FDASIA at Year Two

By Margaret A. Hamburg, M.D.

Margaret Hamburg, M.D.Anniversaries are a time for stock-taking and today, on the second anniversary of the Food and Drug Administration Safety and Innovation Act or FDASIA, I’m pleased to report on the progress we’ve made implementing this multi-faceted law.

To date, we have completed nearly all of the deliverables we had scheduled for the first two years after FDASIA became law. And many of the new authorities under FDASIA are already having a positive impact on health. It’s difficult to cover all of our FDASIA work, but here are some highlights:

Preventing Drug Shortages: Drug shortages, which can have serious and immediate effects on patients and health care professionals, reached an all-time high in 2011, the year before FDASIA was enacted. In response to a Presidential Executive Order in December of that year, FDA issued an interim final rule to amend and broaden FDA regulations requiring certain manufacturers to give early notification of production interruptions that could cause drug shortages. FDASIA further broadened this requirement by requiring that other prescription drug manufacturers provide notification and also gave FDA additional authorities. In October 2013 FDA proposed a rule to implement these authorities and issued a strategic plan for addressing drug shortages. So far, with the help of early notifications, FDA was able to prevent 282 shortages in 2012 and 170 shortages in 2013. The number of drug shortages that did occur has also declined.

Promoting Innovation: FDASIA includes many provisions designed to encourage innovation. We have held meetings on the use of meta-analyses in drug applications; put in place a plan for implementing a benefit-risk framework for drug reviews, and issued a variety of guidance documents covering such topics as drug studies in children, abuse-deterrent drug development, antibacterial drug development and expedited review and development programs for serious diseases.

This latter guidance provided information that sponsors needed to know about our new Breakthrough Therapy designation that was part of FDASIA. This option exists for new drugs intended to treat a serious or life-threatening disease that, preliminary clinical evidence suggests, could provide a substantial improvement over available therapies. As of June 23, we had granted 52 requests for this designation, and of those, approved four new drugs and two new indications for previously approved drugs.

As part of our implementation of the FDASIA-related provisions related to medical devices, we proposed a strategy and recommendations for a risk-based health information technology (health IT) framework that would promote product innovation while maintaining appropriate patient protections and avoiding regulatory duplication; issued a proposed rule for implementing FDASIA’s streamlined new procedures for reclassifying a device; and published a final rule on a medical device unique identification or UDI with implementation in accordance with the timetable set in the law. UDIs will help the FDA identify product problems more quickly, better target recalls and improve patient safety. The riskiest medical devices will start bearing their UDI by September 24th.

Establishing and Strengthening User Fee Programs: An important element of FDASIA was reauthorizing user fees for prescription drugs and medical devices and creating new user fee programs for generic drugs and biosimilar biological drugs. User fees on some types of applications offer an important source of funding to support and maintain key activities, including FDA’s staff of experts who review the thousands of product submissions we receive every year. Since FDASIA took effect, review times for medical devices have been declining.  Our prescription drug user fee program is meeting or exceeding almost all of our performance goals agreed to with industry. We have acted on 54 percent of the generic drug applications, or amendments and supplements to generic drug applications which were pending in our inventory as of October 1, 2012. This helps ensure that consumers can have access to more low-cost drugs. And we have been able to provide advice concerning most of the 93 submissions from companies who are developing biosimilar biological drugs under a pathway that could also ultimately lower costs for consumers.

Enhancing Patient Engagement: A hallmark of FDASIA was a series of provisions intended to tap the patient perspective. Our Patient-Focused Drug Development Program allows us to more systematically obtain the patient’s perspective on a disease and its impact on the patients’ daily lives, the types of treatment benefit that matter most to patients, and the adequacy of the available therapies for the disease. In accordance with FDASIA, we have held patient meetings on eight diseases and have plans for meetings on 12 more. We have learned a great deal from patients in terms of their views of the symptoms of their condition, their feelings about how it affects their life, and their thoughts on ideal treatments and on participation in clinical trials to aid future drug development.  A FDA Voice blog post on patient reports captures these patient perspectives and much more.

Finally, Title VII of FDASIA provided FDA with numerous new authorities to protect the drug supply chain. We thought now was a good time to provide the public with a more detailed description of our work on Title VII, so we asked Howard Sklamberg, Deputy Commissioner for Global Regulatory Operations and Policy, to write a separate blog on that topic.

