a cliché, but in truth it does take a global village to give regulatory scientists the tools they need to ensure that the exciting new technologies will translate into products that are safe, effective and will enhance your life.

William Slikker, Jr., Ph.D., is the Director of FDA’s National Center for Toxicological Research

World Health Assembly Strengthens Regulatory Standards

By: Margaret Hamburg, M.D.

The World Health Assembly is the decision-making body of the World Health Organization (WHO), attended every year by the leading government health officials from its 194 member nations. Recently, I was pleased to participate as a member of the U.S. delegation in the 67th meeting of this important group in Geneva, Switzerland.

Margaret Hamburg at World Health Assembly

Commissioner Margaret Hamburg speaks at the World Health Assembly

One of the key topics addressed during this year’s assembly was the critical role played by regulatory systems to ensure the safety, quality and efficacy of medical products. Resolutions addressed the need to monitor and act on the rise in antimicrobial resistance; strengthen regulatory systems; and enhance access to biotherapeutic products.

As part of the resolution on antimicrobial resistance, the WHO will develop a draft global action plan to combat this problem and member states were urged to strengthen their drug management systems, support research to extend the lifespan of existing drugs, and encourage the development of new diagnostics and treatment options.

The passage of a resolution to strengthen regulatory systems is itself a milestone for global health. It endorses a comprehensive approach to strengthening medical product regulation and it represents a basic change from traditional capacity-building that has focused primarily on sharing of technical expertise. The new systems-oriented approach embraces the need for a strong legal framework, and the use of data and information technology, leadership, governance, partnership, and sustainable financing to strengthen regulatory effectiveness and efficiency.

The adoption of this resolution, co-sponsored by Australia, Brazil, Colombia, Mexico, Nigeria, South Africa, Thailand and the United States, demonstrates a true international partnership across regions, with many nations affirming their commitment to working individually and together to strengthen their regulatory systems. This is the only way governments and their regulatory authorities can continue to build a global product safety net that will benefit patients and consumers around the world.

During the assembly, I  had the privilege of co-hosting with the Mexican Secretary of Health, Dr. Mercedes Juan Lopez,  a special session entitled, “Regulatory Systems Strengthening: Mobilizing People and Resources.” The distinguished panel included Malebona Precious Matsoso, Director General, Department of Health, Government of South Africa; Dr. Mark Dybul, Executive Director, The Global Fund to Fight AIDS, Tuberculosis and Malaria; Dr. Marie-Paule Kieny, Assistant Director-General of the World Health Organization; and Dr. Vincent Ahonkhai, the Senior Regulatory Officer of the Bill and Melinda Gates Foundation. The discussions focused on several important themes, including the multiple benefits of strong regulatory systems for the public health; national security; and economic development and investment.

The panelists highlighted the unique challenges and opportunities faced by regulators because of globalization and the extraordinary increase in the global supply of medical products, and the high cost of regulatory system failures to patients and their trust in the health system. More specifically, the discussions focused on the critical role that regulators play in ensuring access to lifesaving medical products by creating an environment of good regulatory practices that support innovation and research and protect the public from threats resulting from substandard or counterfeit products.

Panelists also reported on progress that is being made as nations increasingly collaborate to share information, reduce inefficiencies, and work toward regulatory convergence. For example, participants learned about the World Health Organization’s decades-long efforts to support countries in strengthening their systems, and of its prequalification program to ensure that select priority essential medicines, diagnostics and vaccines are of quality, safety and efficacy for international procurement agencies and developing countries with limited regulatory capacity.

These kinds of collaborative strategies are essential in this global age. Only by strengthening our international partnerships and building regulatory systems that work together and support each other can we ensure the quality, safety and efficacy of the medical products that the citizens of our nations depend upon.

Margaret A. Hamburg, M.D., is Commissioner of the U.S. Food and Drug Administration

FDA and Pan American Partners Work to Strengthen Regulatory Systems

By: Charles Preston, M.D., MPH

Regulatory systems are essential for good health care because they ensure safe, high quality and effective medicines. However, these systems must be strengthened in many parts of the world — a subject that is a core effort of the Pan American Network for Drug Regulatory Harmonization (PANDRH).

