FDA Teams With National Forum to Reduce Deaths from Heart Disease: Program is first of its kind

By: Heidi C. Marchand, Pharm.D.

In the U.S., only about 1 in every 4 prescriptions is taken as directed by a health care provider – a problem that costs our nation more than 125,000 lives a year. Millions of Americans with heart disease – the nation’s No. 1 killer – are especially vulnerable.

Heidi MarchandTo stem that tide, FDA has teamed with the nonprofit National Forum for Heart Disease and Stroke Prevention to advance the cause of a heart-healthy and stroke-free society.

FDA’s Office of Health and Constituent Affairs has signed a Memorandum of Understanding with the National Forum to promote and increase the use of health knowledge, skills and practices by the public in their daily lives. The five-year agreement is a first-of-its-kind cooperative public education program to reduce the burdens of heart disease and stroke.

Heart disease, which kills 1 in 4 Americans, can be managed. To prevent heart attacks, transient ischemic attacks and other cardiac events, doctors prescribe medications and lifestyle therapies (e.g. heart-healthy diets). Because medication is not readily adhered to – and neither are lifestyle treatments – millions of people suffer from preventable cardiac episodes. As a nation, lack of medication adherence (which can be as simple as not getting a prescription filled or refilled) costs more than $100 billion annually in excess hospitalizations.

To confront this problem, FDA is taking the lead in support of Million Hearts®, a national initiative of the Department of Health and Human Services to prevent 1 million heart attacks and strokes by 2017. A key partner in that mission is the National Forum, whose members include more than 80 U.S. and international organizations representing public, private, health care, advocacy, academic, policy and community sectors.

Together we will:

  • Explore, demonstrate and evaluate innovative health promotion concepts.
  • Exchange information on nutrition, heart disease, and ways to increase the number of patients who take their medication and/or therapy.
  • Identify and systematize best practices in behavior modification education.
  • Develop concepts for community-based interventions.

Our goals are clear: create recommendations to improve compliance with prescribed medical therapies and implement the recommendations to improve the lives of patients living with heart disease.

FDA’s Dr. Helene Clayton-Jeter and Dr. Fortunato “Fred” Senatore are leading a diverse team in identifying strategies to help patients take their medicines as directed and follow the advice of their doctors.

Concurrently, the National Forum will recruit a Therapy Adherence Steering Committee, made up of experts and stakeholders from physician and nursing groups, pharmacy (retail/system), behavioral health, consumer/patient groups and others invested in complying with medical therapy.

We’ll then jointly develop action plans for high-probability, high-yield strategies to promote heart health by helping ensure that patients take their medicines and adopt healthier lifestyles. Our plan is to complete all steps in the next several years.

We cannot fix this problem overnight. But by addressing it strategically, we can move forward and improve the odds of preventing and surviving heart disease and stroke among Americans.

Heidi Marchand, PharmD, is Assistant Commissioner in FDA’s Office of Health and Constituent Affairs

FDA’s Keynote Address to the Annual Conference of the Food and Drug Law Institute

By Stephen Ostroff, M.D.

Today marks the start of my third week as Acting Commissioner of FDA and I “celebrated” by giving a keynote address to attendees at the annual conference of the Food and Drug Law Institute (FDLI). Few places offer a more appropriate stage for a newly designated leader of FDA. As our names suggest, our organizations have a lot in common.

Stephen OstroffFor decades, the FDA and FDLI have worked together to educate and inform the broad “food and drug” community about the latest developments in our field and FDA’s critical and complex role in promoting and protecting the public health.

It’s been an exciting, busy, and rewarding first three weeks since moving into my new office from the position of Chief Scientist. The FDLI annual meeting offered me the opportunity to highlight a number of FDA’s accomplishments over the last year. The credit for these achievements in no small measure goes to the immensely talented employees at FDA who are committed to assuring safe and nutritious foods, providing effective and high quality medical products, and reducing harm from tobacco products. Credit for these achievements also reflects the extraordinary leadership of my predecessor, Dr. Peggy Hamburg, over the last 6 years.

So today, I’m pleased and honored to present to this audience some of FDA’s accomplishments and challenges, and also to extend my sincere appreciation to FDA’s dedicated work force, who make my new job much easier. But much more importantly, our work force makes the lives of so many Americans safer and healthier. It is with great pride that I look forward to continuing to work with all of you in support of this noble goal.

Stephen Ostroff, M.D., is Acting Commissioner of the U.S. Food and Drug Administration

Providing Timely Patient Access to High-Quality, Safe and Effective Medical Devices

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

We know that patients with life-threatening or irreversibly debilitating conditions lack treatment and diagnostic options. For these patients, earlier access to promising new devices is critically important. At the same time, delayed access may mean the difference between life and death, or may result in irreversible disability.

