From the New CFSAN Director: Reflections on My First Two Months

By: Susan Mayne, Ph.D.

I have been the director of FDA’s Center for Food Safety and Applied Nutrition (CFSAN) for two months now. What I have enjoyed the most about this new job has been getting to know the people in CFSAN, who come from incredibly varied and interesting backgrounds. I am truly impressed by their commitment to excellence and dedication to our mission to protect and promote public health.

Susan MayneI have also been struck by the depth and breadth of expertise involved in every initiative CFSAN undertakes. So many scientific disciplines are involved: We rely on the insights of our medical officers, toxicologists, epidemiologists, biologists, chemists, behavioral scientists, and nutritionists. Working with our scientists are our policy and communications experts, economists and lawyers. We all have the same goal: to give the safety of food and cosmetics and nutrition issues the thorough and careful consideration they deserve.

We stand on two legs: strong science and our ability to create policy and regulatory solutions to address public health concerns. The scientific fields in which we work, from genomics to toxicology, are advancing rapidly. The use of new technologies can make our science better and help us to get the information we need more quickly. Yet the constant evolution and adoption of new scientific methods can also pose unique challenges — for example, in interpreting trends in food safety and foodborne illness.

When considering the science of food and cosmetic safety, we assess the scientific certainty, severity, and likelihood of any given risk, and identify those people who would be most vulnerable. We consider what additional research can be undertaken to better clarify the science for decision-making, and use what we currently understand to determine whether the risk can be avoided.

For each issue, we need to examine the full range of options, ranging from consumer education to regulation to enforcement. For regulatory options we work with our legal teams to consider what is possible within our authorities. What are we empowered to do and how does our work intersect with that of other federal agencies? If we take an action, what is the international context, and are there foreign trade implications? What are the views of groups that will be most affected by our decisions, on both the consumer and industry sides? What are the costs and benefits? Have we thoughtfully considered how to ensure high levels of compliance?

I have observed with a great sense of satisfaction how we work together with other federal partners. For example, leaders from the Centers for Disease Control and Prevention (CDC) visited our center recently to share information and discuss how we can best support each other in our joint commitment to food safety. In the brief time I have been here, I have also observed interactions with the U.S. Department of Agriculture, the National Institutes of Health, and the Environmental Protection Agency.

CFSAN’s work is funded by taxpayers and affects people’s lives every day. Our work has real consequences for consumers, businesses, and industry. I have learned the importance of engaging in meaningful conversations with those outside of government, who are affected by our decisions. As we talk to our industry stakeholders, we benefit from their expertise and better understand the real-world constraints they face, and that ultimately helps us to put forth more effective policy. Similarly, we value hearing the perspectives of consumers, medical groups, and the scientific community, which often highlight areas where additional FDA focus is needed to protect public health. In our communications, we strive to accurately convey the risks and/or benefits of any food or product, and to rapidly communicate any emerging health concerns.

I have observed an amazing array of public health issues coming across my desk at CFSAN over the past two months. I am energized by the diverse breadth and depth of activity, and look forward to the challenges and opportunities ahead, and to sharing my thoughts and experiences with you on Twitter and in future blog posts.

Susan Mayne is the Director of FDA’s Center for Food Safety and Applied Nutrition

In a country full of differences, common ground

By: Michael Taylor, Howard Sklamberg and Camille Brewer

We are headed to a meeting in Delhi. Through our taxi windows a vibrant India swirls around us: green and yellow motorized rickshaws and Vespas dart through the crowded city streets, zipping around buses, trucks and the occasional courageous pedestrian. It looks and feels like no city in the United States.

Michael Taylor

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

We are struck by how different it all seems, with many manifestations of traditional Indian lifestyle and culture — saris and turbans worn by many women and men, cattle and monkeys in the streets, and street food of all kinds — mixing with advanced urban infrastructure, intense commercial activity, and Western brand names all around.

We’ve come to this amazing country to discuss with government officials and industry leaders some important changes to our food safety system that will  affect food exports from here to the United States. But we are also here to sign a Memorandum of Understanding (MOU) with the government of India, “intended to develop opportunities for cooperative engagement in regulatory, scientific, and technical matters and public health protection that are related to…food products.” It admittedly sounds like a bit of legalese, but what it means is that it’s critical that our two nations work together on food safety issues.

