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

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

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

Using electronic health records to help advance drug development and safety monitoring

By: Janet Woodcock, M.D.

Not long ago, electronic health records (EHRs) were an idea solely for the future. Today, they’re a reality. Paper records are becoming part of the past. These days, when patients go to their physician’s offices, they are much more likely to have their care documented electronically. EHRs give health care professionals more data to provide patients higher levels of quality care and safety.

Janet WoodcockNow that EHRs are more widely used, they collectively represent huge amounts of important data about the medical products and prescription drugs patients are using. Significant amounts of information in patient EHRs may be used in clinical research, with appropriate protection of patient privacy, to aid the development of new and more effective medical therapies or to provide information on using existing treatments more effectively and safely. These data, combined with other sources of electronic healthcare data such as information from healthcare claims, are being used to better understand the performance of medical products.

A key challenge for the research community is to effectively harness the data contained in EHRs. There are many kinds of EHRs and many ways to collect and store electronic data. To readily understand and combine information from different sources, we need to further standardize the data and the way it is exchanged. This work will allow computer systems to better “talk” to each other and, ultimately will lead to better treatment decisions as clinicians will have a more complete picture of their patients’ medical histories, including visits with other providers. 21st Century data sharing also will expand opportunities for researchers to ask questions that may improve our understanding of how and when drugs should be used. EHRs are only part of the puzzle, though. Defining standards for capturing data from clinical trials, and using standard terms for items such as “adverse events” or “treatments” will allow researchers to combine data from different clinical studies to learn more.

At FDA, we’re working to help realize the potential of electronic healthcare data to better protect and promote public health. FDA’s pilot program for the agency’s Sentinel System, dubbed Mini-Sentinel, uses electronic healthcare data, principally claims data but also including data from EHRs, to monitor the safety of FDA-regulated medical products.

Here’s a quick snapshot of how Mini-Sentinel works: 18 large health care organizations across the country serve as data partners for Mini-Sentinel. When FDA safety scientists have a safety question they can submit “queries” to the Mini-Sentinel data partners about the drugs being used by the patients cared for by their organization. Each partner organization maintains its own secure and privacy-protected data, in some but not all cases including EHR as well as claims data, but with the use of a common data model, the necessary information from all of the different systems can be analyzed in the same way. This capability enables Mini-Sentinel to provide answers to FDA questions about drug safety. The Mini-Sentinel system can survey more than 350 million person years of observation, 4 billion pharmaceutical dispensings, and 4.1 billion patient encounters. Thanks to the ability to access data from various sources, the Mini-Sentinel system can use the information from potentially more than 150 million covered lives in our nation’s health care system to help answer important drug safety questions.

FDA is actively engaged with standards-setting organizations to develop solutions that aid researchers, medical product developers and healthcare professionals in their efforts to increase our collective knowledge and tools in medicine. We collaborate with, and support others in our health care system and in the research community who are working on efforts to harness the power of electronic healthcare data. We applaud those endeavors and encourage others to join these efforts.

Janet Woodcock, M.D., is Director of FDA’s Center for Drug Evaluation and Research

FDA Encourages Medical Device Data System Innovation

By: Bakul Patel

Thanks to advances in digital health, doctors and their patients are more frequently using computer systems to collect medical data that can provide useful information on a patient’s health.

Bakul PatelSome of these systems, referred to as “medical device data systems,” are off-the-shelf or custom hardware or software products that transfer, store, convert format, and display medical device data without modifying it, and without controlling or altering the functions or parameters of any connected medical devices.

Medical device data systems can collect and store data from a variety of other medical devices, including glucose meters, blood pressure cuffs, and weight scales. This data can be used at home to track certain information or it can be stored for a doctor to review at a later time.

Medical device data systems can be used in hospitals to collect information and data from other medical devices including bedside monitors and infusion pumps. This information can then be stored in a patient’s electronic health record for a more complete review of a patient’s total health.

In 2011, FDA issued a regulation down-classifying medical device data systems. Since that time, FDA has gained additional experience with these types of technologies, and has determined that these devices pose a low risk to the public.

Today, given the low level of patient risk, we are proposing a compliance policy under which medical device data systems should see their burdens reduced.

Why would we do that?

Since our 2011 action, we’ve been working with two other federal agencies that oversee health IT – The Office of the National Coordinator for Health IT (ONC) and the Department of Health and Human Services, and the Federal Communications Commission (FCC) on a proposed risk-based regulatory framework for health IT that promotes innovation, protects patient safety, and avoids regulatory duplication. In the course of our work on the proposed framework, we sought extensive public feedback. And we listened.

In light of those discussions, we believe that medical device data system products pose little risk. While every medical device and procedure carries a certain level of risk, the health IT report proposes a risk-based framework – where we use our regulatory tools, resources, and expertise where they are most needed – and that’s with devices that carry  greater levels of risk.

This allows developers of medical device data systems to focus on making these products better able to operate amongst various devices and technology systems – resulting in stronger products.

Today’s proposed guidance for manufacturers of medical device data systems is thus consistent with the health IT report we issued earlier this year with ONC and FCC on the proposed framework. That report placed health IT products in three categories according to their risk to patients. FDA’s regulatory oversight of health IT products is focused on the devices that pose higher risk to patients.

Medical device data systems are critical to the success of digital health because they transfer, store, convert, and display a variety of information from medical devices critical to understanding an individual’s health. These systems are the foundation for intercommunication and interoperability among devices and between medical devices and other health IT.

Because they pose such a low risk, FDA does not intend to enforce compliance with the regulatory controls that apply to medical device data systems. FDA believes that this will encourage greater innovation in the development and maturation of these systems.

