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

Recent Progress on Demographic Information and Clinical Trials

By: Barbara D. Buch, M.D.

At FDA, one of our foremost responsibilities is to evaluate and if medical products meets the appropriate standard, to approve or clear drugs, biological products and medical devices. We know that these products are safer and more effective for everyone when they are tested in clinical trials that include diverse populations.

Dr. Barbara BuchThe design and analysis of clinical trials has evolved significantly over the last three decades.  FDA now has a variety of statutory, regulatory, and policy-related tools at its disposal that provide a framework for guiding medical product sponsors and FDA review teams in the collection, subset analyses, and communication of these data.

Collecting and analyzing information in clinical trials about sex, age, and race/ethnicity, makes it possible for individuals or groups considering a treatment option to look at the information and ask, “Was there anyone like me in the clinical studies? And if so, how did they do?”

Section 907 of the Food and Drug Administration Safety and Innovation Act (FDASIA) directed FDA to look at these questions on a broader scale: to investigate how well demographic subgroups (sex, age, race and ethnicity) are included in clinical trials; whether they are analyzed for safety and effectiveness by these subgroups; and to improve on making the resulting information available to the public. After systematically reviewing 72 medical product applications, FDA published a report, in August 2013, which concluded that FDA has been doing a good job, but we acknowledged we could do better.  In August of last year we came up with a plan to improve our performance. The Action Plan includes 27 action items focused on three priorities:

  • Quality: to improve the completeness and quality of demographic subgroup data collection, reporting and analysis;
  • Participation: to identify barriers to subgroup enrollment in clinical trials and employ strategies to encourage greater participation;
  • Transparency: to improve the public availability of demographic subgroup data.

Since the release of the report, FDA has formed an agency-wide steering committee, which I chair. FDA has made significant progress.

So far, FDA:

  • Has launched the Drug Snapshots web page that extracts Demographic Subgroup Data for FDA approved products. The information in a drug trials snapshot is taken from the data submitted in a new drug application or a biologic license application. It includes information on study participants, how the study was designed, the results of the efficacy and safety studies and the differences in side effects and in benefits among sex, race and age groups.
  • Is leveraging IT platforms already in place to support electronic submissions that enhance FDA’s systems for collecting, analyzing, and communicating standardized data collection categories by age, racial and ethnic groups in submitted applications. This will facilitate harmonized data collection and analysis of subgroup outcome trends, and diverse clinical information in diverse populations over the total product life cycle in a standard way. These systems are also developed to facilitate industry’s data input and allow for better tracking of these data.
  • Has added education/training for reviewers about demographic inclusion, analysis, and communication of clinical data. We have also developed plans to incorporate details of demographic subgroup analyses in review templates.
  • Has proposed changes (to the MedWatch adverse event reporting forms to enhance the clarity and utility of the demographic information FDA is able to collect in the post-market setting. These include collecting data about race/ethnicity and age.
  • Has launched a study with health care professionals to improve usability and understanding of medical device labeling, including instructions for use.
  • Is working with industry to try to establish best practices and ways to help ensure appropriate use of enrollment criteria in clinical trial protocols.
  • Has established a joint working group with the National Institutes of Health (NIH) to create a framework for collaborating and exchanging information on inclusion policies, practices and challenges.
  • Is participating with NIH in a session at the Society for Clinical Trials annual meeting in May 2015, on approaches to clinical trial study design and analyses that maximize sex-specific data reporting.

We are proud of our progress to date – but we can always do more. That is why in early 2016, FDA will host a public meeting to gain insight and feedback. Watch this space for details, as well as new developments in our quest to integrate more fully the demographics of patient populations into our review of medical products.

Barbara D. Buch, M.D., is the Chair of the 907 Steering committee and the Associate Director for Medicine in FDA’s Center for Biologics Evaluation and Research

 

European Medicines Agency/FDA Patient Engagement Fellowship: A Time to Learn and Share

By: Nathalie Bere, MSc

I recently returned from a two-week fellowship at the FDA Headquarters in Silver Spring, Md. My mission was to learn about the FDA’s engagement with patients. And, at the same time, to share information on how we involve patients in our work here at the European Medicines Agency (EMA).