FDA laid out a three-year plan for implementing FDASIA and we’re on our way to achieving our stated goals. To help the public follow our progress, we set up a dedicated webpage—the FDASIA-Track. It provides useful links to each action and is updated on a regular basis.

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

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

The Commissioner’s Fellowship Program: A Win-Win for FDA and Public Health

By: Dr. Stephen M. Ostroff

As part of my FDA Voice blog series on the important work going on in FDA’s Office of the Chief Scientist (OCS), I’d like to highlight an FDA program that is giving top-tier, early career health care professionals, scientists, and engineers the chance to gain broad exposure to FDA regulatory science and scientific review opportunities. Led by OCS’s Office of Scientific Professional Development, the Commissioner’s Fellowship Program (CFP) is accepting applications from April 16 to May 26, 2014. Those who are accepted into the CFP will be joining FDA’s 7th class of Fellows.

Stephen OstroffDuring the two-year program, Fellows complete rigorous graduate-level coursework and conduct cutting-edge research on targeted scientific, policy, or regulatory issues under the mentorship of an FDA senior-scientist preceptor.

In the CFP, a Fellow is able to gain real experience in an FDA biology, physics, or engineering lab, work with a clinical review team, or work at a regional field laboratory or office. The coursework provides a common core understanding of the science behind regulatory review, encompassing activities across all FDA-regulated product areas.

Specific Fellow projects may focus on FDA review of sponsor applications for new products, monitoring product quality and safety, or other scientific or engineering topics. Fellows work closely with FDA scientists to create better research and evaluation tools and approaches, like assays for chemical or pathogen detection, or methods to assess clinical or health care data. Other science and policy areas of focus may involve foods or medical products in disciplines ranging from laboratory sciences to engineering, law, and ethics.

FDA launched the Fellowship Program in 2008 to achieve three critical goals:

1)      Attract to FDA top-tier scientists who can help tackle targeted regulatory science areas;

2)      Provide regulatory science training to expand the pool of experts;

3)      Recruit top scientific talent — scientists who may not have considered FDA in planning their career.

Since the program started, FDA has graduated 164 Commissioner’s Fellows, 75% of whom continued to work at FDA after completing the program. Our graduates have produced 175 publications based on their Fellowship work, represented FDA with 211 regulatory science presentations, authored or co-authored 917 reviews – ranging from original applications to supplements – and 26 Fellows have been the proud recipients of FDA Honor Awards.

The Fellows have brought an infusion of innovative ideas, new talents, and skills to FDA to help build the strong scientific foundation we need in our research and review activities. In turn, the CFP has enabled Fellows to develop their regulatory expertise and work confidently in the FDA environment.

Those Fellows who pursue careers outside FDA bring a deeper understanding of regulatory science and of FDA to their organizations. They enrich the regulatory science enterprise, whether by improving the quality of applications to FDA or by applying the knowledge and tools they’ve acquired through the CFP to develop practical solutions to an important public health challenge.

Stephen M. Ostroff, M.D., is FDA’s Acting Chief Scientist

For more information on eligibility criteria for the FDA Commissioner’s Fellowship Program and to apply for the upcoming class, please visit this Web link:

FDA Commissioner’s Fellowship Program Application Checklist

Interested in a Science Career at FDA? Our Web Portal Opens the Door

By: Jesse Goodman, M.D., M.P.H.

As a physician and a scientist, I value being part of a rich, vibrant scientific community. Since coming to FDA, I’ve been gratified to help lead and support a large group of talented, dedicated scientists who are passionate about what they do. Because science is at the core of everything we do at FDA, the majority of FDA’s staff are scientists, including engineers and medical professionals. A robust scientific workforce strongly engaged in the new sciences is critical to the success of FDA’s mission to protect and promote the public health.

Jesse GoodmanUnfortunately, I am often reminded that many people are unfamiliar with the cutting-edge research going on at FDA, and how important top-notch science and research are to our mission. Scientists, including those who may be exploring career options, are often unaware of the myriad scientific disciplines and expertise FDA must have to advance and apply the science required to assess the increasingly complex products we regulate. The outside world knows too little about the many innovative activities FDA scientists engage in, often with a wide range of collaborators, to keep our foods and medicines safe and help speed new therapies from bench to bedside.