Jeffrey ShurenIn weighing the benefits and risks of new technologies for these patients, we understand the need to place greater weight on the benefit of earlier access, and to also account for the risks of delayed access. That’s why  we’ve developed the Expedited Access Program (EAP): to speed qualifying devices to patients with life-threatening or irreversibly debilitating conditions without compromising FDA’s high standards for safety and effectiveness.

Under this voluntary program, sponsors of devices for life-threatening or irreversibly debilitating conditions that meet an unmet need can request an EAP designation. Also under this program, CDRH staff- including senior management – work collaboratively with developers of such devices earlier and more often. These efforts include the creation of a Data Development Plan that provides predictability and leverages postmarket data collection. The Data Development Plan will shift premarket data collection to the postmarket setting, to the extent appropriate, taking into account the public health benefit of these devices, while still meeting the U.S. approval standard of reasonable assurance of safety and effectiveness. Starting April 15th, this program will be up and running and we will begin to accept requests for EAP designation.

The premarket data must be adequate to support FDA’s high standard for premarket review but can include data based on an intermediate endpoint or a surrogate endpoint reasonably likely to predict clinical benefit.

Another important feature of the EAP is how FDA decides that the benefits of a novel device for patients with life-threatening or irreversibly debilitating conditions outweigh its risks. Under the EAP, FDA may accept a greater degree of uncertainty if it is sufficiently balanced by other factors, including the probable benefits to having earlier access to the device.

If, after careful analysis, FDA determines that some data can be collected after the device is on the market, then patients in need will benefit sooner. A few of the factors that can enter into this analysis include a low probability of serious harm, a high likelihood that postmarket surveillance can quickly identify instances of serious patient harm and a high likelihood that postmarket data collection will be completed in a timely manner.

We consider this balancing of premarket and postmarket data collection to be so important that we made it one of our three 2014-2015 strategic priorities, along with strengthening the clinical trial enterprise and providing excellent customer service.

Today, we’re taking steps to implement that priority. In addition to issuing a guidance document outlining our EAP program for devices to treat or diagnose life-threatening or irreversibly debilitating conditions, we’re issuing a guidance on balancing premarket and postmarket data collection. It describes the circumstances under which postmarket data collection is appropriate for PMAs, whether or not they meet the criteria for the EAP, and provides many useful examples.

Once EAP products come to us for review, they will qualify for priority review. This feature, combined with the other elements of the EAP program, will reduce the time it takes to develop important new medical devices for patients with unmet medical needs and it will do so without ever lowering our standards.

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

FDA Advances Medical Product Innovation

By: Margaret A. Hamburg, M.D.

On March 10, I had the pleasure of appearing with my colleague Dr. Francis Collins before the Senate Committee on Health, Education, Labor and Pensions to testify at a hearing on the subject of “Continuing America’s Leadership in Medical Innovation for Patients.” I thought the broader public health community would be interested in my oral testimony, and so I am sharing it here:

Margaret Hamburg, M.D.“Thank you, Mr. Chairman and Members of the Committee. I’m very pleased to be here today to discuss our shared goal of speeding innovative treatments to patients. FDA looks forward to working with you on this important effort.

As you have noted, this will be my last appearance before the Committee, as I am stepping down, but I want to thank you for your support over the years, and our constructive engagement with this committee to advance FDA’s public health mission.

I came to the Agency at a time of considerable uncertainty and change in the biomedical product industry; a time when dramatic advances in science and technology, some that my colleague Dr. Collins just outlined, demanded new models and approaches.

In turn, we took a very serious look at our role in advancing biomedical product innovation to ensure that we would be a gateway, not a barrier, to the delivery of better, safer and more effective treatments and cures.

In fact, this has been a high priority for me throughout my tenure and I’m very pleased, as Sen. Murray noted, last year, we approved the most new drugs in almost 20 years, and more orphan drugs than ever before. Forty-one percent of these new approvals were first-in-class products, resulting in a breathtaking array of truly innovative new therapies for patients.

Today, FDA approves drugs faster on average than all other advanced nations: 40 days faster than Japan; 70 days faster than Canada; and 174 days faster than Europe. And FDA has made substantial improvements in the efficiency of medical device reviews as well.

Moreover, we’ve accomplished this while remaining the gold standard around the world for safety and effectiveness.

Yet despite these successes, too many diseases still await treatments and cures.  Serious public health needs, such as treatments for Alzheimer’s disease, are not being met. And rising R&D expenditures are not matched by a proportionate discovery of new treatments.

In this context, I want to address concerns raised by some that FDA regulation is the principal obstacle to the development of innovative treatments, and suggestions that FDA’s authorities and procedures must be fundamentally restructured.

As a physician, I know that if you incorrectly diagnose a patient’s condition, the treatment that you’ll prescribe is unlikely to work. Unless we correctly diagnose why cures are still lacking for many diseases, we’re unlikely to find the solutions that will actually deliver those cures so let me give you three examples of misconceptions.