Nathalie BereThe EMA is responsible for the scientific evaluation primarily of innovative and high technology medicines developed by pharmaceutical companies for use in the 28 current EU member states as well as in the European Economic Area (EEA) countries Iceland, Liechtenstein and Norway. Experts participate in the work of the EMA as members of its scientific committees, working parties, scientific advisory groups, or as members of assessment teams evaluating medicines. They are chosen on the basis of their scientific expertise. The patients and health care professionals’ voices are also fully integrated within the work at the EMA.

At the beginning of December, as I stood outside the buildings at the FDA’s White Oak Campus, I wondered if this somewhat challenging task was going to be feasible within such a short timeframe. I felt that it was very important for me to not only capture the essence of the work at the FDA but to really learn about the different challenges and issues they have faced and how they have been handled. Overall, I wanted to be able to identify areas which could ultimately benefit from an exchange of EMA/FDA experience.

I had no need to worry. I was received openly and positively within the FDA offices by all the staff who took time from their busy schedules to meet me and share their respective work practices. An extensive schedule had been set up to give me the opportunity to learn about the relevant offices and divisions, as well as attend two Advisory Committee Meetings and participate in a Patient Representative Training Webinar. I also had several opportunities to share information with FDA colleagues on how EMA involves patients throughout the development, evaluation, and surveillance of medicines.

It was enlightening to learn that, overall, many of the challenges and benefits of working with patients are remarkably similar for the two agencies.

Engaging with patients is a vital part of any regulator’s work, and this is recognized as a high priority by both the EMA and FDA. Of course, there are differences in the way each agency achieves this, due in part to their different review processes. However, there are definitely areas where I believe each agency can benefit from the other’s experience.

For example, the EMA can benefit from the FDA’s experience in organizing and conducting public events such as advisory committee meetings and patient-focused drug development meetings where FDA experts reach out and gather data from the audience.

Other promising concepts for the EMA include the FDA’s “patient representative program,” comprising a pool of interested, screened and trained patients who bring the patient voice to the FDA discussions about new and already approved drugs and devices and policy questions. Still more interesting patient-specific communication tools used by FDA are webinars, interactive live-chats and a dedicated newsletter used for training and raising awareness.

In turn, the FDA could benefit from EMA’s experience of engaging with patients earlier during its discussions on specific product assessments. In the EMA’s system patient input can be regularly solicited throughout the medicine’s lifecycle, e.g. in all expert meetings, through written patient consultations, and by patients as voting members within committees.

Other areas that could benefit the FDA include: patient review of all package leaflets and safety communications, and the establishment of a permanent group of patient/consumer organizations that provide a platform for exchange of information on general issues within the EU system.

Now that I  am back at the EMA’s London headquarters after quite a hectic, but enriching experience, I hope  there will be an opportunity at EMA to reciprocate with my new FDA colleagues, who invited me so warmly into their workplace.

This fellowship has provided an opportunity for both the EMA and the FDA to gain an understanding of each other’s respective programs of engaging with patients, and a rich source of valuable information has been shared.

We look forward to further collaboration and regular sharing of information on patient engagement.

I would like to thank Sabine Haubenreisser, EMA Liaison Official to the FDA, based at White Oak; Heidi Marchand, Assistant Commissioner of the Office of Health and Constituent Affairs; and Health Programs Coordinator Andrea Furia-Helms, who facilitated this fellowship.

International Programs and EMA International Affairs:

Nathalie Bere, MSc, works in patient relations in the Stakeholder and Communication Division of the European Medicines Agency in London. 

Through the EMA/FDA confidentiality arrangements our organizations have established procedures to enable our organizations to share information that is not public. These arrangements also facilitate the exchange of staff, including secondments and fellowships, to work together on defined topics and foster increased dialogue and cooperation.

The Meaning of Wearing Red

By: Margaret A. Hamburg, M.D.