So I’m delighted that we have now launched a comprehensive, one-stop web portal – FDA Science Careers and Scientific Professional Development - to showcase FDA’s exciting, multidisciplinary scientific work force and culture and how important science is to our public health mission. We want scientists – from students, to recent grads, mid-career, and seasoned professionals – to be aware of the diversity of FDA’s career opportunities so that we may continue to attract top scientists, including engineers and medical professionals who want to use their expertise to make a real difference in the world.

Entering our career portal, you will have access to the latest information on our fellowship programs and our internship, graduate, and faculty programs, which help us attract outstanding scientific academic talent. These opportunities include:

Once on board, FDA scientists benefit from a dynamic, state-of-the-art, scientific professional development culture, with daily opportunities to attend a variety of scientific courses, seminars, and workshops. You can find out more about FDA’s efforts to support scientific professional development through the career portal’s Training and Development section. FDA-sponsored scientific engagement ranges from cross-agency and external collaborations – including FDA’s Centers of Excellence in Regulatory Science and Innovation - to lectures by global scientific thought leaders.

For scientists and other professionals who want to make a real difference in the world, I can think of no better place to work than FDA. The opportunities to build a rewarding career and work on exciting and important issues while protecting and promoting our nation’s health are exceptional.

Jesse L. Goodman, M.D., M.P.H., is FDA’s chief scientist.

FDA Confers with International Counterparts to Advance Regulatory Science

By: Margaret A. Hamburg, M.D.

I have recently returned from the 8th International Summit of Heads of Medicines Regulatory Agencies, which was hosted on December 3-6, 2013, by the Netherlands’ Medicines Evaluation Board in Amsterdam. These annual meetings are an important forum for the exchange of information, views and regulatory strategies among the chief executives of major and like-minded medicines regulatory agencies. I was particularly pleased to be able to contribute to these discussions as a speaker on a panel on regulatory science together with Dr. Tatsuya Konda, M.D., Ph.D., the chief executive of Japan’s Pharmaceuticals and Medical Devices Agency.

Margaret Hamburg, M.D.The theme of this year’s summit was “Changes in the Regulatory Landscape,” and my foreign colleagues and I had plenty to talk about. Overcoming the challenges and reaping the benefits of regulatory science is even more critical today, when the FDA and other regulatory agencies face new and growing tasks in the global marketplace. All of us have to contend with the huge changes in the size and nature of international trade caused by emerging markets, developing economies, and increased cross-border flows of goods, information and capital.

As regulators, my international counterparts and I have many issues in common. They include the increasing complexity of new drug products and drug development; growing geographic distribution of markets; greater demands for public accountability and transparency in our work; budgetary and political challenges to regulatory oversight; and, the overriding need to keep up with the rapid changes in science and technology. Given these shared concerns, building cross-border partnerships and finding common solutions is paramount.

I reiterated to the conference our goal to encourage and strengthen cooperation and collaboration among those nations that are actively working to advance regulatory science. Regulatory science endeavors to use current and emerging knowledge to create new tools, standards and approaches for reliable assessment of the safety, effectiveness, quality and performance of medical products. At its best, this process is based on findings, evaluations, discussions and collaboration by scientists throughout the world.  And it is meetings like the recent summit in Amsterdam that help enhance this cooperation and the development of strategies that promote and strengthen the understanding, acceptance and application of regulatory science.

As the FDA embraces its international role in today’s complex regulatory environment, we fully accept the need to think and act globally more than ever before. I look forward to working with other nations’ regulators, the academic community, non-governmental organizations and industry as we join forces to advance regulatory science, the road to even better protection and advancement of the public health.

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

Personalized Medicine: The Future is Now

By Margaret A. Hamburg, M.D.

Margaret Hamburg, M.D.The difference between science and science fiction is a line that seems ever harder to distinguish, thanks in part to a host of astonishing advances in medical science that are helping to create a new age of promise and possibility for patients.

Today cancer drugs are increasingly twinned with a diagnostic device that can determine whether a patient will respond to the drug based on their tumor’s genetic characteristics; medical imaging can be used to identify the best implantable device to treat a specific patient with clogged coronary arteries; and progress in regenerative medicine and stem cell therapy using a patient’s own cells could lead to the replacement or regeneration of their missing or damaged tissues. Given these trends, the future of medicine is rapidly approaching the promising level of care and cure once imagined by Hollywood in futuristic dramas like Star Trek.

