FDA’s New Roadmap for Progress: Strategic Priorities 2014-2018

By: Margaret A. Hamburg, M.D

The U.S. Food and Drug Administration regulates products that represent about 20 cents of every dollar American consumers spend on products. This includes the safety and effectiveness of drugs, medical devices, and vaccines, the safety of blood supply to food supply, cosmetics, dietary supplements, products that emit radiation, and more recently, tobacco. This fact can be easy to gloss over, but if one pauses for a moment to reflect on this fact, it is clear that the FDA’s regulatory role is large and truly meaningful to all of our everyday lives.

Margaret Hamburg, M.D.When the FDA was first established, our regulated industries were predominantly local, the volume of imported products was low, and even the movement of goods across country was minimal. But times have changed, and so have the strategies we employ to address those changes. Over the last five years alone, the FDA’s regulatory portfolio has increased to now include regulating tobacco products, developing a new global system for protecting food safety, and addressing challenges created by the global expansion of research, commerce and trade.

In fact, more often than not today, a drug or medical product that ends up on the shelves of an American drugstore or in our hospitals will come, at least in part, from some foreign source. Nearly 40 percent of finished medicines that Americans now take are made elsewhere, as are about 50 percent of all medical devices. Approximately 80 percent of the manufacturers of active pharmaceutical ingredients used in the United States are located outside our borders.

These and other new challenges and transformative developments in global science, technology and trade are rapidly altering the environment in which we work to fulfill our broad public health mission. In order to continue to carry out that mission, we need a set of clearly defined priorities and goals, as well as the strategies for reaching them. Therefore, I am pleased to announce the release of a revised set of FDA Strategic Priorities which will guide the agency in how we continue to promote and protect the health of the American public.

The new Strategic Priorities document sets the path for our Agency over the next four years. It establishes a framework for integrating our five strategic priorities – regulatory science, globalization, safety and quality, smart regulation, and stewardship.

Although each priority is significant in and of itself, the priorities are also interconnected and must not be addressed in isolation. In addition, this new roadmap sets forth FDA’s core mission goals and objectives, such as improving and safeguarding access to the products FDA regulates – and promoting better informed decisions about their use.

The Strategic Plan has been in development for more than a year and was created by a hard-working team of talented and knowledgeable FDA employees representing programs from across the agency. While this team drove the Plan’s creation, it is backed by the commitment of all of us at the FDA. My hope is that these priorities, which will be repeatedly cited in our speeches, policies and writings, will serve as our foundational guidepost, providing the strategic direction to help the agency continue to provide the level of service and protection the American people deserve.

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

20 Years of Improving Women’s Health: 1994 – 2014

By: Margaret A. Hamburg, M.D.

Margaret Hamburg, M.D.As we celebrate the 20th anniversary of the FDA’s Office of Women’s Health, I would like to highlight some of the work we’ve done to help improve women’s health, both looking across FDA and within the office. Whether it is approving new treatments for chronic conditions like heart disease, conducting research or helping to protect pregnant women from foodborne illnesses, the work we do at FDA makes a difference throughout a woman’s life.

Consider our product approvals. In 1996, for example, our agency approved a product for use in Pap smears that revolutionized the detection of cervical cancer; ten years later we approved the first vaccine for the prevention of this cancer. We have also approved advances in breast imaging, including 3D breast tomosynthesis and automated screening ultrasound.

We have encouraged innovation in lupus treatment and approved the first new lupus drug in 50 years. And we approved the latest generation of cardiac synchronization therapy devices which our own FDA scientists have shown particularly benefit women with heart failure.

FDA has also supported research to help us better understand how medical products affect women. Since 1994, the Office of Women’s Health research program has provided $30 million to support over 300 research projects, workshops, and trainings on a wide range of topics including cancer, HIV and osteoporosis. More than 25 percent of these research dollars have been directed at cardiovascular disease, the number one killer of women, with studies examining such issues as QT interval prolongation (a disorder of the heart’s electrical activity), how breast cancer drugs can affect the heart, and sex differences in various cardiac interventional therapies. FDA’s medical product centers have also sponsored women’s health research and initiatives such as the Health of Women Program that promote a better understanding of sex differences.

