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

FDA’s multi-pronged approach helps meet the challenge of bringing new and innovative antibiotics to patients who need them

By: Edward M. Cox, MD, MPH

With a growing number of infections becoming increasingly resistant to our current arsenal of antibiotics, developing new antibiotics to treat serious or life-threatening infections has become a key priority.

Edward Cox interview

There are significant scientific and economic challenges inherent to the development of new antibiotics. From a scientific standpoint, many patients with bacterial infections are often very sick and need to begin antibiotic therapy immediately, without further complications that enrollment in a clinical trial might involve. Moreover, it can be difficult to conduct a clinical trial involving very sick patients.

From an economic standpoint, antibiotics may be perceived as less potentially profitable for a company because they are generally taken only for a short period of time and often only for one course of treatment, by any given patient. Compare this to the long, dependable income stream from a diabetes medicine or a blood pressure medicine that a patient takes indefinitely, often for the rest of their life. These economic realities, which are rooted in the biology of acute bacterial infections, can make it challenging for a company to justify large expenditures for the development of drugs in this area, as a recent report by Eastern Research Group (ERG) affirms.

Provisions in a law passed a little over two years ago, commonly known as the GAIN Act, or the Generating Antibiotics Incentives Now Act, is helping to stimulate the development of new antibiotics. Under GAIN, certain antibacterial or antifungal drugs intended to treat serious or life-threatening infections can be designated “Qualified Infectious Disease Products” (QIDPs). As part of its QIDP designation, a drug receives priority review and can also receive fast track designation at the sponsor’s request. At the time of approval, a product with QIDP designation may be eligible for an additional five years of marketing exclusivity, exclusive marketing rights without competing with a generic drug product. To date FDA has granted 52 QIDP designations to 35 different unique molecules. We are already beginning to approve new antibacterial drugs with this beneficial QIDP designation.

FDA is working hard to streamline requirements for clinical trials for studying new antibacterial drugs and the provisions of the GAIN act are being actively implemented, but more is needed. There are still significant economic and scientific challenges in the development of new antibacterial drugs that need to be addressed. Additional financial incentives as well as new approaches for studying antibacterial drugs such as common clinical trial protocols could provide other important means to stimulate antibacterial drug development. We also need cutting-edge science to stimulate the development of new and innovative antibacterial drugs. To help drive this effort, FDA has assembled our Antibacterial Drug Development Task Force, a group of expert scientists and clinicians from within FDA, to consider opportunities to promote antibacterial drug development.

To advance this field, our Task Force is working with many leaders including those drawn from academia, regulated industry, professional societies, patient advocacy groups and government agencies. For example, FDA has contributed to the efforts of the Biomarkers Consortium of the Foundation for the National Institutes of Health to develop new endpoints for studying antibacterial drugs. FDA also works closely with the Clinical Trials Transformation Initiative (CTTI), a key group of dedicated scientists focused on advancing clinical trials for more efficient drug development. As a result, FDA and CTTI have helped convene a variety of important scientific meetings and activities on vital topics related to efficient clinical trial designs for testing new antibiotics. Our Task Force has also helped FDA team up with colleagues at the Brookings Institution’s Engelberg Center for Health Care Reform to help galvanize the scientific community’s efforts in new antibiotic drug development. August, 2012 began the first Brookings Council for Antibacterial Drug Development (BCADD) meeting, with meetings that occur approximately twice a year.

FDA and our Task Force members have also been busy on our own.  In February of 2013 we held a public meeting focused on creating an alternative approval pathway for certain drugs, such as antibacterial drugs, that are intended to address unmet medical need. We have also asked the public for their thoughts; in March of 2013, we issued a Federal Register Notice seeking input from the public on a wide range of topics related to antibacterial drug development. FDA has generated a number of guidance documents for industry, in draft and final form, that describe FDA’s scientific thinking with regard to developing new antibacterial drugs.

As part of our Task Force’s collaborative efforts, FDA is working closely with The National Institutes of Health (NIH) to further advance the development of new antibacterial drugs. Together, we are hosting a two-day Public Workshop to identify strategies for promoting clinical trials for antibacterial drugs and encouraging partnerships to accelerate their development. The ERG report will be presented at the workshop and other specific issues will be discussed including:

  • Priorities and strategic approaches to conducting clinical trials for antibacterial drugs
  • Regulatory pathways—including streamlined development programs for antibacterial drugs for patients with limited or no treatment options
  • Clinical trial design issues such as the development of common clinical protocols; using common control groups; statistical analysis issues; sharing data across trials (and data standards); appropriate clinical trial endpoints; and lessons learned from other therapeutic areas
  • The role of public-private partnerships in advancing the scientific and clinical trials enterprises

The work of the FDA Task Force as well as the GAIN Act have provided good first steps toward strengthening the antibacterial drug pipeline, but as the findings from the ERG report indicate, the forecast for antibacterial drug development likely will include a less than robust pipeline. Thus, additional attention on both financial incentives, new approaches for studying antibacterial drugs such as common protocols, as well as streamlined development pathways, likely will be needed to improve the climate.