But these examples are not science fiction. They are very real achievements that demonstrate the era of “personalized medicine” where advances in the science of drug development, the study of genes and their functions, the availability of increasingly powerful computers and other technologies, combined with our greater understanding of the complexity of disease, makes it possible to tailor treatments to the needs of an individual patient. We now know that patients with similar symptoms may have different diseases with different causes. Individual patients who may appear to have the same disease may respond differently (or not at all) to treatments of that disease.

FDA has been playing a critical role in the growth of this new era for a number of years. Even before I became FDA Commissioner the agency was creating the organizational infrastructure and putting in place the regulatory processes and policies needed to meet the challenges of regulating these complex products and coordinating their review and oversight. It has been my pleasure to serve at FDA during this next exciting period and to help ensure that the agency continues to prioritize this evolution by anticipating, responding to, and encouraging scientific advancements.

I am very pleased to be able to present a new report by FDA as part of our ongoing efforts in this field. Paving the Way for Personalized Medicine: FDA’s Role in a New Era of Medical Product Development describes many of the exciting developments and looming advances in personalized medicine, lays out the historical progress in this field, and examines FDA’s regulatory role: from ensuring the availability of safe and effective diagnostic devices, to addressing the challenges of aligning a drug with a diagnostic device, to post-market surveillance.

Outside collaboration and information sharing is essential for this field to flourish. On Tuesday, the American Association for Cancer Research and AdvaMedDX held a fruitful daylong conversation on personalized medicine to treat cancer. I was one of the speakers, participating in a conversation with Dr. Francis Collins, the head of the National Institutes of Health. Our discussion focused in part on current status of drug and diagnostic co-development and the challenges and potential of whole genome sequencing, where data can be collected on a patient’s entire genetic makeup at a reasonable cost in a reasonable amount of time.

FDA is committed to fostering these cooperative efforts, as it will require the full force of government, private industry, academia and other concerned stakeholders to maximize our efforts and fully realize the promise of personalized medicine. Our new report outlines that commitment, and helps chart the way forward so that more people can live long and prosper.

Margaret A. Hamburg is the Commissioner of the Food and Drug Administration

At the Center of Innovative Safe and Effective New Biologics

By: Karen Midthun, M.D. 

We’ve all read news reports of research achievements that promise exciting and powerful new treatments such as gene therapies to treat diabetes and cell therapies to rebuild failing hearts.  

These medical products are biologics and may seem like the stuff of science fiction. But they could transform the way doctors treat certain illnesses and conditions. Other, more traditional biologics, such as vaccines and blood products, may play an important role in protecting against bioterrorism

As the part of FDA that has regulatory authority over many of these products, the Center for Biologics Evaluation and Research (CBER) plays a critical role in their development through its regulatory oversight and research. CBER comprises a variety of offices, including three product offices responsible for 1) gene, cell, and tissue therapies, 2) vaccines and allergy products and 3) blood and blood products. 

Biologics differ from chemically manufactured drugs; they are usually derived from living sources (humans, animals, microorganisms). Work in this field is demanding because of the unique challenges biologics pose to manufacturers as well as to the reviewers at CBER. For example, the sensitive makeup of some biologics (e.g., DNA and cells) means they can’t be sterilized, so great care is needed in manufacturing them. In addition, biologics are complex and often based on new scientific knowledge that CBER reviewers must be familiar with. 

One way CBER meets the challenges of reviewing these products is by conducting its own research, which creates new knowledge and helps advance development of innovative medical products. CBER shares this knowledge by publishing results in peer-reviewed journals, drafting guidance documents to assist in product development, and sharing information through global collaboration and conferences with colleagues in research institutes, government agencies, industry, and stakeholders. Scientists at CBER can bring this added knowledge to their review of new products. CBER research  enhances CBER reviewers’ ability to evaluate a product’s safety and effectiveness—and to spot problems in product development that might not be recognized by manufacturers. 