The results have been impressive: OWH’s research alone has been published in over 290 articles in peer-reviewed journals and has made impact on the regulatory decision-making process, including guidance documents, label changes, and standards development. Indeed, FDA’s guidance to industry is an important way that the agency has been helping to address important issues in women’s health.

Over the years, FDA guidance has encouraged greater inclusion of women in clinical trials and the evaluation of sex differences. Our own analysis last year found that women make up about half of the representation in these studies, but the numbers are lower for medical devices. So we have more to do and recently issued guidance to medical device developers to address this concern.

We have also made great strides in our communication and outreach to women during the past two decades. OWH’s Take Time to Care Program has built partnerships with other government agencies, retailers, and national organizations that provide millions of women with FDA safety information. Over the years, we have launched other educational initiatives like the Food Safety for Moms-to-Be and expanded the women’s health resources available via our “For Women” website and social media to make sure that women have tools to help them make informed decisions about the use of FDA-regulated products.

I am pleased at how much we have done to promote and protect women’s health since 1994. At the center of much of this change has been the consistent, driving force of the Office of Women’s Health and its determined leader, Marsha Henderson. I encourage you to check out OWH’s 20th Anniversary brochure to learn more about the progress that has been made. And I hope that you will collaborate with us on the work that still needs to be done.

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

Clinical Trials: Enhancing Data Quality, Encouraging Participation and Improving Transparency

By: Margaret A. Hamburg, M.D.

Today FDA is announcing important steps that the agency plans to take to enhance the collection and availability of clinical trial data on demographic subgroups – patient populations divided by sex, race/ethnicity or age.

Margaret Hamburg, M.D.Section 907 of the 2012 FDA Safety and Innovation Act directed us to take a closer look at the extent to which clinical trial participation and the inclusion of safety and effectiveness data by demographic subgroups is included in medical product applications, report our findings, and then, within one year, produce an action plan with recommendations for improvements.

Our report, issued on August 20, 2013, found that the agency’s statutes, regulations, and policies generally give product sponsors a solid framework for providing data in their applications on the inclusion and analysis of demographic subgroups. Overall, sponsors are describing the demographic profiles of their clinical trial participants, and the majority of applications submitted to FDA include demographic subset analyses. We also found that FDA shares this information with the public in a variety of ways. Now, one year later, we’re releasing the FDA Action Plan to Enhance the Collection and Availability of Demographic Subgroup Data, which we developed after extensive interaction with stakeholders.

The action plan includes 27 action items that are designed to meet three overarching priorities – improving the completeness and quality of demographic subgroup data collection, reporting and analysis (quality); identifying barriers to subgroup enrollment in clinical trials and employing strategies to encourage greater participation (participation); and, making demographic subgroup data more available and transparent (transparency).

In addition to the action plan, we’re publishing a final guidance entitled, “Evaluation of Sex-Specific Data in Medical Device Clinical Studies.” It was written in response to the fact that certain medical devices may yield different responses in women than men, and yet women are under-represented in some medical device studies. This has led to less information for women regarding the risks and benefits of using these devices.

The guidance includes recommended methods for clinical study design and conduct to increase enrollment of men and women, if needed, and ways to analyze data for sex differences. FDA has held a series of public workshops to raise awareness about common strategies for enhancing recruitment and retention of women in medical device clinical trials. Fully integrating this final guidance into the templates used by FDA’s reviewers of medical devices, and providing a webinar for industry on how to use the guidance, comprise one of the 27 items in our action plan.

I hope you’ll find that the action plan is responsive and pragmatic and, most importantly, when fully implemented, it will improve medical care and public health. Many of the steps it outlines will have a broad impact on the work of FDA’s medical product centers and will require great thought and planning as they are implemented, depending on current evidence and available resources. The action items range from relatively short-term goals that can be achieved in a year, to others that will take 1-3 years, to a small number that will require a longer period, 3-5 years, to achieve.