Howard Sklamberg

Howard Sklamberg, FDA’s Deputy Commissioner for Global Regulatory Operations and Policy

Why? Well, India is the 7th largest supplier of food to the United States. The great amount of Indian food products that wind up on the dinner tables of Americans every night — including shrimp, spices, and rice — reflects the increasing globalization of our own country’s food supply, 15 percent of which consists of foreign products. Many of these goods come from any one of India’s 29 states, produced by thousands of different companies.

The signing of this MOU with the Export Inspection Council of India is the next step in enhancing our regulatory cooperation with this nation of 1.2 billion people. Last year, while here, FDA Commissioner Margaret A. Hamburg, M.D., signed a similar arrangement between FDA and the Indian Department of Health and Family Welfare, a Statement of Intent focused on medical and cosmetic product safety.

And while these documents serve as important, even historic, markers of our nations’ shared commitment to quality drug and food products, we’ve also discovered we have a lot in common with those we’ve met on our journey — which is taking us from the stalls of nut and spice vendors in Old Delhi to a shrimp processing facility in a remote part of Andhra Pradesh.

Camille Brewer

Camille Brewer, M.S., R.D., Director of International Affairs at FDA’s Office of Foods and Veterinary Medicine.

We had a lot of information to share on this trip. The Food Safety Modernization Act (FSMA), signed into law by President Obama in 2011, mandates a food safety system that is preventive rather than reactive, and in which foreign food producers are held to the same safety standards as our domestic farmers and food companies. Under FSMA’s new import safety system, we will continue targeted border checks, but the new system makes importers in the U.S. accountable to FDA for verifying that their foreign suppliers are using methods to prevent food safety problems that provide the same level of public health protection as those used by their U.S. counterparts.

Under FSMA, this new accountability for importers will be backed up by more overseas inspections by FDA, and, crucial for the purposes of this trip, more active partnership with our foreign government counterparts. We need it to strengthen assurances of food safety and capitalize efficiently on the efforts of all participants in what is becoming a truly global food safety system. FSMA is a game changer for food safety and for our food safety partners around the world, and we wondered how our talk about its implementation would be received.

But the Indians are no strangers to sweeping change to improve food safety.

India Shrimp Plant

FDA’s Howard Sklamberg (left) and Michael Taylor (center) tour Waterbase Ltd, a shrimp processing plant and farm in Nellore, India.

Our counterparts, known as the Food Safety and Standards Authority of India (FSSAI), are also undergoing a significant regulatory overhaul, known as the Foods Safety and Standards Act. Passed in 2006, it was the law that actually created FSSAI. At its core, the Act seeks to ensure that India’s food industry is adhering to international, science-based standards for food safety. Not unlike FSMA, this law poses many challenges in terms of how it can be successfully implemented, with both laws mandating comprehensive change, including marked increases in authority that require new resources to implement.

India MOU signing

FDA’s Howard Sklamberg (left) and Michael Taylor (center) sign a Memorandum of Understanding with the government of India

Although we don’t know most of the 22 official languages spoken here, we nonetheless realized after meeting with FSSAI that we “speak the same language” in terms of our food safety challenges and solutions. The FSSAI leaders conveyed real concern about protecting the Indian consumers they serve and, like us, they understand that in an increasingly global world, you can’t “go it alone” when it comes to food safety. Commissioner Hamburg, speaking of the global drug supply and how to make it safer, once described the need for a “coalition of regulators.” That same need exists for the world’s food supply.

We left our meeting with FSSAI assured that we are on the same page with our Indian colleagues about our food safety goals, as well as the amount of work — and collaboration — needed to achieve them.

The sounds and sights of Delhi and D.C. are certainly different. But with our MOU signed, we look forward to building our partnership with India, recognizing that sometimes the most fruitful relationships result when people with diverse perspectives come together to find common ground.

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

Howard Sklamberg is FDA’s Deputy Commissioner for Global Regulatory Operations and Policy

Camille Brewer, M.S., R.D., is Director of International Affairs at FDA’s Office of Foods and Veterinary Medicine.