Thanks to all of this work, CBER has approved important new products over the past couple of years, including 1) the first over-the-counter test that enables consumers to determine their own HIV (the AIDS virus) status in about 30 minutes—in private, 2) five stem cell products derived from cord blood (placenta-umbilical cord) for use in rebuilding the populations of blood forming cells and the immune system; 3) three influenza vaccines that protect against four strains of influenza virus rather than the previous limit of three strains, and 4) two other influenza vaccines, which are produced using mammalian cells or insect cells, rather than with eggs, as is customary. These two new production techniques for influenza vaccine offer the potential for faster startup of the manufacturing process than egg-based manufacturing, as well as the ability to rapidly address an unexpected, spreading epidemic. These vaccines also offer an alternative for individuals who are allergic to egg products. 

Importantly, CBER’s product safety efforts don’t stop after a product goes to market. The Office of Biostatistics and Epidemiology works with collaborators such as Medicare and the FDA Sentinel program on projects that can help evaluate whether certain adverse reactions are caused by approved treatments. 

As medical innovation accelerates in the 21st Century, CBER will continue to be at the forefront of ensuring the development of innovative safe and effective biologics. 

Karen Midthun, M.D., is Director of FDA’s Center for Biologics Evaluation and Research

FDA Commemorates 30th Anniversary of the Orphan Drug Act

By: Gayatri R. Rao, M.D., J.D.

Gayatri R. Rao, M.D., J.D., is Director of FDA's Office of Orphan Products Development

When President Reagan signed the Orphan Drug Act 30 years ago, he enacted a critically important piece of health care legislation. The passage of this Act on January 4, 1983, was monumental because it created—for the first time—incentives to develop desperately needed medical products for Americans suffering with rare diseases. Until that point, development of such products was very limited. For instance, in the decade leading up to the passage of the Orphan Drug Act, only 10 industry-supported products for rare diseases were brought to market.

The Office of Orphan Products Development (OOPD) was formed at FDA more than 30 years ago, prior to the passage of the Orphan Drug Act, because FDA recognized that rare diseases, when taken together, posed a significant national public health issue. Once the Orphan Drug Act was passed, OOPD became responsible for administering the incentive programs created to spur the development of medical products for rare diseases, namely the Orphan Drug Designation Program and the Orphan Products Grants Program. These products include drugs, biologics, medical devices, and medical foods for the treatment of rare diseases.

As FDA commemorates the passage of this important legislation, we look back over the last 30 years with pride. Since its passage, over 2700 products in development have been designated as orphan drugs through the Orphan Drug Designation Program and over $290 million has been awarded to clinical studies through the Orphan Products Grants Program.  These programs, along with the critical, collective efforts of the Center for Drug Evaluation and Research’s (CDER) Rare Diseases Program, and those of many individuals across FDA, have helped to bring over 400 orphan products for rare diseases to the market.

We also commemorate the more than 30 years of dedicated service from every member of the rare disease community:

  • the patient advocates, who spurred national awareness about the challenges that people with rare diseases face and who continue to support families, educate the community, and drive research into their diseases;
  • the legislators who heard the voices of rare disease advocates and worked to champion the passage of the Orphan Drug Act;
  • the research community, which continues to leverage resources and foster collaborations among academia and industry stakeholders;
  • the clinicians, who support the medical needs of families with rare diseases and work to advocate on behalf of the community;
  • and industry, including pharmaceutical and biotech companies, angel investors, and venture capitalists who, in the spirit of the Orphan Drug Act, have come together to develop products for rare diseases.

Our many successes give us a reason to celebrate 30 years of hard work to provide diagnostic or treatment options to those with rare diseases. But we are keenly aware that there is still a challenging road ahead. We at FDA remain firmly committed to working with the rare disease community to tackle those challenges and to find new diagnostic tools and treatments for the millions of patients with rare diseases.

Gayatri R. Rao, M.D., J.D., is Director for The Office of Orphan Products Development

FDA Voice Interviews Jesse Goodman, M.D., M.P.H., on the DARPA and NIH Project Collaboration: Human on a Chip

FDA Voice: FDA has embarked on an exciting collaboration with the Defense Advanced Research Projects Agency (DARPA) and NIH—to develop a groundbreaking tool that could help bring new treatments to patients faster, more cheaply, and more safely. Can you talk about this new technology?