Although the plan certainly places significant responsibilities on FDA’s medical product centers and other FDA offices, it also engages our partners inside and outside of government to share the responsibility for this important mission. For example, industry is being asked to help develop and share best practices for encouraging broad clinical trial participation, and the National Institutes of Health will be participating in several research projects with FDA.

We know that richer information is collected when different subgroups are enrolled in pivotal studies for medical products. This kind of enrollment in turn gives us greater assurance in the safety and effectiveness of the medical products used by a diverse population.

To set the plan in motion quickly, FDA is setting up a steering committee that will oversee implementation, come up with metrics for measuring progress and be responsible for planning a public meeting to be held within 18 months after release of the plan. FDA has already set up a website where the public will be able to track the agency’s implementation progress. That website will be updated on a regular basis.

Also, we’re reopening our Section 907 public docket to solicit comments for the action plan. I encourage everyone to review the document and consider how you might be able to partner with FDA and others in encouraging necessary and appropriate demographic subgroup diversity and representation.

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

Providing Easy Access to Medical Device Reports Submitted to FDA since the Early 1990s

By: Taha A. Kass-Hout, M.D., M.S. and Jeffrey Shuren, M.D., J.D.

Taha Kass-Hout

Taha A. Kass-Hout, M.D., M.S.

In addition to food and drugs, FDA has regulatory oversight of tens of thousands of medical devices ranging from bandages and prosthetics to heart valves and robotics. These products are used by millions of Americans, and they are essential, well-performing tools of modern healthcare, but occasionally they present a safety issue due to risks not identified in prior studies, a malfunction, a problem with manufacturing, or misuse.

These incidents are collected in a publicly available FDA database called MAUDE – short for Manufacturer and User Facility Device Experience. As part of the openFDA project, there is now an Application Programming Interface (API) for this dataset, which provides a way for software to interact directly with the data. This API will allow developers and researchers to easily query thousands of reports dating back to the early 1990s.

The API can be a powerful tool for generating hypotheses for further investigation or inquiry and can inform the development of safer, more effective technologies. For example, it can help identify new, potential safety signals as well as which classes of devices may be associated with particular adverse events.

Jeffrey Shuren

Jeffrey Shuren, M.D., J.D.

There are some necessary caveats to this API. The dataset is a record of reports submitted to FDA, and not a definitive accounting of every incident with every device. It may contain incomplete, inaccurate, unverified, or biased data. Thus, it cannot be used to determine incidence. And the appearance of a device in a report does not mean that cause-and-effect has been determined. Therefore, these data should be used in the context of other available information. It’s also important to note that the data made available under this initiative do not contain anything that potentially could be used to identify individuals or reveal other private information.

This API is the latest in a series of openFDA releases that have made publicly available data more easily accessed and queried. We believe that these tools can be used by developers and researchers to make insights that fuel new, innovative products (such as mobile apps and websites), and that help protect and promote the public’s health. Over the last two months, openFDA has released several APIs related to drugs, food, and devices. Together, they help provide perspective on the work FDA is doing, and make the public health data the agency is developing easier to access and utilize.

By design, openFDA is a research and development project that draws on community involvement. We are actively involved in the openFDA communities on GitHub and StackExchange, and encourage people interested in the project to participate in those communities. Together, we can make openFDA into a more useful, more powerful resource for the protection and advancement of the public health.

In addition to providing datasets, openFDA encourages innovative use of the agency’s publicly available data by highlighting potential data applications, and providing a place for communities to interact with one another and with FDA domain experts.