First is the incorrect but commonly repeated assertion that FDA’s approval of new drugs lags behind other countries. The reality is starkly different: over 75% of the new drugs approved by Japan, EU, Canada, Australia Switzerland and FDA from 2004 to 2013 were approved first by FDA, according to a recent report by the British-based Centre for Innovation in Regulatory Science. The result is that Americans are far more likely to get first access to a new medicine before patients abroad.

Second, FDA is said to be rigid and inflexible in its approach to requesting and using data for approval of a new drug. In fact, FDA’s clinical trial requirements have been steadily increasing in flexibility:

  • 45% of new drugs are approved based on a surrogate endpoint;
  • one-third are approved on the basis of a single clinical trial;
  • Last year, we used expedited approval processes for more drugs than ever before – about 66%.

And thanks in part to the new authority that you gave us in FDASIA, 74 drugs had received the new “breakthrough” designation.

My final example is the concern that investment in biotechnology has dropped precipitously in the United States, and that the FDA is to blame. But in the words of The National Venture Capital Association (NVCA), “Biotechnology investment dollars rose 29 percent in 2014 to $6.0 billion . . , placing it as the second largest investment sector for the year in terms of dollars invested.”  And Jonathan Leff, a leading biotechnology investor affiliated with NVCA, said that one of the two reasons for the increased investment in biotechnology is the improved regulatory climate in recent years at FDA.

I cite these examples to suggest not that the world of biomedical research and product development is all fine, but to urge that we start with the right diagnosis. We do not want solutions based on inaccurate diagnoses.

I caution against solutions that seek to lower the safety and effectiveness standards for approval of the medical products on which Americans rely. Remember that the great leaps forward in evidence-based medicine of the last 50 years have come in part because of the high standards for product approval that Congress put in place after a series of disasters involving unsafe and ineffective medical products. Those standards have also boosted the confidence that Americans place in medical products and that the world places in the American biomedical product industry.

Together, we can build on the progress that has been made in recent years, to further advance biomedical science and improve the lives of patients. And there are some areas from the FDA perspective that I believe we can all agree need to be improved.

First, patients are uniquely positioned to inform medical product development. Treatments can better meet their needs if we can capture science-based, disease-specific patient input to incorporate in the development and review process.

Second, more attention needs to be given to the development of “biomarkers” and surrogate endpoints. These can help scientists identify and target successful medical treatments and shorten drug development times as Dr. Collins was noting in his remarks.

FDA has accepted hundreds of biomarkers and surrogates, such as blood pressure changes, blood sugar reduction, and tumor shrinkage. Yet biomarkers are still lacking for many diseases, such as Alzheimer’s. The biggest obstacle is that scientists do not sufficiently understand the causes of Alzheimer’s and other diseases to identify drug targets or identify which patients will benefit from certain drugs. To solve this problem we must support the establishment of strong public-private partnerships, bringing the best minds together to develop the science that we need.

Third, evidence from clinical experience (called “real world evidence” or “big data” by some) provides a vital tool to monitor medical products in use in the marketplace. FDA’s Sentinel Initiative, with more than 170 million lives, is one of the largest uses of this type of information in healthcare and proving vital for monitoring safety and emerging safety concerns. The science of using evidence from clinical experience to establish product effectiveness is still in its infancy. Real progress demands that we develop the methodologies needed to harness its promise.

And fourth, FDA and industry agree that the Agency must be able to attract and retain talented scientists to review cutting-edge products. We look forward to working with you to improve our ability to hire and retain these experts.

So let me close by underscoring that speeding innovation while maintaining standards for safety and efficacy serves patients well, supports the needs of our health care system, and has enabled the medical product industry in this country to thrive. And so I thank you for your support for our efforts at FDA and the work you are going to be doing going forward to advance that work and the work of all our colleagues in the biomedical research community so we can deliver on the promise of science for patients.”

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

Bacterial Infections Associated with Duodenoscopes: FDA’s Actions to Better Understand the Problem and What Can be Done to Mitigate It

By: William Maisel, M.D., M.P.H.

Duodenoscopes are flexible, lighted tubes that are threaded through the mouth, throat, and stomach into the top of the small intestine (duodenum). Duodenoscopes are used in more than 500,000 procedures, called endoscopic retrograde cholangiopancreatography—or ERCP—in the United States each year. The procedure is the least invasive way of draining fluids from pancreatic and biliary ducts blocked by tumors, gallstones or other conditions. The duodenoscope is different than the endoscopes used for routine upper gastrointestinal endoscopy or colonoscopy. The duodenoscope is a more complex instrument than other endoscopes and can be more difficult to clean and disinfect.

William Maisel, M.D., M.P.H.In the fall of 2013, the Centers for Disease Control and Prevention (CDC) notified the FDA of a potential association of multidrug resistant bacterial infections and duodenoscopes. This raised a number of issues that needed to be investigated. Which duodenoscopes were involved? Was the problem unique to one model or to different models and manufacturers? Were the proper cleaning and disinfection protocols followed in the hospital where the infections occurred? Are the cleaning and disinfection protocols adequate? If not, what are the alternatives? Which device design features, if any, contributed to the outbreak? What could be done to prevent future outbreaks?