Last night I had the pleasure of attending the annual Woman’s Day Red Dress awards ceremony in New York City. The event is one of the highlights of American Heart Month, and it was created by that magazine to educate Americans about, and help fight, heart disease, which has become the number one killer of women. Many are surprised to learn that while breast cancer is the cause of death of one in every 31 American women, one of every three women dies of heart disease. So I found it particularly meaningful, both as a doctor and a woman, to be honored for FDA’s work to improve women’s cardiovascular health.

Commissioner Hamburg at Event

FDA Commissioner Margaret A. Hamburg, M.D., at the Woman’s Day Red Dress awards ceremony in New York City

One of our efforts toward this end that was cited by the magazine was the proposal to update the Nutrition Facts Label. The proposed updates would more prominently highlight calorie and serving size information, inform consumers about “added sugars,” update the daily values for nutrients, and ensure that the serving size requirements reflect the amounts of food people actually consume. They would encourage consumers to use the label to take note of foods high in sodium, saturated fat, and trans fat, which can increase the risk of coronary heart disease.

We also published final rules on restaurant menu and vending machine labeling. Calorie information is the key component of these requirements, and obesity is associated with a range of heart disease related problems. The new rules also require that other nutrition information, such as sodium, is provided upon the consumer’s request. High sodium intake can increase blood pressure, a major risk factor for heart disease. As with the nutrition facts label, these menu labeling requirements will give consumers nutrition information they need to be able to make healthy food choices for themselves and their families.

Another part of FDA that matters for cardiovascular health is our Center for Tobacco Products. Though its work is designed to protect the health of all Americans, it has special significance for women who, sadly, are catching up to men in the prevalence of tobacco-related diseases.

In the last 50 years, a woman’s risk of dying from smoking has more than tripled, and is now equal to that for men – not what we desire when we talk about equality. The more than 20 million women in the U.S. who smoke cigarettes are at risk not just for heart attacks, lung cancer, and strokes, but also emphysema and other serious chronic illnesses such as diabetes.

Our actions on smoking and nutrition have been complemented by the work of the Office of Women’s Health. Its outreach initiatives have helped provide women with tips and resources they can use to make better heart health decisions for themselves and their families. This Office has also supported research on treatment of heart disease in women.

FDA’s responsibilities also include reviewing, approving, and helping advance new and innovative medical products to diagnose, treat and prevent heart disease, including life-saving medical devices such as artificial hearts, stents, and heart valves, essential tests like echocardiograms, and important drugs for hypertension, lowering cholesterol and treating other aspects of cardiovascular disease.

Over the years, FDA’s support of women’s health has grown thanks to scientific advances, changes in society, and improvements in the agency itself. We will continue to promote these goals, not just in the area of cardiovascular health, but in women’s health more generally.

Of course, we can’t do it alone. And that’s why I sincerely welcome such events as the National Wear Red Day and Woman’s Day’s Red Dress awards. They help focus our nation’s attention and energy on the fight against women’s heart disease to which we, at FDA, are fully committed.

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

Measles Vaccine Is Safe and Effective – And Should Be Used

By: Margaret A. Hamburg, M.D.

In recent weeks we’ve seen an alarming outbreak of measles; a highly contagious and serious virus, especially in babies and young children who have not been vaccinated. This outbreak is particularly disturbing because measles was effectively eliminated from the United States in 2000 thanks to nearly universal vaccination, the single best way to prevent the spread of this disease.

Margaret Hamburg, M.D.Vaccination works with the body’s natural defenses to help it safely develop immunity to the measles. When more people are vaccinated, there are fewer opportunities for the disease to spread. A community generally needs more than ninety per cent of its members to be immunized against the virus in order to protect those who can’t be.

Today, there are two safe and effective FDA-approved vaccines. More than 95% of the people who receive a single dose will develop immunity. And a second dose conveys immunity to nearly everyone who did not respond to the first dose. Simply put, these vaccines are safe and effective, and serious side effects are rare.