Taha A. Kass-Hout, M.D., M.S., is FDA’s Chief Health Informatics Officer and Director of FDA’s Office of Informatics and Technology Innovation

Jeffrey Shuren, M.D., J.D., is Director of FDA’s Center for Devices and Radiological Health

See more at: http://blogs.fda.gov/fdavoice/#sthash.COpthK14.dpuf

Curbing Risk, Not Medical Innovation, in Personalized Medicine

By: Jeffrey Shuren, M.D., J.D.

Innovative new tests are routinely submitted to the Food and Drug Administration to assure they are safe and effective. They include genetic tests that help oncologists decide whether a patient is a good candidate for a drug that treats melanoma as well as tests that are capable of sequencing the entire human genome.

Jeffrey ShurenBut many tests never undergo FDA premarket review to determine whether they are accurate, reliable, and clinically meaningful. These are laboratory developed tests (LDTs) designed, manufactured and intended to be used in a single laboratory.

FDA has exercised enforcement discretion over LDTs since 1976, when the agency first obtained comprehensive authority to regulate all in vitro diagnostics as medical devices. In those early days, LDTs were relatively simple, low risk, often for rare conditions, and generally only available on a limited basis.

But LDTs have evolved and proliferated because of advances in technology and evolving business models. Today, many LDTs are more complex, have a nationwide reach and have higher-risk uses such as detection of risk for breast cancer and Alzheimer’s disease. And yet they don’t undergo premarket review – or have adequate controls in place to assure proper test design and development, even when they compete with FDA-approved IVD test kits that conventional manufacturers market.

That’s concerning. Without appropriate safeguards, neither patients nor their health care providers can be assured that these tests are safe and effective. This is particularly troubling when an FDA-approved test is available, because it puts patients at unnecessary and avoidable risk. It also stifles innovation by creating disincentives for conventional manufacturers to invest in developing new, medically important tests.

We believe that LDTs serve an important role in health care and that there are many good tests on the market. Unfortunately, FDA is also aware of faulty or unproven LDTs, including ones that could cause patients to be inappropriately treated for heart disease; cancer patients to be exposed to inappropriate therapies or not get effective therapies; incorrect diagnosis of autism; and unnecessary antibiotic treatments.

That’s why FDA intends to propose a risk-based oversight framework that would appropriately balance assuring that patients and providers receive safe and effective tests with promoting innovation.

It would phase in enforcement of premarket review, quality systems, and adverse event reporting requirements for high- and moderate-risk LDTs over many years, beginning with the highest-risk tests (which include companion diagnostics—crucial to personalized medicine by targeting treatments for cancer, heart disease and other conditions) to give laboratories time to comply. Moreover, we intend to leverage existing programs, such as third party review and third party inspection as appropriate, and explore opportunities to work with entities that have experience with labs, thereby creating more efficiencies for labs to meet applicable FDA requirements.

On the other hand, under our upcoming proposed framework, we intend to continue exercising enforcement discretion with respect to the premarket review requirements for tests that labs make for rare diseases, to address an unmet need, or that are low risk.

Labs and conventional manufacturers serve as vitally important sources of innovative test development. Through smart, appropriately tailored oversight, we can best promote product development by all test developers and best serve patients and their healthcare providers.

When everyone plays by the same rules, innovation and society benefit.

Jeffrey Shuren, M.D., J.D., is Director of FDA’s Center for Devices and Radiological Health

Achieving our Mission through Enhanced IT Service Delivery

By: Walter S. Harris, M.B.A, P.M.P.

At its core, FDA is an information- and process-driven organization. Day-in and day-out, FDA’s experts make thousands of weighty and complex decisions by evaluating, and allowing access to, life-sustaining, life-enhancing and life-saving products. This is done using a vast amount of sophisticated and reliable data. And it is done while continuously engaging with consumers, patient representatives, industry, academia and other government agencies.

Walter HarrisSince the establishment of the Office of Information Management and Technology (OIMT) seven months ago, we have fundamentally changed how we support the Agency’s mission — primarily, to increase transparency, and better align functions and resources to achieve more efficient and improved customer support and services. To further these objectives, we have taken the following steps to help transform our service to our internal and external stakeholders.