Even before FDA was notified of the infections by the CDC, FDA was working to strengthen cleaning and disinfection protocols of complex instruments like duodenoscopes to maximize patient benefit and reduce safety risks. We held a public meeting to discuss the scientific challenges, published a draft guidance in 2011 on cleaning and disinfecting or sterilizing medical devices in health care settings and collaborated with standards developing organizations working to develop national and international standards. Since becoming aware of the 2013 infections and additional bacterial infections associated with duodenoscopes, we have further accelerated our work in this area. Specifically, we have gathered and reviewed information from facilities where the infections occurred, identified and studied the devices in question, collected and analyzed information from the manufacturers, analyzed medical device adverse event reports submitted to FDA, and reviewed the relevant published scientific literature.

We have been actively working with federal partners, manufacturers, hospitals, medical professional societies, and other stakeholders to better understand the issues that contribute to these infections and what can be done to mitigate them.

The FDA strives to provide the public with evidence-based information that patient and health care providers can use to make informed decisions. Once we developed a sufficient understanding of the issues to provide recommendations to help mitigate the risk, we issued a Safety Communication. The communication raised awareness that transmission of infections associated with duodenoscopes has occurred even when manufacturing reprocessing instructions were followed properly and that the complex design of duodenoscopes may impede effective cleaning. The Safety Communication included recommendations for patients, health care providers, and health care facilities about the steps they can take to minimize the risk of infections associated with these devices.  Health care facilities should thoroughly clean and disinfect duodenoscopes between uses and have in place a comprehensive quality program for reprocessing. In addition, a duodenoscope that is suspected of being associated with a patient infection following ERCP should be taken out of service and meticulously cleaned and disinfected until it is verified to be free of pathogens.

The Safety Communication is only one step to address this problem. We continue our work in collaboration with federal partners, health care facilities and manufacturers to evaluate alternative cleaning protocols, test antibiotic-resistant organisms to assess their susceptibility to high-level disinfectants and explore additional strategies to reduce the risk of infections, such as the use of surveillance cultures of duodenoscopes.

So what should a patient do if they are advised to undergo a procedure with a duodenoscope? They should discuss with their health care provider the benefits and risks of the procedure and any alternatives for their condition. Fortunately, the vast majority of ERCPs are conducted without incident and often to the patient’s great benefit. For most patients, the benefits of this potentially life-saving procedure far outweigh the risks of possible infection.

William Maisel, M.D., M.P.H., is FDA’s Deputy Center Director for Science and Chief Scientist for its Center for Devices and Radiological Health.

Moving Toward a National Medical Device Postmarket Surveillance System

By: Jeffrey Shuren, M.D., J.D. and Thomas P. Gross, M.D., MPH

Jeffrey Shuren

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

Despite rigorous premarket evaluation, what really counts is how well a medical device works when it’s used day-to-day by patients, caregivers and clinicians. Beyond clinical trials, real-life patient experience may reveal unanticipated device risks and confirm long-term benefits. Similar to other medical products such as drugs or vaccines, medical devices offer vital, sometimes life-saving, benefits, but they must be balanced against certain risks. A strong postmarket surveillance system can provide more robust and timely benefit-risk profiles for devices so that providers and patients can make better informed health care decisions.

In 2012, CDRH laid out a strategy to strengthen the nation’s postmarket surveillance system for devices. As described in that strategy, our vision for medical device postmarket surveillance consists of a national system that quickly identifies poorly performing devices, accurately characterizes and disseminates risk and benefit information about real-world device performance, and efficiently generates data to help support premarket clearance or approval of new devices and new uses of currently marketed devices.

Thomas Gross, MD, MPH, Director, Office of Surveillance and Biometrics in FDA’s Center for Devices and Radiological Health

Thomas Gross, MD, MPH, Director, Office of Surveillance and Biometrics in FDA’s Center for Devices and Radiological Health

We cannot create a system like this alone. Achieving our vision for a national system requires thoughtful input and active participation from many key national and international stakeholders—now and in the future.  In 2013, after receiving public input on the 2012 strategy, we published an update that described the five major steps the FDA would take to create a National Medical Device Postmarket Surveillance System (MDS):

(1) Establish a multi-stakeholder Medical Device Postmarket Surveillance System Planning Board to identify the governance structure, practices, policies, procedures, methods and business model(s) necessary to facilitate the creation of a sustainable, integrated medical device postmarket surveillance system.

(2) Establish a unique device identification (UDI) system and promote its incorporation into electronic health information.

(3) Promote the development of national and international device registries for selected products.

(4) Modernize adverse event reporting and analysis.