Edward M. Cox, MD, MPH, is Director, Office of Antimicrobial Products, in FDA’s Center for Drug Evaluation and Research

A Milestone in our Partnership with Mexico on Food Safety

En Español

By: Michael R. Taylor

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

signing ceremony in Mexico

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

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

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

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

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

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

On the road from Mexico: a model for regulatory cooperation

En Español

By: Margaret A. Hamburg, M.D.

Margaret Hamburg

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

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

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

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

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

Margaret Hamburg and Mike Taylor at mushroom farm

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

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

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

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

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

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 reminder of the promise and limitations of abuse-deterrent properties

By: Douglas C. Throckmorton

The ongoing growing amount of drug abuse in our nation, particularly with prescription pain relievers known as opioids, has prompted a lot of talk about the potential of opioids with “abuse-deterrent” properties to help combat this public health problem. But care must be taken in putting  too much promise into abuse-deterrent technology at this time because the science is still relatively new and evolving.

Douglas C. Throckmorton, M.D.While the FDA strongly supports the development of products with effective abuse-deterrent properties and believes they can make a real difference, abuse-deterrent properties do not make an opioid impossible to abuse, and do not prevent overdose and death – they only makes certain kinds of abuse more difficult or less rewarding.

Current abuse-deterrent technologies tend to focus on making the drug either harder to crush, which makes them harder to snort or inject; harder to extract, which means the opioid cannot be easily separated from the other ingredients in the drug for purposes of abuse; more difficult to abuse orally, which is the most common form of opioid abuse; or  less attractive for abuse (e.g., the drug may contain an ingredient that counteracts the action of the opioid, making the drug less “likeable” or even unpleasant).

This week, FDA approved a new prescription opioid tablet called Targiniq ER, which contains a combination of the opioid pain medicine oxycodone and a drug called naloxone, an opioid antagonist. Naloxone can block the euphoric effects of opioid medicines and is used most often to treat an overdose. The science behind this particular abuse-deterrent formulation works like this: If the Targiniq ER tablet is taken as directed (i.e., swallowed according to its approved use), the naloxone will not interfere with the oxycodone. If, however, the tablets are crushed into a powder and snorted or injected, the naloxone inside the tablet will be absorbed and block the desired effect from the oxycodone.

Targiniq ER joins OxyContin (oxycodone) as the second drug FDA has approved with labeling describing the product’s abuse-deterrent properties consistent with FDA’s 2013 draft guidance for industry Abuse-Deterrent Opioids –Evaluation and Labeling which states that for claims to be made, they must be based on robust, compelling, and accurate data and analysis, and the description of the abuse-deterrent properties or potential to reduce abuse must be clearly and fairly communicated.

OxyContin gets its abuse-deterrent properties differently than Targiniq, by including ingredients that make the tablet hard to crush or dissolve. Efforts to pulverize the tablets into a powder result in a chemical reaction that makes the crushed tablet into a gooey gel that makes it more difficult to be inhaled or injected the way drug abusers would like.  While Targiniq and OxyContin use different abuse-deterrent technologies, they serve the same purpose: they are expected to help deter the often lethal practice of snorting or injecting prescription drugs.

In the context of this important and evolving area of science, FDA is very encouraged to see another drug with proven abuse-deterrent properties come to the market. We do need to remember that “abuse-deterrent” is not the same as “abuse-proof” and even abuse-deterrent formulations can be abused and people who take them can overdose and die.  For example, someone who wants to “get high” from prescription opioids can still swallow more than the prescribed amount, and this simple but common form of abuse can result in overdose and death.

Currently available products with abuse-deterrent properties are an important step in the right direction, but there is much more work to be done. The technologies involved in abuse deterrence and methods for evaluating whether those technologies actually deter abuse are rapidly evolving. To address this rapid change, FDA is working with many drug makers to advance the science of abuse deterrence and to help them navigate the regulatory path to market as quickly as possible. While FDA strongly supports a transition to opioids with abuse-deterrent properties, we do not believe it is feasible or in the interest of public health at this time to require all opioid products to have such properties.

To help support the safe use of all opioid products, FDA is working in many other ways to help prescribers and patients make the best possible choices about how to use these powerful drugs. Our goal is to find the balance between appropriate access to opioids for patients with pain and the need to reduce the tragedies of their abuse and misuse.

Douglas Throckmorton, M.D., is Deputy Center Director for Regulatory Programs in FDA’s Center for Drug Evaluation and Research

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