  • Reorganized the Office of Information Management into a more stable structure that is focused on our customers and the delivery of services. This new IT structure includes robust leadership, increased scientific capability and closer attention to IT’s business and customer needs, including a new IT audit and compliance program.
  • Hired the first Chief Health Informatics Officer (CHIO), Taha Kass-Hout, MD, M.S., to promote and develop innovative enterprise solutions and identify opportunities for transparency and availability of FDA’s public health data to our consumers while ensuring accountability and privacy. With the launch of openFDA, we have demonstrated our ability to respond quickly and accurately to emerging scientific, technological and economic trends.
  • Requested that the CIO Council, FDA’s IT governance board with representation across all of its Centers, focus on opportunities to consolidate IT solutions into capabilities that benefit the agency, eliminating duplication of efforts and creating possibilities for reinvestment.
  • Creating an IT service cost-allocation model that will include a service catalog and identification of cost drivers for IT services.
  • Restructuring our IT portfolio to a service based portfolio model that is in alignment with our cost allocation model.

OIMT, together with IT leaders in the Centers, will transform our IT operation to minimize redundancies, streamline IT, and enhance customer service while lowering IT costs to the agency. We continue to seek opportunities to  identify and tackle issues, improve communications across functional lines, and more fully capitalize on the expertise of our talented staff.

These are exciting endeavors and I am proud of the efforts IT leaders across the FDA have taken to focus on customer service. With a renewed emphasis on service delivery to enable mission outcomes, we are better able to use resources in a manner that will achieve greater efficiency, improve support across the FDA, and provide results that benefit the public health.

Walter S. Harris, M.B.A, P.M.P., is FDA’s Deputy Commissioner for Operations

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

A Curriculum for Medical Device Progress

By: Francis Kalush, Ph.D.

Horace, the greatest Roman poet of antiquity, spoke of the need to “seek for truth in the groves of Academe” — and in the last four years, my colleagues in FDA’s Center for Devices and Radiological Health (CDRH) and I took his advice. In scores of meetings and two large workshops, we consulted with hundreds of academics about a novel idea: a university-level program to address an important public health need by stimulating the development of new medical devices.

Francis KalushIn 2011, CDRH embarked on an Innovation Initiative to help accelerate and reduce the cost of the development and regulatory evaluation of safe and innovative medical devices. Through that and other programs, we learned that the delivery of new therapies to patients can be accelerated if medical device innovators — including entrepreneurs and university students and faculty — understand FDA’s regulatory processes. We then established the Medical Device Technology Innovation Partnership, and tasked it with developing an educational program that would explain FDA’s standards and procedures for evaluating and approving or clearing medical devices.

This learning tool grew from collaborations with Stanford University, University of Virginia, Howard University, The Johns Hopkins University, University of Maryland at College Park and at Baltimore, and University of Pennsylvania.

The program, called the National Medical Device Curriculum, will provide students at academic institutions and science and technology innovators with the core information about the regulatory pathway to market. This includes an understanding of the expertise needed to design, test and clinically evaluate devices; identify the root causes of adverse events and device malfunctions; develop designs for devices with repetitive functions; and, navigate FDA’s regulatory process.

The mode of the curriculum is a series of fictional case studies based on real-world medical device scenarios. The four learning tools developed so far cover the following subjects: the regulatory pathways for medical devices; safety assurance and risk management planning; and the regulatory pathways for novel devices and for devices that are substantially equivalent to already marketed predicate devices.

Each of these fictionalized case studies includes a student module and an instructor’s guide with ideas for exercises and discussion in class. The curriculum was tested at several universities and received high praise. For example:

  • William E. Bentley, from the University of Maryland James Clark School of Engineering found that the case studies “are of tremendous pedagogical value, and we are definitely incorporating them into our curriculum.”
  • ŸArthur L. Rosenthal, Ph.D., a professor at Boston University’s College of Engineering, used the case studies to teach advanced biomedical product design and development and reported that “the students found the material engaging as well as providing essential context for their projects.”
  • ŸYouseph Yasdi, Ph.D., MBA, executive director at The Johns Hopkins Center for Bioengineering Innovation and Design, found that the cases are “a good fit” for his program to train engineers to better understand regulatory issues.