From New Jersey to New Delhi, a global focus on quality

By: Howard Sklamberg and Cynthia Schnedar

As we walked through the bustling, ancient city streets of Old Delhi last week, teeming with tourists and shop keepers selling spices and saris, we were struck by how resplendent this country is, and just how much it offers the world.

Howard Sklamberg

Howard Sklamberg, J.D., FDA’s Deputy Commissioner for Global Regulatory Operations and Policy

This is certainly true about prescription drugs. India is a significant exporter of generic drugs to the United States. The American people benefit tremendously from generic drugs, as more and more generic medications reduce costs for patients, and the American healthcare system. The rise of India’s pharmaceutical star is one of the reasons why our trip to India is so important.

While here, we have had a chance to meet with our regulatory counterparts in the Indian government, as well as the drug manufacturers that are either based here, or who have facilities in the country. Needless to say, we are learning a great deal.

It’s no secret there have been challenges associated with the quality of generic drugs coming out of some facilities in India. Some people have asked us here if the FDA is “singling out” India for increased inspections. We simply reply that increased exports to the U.S. result in increased inspection, no matter where you are in the world. FDA inspections ensure that when a firm wants to export drugs to the United States, the drugs meet FDA standards and will be of the quality patients and consumers want and deserve.

Cynthia Schnedar

Cynthia Schnedar, J.D., Director of the Office of Compliance at FDA’s Center for Drug Evaluation and Research

And we’ve been happy to hear that this focus on quality is, in fact, a shared goal, held by both the Indian — and India-based — regulators and pharmaceutical manufacturers with whom we’ve met. They understand what we mean when we tell them the FDA is interested in helping to build a global network of quality; that it doesn’t matter whether a drug is made in Hoboken or Hyderabad, if it is intended for use in the United States, the drug, and the way and under what conditions it’s produced, will be reviewed using the same standards and levels of scrutiny.

That scrutiny, by the way, doesn’t always have to have negative results. The inspections associated with drug production have been a central discussion point on this trip, and we’ve brought news that has been well-received, especially by the drug industry. We shared our proposed plan to create a new approach to facility inspections, one that will not only note problems, but will also allow our inspectors to document where a firm’s quality management system exceeds what would be required to meet regulatory compliance. To put it simply: the inspections can yield also carrots, and not just sticks.

Meeting in India

Last week, FDA’s Howard Sklamberg and Cynthia Schnedar participated in a panel discussion on drug quality with drug associations in India

So what are the carrots? These findings could be used to influence the frequency of our inspection of a particular facility, and possibly even support regulatory flexibility around post-approval manufacturing changes. These kinds of decisions would be anchored by data that proves that the risks of manufacturing problems in a certain facility are minimal.

We have often said we cannot inspect our way to absolute drug quality. Many of our discussions on this trip have focused on the importance of firms enhancing their own “quality cultures.” And, to that end, we know there are initiatives we can take to help them succeed. For example, we will be piloting a new questionnaire that could be used to further standardize inspections, with the goal of uniformly harvesting the kind of data that supports accurate measures of quality. We believe that by improving the inspection process in this way, future “metrics” that define quality will be understood and aspired to by manufacturers — no matter where they are in the world.

CEO meeting in India

Last week, FDA’s Howard Sklamberg and Cynthia Schnedar met with pharmaceutical CEOs in India to discuss drug quality

Of course, enforcement has been, and will continue to be, an important part of our program to ensure drug quality. Enforcement is a particularly appropriate tool when a firm does not submit accurate data to us. FDA relies on information to do its job, and faulty information means that we cannot ensure the quality of the drugs that the firm produces.

It is already clear to us, after speaking with regulators and industry leaders here, that India intends to be part of that global community that is committed to producing the highest quality of drugs possible. Through workshops and joint inspections, we continue to work with the Indian government to raise awareness and understanding of our inspections processes. And to the industry leaders we have met with here, we have pledged to continue to collect their feedback on how we might be able to help them improve regarding quality issues, and to incentivize them to do so.

India has a significant spot in the constellation of drug-producing nations. As one Indian official so eloquently said to us, we have “a galaxy” in common. And, we are happy to add, that the brightest star in that galaxy may just be our shared commitment to a global system of drug quality.