Before the first measles vaccine was approved in 1963, hundreds died from the disease each year. Others developed pneumonia, lifelong brain damage or deafness.

Let’s not return to these grim statistics. There is no shortage of measles vaccine. It should be used by everyone who has not been vaccinated to prevent measles and the potentially tragic consequences of the disease.

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

Technology Transfer—Transforming Food Safety with the GenomeTrakr Collaboration

By: Alice Welch

In my last blog post I discussed how FDA’s Technology Transfer program helps drive innovation by building collaborations that can solve today’s public health challenges using leading-edge science. This blog post describes one of those FDA collaborations—a pathogen detection network that is transforming food safety.

Alice WelchAccording to the Centers for Disease Control and Prevention (CDC), foodborne disease outbreaks are responsible for about 48 million illnesses, 325,000 hospitalizations, and 3,000 deaths every year in the United States. The annual toll for Salmonella poisoning alone in this country is 1 million illnesses, 19,000 hospitalizations, and nearly 400 deaths. As the world becomes even more interconnected, FDA has recognized the urgency of creating new approaches and better tools to detect food contamination and stop outbreaks in their tracks.

The FDA-established GenomeTrakr is an innovative response to this global public health challenge. Using a cutting-edge technology called Whole Genome Sequencing (WGS), FDA’s Center for Food Safety and Applied Nutrition (CFSAN) and Office of Regulatory Affairs (ORA) are collaborating with federal and state public health laboratories to build a publicly accessible genomic database called GenomeTrakr. GenomeTrakr enables us to compare some of the bacterial pathogens that cause foodborne diseases and trace them back to their sources faster and more precisely than traditional methods.

WGS is a laboratory process that identifies the complete DNA sequence of an organism’s genetic material at a single time. The process is being used together with GenomeTrakr to identify pathogens isolated from food or environmental samples and compare them to pathogens isolated from sick patients. If the isolates from food or environmental samples match the pathogens taken from the sick patients, scientists can establish a reliable link that helps characterize the size and location of the foodborne disease outbreak. It can even help public health officials determine which ingredient in a multi-ingredient food is causing the outbreak—so that we can get contaminated food out of the food supply. Used by epidemiologists in combination with traditional methods, WGS is advancing our understanding of contaminations in the food supply.

Pathogens evolve very quickly and have thousands of genetic variations. After spending time in a particular geographic location, a pathogen like Salmonella begins to acquire unique genetic signatures that identify it as coming from that location. Until recently, some strains of Salmonella have looked much the same to us, no matter where we found them, because some of the older methods of testing have been unable to distinguish between certain strains of pathogens. But WGS can detect unique signatures within and between species with far greater precision than previous methods, which makes it one of our biggest secret weapons in tackling foodborne illness outbreaks.

FDA scientists and our collaborators in federal and state public health laboratories are using WGS and the GenomeTrakr database to identify those unique signatures. The signatures can often tell us, for example, if a Salmonella that has contaminated a certain part of the food supply is from the U.S. West Coast, New England, or even Germany. FDA and state lab scientists upload the entire genome sequence for a pathogen into the GenomeTrakr database at the National Center for Biotechnology Information, where it’s available for further use. As the database continues to grow, it’s becoming an increasingly powerful tool to help investigations home in faster on the root causes of outbreaks and track their location.

The potential of technologies like WGS to enhance food safety could not be realized without the development of a powerful database like GenomeTrakr. But to build that kind of database FDA needed to form a web of collaborations. Enter FDA’s Technology Transfer team. It plays a critical role in working with our researchers to create the successful relationships that make huge databases like GenomeTrakr work.

To achieve CFSAN’s vision, FDA’s Technology Transfer team worked with CFSAN researchers to create agreements tailored to the project’s needs. The team drafted collaboration agreements that included provisions for establishing relationships between FDA and state laboratories to perform WGS and upload genome sequences into GenomeTrakr. Once CFSAN’s project concept and goals were established, Technology Transfer experts negotiated and put agreements in place so FDA could begin linking federal and state partners to advance the use of WGS across public health.