Bakul Patel is senior policy advisor in FDA’s Center for Devices and Radiological Health.

FDA Leverages Big Data Via Cloud Computing

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

Last year, I worked with a group of colleagues throughout the Food and Drug Administration (FDA) on a project that is critical for the agency’s future: the modernization of our information technology platforms to prepare for the influx of “Big Data”—the enormous data sets we receive daily from manufacturers, health care providers, regulatory bodies, scientists and others.

Taha Kass-HoutThese data sets are not only larger than ever before, they are also arriving more frequently than ever and varying enormously in format, and quality.

This year alone, we expect to receive somewhere between 1.5 and 2 million submissions through our eSubmission Gateway – and some submissions can now be as large as a Terabyte (one trillion bytes) in size. This is the very definition of a big data.

But, at FDA, we view it as an opportunity and a challenge. To meet both, we are building an innovative technology environment that can handle vast amounts of data and provide powerful tools to identify and extract the information we need to collect, store and analyze.

A key example is our recent leveraging of cloud computing.

“Cloud computing” is, basically, computing on demand. Think of how you use water, or electricity, at the same time as do your neighbors and millions of others. You pay only for what you use, and service is always guaranteed. You don’t need to wait till your neighbor is done to use the washer or dryer because there is only enough electrical capacity to handle one person at a time.

The same is true of cloud computing, which stores data on the Internet, rather than on the hard drive or drives of computers. In essence, it gives us the ongoing, simultaneous capacity to collect, control and analyze enormous data sets.

For example, FDA, partnering with state and local health organizations, identifies thousands of foodborne pathogen contaminants every year. We sequence, store and analyze this data to understand, locate, and contain life-threatening outbreaks. Again, cloud computing aids us in this effort.

Finally, FDA has some of the world’s most valuable data stores about human health and medicine. Through OpenFDA, our newest IT program, we are making some of these existing publicly available data sets more easily accessible to the public and to our regulatory stakeholders in a structured, computer readable format that will make it possible for technology specialists, such as mobile application creators, web developers, data visualization artists and researchers to quickly search, query, or pull massive amounts of public information instantaneously and directly from FDA datasets on an as needed basis. OpenFDA is beginning with an initial pilot program involving the millions of reports of drug adverse events and medication errors that have been submitted to the FDA from 2004 to 2013 and will later be expanded to include the agency’s databases on product recalls and product labeling.

OpenFDA promotes data sharing, data access, and transparency in our regulatory and safety processes, and spurs innovative ideas for mining the data and promoting the public health.

Big data is important to the way we carry out regulatory science, which is the science of developing new tools and approaches to assess the safety, efficacy, quality, and performance of FDA-regulated products. Through innovative methods such as cloud computing, we are taking advantage of this flood tide of new information to continue to protect and promote the public health.

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.

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

OpenFDA: Innovative Initiative Opens Door to Wealth of FDA’s Publicly Available Data

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

Today, I am pleased to announce the launch of openFDA, a new initiative from our Office of Informatics and Technology Innovation (OITI). OpenFDA is specifically designed to make it easier for web developers, researchers, and the public to access and use the many large, important, health data sets collected by the agency.

Taha Kass-HoutThese publicly available data sets, once successfully integrated and analyzed, can provide knowledge and insights that cannot be gained from any other single source.

Consider the 3 million plus reports of drug adverse reactions or medication errors submitted to FAERS, the FDA Adverse Event Reporting System (previously AERS), since 2004.

Researchers, scientists, software developers, and other technically-focused individuals in both the private and public sectors have always been invited to mine that publicly available data set – and others – to educate consumers, which in turn can further our regulatory or scientific missions, and ultimately, save lives.

But obtaining this information hasn’t always been easy.

In the past, these vast datasets could be difficult for industry to access and to use.  Pharmaceutical companies, for example, send hundreds of Freedom of Information Act (FOIA) requests to FDA every year because that has been one of the ways they could get this data. Other methods called for downloading large amounts of files encoded in a variety of formats or not fully documented, or using a website to point-and-click and browse through a database – all slow and labor-intensive processes.

openFDA logoOpenFDA will make our publicly available data accessible in a structured, computer-readable format. It provides a “search-based” Application Programming Interface – the set of requirements that govern how one software application can talk to another – that makes it possible to find both structured and unstructured content online.

Software developers can now build their own applications (such as a mobile phone app or an interactive website) that can quickly search, query or pull massive amounts of public information instantaneously and directly from FDA datasets in real time on an “as-needed” basis. Additionally, with this approach, applications can be built on one common platform that is free and open to use. Publicly available data provided through openFDA are in the public domain with a CC0 Public Domain Dedication.

Drug adverse events is the first dataset – with reports submitted from 2004 through 2013 available now.

Using this data, a mobile developer could create a search app for a smart phone, for example, which a consumer could then use to determine whether anyone else has experienced the same adverse event they did after taking a certain drug.

As we focus on making existing public data more easily accessible, and providing appropriate documentation and examples to developers, it’s important to note that we will not release any data that could be used to identify individuals or reveal other private information.

OpenFDA uses cutting-edge technologies deployed on FDA’s new Public Cloud Computing infrastructure enabled by OITI, and will serve as a pilot for how FDA can interact internally and with external stakeholders, spur innovation, and develop or use novel applications securely and efficiently. As we move forward with the early stages of openFDA, we will be listening closely to the public, researchers, industry and all other users for their feedback on how to make openFDA even more useful in promoting and protecting the public health.

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.