(5) Develop and use new methods for evidence generation, synthesis, and appraisal.

Over the past year, we’ve made tremendous progress in laying the groundwork for this national system. We have begun implementing the UDI rule, including development of a Global UDI Database (GUDID) as the repository for information that unambiguously identifies devices through their distribution and use. We continued to build registry capabilities both domestically (such as the National Breast Implant Registry) and internationally (such as the International Consortium of Vascular Registries).  And we established a Medical Device Registry Task Force consisting of key registry stakeholders under CDRH’s Medical Device Epidemiology Network (MDEpiNet) Program. Importantly, we also commissioned the Engelberg Center for Health Care Reform at the Brookings Institution to convene and oversee deliberations of the Medical Device Postmarket Surveillance System Planning Board.

Today, we are happy to announce the release of the Planning Board’s report Strengthening Patient Care: Building an Effective National Medical Device Surveillance System, which outlines recommended steps toward achieving the MDS and strategies for implementation. The report provides a pathway to realizing a national system that harnesses novel data sources, modern analytical techniques and the participation of all stakeholders to optimize patient care. Interested stakeholders will be able to share their feedback on the report through a public docket.

In the coming months, we will also get reports from the Medical Device Registry Task Force. As noted in the 2013 Update, these reports will address significant issues such as defining effective registry governance and data quality practices, which will enrich the national dialogue on development of registries as a crucial source of data on device performance.

Our vision of a National Medical Device Postmarket Surveillance System is a 21st Century solution to an age-old problem. The system relies on the experience gained by health care providers in their daily use of medical devices leveraged by modern technology. This experience, made possible by new tools and systems unimaginable a generation ago, gives us real-time data about what happens to patients in clinical practice. We will be able to leverage these capabilities not only to quickly identify poorly performing devices, but also to facilitate device approval/clearance and patient access, to reduce postmarket data collection for manufacturers, and to better inform healthcare decisions by providers and patients alike.  We look forward to overcoming the challenges and embracing the opportunities that lie ahead. We are optimistic that with the engagement of the public and private sectors, we can collectively build a medical device postmarket surveillance system that will achieve all of our goals.

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

Thomas Gross, MD, MPH, Director, Office of Surveillance and Biometrics in FDA’s Center for Devices and Radiological Health

Smart Ways to Manage Health Need Smart Regulation

By: Bakul Patel, M.S., M.B.A. and Jeffrey Shuren, M.D., J.D.

Engaged patients! Quantified self! Lifelogging! These buzzwords describe an exciting technology-based, patient-centered approach to living healthier. The myriad of systems that record, share, and use personal and health data have become a significant help for many of us by putting information at our fingertips to use when and where we think it might help promote a healthy lifestyle. The ultimate goal of these products is to improve our quality of life.

Bakul Patel

Bakul Patel, Associate Director for Digital Health in FDA’s Center for Devices and Radiological Health

From wearable sensors to simple tracking apps, more and more consumers are choosing to use technology to monitor their health and motivate them to engage in health-promoting activities. These products, which may count steps, calculate burned calories, or record heart rates and sleep cycles, all have the goal of helping individuals to live a healthy lifestyle.

The FDA seeks to advance public health by promoting innovation and development in this area by continually adapting our regulatory approach to technological advances to meet the needs of patients and consumers.

This week, we finalized our guidance on medical device data systems (MDDS), and we recently issued two draft guidance documents that outline our thinking about low-risk devices intended to promote general wellness, and our risk classification approach to medical device accessories. We committed to issue these guidances in the FDASIA Health IT Report of April 2014.

Through these actions, we continue to clarify which medical devices are of such low risk that we will no longer focus our regulatory oversight on them or we will regulate them under a lower risk classification, narrowly tailoring our approach to the level of risk to which patients or consumers are exposed.

Jeffrey Shuren

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

The MDDS guidance confirms our intention to not enforce compliance with applicable regulations for technologies that receive, transmit, store, or display data from medical devices. We hope that finalization of this policy will create an impetus for the development of new technologies to better use and display this data. We also updated the Mobile Medical Apps guidance to be consistent with the MDDS final guidance. We will discuss our MDDS approach at an upcoming webinar.

Last month, the FDA also proposed to not examine regulatory compliance for low risk products that are intended only for general wellness. These products are designed to maintain or encourage a general state of health and may associate a healthy lifestyle with reducing the risk or impact of certain diseases or conditions. We hope this policy fosters the development of low-risk products intended to promote a healthy lifestyle.

And finally, we issued draft guidance proposing to regulate medical device accessories based on the risks they present when used as intended with their parent devices and on the level of regulatory controls necessary to assure their safety and effectiveness, independent of the risks of their parent devices. Some accessories can have a lower risk profile than that of their parent device and, therefore, may warrant being regulated in a lower class. For example, an accessory to a Class III parent device may pose lower risk that could be mitigated through general controls or general and special controls and thus could be regulated as Class I or Class II.