More case studies are being planned to help train the next generation of entrepreneurs and keep the U.S. a leader in medical device innovation. Regulatory training is particularly important in the development of medical devices, as the industry is heavily populated by small companies that may not have the expertise to navigate FDA’s requirements.

The National Medical Device Curriculum is a step forward in our Agency’s efforts to encourage and facilitate the development of new medical products — drugs, biological products and medical devices — that has been made possible by the great scientific breakthroughs in the last two decades, such as the mapping of the human genome and the invention of nanotechnology. Those of us who worked on this novel curriculum hope it will encourage and advance the development of new devices for patients and help protect and promote the public health.

Francis Kalush, Ph.D., is a senior science advisor at FDA’s Center for Devices and Radiological Health

OpenFDA Provides Ready Access to Recall Data

By: Taha A. Kass-Hout, M.D., M.S.

Every year, hundreds of human and animal foods, drugs, and medical devices are recalled from the market by manufacturers. These products may be labeled incorrectly or might pose health or safety issues. Most recalls are voluntary; in some cases they may be ordered by the U.S. Food and Drug Administration. Recalls are reported to the FDA, and compiled into its Recall Enterprise System, or RES. Every week, the FDA releases an enforcement report that catalogues these recalls. And now, for the first time, there is an Application Programming Interface (API) that offers developers and researchers direct access to all of the drug, device, and food enforcement reports, dating back to 2004.

Taha Kass-HoutThe recalls in this dataset provide an illuminating window into both the safety of individual products and the safety of the marketplace at large. Recent reports have included such recalls as certain food products (for not containing the vitamins listed on the label), a soba noodle salad (for containing unlisted soy ingredients), and a pain reliever  (for not following laboratory testing requirements).

At present, FDA provides various ways to access the recalls data, including an RSS feed, a Flickr stream, and a search interface. This new API supplements these sources as the first, and one-call, access to the entire enforcements archive. The hope is that this API will be useful to developers and researchers interested in FDA enforcement actions. Developers can now call into the API to add recalls data to mobile apps or consumer websites. And researchers could use the API to study individual manufacturers, product categories, or specific foods or drugs.

The recalls database is the second dataset to be released on openFDA. Since openFDA debuted on June 2, 2014, the website has generated considerable interest. In the past five weeks, the site has had 34,000 sessions (two-thirds are new sessions) from 26,000 unique visitors worldwide that generated 80,000 page views.

The adverse events API has been accessed by 18,000 Internet connected devices, with nearly 2.4 million API calls since the launch.  At least one new website, http://www.researchae.com, has been created to allow any user to submit queries on the adverse events data, and several other companies are integrating the data into their products and services. It is also being accessed by researchers inside and outside FDA and by journalists as well.

More APIs will follow in the weeks ahead. OpenFDA is taking an agile (development in small chunks of iterations) approach in the creation and release of these APIs, with the objective of getting feedback from developers and researchers (as well as from industry and the public) at the GitHub and StackExchange forums that serve our project. We plan to incorporate some of the feedback into future iterations of the API. Accordingly, as we learn more about how the public might seek to use this data — and as a result of our agile and user-centered methodologies — the API structure may change in quite a bit in the coming months. It’s also important to note that this API, like all others on openFDA, are in beta and are not ready for clinical use. However, their contribution to FDA’s public health mission already now grows every day.

Taha A. Kass-Hout, M.D., M.S., is FDA Chief Health Informatics Officer and Director of FDA Office of Informatics and Technology Innovation

Developing new tools to support regulatory use of “Next Gen Sequencing” data

By: Carolyn A. Wilson, Ph.D.

