Rare Diseases at FDA: A Successful Year for Orphan Products

By: Gayatri R. Rao, M.D., J.D.

2014 was a strong year for rare disease product development at FDA. It was also a year of significant firsts.

Dr. Gayatri RaoIn recognition of Rare Disease Day, February 28th, we want to reflect on the progress we have made thus far as we renew our commitment to rare disease patients. A rare disease is generally defined as a disease which affects fewer than 200,000 Americans a year. At FDA, the commitment to increase access to diagnostics and treatments to change the day-to-day reality of those living with rare diseases began over 30 years ago with the passage of the Orphan Drug Act.That commitment has steadily increased since then.

In 2014, we received our highest number to date of new requests for orphan drug designation. We received over 440 requests while just 7 years ago, we received less than half of that. We designated and approved more orphan drugs in 2014 than we had in previous years – nearly 300 drugs were designated and 48 were approved, including both novel and repurposed drugs. In 2014, 41% of all novel new drugs approved by the Center for Drug Evaluation and Research were for the treatment of rare diseases. Many of these orphan drug approvals were new and innovative, including Sylvant, to treat Castleman’s disease, which results in excessive lymph node growth, and Impavido, to treat forms of the tropical disease, leishmaniasis.

2014 was also a year of firsts for rare disease product development:

There were firsts in device development. For example, the Center for Biologics Evaluation and Research approved its first device through the Humanitarian Device Exemption (HDE) pathway. This device, CliniMACS CD34 Reagent System, helps to mitigate potentially serious immune reactions associated with stem cell transplantation in patients with acute myeloid leukemia.

FDA produced in 2014 its first agency-wide blueprint to accelerate the development of therapies for pediatric rare diseases – a report and strategic plan outlining how to address issues for developing products for this population.

2014 saw the issuance of the first rare pediatric disease priority review voucher for the treatment of mucopolysaccharidosis type IVA (Morquio A syndrome), a rare lysosomal storage disease which affects about 1000 patients in the United States and can lead to debilitating and life-threatening abnormalities of bones, joints and the heart.

In recognition of Rare Disease Day 2015, the international rare disease community is coming together to pay tribute to the millions of individuals impacted by rare diseases all over the world. Through the solidarity and commitment of many stakeholders – patients and families, healthcare professionals, researchers, companies, and policy makers – the awareness of the daily challenges that are unique to each rare disease and the efforts to create solutions has risen exponentially in the past several decades. As members of the rare disease community, we are proud of our collective accomplishments but remain acutely aware of how much more there is still to be done. Given how 2015 is already shaping up, we expect that by working together, we will continue to make great strides in developing much needed products for the millions of patients living with rare diseases.

Gayatri R. Rao, M.D., J.D., is FDA’s Director for The Office of Orphan Products Development

Shedding some light on FDA’s review of sunscreen ingredients and the Sunscreen Innovation Act

By: Theresa M. Michele, M.D.

With recent record snowfalls in many parts of the country, the use of sunscreens may not have been on many people’s minds. But here at FDA, sunscreens have been a front-and-center issue.

Theresa Michele, M.D.On November 26, 2014, Congress enacted the Sunscreen Innovation Act (SIA) that provides a new process for the review of safety and effectiveness of nonprescription sunscreen active ingredients. Among other things, the SIA creates timelines for FDA review.

Before the law was enacted we followed the regulatory process known as the Time and Extent Applications process, or TEA process for sunscreen active ingredients. This regulatory process provides, among other things, a mechanism for sponsors to request that FDA evaluate active ingredients that are used in over-the-counter (OTC) drug products, particularly those marketed in other countries. The TEA process can be summarized in two basic steps. Step 1 is FDA’s determination of eligibility, made upon a showing that the ingredient has been marketed over-the-counter in one or more countries for a material time and extent. Step 2 is FDA’s evaluation of the data to determine whether the ingredient is generally recognized as safe and effective (GRASE) for its intended use in an OTC drug product as described in the relevant regulation. If, after review of the data, FDA ultimately finds the ingredient to be GRASE for its intended OTC use, the ingredient may enter the U.S. marketplace. There were eight TEAs for sunscreen ingredients submitted to FDA before the SIA went into effect.

On January 7, we met the first requirement of the SIA. In doing so, we announced our tentative determinations that six of these ingredients are not GRASE for use in sunscreens because we need more data from the manufacturers to help establish the safety and effectiveness of these products.

Today, we completed another requirement by taking initial action on the last two pending ingredients, ecamsule and enzacamene. We tentatively determined, as we had with the other six ingredients, that we need more data to decide if these ingredients are, in fact, GRASE for use in OTC sunscreen products. Information about the SIA and our recent actions under the law are available on our new web page for this topic.

At this time there is not enough generally available data to determine whether any of the ingredients under review meet FDA’s safety and effectiveness standards.

We know our careful actions to seek more information may be disappointing to some who would like to see additional sunscreen products on the market immediately, but I’d like to take this opportunity to clarify some misconceptions about the SIA and the process for making sunscreen ingredients available for use in OTC products marketed without individual premarket review in the U.S.:

  • The law does not change FDA’s standard for general recognition of safety and effectiveness. The SIA requires strict deadlines for FDA to take action on these ingredients, but it does not relax the FDA’s scientific standards for evaluating the ingredient’s safety and effectiveness, or our need for adequate data on which to base such determinations.
  • The law does not provide FDA with additional resources. Recognizing the public health importance of sunscreen use, the FDA is proceeding as quickly as practicable to meet the requirements of the legislation. To assist in this process and to reduce the negative impact on other work, FDA is requesting funds for implementation of the SIA as part of the President’s fiscal year (FY) 2016 budget.
  • The SIA does not guarantee that products with additional sunscreen ingredients will be on the market in a specified timeframe. Because additional data are needed for each of the eight sunscreen ingredients, timelines for FDA actions are triggered by industry’s submission of required data.
  • There is apparent confusion as to why ingredients that have been on the market for years in other countries cannot be used in the U.S. without further review by FDA. While information on marketing history in other countries is helpful, what we can learn from it is limited. For example, such information doesn’t tell us anything about the long-term effects from use of the ingredient or how much is absorbed. Because of the widespread daily use of sunscreen products by a broad population, including babies and pregnant women, FDA has proposed data requirements that will allow us to determine that sunscreen ingredients are generally recognized as safe and effective. These data requirements were unanimously supported by a panel of scientific experts at a recent public Advisory Committee meeting on sunscreens.

We cannot achieve success in bringing additional sunscreens to market on our own. FDA is committed to doing our best to meet the new statutory deadlines, and we will be transparent in our process and progress. Successful implementation of the SIA will require a cooperative effort with industry and other stakeholders. We look forward to continuing this important work.

Theresa M. Michele, M.D., is the Director of the Division of Nonprescription Drug Products in FDA’s Center for Drug Evaluation and Research’s Office of New Drugs

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

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