Through such smart regulation we can better facilitate innovation and at the same time protect patients.

Bakul Patel is Associate Director for Digital Health in FDA’s Center for Devices and Radiological Health

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

A Year of Significant Progress in Public Health

By: Margaret A. Hamburg, M.D.

Margaret Hamburg, M.D.A new year offers both an opportunity to look forward and an opportunity to reflect on the achievements of the previous year. And, in 2014, FDA’s accomplishments were substantial, touching on many of the agency’s broad responsibilities to protect and promote the public health.

Whether our achievements involved medical product safety and innovation, food safety and nutrition, tobacco control, or other areas of our important work, all were accomplished thanks in large part to our ability to respond to evolving needs and opportunities including the embrace of new approvals, technologies and cutting-edge science.

Consider these highlights:

Drug Approvals: This past calendar year, FDA approved 51 novel drugs and biologics (41 by CDER and 10 by CBER), the most in almost 20 years. Among CDER’s 2014 approvals are treatments for cancer, hepatitis C and type-2 diabetes, as well as the most new drugs for “orphan” diseases since Congress enacted the Orphan Drug Act over 30 years ago. Seventeen of these new approvals are “first in class” therapies, which represent new approaches in the treatment of disease. In addition, CBER approved many important biological products in 2014, including a number of groundbreaking vaccines for meningitis B, the flu, and certain types of Human Papillomavirus, the latter of which is expected to prevent approximately 90 percent of the cervical, vulvar, vaginal and anal cancers caused by HPV.

These developments are a testament not just to our expanding understanding of human biology, the biology of disease and the molecular mechanisms that drive the disease process, but also to FDA’s innovative approaches to help expedite development and review of medical products that target unmet medical needs, while adhering to the established standards for safety and efficacy. These include enhanced guidance to shape the research and development agenda, early input on clinical study needs and design, expedited review programs, targeted regulatory advice and other tools and incentives that spur investment and innovation in new medical products to address unmet medical needs.

Opioids: This past year FDA took several actions to address the abuse of opioid drugs. First, we approved abuse deterrent labeling for three opioid products that are designed to deter prescription drug abuse. These drugs used different technologies to combat the abuse problem in different ways, such as by making the product resistant to crushing or dissolving or using “aversive technology” to discourage users from taking more than the approved dosage of the drug. To help encourage the development of more drugs in abuse-deterrent forms, we are also working to provide additional advice to manufacturers. Although abuse-deterrent opioid drugs are not a silver bullet to prevent opioid abuse, we believe that our work in this area will give physicians effective new treatment options with less risk of abuse.

FDA also worked to improve the treatment of patients who overdose on opioids. We approved a new dosage form of naloxone, with an autoinjector to enable a caregiver to administer the drug in the emergency treatment of opioid overdose (as it rapidly reverses the effects of an overdose). While we continue to support development in this area, this approval offers a new valuable tool to help prevent the tragedy of opioid drug overdose.

Antibiotic Resistance: We made important strides in confronting the growing resistance of some bacteria to antimicrobial drugs. Our efforts, which are a critical part of the recently unveiled National Strategy on Combating Antibiotic Resistant Bacteria, offer a multi-pronged approach that recognizes that to effectively address this challenge means simultaneously addressing the many different causes for increasing antibiotic resistance. One important response has been efforts to expand the pipeline of new medical products, including therapeutics to treat and cure infection, diagnostics to aid in the identification of the cause of infection and of resistant infections, and vaccines to help prevent infection with bacteria in the first place.

These efforts are already having an impact. In 2014, FDA approved four novel systemic antibiotics. In contrast, only five new antibiotics had been approved in the previous ten year period.

In addition to working on the human medical product side, we also developed and, over the next two years will be implementing, an important complementary strategy to eliminate the use of medically important antibiotics for growth promotion in food-producing animals. This strategy, once fully implemented, also will bring the remaining uses of such drugs to treat, control or prevent disease in these animals under the oversight of veterinarians. All 26 animal health companies who produce those drugs have committed to participate, and 31 products already have been withdrawn from the market.

Pharmacy Compounding: We continued to respond effectively to the 2012 outbreak of fungal meningitis that was linked to contaminated compounded drugs. This included conducting more than 90 inspections of compounding facilities across the nation in the past year. As a result, numerous firms that engaged in poor sterile practices stopped making sterile drugs, and many firms recalled drugs that have been made under substandard conditions. Where appropriate, we have worked with the Department of Justice to pursue enforcement action against some of these facilities.

We also have continued to implement the compounding provisions of the Drug Quality and Security Act (DQSA), and to develop and implement policies to address compounding by state-licensed pharmacies and the new category of registered outsourcing facilities.