When you’re thirsty, you don’t want to take a drink from a fire hose. And when scientists are looking for data they don’t want to be knocked over with a flood of information that overwhelms their ability to analyze and make sense of it.

Carolyn WilsonThat’s especially true of data generated by some types of both human and non-human genome research called Next Generation Sequencing (NGS). This technology produces sets of data that are so large and complex that they overwhelm the ability of most computer systems to store, search, and analyze it, or transfer it to other computer systems.

The human genome comprises about 3 billion building blocks called nucleic acids; much medical research involves analyzing this huge storehouse of data by a process called sequencing—determining the order in which the nucleic acids occur, either in the entire genome or a specific part of it. The goal is often to find changes in the sequence that might be mutations that cause specific disease. Such information could be the basis of diagnostic tests, new treatments, or ways to track the quality of certain products, such as vaccines made from viruses.

NGS is a complicated technique, but basically it involves cutting the genome into millions of small pieces so you can use sophisticated chemical tricks and technologies to ignore the “junk” you don’t need, and then make up to hundreds of copies of each of the pieces you want to study. This enables additional techniques to identify changes in the sequence of nucleic acids that might be mutations. NSG enables scientists to fast-track this process by analyzing millions of pieces of the genome at the same time. For comparison, the famous human genome sequencing and analysis program that took 13 years to complete and cost $3 billion could now be completed in days for a few thousand dollars.

Man with HIVE Computer

The Center for Biologics Evaluation and Research (CBER) supported the development of High-Performance Integrated Virtual Environment (HIVE) technology, a private, cloud-based environment that comprises both a storage library of data and a powerful computing capacity being used to support Next Generation Sequencing of genomes.

In order to prepare FDA to review and understand the interpretation and significance of data in regulatory submissions that include NGS, the Center for Biologics Evaluation and Research (CBER) supported the development of a powerful, data-hungry computer technology called High-Performance Integrated Virtual Environment (HIVE), which can consume, digest, analyze, manage, and share all this data. HIVE is a private cloud-based environment that comprises both a storage library of data and a powerful computing capacity. One specific algorithm (set of instructions for handling data) of HIVE that enables CBER scientists to manage the NGS fire hose is called HIVE-hexagon aligner. CBER scientists have used HIVE-hexagon in a variety of ways; for example, it helped scientists in the Office of Vaccines Research and Review study the genetic stability of influenza A viruses used to make vaccines. The scientists showed that this powerful tool might be very useful for determining if influenza viruses being grown for use in vaccines were accumulating mutations that could either reduce their effectiveness in preventing infections, or even worse, cause infections.

There’s another exciting potential to HIVE-hexagon research: the more scientists can learn about variations in genes that alter the way they work—or make them stop working–the more they can help doctors modify patient care to reflect those very personal differences. These differences can affect health, disease, and how individuals respond to treatments, such as chemotherapy and influenza vaccines. Such knowledge will contribute to advances in personalized medicine.

Team members at work in FDA's HIVE server room.

CBER scientists showed that HIVE might help scientists determine if influenza viruses being grown for use in vaccines were accumulating mutations that could either reduce their effectiveness in preventing infections or cause infections. Genome studies supported by HIVE will also contribute to advances in personalized medicine.

Because CBER’s HIVE installation has been so successful we are now collaborating with FDA’s Center for Devices and Radiological Health (CDRH) to provide a second installation with greater capacity and computer power that takes advantage of the high-performance computing capacity there. When ready and approved by FDA for use, we will use this powerful, CBER-managed, inter-center resource to handle regulatory submissions.

HIVE-hexagon and its innovative NGS algorithms are just one major step CBER has taken recently as it continues its pioneering work in regulatory research to ensure that products for consumers are safe and effective. I’ll tell you about other exciting breakthroughs in my next update on CBER research.

Carolyn A. Wilson, Ph.D., is Associate Director for Research at FDA’s Center for Biologics Evaluation and Research.

For more HIVE photos go to Flickr