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

Dr. Frances Kelsey, Who Protected Americans from Thalidomide, Turns 100

By: John Swann, Ph.D.

Today marks the 100th birthday of one of America’s most celebrated public servants. Frances Oldham Kelsey, Ph.D., M.D., was born in Cobble Hill, Vancouver Island, British Columbia, and earned her Ph.D. in pharmacology and her M.D. at the University of Chicago. She was on the faculty of the University of South Dakota and practicing medicine when, in 1960, she accepted the offer to become a medical officer at FDA.

John SwannA month after assuming her position she was assigned the review of a new drug application for thalidomide, a sedative that had been used by expectant mothers and many others in dozens of countries since the late 1950s. U.S. law at the time required a firm to provide evidence of a drug’s safety as a requirement for sale. Despite the global popularity of this drug, and despite a constant and increasing pressure from the firm to approve the application, Dr. Kelsey refused to do that without adequate evidence that the drug was safe, a decision that was supported by her colleagues and superiors.

By late 1961 scientists discovered that thalidomide was responsible for crippling birth defects in thousands of babies in many parts of the world. Thanks to Dr. Kelsey’s “exceptional judgment in evaluating a new drug” — as her firm stand was described in the President’s Award for Distinguished Federal Civilian Service she received from President John Kennedy — the U.S. was mostly spared the tragedies. But the close encounter with a public health catastrophe convinced Congress and the White House to resuscitate proposals to revitalize the regulation of pharmaceuticals. The result was the 1962 enactment of the Kefauver-Harris Drug Amendments that mandated “substantial evidence” of a drug’s effectiveness as developed by “experts qualified by scientific training,” in addition to evidence of a drug’s safety, and provided for greater oversight of drug investigations. These and other requirements in the new law established a global standard for the evaluation of drugs.

Frances Kelsey

Dr. Kelsey today, pausing between crossword puzzles.

After 1962, Dr. Kelsey oversaw the evaluation of investigational drugs and, later, of oncologic drugs and radioisotopes. Concerns in the agency with problematical clinical investigations continued in the early 1960s, such that FDA created the Division of Scientific Investigations in 1967 and placed Dr. Kelsey in charge. She remained in this position until 1995. The division engaged in inspections of clinical investigators, animal studies, and institutional review boards involved in drug trials. Thus, Dr. Kelsey helped ensure the reliability of data vital to FDA’s evaluation of therapeutic products over a span of four decades.

Frances Kelsey, the recipient of the highest honor that can be bestowed on a federal civil servant, officially retired from FDA in 2005, but her commitment to the integrity of science in service to the public health continues to inspire those in the FDA and beyond.

To learn more about the life and work of Dr. Kelsey, see her “Autobiographical Reflections.”

More about thalidomide and the 1962 Kefauver-Harris Drug Amendments that came out of this crisis can be seen at http://www.fda.gov/Drugs/NewsEvents/ucm320924.htm.

John Swann, Ph.D., is an Historian at FDA

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

A Blueprint for Helping Children with Rare Diseases

Editor’s Note: This blog has been updated to provide additional information about our use of expedited programs to speed rare disease medical product development.

By Jill Hartzler Warner, J.D.

Jill WarnerThe U.S. Congress and the Food and Drug Administration have long focused on bringing new therapies to patients with rare diseases, including children.

Two years ago this week, Congress made another contribution to this effort by enacting the Food and Drug Administration Safety and Innovation Act (FDASIA). The law directs our agency to take two actions to further the development of new therapies for children affected by rare diseases: (1) to hold a meeting with stakeholders and discuss ways to encourage and accelerate the development of new therapies for pediatric rare diseases, and (2) issue a report that includes a strategic plan for achieving this goal.

There are unique challenges when developing drugs, biological products and medical devices for the pediatric population. Not only is there the potential for children to respond differently to products as they grow but there are also additional ethical concerns for this patient population.

But these challenges are further compounded when developing therapies for pediatric rare diseases. For example, rare disease product development, by definition, means there is only a small potential group of patients available to participate in clinical studies that can help determine whether a product is safe and effective.

In our FDASIA meeting in January, we heard a variety of suggestions on clinical trial design and data collection from hundreds of the participating stakeholders from academia; clinical and treating communities; patient and advocacy groups; industry and governmental agencies.

These discussions helped inform our Strategic Plan for Accelerating the Development of Therapies for Pediatric Rare Diseases, which we posted on our website today. It outlines how we plan to meet the following four objectives:

Enhance foundational and translational science. Our strategy is to fill essential information gaps through such measures as fostering the conduct of natural history studies for pediatric rare diseases and by identifying unmet pediatric needs in medical device development. We also plan to issue guidance for sponsors on common issues in rare disease drug development and to refine and expand the use of computational modeling for medical devices.

Strengthen communication, collaboration, and partnering. Robust cooperation within FDA, among agencies, governments and private entities is necessary to enable the exchange of information on the issues of developing treatments for pediatric rare diseases. Single entities by themselves usually don’t have sufficient resources or expertise to overcome the product development challenges posed by pediatric rare diseases.

Advance the use of regulatory science to aid clinical trial design and performance.  Regulatory science helps develop new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of all FDA-regulated products. Of note, we plan to facilitate better understanding of biomarkers and clinical outcome assessments that are useful for the development of treatments for pediatric rare diseases. We also plan to further develop the expedited approval pathway for medical devices intended to treat unmet medical needs; and use FDA’s web-based resources to update and expand awareness of issues involving the development of medical products for pediatric rare diseases.

Enhance FDA’s review process. Our strategies include fostering efforts to learn patients’ and caregivers’ perspectives and incorporating this information into medical product development. We also plan to further develop and implement a structured approach to benefit-risk assessment in the drug review process and establish a patient engagement panel as part of the medical device advisory committee process.

The report notes our use of expedited programs to speed rare disease medical product development. For example, the accelerated approval program allows for approval of products to treat serious and life-threatening diseases based on an effect on a surrogate marker, such as blood test, urine marker, or an intermediate clinical endpoint, that is believed to be reasonably likely to predict clinical benefit to the patient. Under accelerated approval, further studies are required after approval to confirm that the drug provides a clinical benefit to the patient.

More than 80 new products have been approved under the accelerated approval program, and many of these have been for rare diseases. But it’s important to note that in some cases FDA exercises regulatory flexibility to approve drugs under the traditional approval pathway, rather than under the accelerated approval program. In fact, most of the recent new drug approvals for rare diseases have been approved under the traditional approval pathway because FDA has determined that the drug provides a clinical benefit to the patient. Such approvals make new drugs available to patients, and also mean that companies are not required to do confirmatory trials after approval.

FDA is committed to continuing its use of expedited programs and regulatory flexibility to speed development and approval of safe and effective drugs for all patients with rare diseases, and the strategies outlined in this plan will help us achieve a major goal of FDASIA and for our agency, which is to speed the development of therapies for children with rare diseases.

 

Jill Hartzler Warner, J.D., is FDA’s Associate Commissioner for Special Medical Programs

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 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.