Since the first state public health lab collaboration was established in February 2012, FDA, along with other international, federal, and state laboratories have added genome sequences for more than 11,000 isolates to the GenomeTrakr database, and we are already seeing impressive results! In early 2014, through a partnership with CDC, FDA and state department of health laboratories used GenomeTrakr to match environmental and food samples with human biological samples, which helped FDA confirm the source of Listeria in an outbreak.

This collaboration is just one of many that our Technology Transfer team has helped create to support FDA efforts to speed innovation in public health. Stay tuned for my next post, where I’ll discuss an FDA invention that is preventing hundreds of thousands of Africans from contracting the debilitating disease of Meningitis.

Learn more:  Whole Genome Sequencing: The Future of Food Safety

HHS Innovates Award Paves Way for the Future of Food Safety and PulseNet

Alice Welch, Ph.D., is Director of FDA’s Technology Transfer Program

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

A big step to help the patients most in need

By: Peter Lurie, M.D., M.P.H.

Today, I had the pleasure of announcing an important measure intended to help streamline expanded access to investigational drugs. We heard concerns from patients and physicians that the process for gaining access to investigational drugs was too difficult, and pulled together a team to find a way to make that process simpler. Today, we’re introducing a much simpler draft form for comment that, when finalized, should accelerate patient access to investigational drugs. We know what an important tool this will be for physicians who treat those patients with serious or immediately life-threatening diseases or conditions for which there are no comparable alternative treatments.

Dr. Peter LurieThe new draft document, entitled “Individual Patient Expanded Access Applications: Form FDA 3926,” includes a simplified application form that, when finalized, will be used for requesting the medications, and is designed to greatly simplify and accelerate the process by which a physician can request that FDA permit the use of an experimental — so-called “investigational” — drug or biological product while it’s still being tested to establish its safety and effectiveness.

The draft guidance and draft form continue a policy that started in the early years of the AIDS epidemic when FDA authorized, in certain cases, “compassionate use” of unapproved investigational drugs. In 2009, FDA made these rules broader and clearer. However, concerns persisted that the existing application form was too complex: it called for 26 separate types of information and seven attachments. In fact, it was originally designed for manufacturers seeking to begin human testing, not for physicians seeking use by single patients.

FDA authorizes the vast majority of expanded access requests, typically within days or even hours. However, FDA is committed to streamlining its processes wherever possible. The agency therefore tasked a special working group with designing a form more suitable for use by a physician not necessarily familiar with the IND process. The revised process, when finalized, will not change the agency’s rigorous requirement that all medical products on the market be studied in clinical trials in order to be FDA-approved as safe and effective. As before, expanded access to an investigational medication may be available when there is no other product that can diagnose, monitor, or treat the patient’s disease or condition, and the patient is not and cannot be enrolled in a clinical study testing it.

But we know why patients want access to these drugs and we know how busy their treating physicians can be. So we streamlined the new draft form to be shorter and simpler for physicians to fill out. The new draft form, when finalized, will require only eight elements of information and a single attachment. We estimate that physicians will be able to complete the finalized version of the form in just 45 minutes, as compared to the 100 hours listed on the previous form.

Additionally, to further assist the physician seeking access to an experimental therapy, we have redesigned our website to make it easier to navigate and to explain the new proposed process in detail.

For years, FDA has maintained a staff dedicated to assisting physicians and patients to navigate our system. These efforts will continue. The new draft guidance and draft form are the latest examples of FDA’s determined effort to minimize unnecessary red tape, increase efficiency and better serve patients in need.

Peter Lurie M.D., M.P.H. is associate FDA commissioner for public health strategy and analysis.

Making the Case for Critical FSMA Funding

By: Michael R. Taylor

Over the past two years, my colleagues and I have written here about what FDA is doing to create the preventive, risk-based food safety system mandated by the FDA Food Safety Modernization Act (FSMA). We’ve taken you along on our visits to farms and food facilities to get input on the FSMA rules we have proposed. We’ve described the changes we’re making within FDA and the framework we’re building to implement those rules after they become final in late 2015 and early 2016.