Dr. Goodman:  Yes, it’s what we’re calling Human on a Chip. This is an ambitious project to create a tool that could revolutionize toxicology testing and it’s something I’m really excited to talk about.  Scientists have relied largely on animal studies to determine if a drug is toxic before testing it in humans.  And while animal testing is useful, it’s also expensive, time consuming, and has drawbacks. For example, it doesn’t always detect toxic effects specific to humans and doesn’t usually provide information about the role that genetic differences within human populations play in toxicity. It can also generate false alarms, showing an effect in animals that doesn’t predict an actual effect in people, which leads us to abandon promising new drugs. FDA is collaborating with DARPA, NIH, and the scientific community to spur innovation in this field by exploring how tools like Human on a Chip can be integrated into our development tool box to improve testing for toxicity and potentially reduce the need for animal testing.

FDA Voice:  Can you describe Human on a Chip?

Dr. Goodman: Researchers are developing microsystems using human cells to test the effects of drugs or other substances. For example, scientists have developed a micro machine chip with human lung cells that grow on a surface to form a lung-like tissue that has both air spaces and blood circulation. FDA is supporting the coupling of this chip to a heart-like chip that beats and pumps blood. We can use this type of system to evaluate, with human cells, how specialized organs like the lung and heart react to a specific chemical.

The Human on a Chip builds on this approach. FDA’s collaboration with NIH and DARPA aims to create a 3D representation of 10 different human organ systems that mimic the processes and activities of those systems, potentially linking them to form a system with major features of human biology. For instance, in a living human, the interactions of heart, lung, kidney, and liver are crucial in the functioning of all 4 organs, and all are common targets of toxicity. A tool that creates and links organ-like systems will enable scientists to observe a substance’s effects on several interacting systems simultaneously. This can make it possible to test for beneficial effects as well as for toxicity.

Once these systems are refined, if successful, they could not only improve testing beyond currently available tools, but could also be engineered to mimic disease states or be implanted with cells with a specific genetic background that is involved in specific diseases or drug interactions.

FDA Voice:  Why transform toxicology testing?

Dr. Goodman: Toxicity has been a major challenge in medical product development and in assessing environmental hazards. Technologies like Human on a Chip could help shrink the time frame it takes for new treatments to move to human testing and approval. These new tools can help identify toxicity earlier in product development, thus protecting patients, lowering development costs, and speeding new treatments to patients in need.

Human on a Chip could also contribute to developing medical countermeasures because the diseases and conditions we might need to treat in a public health emergency—like anthrax, smallpox, pandemic influenza, and radiation and toxin exposure—rarely occur naturally, often making animal models the only available tools for evaluating a new treatment’s effectiveness.

FDA Voice:  What makes FDA essential to this collaboration?

Dr. Goodman:  Our FDA scientists have vast experience using available tools to make tough scientific decisions about the safety and effectiveness of a multitude of products. They’ve seen what works and what doesn’t, and thus can provide insights and help solve challenges in defining how best to develop and evaluate new tools. Before accepting a new tool for use, FDA scientists must have the needed scientific data on how it performs to ensure that it is as safe and effective as possible. Once FDA accepts a scientific tool, industry can use it for its qualified purpose during product development.

FDA Voice:  In what other ways has FDA worked to drive innovation in toxicology testing?

Through the Critical Path and Advancing Regulatory Science initiatives, we are working to harness the use of new science and technology to transform regulatory science and help get needed products to people quickly and safely. FDA identified transforming toxicology as one of the eight priority areas where collaborative regulatory science research is essential and offers huge opportunities. In addition to Human on a Chip, FDA is collaborating with other Federal agencies, academia, and industry to bring new science to toxicology, such as on the cell-based Tox-21 project with EPA and NIH, and on FDA grants to evaluate cell-based approaches to evaluate risks of reproductive and developmental toxicity.

My office has also formed a new FDA-wide council, together with scientists from across the agency, to explore, promote, and coordinate efforts concerning chemical and toxicology-related issues. FDA’s partnership throughout the development and evaluation cycle is critical to ensuring that exciting new tools and approaches like Human on a chip speed the delivery of safe and effective new treatments to people who need them.

Jesse L. Goodman, M.D., M.P.H., is FDA’s Chief Scientist and Deputy Commissioner for Science and Public Health

Collaboration for a Global Product Safety Net

By: Mary Lou Valdez

If it takes a village to raise a child, in today’s economy it takes the support and commitment of a global community to ensure the safety of the food we eat and the medications we rely on.