Food Safety: Over the past year, the Agency has made great strides in implementing the landmark FDA Food Safety Modernization Act (FSMA). Through our proposed rules for preventive controls requirements for both human and animal food, standards for produce safety, foreign supplier verification programs, third party auditor accreditation, focused mitigation strategies to prevent intentional adulteration of food aimed at causing large-scale public health harm, and requirements for sanitary transportation practices to ensure the safe transport of food, we are working to ensure the safety of American consumers related to the foods they eat.

Nutrition: Good health depends not just on food safety, but also on what we choose to eat. FDA plays an important role in promoting good nutrition and healthy food choices by helping consumers understand the importance and benefits of good nutrition – and of being able to make informed choices about what we eat.

New rules in 2014 to finalize requiring calorie information on restaurant menus and vending machines give our citizens information they need to make healthy food choices and hopefully help reduce the epidemic of obesity in the United States. We also proposed changes to the familiar “Nutrition Facts” label on packaged foods which, when finalized, will give our citizens updated nutrition information, reflecting the most current nutrition science, to help them make healthy choices when purchasing packaged foods.

Tobacco Control: There are few areas that have as profound an impact on public health as tobacco products, which is why, five years ago, Congress gave FDA the responsibility to oversee the manufacture, marketing, distribution, and sale of tobacco products.

Over the past year, we worked with state authorities to conduct more than 124,000 inspections of retailers to enforce the ban on the sale of tobacco products to children. We unveiled the first of its kind national public education campaign—The Real Cost—to reduce youth smoking. And we took the first steps towards extending the agency’s tobacco product authority over additional products such as electronic cigarettes (e-cigarettes), cigars, pipe tobacco, nicotine gels, waterpipe (hookah) tobacco, and dissolvables not already subject to such authority through our proposed “Deeming Rule.” In addition, as part of ongoing work on product review decisions, eleven tobacco products that were allowed to enter the market during a provisional period established by the Tobacco Control Act were found “not substantially equivalent” to a predicate tobacco product. As a result of this finding, these products can no longer be sold or distributed in interstate commerce or imported into the United States.

Ebola: The tragic Ebola epidemic in West Africa demonstrates that we do not have the luxury of closing our eyes – or our borders – to the public health problems that exist in the rest of the world. I’m proud that FDA has played an important role in the response to this disease, working closely with colleagues in our government as well as the scientific community, industry and a range of other organizations and nations. We have helped facilitate the development, testing, manufacture, and availability of investigational products for use in diagnosing, treating and preventing Ebola, and worked with sponsors and health care providers to facilitate access to these products as clinical circumstances warrant. In August 2014, FDA designated the drug Z-Mapp as an orphan drug for Ebola, with the hope that this would incentivize further development and study.

And I’m very pleased to report that FDA is represented on the ground in West Africa by dedicated officers of the Commissioned Corps of the Public Health Service who continue to staff and operate the Monrovia Medical Unit in Liberia that was built to treat the health workers who became ill responding to the outbreak. Like everything FDA does, both at home and abroad, our actions on Ebola represent our agency’s continuing commitment to health and safety, and the use of science to advance these important goals.

I am extremely proud of our accomplishments in 2014, and I am confident that FDA will have a successful 2015, as we continue our work to protect and promote the public health.

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

FDA’s FY 2016 Budget Request

By: Margaret A. Hamburg, M.D.

Margaret Hamburg, M.D.FDA oversees products that represent more than 20 cents of every dollar that American consumers spend. Today, FDA presented its FY 2016 budget to Congress.This sensible budget request will help ensure that FDA can continue to fulfill its vast responsibilities to protect the public health, safety, and quality of life of the American public.

I want to share the cover letter that I wrote to Congress outlining some of our specific proposals.

 

Letter from the Commissioner

I am pleased to present the FY 2016 Food and Drug Administration (FDA) Budget.

FDA fulfills its important mission to promote and protect health in an increasingly complex and globalized world in many ways.  The scope of our work includes assuring that foods are safe, wholesome, sanitary and properly labeled; ensuring that human and veterinary drugs, vaccines and other biological products, and medical devices intended for human use are safe and effective; and regulating tobacco products.  We also play a lead role in protecting the public from electronic product radiation and assuring that cosmetics and dietary supplements are safe and properly labeled.  Finally, we have devoted – and will continue to devote – substantial resources to advancing the public health by helping to speed product innovations.

FDA’s responsibilities continue to expand as we work to fulfill the mandates of groundbreaking legislation passed in recent years, including the Family Smoking Prevention and Tobacco Control Act of 2009, the Patient Protection and Affordable Care Act of 2010, the Food Safety Modernization Act (FSMA) of 2011, the FDA Safety and Innovation Act (FDASIA) of 2012, and the Drug Quality and Security Act of 2013.  Further, with so many FDA-regulated products manufactured in whole or in part outside of our borders, FDA is keenly focused on the complexities of regulating in a global marketplace.