Michael Taylor

Michael Taylor

Now we’re at a critical juncture as Congress considers the funding that will help transform all the plans and preparations we’ve shared with you into protections that will greatly reduce the number of illnesses caused by contaminated foods and greatly increase consumer confidence in the safety of our food supply. President Obama’s FY 2016 budget request, released to Congress yesterday, would provide an additional $109 million for FSMA implementation. In the current fiscal year, FDA received an additional $27.5 million.

Why do we need this money? Because a lot of work must be done right now to ensure that the FSMA rules are implemented smoothly and effectively in late 2016 and 2017. Let me give you a few examples of areas in need of additional funding that, through FSMA, will transform the food safety system into one that prevents hazards instead of just responding to them.

Under FSMA, our approach to food safety inspections and compliance will be fundamentally different. FDA will deploy inspectors who are specialized in specific food commodities, rather than covering a broad range of FDA-regulated products. Backed by technical experts, they will assess the soundness and performance of a facility’s overall food safety system. Achieving this will require a major reorientation and retraining of more than 2,000 FDA inspectors, compliance officers and other staff involved in food safety activities.

While FSMA has given us new enforcement tools to use against those who flout safety requirements, the vast majority of food producers want to comply and keep their products safe. FDA will be issuing guidance documents that will be essential to helping industry meet FSMA requirements. Funds are needed now for FDA to recruit additional experts who can ensure that guidance development is based on the best science and knowledge of industry practices. These experts will also collaborate with industry, academia, and state extension services to ensure that their concerns are heard, that their advice is sought and used, and that the guidance documents reflect the most cost-effective solutions.

I cannot say enough about the importance of education and technical assistance to help farmers, processors and importers—especially small businesses—implement the new standards. Approximately 300,000 entities could be subject to the final FSMA rules. FDA wants to make a substantial investment in providing such assistance and making training materials widely available. In addition to direct technical assistance, FDA would use a large portion of these resources to provide financial support to state agencies and public-private-academic collaborative entities, such as the Produce Safety Alliance and the Preventive Controls Alliance. FDA has also joined with the U.S. Department of Agriculture’s National Institute of Food and Agriculture (NIFA) in providing grants that will fund food safety training for small, sustainable and organic farm owners and food processors.

We cannot make FSMA a reality without our state partnerships. There are more than 3,000 state, local and tribal government agencies involved in food safety. To align state programs with FDA’s new facility inspection and compliance approach, the agency will provide states with funds for inspector training, information sharing capacity with FDA and other states, state laboratory coordination, and inspector certification programs. These preparations have already begun but they must be accelerated in 2016 if the states are to be prepared to conduct sound, consistent inspections when industry must comply with the new prevention standards starting in late 2016. In addition, to successfully implement the produce safety rule, FDA must build state partnerships and capacity in 2016 to provide education and technical assistance to growers.

About 50 percent of fresh fruits, 20 percent of fresh vegetables, and 80 percent of seafood consumed by Americans comes from other countries, so it is clearly essential to modernize how we ensure the safety of imported foods. The Foreign Supplier Verification Program (FSVP) mandated by FSMA, will require importers to implement supplier verification plans to help ensure food produced overseas meets U.S food safety standards. This shift presents an enormous challenge for both FDA and food importers, given that last year there were approximately 88,000 consignees receiving food shipments and, in 2013, 12 million entries for FDA to oversee. FSVP will require a substantial regulatory development process, increased staffing and the training of more than 400 investigative and compliance personnel within FDA to enforce the regulation. It will also require extensive training and technical assistance for importers.

Those are just the highlights; there’s much more to be done. The bottom line is that without investment now, and sustained funding afterwards, there is the risk that the implementation of FSMA will be uneven or even delayed. This would be bad for everyone, including those who must meet the new standards and those who must enforce them. Most importantly, it would be bad for consumers, who want to be sure that the foods they are eating and serving their families are safe.

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