Howard Sklamberg is FDA’s Deputy Commissioner for Global Regulatory Operations and Policy

Cynthia Schnedar, J.D., is Director of the Office of Compliance at FDA’s Center for Drug Evaluation and Research

FDA Continues to Lead in Precision Medicine

By: Janet Woodcock, M.D.

Everyone knows that different people don’t respond the same way to medications, and that “one size does not fit all.” FDA has been pushing for targeted drug therapies, sometimes called “personalized medicines” or “precision medicines,” for a long time.

Janet WoodcockTargeted therapies make use of blood tests, images of the body, or other technologies to measure individual factors called “biomarkers.” These biomarkers can then be used to determine who is most likely to benefit from a treatment, who is at higher risk of a side effect, or who needs a different dose. Targeting therapy can improve drug safety, and make sure that only people likely to have a good response get put on a drug.

Targeted therapies have gained public attention since President Obama announced a Precision Medicine Initiative in his most recent State of the Union address. This initiative will reinforce our work at FDA, where development of targeted drug therapies has been a priority since the 1990s. In 1998, FDA approved the targeted therapy, Herceptin (trastuzumab), offering new hope for many patients with breast cancer. High levels of a biomarker, known as “HER-2,” identified breast tumors that were more likely to be susceptible to this drug.

Since the approval of Herceptin, the development of targeted therapies has grown rapidly. FDA’s Center for Drug Evaluation and Research (CDER) approved 30 targeted therapies since 2012, including Kalydeco (ivacaftor), a targeted drug for cystic fibrosis. In 2014 alone, eight of the 41 novel drugs approved were targeted, including:

  1. Lynparza (olaparib) for the treatment of advanced ovarian cancer.
  2. Blincyto (blinatumomab) for the treatment of B-cell precursor acute lymphoblastic leukemia (ALL).
  3. Harvoni (ledipasvir and sofosbuvir) to treat patients with chronic hepatitis C infection.
  4. Viekira Pak (ombitasvir, paritaprevir, dasabuvir and ritonavir) for the treatment of chronic hepatitis C infection.
  5. Cardelga (eliglustat) for the long-term treatment of Gaucher disease type 1.
  6. Beleodaq (belinostat) for the treatment of peripheral T-cell lymphoma.
  7. Zykadia (ceritinib) to treat patients with non-small cell lung cancer (NSCLC).
  8. Vimizim (elosulfase alpha) for the treatment of Mucopolysaccharidosis Type IV (Morquio Syndrome).

Since the 1990s, FDA has also been working on personalized drug dosing. People differ in how they eliminate a drug—some eliminate it much more slowly than most other people and are susceptible to overdosing, and others eliminate it much faster, and may not get any effect. There are biomarkers to identify people who have these unusual results, and CDER has been actively working for more than 15 years to put these findings into drug labels, so that each patient gets the correct dose, particularly for highly toxic or critically important drugs.

Personalized drug safety has also gotten attention. Often, one person experiences a serious side effect that does not affect thousands of others. Science is beginning to unlock the reasons for these rare toxicities, and the labels of some medicines advise screening people to make sure they are not at high risk for a severe side effect. This can make drugs much safer.

CDER has been recognized with awards from the Personalized Medicine Coalition and the Personalized Medicine World Conference for its longstanding work in this area.

CDER uses a lot of flexibility when reviewing applications for targeted drugs. Targeting people with a good chance of response means fewer people are eligible for a drug. CDER has adapted to the resulting small development programs. For example, among the targeted therapies approved in recent years, almost 60 percent were approved on the basis of one main clinical trial along with supporting evidence. In addition, 90 percent used one or more of FDA’s expedited programs such as Breakthrough, Fast Track, Priority Review and Accelerated Approval.

It is still hard to develop targeted therapies for many diseases, because there isn’t enough scientific understanding of why the disease occurs and what biomarkers would be useful. For many common illnesses, much more research is needed to reveal the individual differences that would enable development of targeted therapies.

We still have much work to do. However, we are pleased to see substantial progress and look forward to continuing our efforts to advance biomarkers, which will help bring additional important new therapies to patients in need.

Janet Woodcock, M.D., is Director of FDA’s Center for Drug Evaluation and Research

FDA Advances Medical Product Innovation

By: Margaret A. Hamburg, M.D.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

 

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