Charles PrestonI had the privilege of representing the FDA at a recent steering committee meeting, and I am happy to report that this network, which includes countries from all over the Western Hemisphere, is ready to adapt to new challenges like globalization, and improve its effectiveness.

In the past, the network has concentrated on upgrading regulatory standards by developing guidances and strengthening regulator capacity through training. There have been many successes, including multiple guidances issued and numerous trainings conducted.  However, there is a recognition that these efforts need new focus.

Thus, PANDRH has a strategic plan for modernizing its activities.

Rather than only developing region-specific guidances, it proposes improving standards by leveraging the work of global bodies, such as the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, and the Pharmaceutical Inspection Cooperation Scheme.

To strengthen capacity for oversight, PANDRH members will work to develop and implement a globally agreed upon set of regulator competencies, and use this to drive curricula and training objectives in the region. By doing this, the regulatory workforce can be professionalized, which will strengthen it for the future.

Another new emphasis will be to use evidence to help set priorities. The secretariat and PANDRH member states will now analyze data from evaluations of regulatory systems in the region to decide on future activities and benchmark success.

The importance of these changes is obvious: in today’s world of global manufacturing, trade and consumption, national regulators must be truly professional and able to implement global standards.

These are exciting developments that portend an auspicious new direction for PANDRH. FDA will continue its active engagement in the network’s efforts. They are essential to achieving a world in which everyone has access to safe, high quality and effective medical products that can protect or restore human health.

Charles Preston, M.D., MPH, is a medical officer in FDA’s Office of International Programs

Ensuring Pharmaceutical Quality Through International Engagement

By: Howard Sklamberg, J.D.

As we’ve written and spoken so much about, the FDA has had to transform itself from a domestically-focused regulatory agency into a 21st century global health organization.  This transformation has come in the face of economic and technological changes that have revolutionized how we carry out our mission. We live in a world where other countries increasingly produce—at least in part—the food and medical products our consumers and patients use in their daily lives.

Howard SklambergProducts the FDA regulates now come from more than 150 countries—many with much less sophisticated regulatory systems than our own. In this international marketplace, 40 percent of our finished drugs are imported, and approximately 80 percent of the manufacturers of active pharmaceutical ingredients used in the United States are located outside our borders.

Ensuring the quality of products in a global environment is a tall order. At every stage in the production of pharmaceutical products, and all along the global supply chain, things can go wrong.  Products can be improperly formulated, manufactured, or packaged. They can be contaminated or counterfeited. And the challenges are multiplied when the supply chain stretches around the world.

FDA is on the ground, around the world, inspecting facilities, developing relationships and providing advice.

But securing the global supply chain requires more than that. It calls for a cooperative and worldwide endeavor. It means working with our regulatory counterparts abroad to build capacity. It means harmonizing our standards for the sake of safer products and greater efficiency. It means engaging with industry and with regional and international organizations.

The Food and Drug Administration Safety and Innovation Act (FDASIA), which Congress enacted in 2012, included some important provisions designed to improve the safety and integrity of imported drugs sold in the United States. Some of the provisions are focused on FDA’s inspectional activities overseas. For example, FDASIA increases FDA’s ability to partner with foreign regulatory authorities to leverage resources through increased information-sharing and recognition of foreign inspections.

We now have more than 60 agreements with foreign counterparts to share certain information in inspection reports and other non-public information that can help us make better decisions about the safety of foreign products.

This type of collaboration not only increases our ability to evaluate pharmaceutical facilities, but allows experts to learn from each other. The result: an outcome whose sum total exceeds its individual parts.

That is exactly why today we announced an initiative to expand on our existing work to ensure that the public has access to quality pharmaceuticals. Through this initiative, and in cooperation with the European Commission (EC) and the European Medicines Agency (EMA), FDA will aim to deepen our reliance on trusted regulators outside of the U.S. who provide equivalent public safety and quality protection.