In FY 2014, we took important steps to finalize a key set of proposed food safety rules; worked to improve the safety of compounded pharmaceutical products by conducting more than 90 inspections and implementing compounding legislation through proposed regulations, guidances, and other actions; published the “deeming rule” to extend FDA’s tobacco authority; and collaborated with federal, international, and industry partners to expedite the development and availability of medical products.  In addition, FDA has worked intensively to respond to the Ebola epidemic in West Africa by facilitating the development and availability of investigational diagnostics, therapeutics, and vaccines with the potential to help combat the epidemic.

FDA continues to seek new ways to obtain the most public health value for the federal dollar as we implement expanded authorities.  The products that FDA regulates are essential to public health, safety, and quality of life and represent over 20 cents of every consumer dollar spent on products in the United States.  Yet, in terms of our FDA budget, each American taxpayer contributes approximately $8 per year for the vast array of protections and services provided by FDA.

In FY 2016, we are requesting essential and timely resources to address critical food and medical product safety issues.  Mindful of the fiscal environment, we have identified targeted reductions where possible and identified long-term needs for additional user fees to balance budget authority growth.  FDA is requesting a total of $4.9 billion to support our various mandates to protect the American people.  This includes a $148 million budget authority increase to focus on the following:

  • delivering a farm-to-table system of prevention, including improved oversight of imported foods, through effectively implementing the final rules required by FSMA;
  • combating the growing threat of antibiotic resistance – in which drugs become less effective, or ineffective, against harmful bacteria;
  • promoting the development and appropriate use of reliable molecular and genetic diagnostics – precision medicine tools – to “personalize” the diagnosis, treatment, and prevention of disease;
  • implementing key FDASIA requirements to improve medical product review and inspections;
  • addressing the safety of compounded drugs;
  • continuing implementation of new requirements for review of sunscreen ingredients under the Sunscreen Innovation Act; and
  • supporting modern facilities to provide the laboratories and office space needed to meet FDA’s expanded legislative mandates.

As a science-based regulatory agency with a public health mission, FDA plays a unique and essential role in promoting and protecting public health and safety.  We are committed to meeting the needs and expectations of the American people.

Margaret A. Hamburg, M.D.

Commissioner of Food and Drugs

FDA Considering How to Tailor its Oversight for Next Generation Sequencing

By: Margaret A. Hamburg, M.D.

FDA is weighing the appropriate regulatory approach to advances in technology that allow physicians to obtain information on large segments of a patient’s genetic makeup very quickly.

Margaret Hamburg, M.D.This technology is known as next generation sequencing, where a single test potentially can be employed to identify thousands—even millions—of genetic variants carried by a single individual. The results of such tests could be used to diagnose or predict a person’s risk of developing many different conditions or diseases and potentially help physicians and patients determine what course of treatment should be used to treat specific individuals.

Reliable and accurate NGS technologies promise to accelerate “personalized” or “precision” medicine, the tailoring of medical treatment to the individual characteristics of each patient. But they also pose some novel issues for FDA in carrying out our mission of protecting and promoting public health.

Most diagnostic tests follow a one test—one disease paradigm that readily fits FDA’s current device review approaches for evaluating a test’s analytical and clinical performance. Next generation sequencing produces a massive amount of data that may be better handled using a new approach.

Last year we took steps to adapt our oversight approach to this new technology with the marketing authorization of the first NGS sequencing instrument, Illumina’s MiSeqDx Instrument and its two tests for cystic fibrosis (CF) mutations. We applied practical regulation to these products: we looked at how accurately the instrument sequenced a representative set of genetic variants across the genome rather than requiring data on every possible variant. Doing so avoided years of data gathering and unnecessary delay in the public’s access to the benefits of this technology while still assuring its accuracy and reliability.

Similar flexibility was employed in assessing the two CF tests. FDA allowed Illumina to leverage a well-curated, shared database of CF mutations to demonstrate the clinical value of its tests, rather than requiring them to independently generate data to support each mutation’s association with the disease.

In the future, next generation sequencing tests may be available to rapidly address new medical knowledge that can be applied in treating patients. Medical knowledge itself can be strengthened through creating databases of research and clinical information tied to particular genetic variants. FDA intends to develop a practical and nimble approach that will allow medical advances to be implemented as soon as possible, using its regulatory flexibility and the power of the information placed into high-quality databases.

This week President Obama unveiled his Precision Medicine Initiative. As part of that effort, FDA has been reviewing the current regulatory landscape involving next generation sequencing as the technology moves rapidly from research to clinical practice. To get the dialogue started, FDA published a preliminary discussion paper in late December that posed a series of questions about how to best assure that tests are not only accurate and reliable, but are available for patients as soon as possible. Public comment is essential, so FDA has opened a public docket and will be holding a public meeting on NGS technology on February 20.

NGS technology is clearly integral to the future of personalized medicine. Whatever approach FDA ultimately adopts must be selected with care to ensure continued innovation in the advancement of medical care and public health for this still evolving technology.

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