This point was made clear in an Institute of Medicine report released on April 4. The report was commissioned by the FDA as the agency addresses the challenges of global supply chains, international trade, and foreign sourcing of foods, feeds, and medical products. It complements the FDA Commissioner’s Report on Global Pathway to Product Safety and Quality released last summer.

Mary Lou ValdezImports of food and drug products regulated by FDA have increased by more than 13 percent per year since 2002, resulting in a four-fold increase of products produced outside of the United States. Approximately 50% of the fresh fruits and 20% of fresh vegetables, as well as 80% of seafood consumed in America comes from abroad. Similarly, more than 80 percent of the active pharmaceutical ingredients used to make medicines are imported. To ensure that the vast array of products Americans depend on are safe, FDA focus can no longer be solely domestic – it must be global.

Since many of the products imported are from emerging and developing countries, the FDA asked the IOM to take a look at the regulatory systems in those countries to identify major gaps and to design a strategy for how the FDA, along with other regulators and stakeholders, can help to strengthen their regulatory systems and build capacity.

Not surprisingly, the IOM found that the hurdles are great in some countries where there is inadequate clean water, electricity, transportation, communication systems and Internet access. Their regulatory agencies often operate with a skeletal staff, outdated equipment and limited or non-existent surveillance systems. In some of the least resourced countries there are weak or no laws governing product safety while product safety is not a high priority in others.

The IOM Committee’s strategy was to focus on the nexus of public health, product safety, development and trade, while recognizing that regulatory systems play an important role. The IOM identifies several core elements of a regulatory system: they must be responsive, outcome-oriented, predictable, risk-based or proportionate and independent. Other important commonalities include an enterprise risk management approach to regulation; focus on securing the entire supply chain; develop a profession of regulators – an “esprit de corps”; and make accountability an essential element of their system. The IOM also acknowledges that industry must play a role in ensuring the safety of its imported products.

To help build regulatory capacity, the IOM recommends that the FDA, other federal agencies and international organizations provide technical expertise, training and tools to strengthen the surveillance system in developing countries.

We take pride in the efforts FDA already has undertaken to support and collaborate with regulatory systems across the globe, such as our foreign training programs on good clinical practice inspections and low acid canned food inspections; a medical products information “hub” for the Americas in collaboration with the Pan American Health Organization; our interagency agreements with the US Agency for International Development to better understand pharmacovigilance systems in Africa and Asia; and our involvement with the World Bank’s Global Food Safety Fund, a partnership of public and private organizations intended to boost food safety capacity around the world. And this is only a short list of our activities.

We welcome the IOM’s call to international and intergovernmental organizations to invest more in strengthening the capacity of regulatory systems in developing countries, and to track progress as a priority of development banks, regional economic communities and public health institutions.

We were pleased that the IOM supports the agency’s risk-based strategy for monitoring and inspecting imported products and recommends that the agency extend this approach by working with strong regulators in other countries to plan inspections and pool data.

However, additional legal authorities would be helpful to accomplish this goal. FDA currently is barred from sharing certain non-public information with other regulatory agencies that might lead to timely identification, prevention, and resolution of emerging threats. Nor do we have the authority to use foreign audit data collected by our foreign regulatory counterparts with strong regulatory systems that would better leverage our limited resources.

Other authorities would be helpful to help us better manage risks. These include the ability to refuse admission of a product if inspection of the manufacturing facility is delayed, limited, or denied; and allow FDA to destroy the low value but large number of unsafe drugs that are coming into the country through international mail, typically purchased over the internet. In order to enhance our risk data, we would like additional information such as unique facility identifier as a condition of registration and import that would make it easier for FDA to properly follow a threat through the supply chain.

To ensure that industry assumes appropriate responsibility for their imported product, it would be helpful for manufacturers to account for the quality and origins of the materials that go into their products and require that manufacturers provide complete information to FDA on threats to the drug supply chain. Furthermore, the use of accredited third parties that meet prescribed standards could provide an additional set of eyes to help ensure the safety of the drug supply chain.

Ensuring the safety of imported food and medicines takes all countries working together, including governments, industry, academia, and other stakeholders. But marshalling the forces of this vast community may not be enough to provide the robust regulatory system we need in today’s global marketplace without new authorities to protect the health of the American public.

Mary Lou Valdez is FDA’s Associate Commissioner for International Programs and Director, Office of International Programs