This mutual reliance initiative builds on our existing relationships with the EC, the EMA, and member states of the European Union. Under this new initiative, the goal is to increase our exchange, with the EC and the EMA, of information that is critical to making decisions that protect the public health. And together we will be more efficient and effective in targeting our resources for inspecting pharmaceutical operations.

This is the latest step in our continuing efforts to improve the quality of pharmaceutical products – a step that will deploy a dedicated FDA team to work with our European counterparts on a host of issues. The team, which will focus full time on pharmaceutical quality, will include experts from our Center for Biologics Evaluation and Research, our Center for Drug Evaluation and Research, and our Office of Global Regulatory Operations and Policy.

As a public health regulatory agency with a global presence, we look forward to strengthening our mutual reliance and capitalizing on our shared interests. The initiative we embraced today signals yet another important step forward for pharmaceutical quality here in the U.S.—and around the world.

Howard Sklamberg, J.D., is FDA’s Deputy Commissioner for Global Regulatory Operations and Policy

Building Expertise and Crossing Boundaries to Improve Oversight

By: Howard Sklamberg, J.D.

To keep the food supply safe, have safe, effective, and high quality medical products, and decrease the harms of tobacco product use, we have to work with the rest of the world.

Howard SklambergAs FDA’s Deputy Commissioner for Global Regulatory Operations and Policy (GO), I oversee FDA’s efforts to further advance its thinking and strategies from a primarily domestic to a globally focused regulator.

GO coordinates the efforts of FDA’s Office of Regulatory Affairs (ORA) and the Office of International Programs (OIP), and works with all of FDA’s product centers on scientific, manufacturing or other regulatory challenges. The highly skilled and dedicated workforce in ORA and OIP is responsible for conducting domestic and foreign inspections, deepening collaborations with local, state and foreign regulatory partners, helping these regulatory partners to strengthen their regulatory systems, and fostering the use of science-based standards and regulatory coherence around the globe to promote the public health of our citizens.

We have to be able to share information with our regulatory partners. We need their help to implement new regulations that have worldwide impact on the oversight of food under the Food Safety Modernization Act and medical products under the Food and Drug Administration Safety and Innovation Act. Working together with these partners, we can ensure an effective public health safety net for our citizens and communities.

An important new priority for FDA is to make fundamental changes in the way we operate in today’s world by aligning our efforts across the agency to keep pace with the acceleration of scientific innovation and the global expansion of the markets. So much of FDA’s work cuts across multiple product areas. How do we make that work as a large and complex agency?

Commissioner Hamburg and senior leaders across the Agency are committed to strengthening our ability to do just that and are collaborating to achieve greater operational and program alignment across the Centers and ORA.

A key part of this process is to enhance specialization across FDA. For ORA, enhanced specialization means that investigators, compliance officers, import reviewers, laboratory personnel, managers and others will have increased technical expertise in a specific commodity area and will work closely with subject matter experts in FDA’s centers. Over time, ORA’s geographic-based model will evolve to a commodity-specific, program-based model that will provide ORA staff the opportunity to gain increased expertise in specific product areas, such as pharmaceuticals, food, animal feed, medical devices, biologics, and tobacco. They will work as part of a team with the staff from other centers, collaborating, for example, with the Center for Drug Evaluation and Research on pharmaceutical oversight or with the Center for Food Safety and Applied Nutrition on food safety issues.

It is especially important that experts in the centers and ORA be engaged in helping to develop compliance policies and priorities. Working with the centers on these broader concerns puts ORA investigators and compliance officers in a better position to implement the preventive approaches contained in new statutes and work together more seamlessly with the centers.

These and other changes that are part of the agency’s focus on program alignment will deepen our knowledge and make us more effective and efficient, with more clarity and coherence in our communications and actions.

This process is still in its early stages. There is a lot of planning still to be done, and we will work to ensure a transparent and inclusive process. Nevertheless, change is coming and I am excited and proud to be part of a transformation that can only strengthen our efforts to safeguard the foods and medical products that are so important in the lives of people all over the world.

Howard Sklamberg, J.D., is FDA’s Deputy Commissioner for Global Regulatory Operations and Policy

FDA Works with China to Ensure Medical-Product Safety

By: Christopher Hickey, Ph.D.

Americans benefit greatly from medical products produced by other countries. Approximately 40 percent of finished drugs in the United States come from overseas, as well as more than 50 percent of all medical devices. About 80 percent of the manufacturers of active pharmaceutical ingredients are located outside the United States.

Christopher Hickey

Christopher Hickey, Ph.D., testifies April 3, 2014.

However, this rapid globalization of commerce presents challenges to regulators who oversee the safety and quality of medical products. Many of these challenges manifest themselves in China. As FDA’s country director for the People’s Republic of China, I testified on April 3, 2014 before the U.S.-China Economic and Security Review Commission, an advisory panel created by Congress, on our work to ensure the safety and quality of medical products produced in China and imported into the United States.

China is the source of a large and growing volume of imported foods, medical products and ingredients. In the years spanning fiscal years 2007 and 2013, the total number of shipments of FDA-regulated products from China to the United States almost quadrupled.

The challenges we see in China mirror those we see in other countries with developing regulatory systems. These issues include problems with data integrity, inadequate implementation of quality systems in manufacturing, and inconsistent regulatory oversight, among others.

As China’s role on the global stage expands, FDA has significantly increased drug and medical device inspections there, but we need to continue to strengthen our efforts. FDA is currently working to use Congressionally-appropriated funding to increase from eight to 27 the number of U.S. staff it posts in China. Visa issues that arose with the Chinese government over new FDA staff assigned there were addressed during Vice President Joe Biden’s visit to Beijing in December, and FDA continues its work to post new staff in Beijing in the coming months.

FDA recognizes that strategic engagement in China starts first and foremost with Chinese regulators. China’s Food and Drug Administration, or CFDA, is responsible for the regulation of food, drugs, and devices for domestic distribution in China, and for regulation of certain exported drugs and medical devices.

Senate Committee Hearing, April 3, 2014

Christopher Hickey, Ph.D., testifies before the U.S.-China Economic and Security Review Commission.

FDA has established a strong working relationship with CFDA. Our office has trained hundreds of Chinese inspectors in areas that include inspecting for good manufacturing practices and assessing the quality of data from sites that conduct clinical trials. Experts from FDA’s Center for Devices and Radiological Health now meet regularly with their counterparts from CFDA under the auspices of the International Medical Devices Regulatory Forum. These investments will pay long-term dividends for the American people: a stronger Chinese regulatory system can only strengthen FDA’s efforts to promote and protect U.S. public health.

Finally, in the area of inspections and enforcement, CFDA inspectors now regularly observe FDA inspections in China. And since 2012, FDA’s Office of Criminal Investigations has worked closely with CFDA to fight against Internet-based, illegal distribution into the U.S. of falsified, counterfeit and adulterated drugs.

FDA’s priorities in China match its global priorities: we work to ensure the safety and efficacy of FDA-regulated products. Manufacturers are best situated to make certain that appropriate processes are in place to ensure safety and quality in production. Regulatory bodies should hold companies accountable for lapses in the production process. Inspections and testing are important tools in that process, but they must be used as part of a larger system that emphasizes a preventive, approach to the production of safe, effective, high-quality medical products.

And in our globalized world, it’s increasingly important that regulatory partners work together to ensure the safety of products as they move through increasingly complex supply chains. Patients and consumers – whether in Beijing or Boston – deserve no less.

Christopher Hickey, Ph.D., is FDA’s Country Director for the People’s Republic of China.

For more information, please visit this Web link:

China’s Healthcare Sector, Drug Safety, and the U.S.-China Trade in Medical Products