FDA’s Sunscreen Guidance outlines safety and effectiveness data recommended for additional active ingredients

Editor’s Note: This blog has been updated since its original posting from 9:00AM EST, November 22, 2016.

By: Theresa M. Michele, M.D.

American consumers rely extensively on over-the-counter (OTC) sunscreens to help prevent sunburn. Certain sunscreens are also used, along with other protective measures, to reduce the risks of skin cancer and early skin aging caused by the sun.

Theresa Michele, M.D.The vast majority of sunscreens available in the United States are marketed under a regulatory framework called the OTC Monograph System. FDA reviews the active ingredients in these products to determine whether the ingredients are generally recognized as safe and effective (GRASE) for OTC sunscreen use.

The Sunscreen Innovation Act (SIA) of 2014 established an alternative process for the review of safety and effectiveness of additional active ingredients for use in sunscreens, and set deadlines for reviewing the ingredients and taking certain other actions. But SIA did not eliminate the need for a GRASE determination for new sunscreen active ingredients before reaching the market without an approved marketing application, and it did not relax the scientific standards for these products. Further, FDA’s review deadlines are only triggered after the data have been submitted to the agency.

Since the SIA was passed, FDA has met all of the deadlines for implementing this complex legislation. That includes inviting public comment on our actions, holding requested meetings with industry, issuing draft and final guidances, issuing proposed and final rulemaking required to date, and issuing a report to Congress on our progress.

When the SIA was enacted, eight sunscreen active ingredients were already under evaluation. The FDA has issued proposed sunscreen orders identifying data we believe is necessary for the agency to make a positive GRASE determination on those within the SIA-required time frame, but has yet to receive the additional data we requested.

Today, as required by the SIA, we released a final guidance document that details the Agency’s current thinking on the specific information we believe we need from sunscreen manufacturers or other interested parties before we can determine that a sunscreen active ingredient is GRASE for use in OTC sunscreens. This guidance will also help clarify FDA’s outstanding requests for additional safety and effectiveness data on the eight active ingredients, including the importance of human absorption data.

Sunscreens are intended to be used on a regular basis in liberal amounts and over large portions of the body surface whenever consumers are exposed to the sun. And yet some sunscreen active ingredients may be absorbed through the skin into the body, making it important to complete studies in humans to determine whether, and to what extent, consumers’ use of sunscreen products as directed may result in unintended, chronic, systemic exposure to these ingredients.

The guidance recommends that industry provide data from a Maximal Usage Trial or MUsT, to help determine if the ingredient is absorbed into the blood and at what level. This type of study is designed to capture the effect of maximal use on absorption into the blood. It is the same standard used by FDA for all topically applied drugs, and especially for drugs that are used routinely over the course of one’s life.

Sunscreens are a valuable tool for sun safety and public health, but of course, are not the only tool. Seeking shade at peak sunlight hours and wearing protective clothing, hats, and sunglasses are key to every sun protection plan. The sunscreen page on FDA’s website provides useful information for sun safety.  

FDA is committed to helping to ensure that sunscreens are safe and effective for U.S. consumers, but we need data to move forward.

We hope the final guidance encourages industry to provide the FDA with the data we need, so that together we can help bring a wider assortment of safe and effective sunscreen products to the American public.

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

Visit to West Coast Farmers and Processors Finds Shared Commitment to Food Safety

By: Stephen Ostroff, M.D.

Most people, even if they live in cities or suburbs, understand that there are many types of farms. But to really appreciate how different farms can be, you have to get out there and see it for yourself. By visiting farms in different parts of the country, you see first-hand the food safety challenges that are unique to a region. Farms are different sizes, grow a variety of crops and don’t follow the same growing and harvesting practices. There’s a varied amount of rainfall by region and season, and irrigation methods differ by crop and location. And so, while farmers confront some of the same issues, there can be real differences in the challenges they face.

What produce farmers and other food producers have in common is that they face new federal standards for the production of safe food. Seven foundational rules to implement the FDA Food Safety Modernization Act (FSMA) were finalized by May of this year. These include the produce safety rule, which establishes enforceable safety standards for the production and harvesting of most fruits and vegetables on farms in the United States and foreign farms that produce these commodities for the United States. They also include the preventive controls for human food rule, which establishes safety standards applicable to food facilities, including those that process fruits and vegetables.

I, along with my colleagues at FDA and state counterparts, visited the farmlands of the Pacific Northwest and California earlier this fall to get a sense of how growers, packers, processors and other stakeholders are getting ready to meet the new standards that apply to them. In September, we visited apple orchards and packing houses in Washington and berry growers in Oregon. We toured irrigation systems and met with stakeholders who included growers, water resources groups and tribal representatives.

FSMA West Coast Farm Tour

Parreira Almond Processing Company: Dr. Ostroff, left, and manager Paul Parreira Jr. at the almond hulling and shelling facility in Los Banos, CA.

In October, we visited stone fruit, table grape, citrus, and lettuce and strawberry fields in northern California. We toured an almond hulling and shelling operation in a visit coordinated by the Almond Alliance of California, and held a roundtable discussion about California’s water supply with farmers, representatives of industry associations and others. We visited a major processor of salad items. We finished the trip with an early-morning visit to the Golden Gate Produce Terminal in San Francisco, a trove of organic and conventional produce, as well as specialty and ethnic foods.

Produce farms have not been regulated like this before – it’s new territory for both the farming community and for FDA. We were asked many questions and received a great deal of feedback about the new regulations. But we found a strong commitment to providing consumers with safe fruits and vegetables and to moving forward in a collaborative fashion. For our part, I think it’s incumbent on FDA to protect public health without requiring a lot of unnecessary steps or measures that don’t achieve that goal.

These trips also highlighted the fact that that many food producers and industry associations have already invested a lot of time and effort in food safety measures. In some instances, what they have put in place goes beyond what is required under FSMA. In both trips, we saw farmers, other food producers, and industry associations stepping up to address past safety issues, including by developing their own on-farm standards and implementing audits to verify that those standards are met. Some developed treatment protocols and funded research to fill data gaps. These efforts will make it much easier to meet the new federal standards.

FSMA West Coast Farm Tour

Wenatchee (WA) Reclamation District: Manager Rick Smith, center, shows Dr. Ostroff, right, and colleagues an open irrigation canal system.

The big challenge for the growers in the drought-stricken Western states is water. The drought makes it difficult for growers to predict from month to month and season to season how much water will be available, where it will come from, and what it will cost. Therefore, many had questions regarding the produce safety rule’s water quality standards.

Our state regulatory partners in Washington, Oregon, Idaho and California brought members of the produce community together to meet us and discuss these issues. I am so grateful for their active involvement in making FSMA a success. Karen Ross, secretary of the California Department of Food and Agriculture, Lisa Hanson, interim director of the Oregon Department of Agriculture, Derek Sandison, director of the Washington State Department of Agriculture, and Pamela Juker, representing the director of the Idaho State Department of Agriculture, are strong voices for agriculture and food safety in the West, and we value their partnership and continued input. Both they and their staffs understand the farmers and have long-standing relationships with them. Through recently announced produce safety cooperative agreements with FDA, we will be partnering with each of these states and 38 others to implement the new produce safety rule.

We also had the opportunity to visit farms that have been in families for generations. These farmers take great pride in their work and are determined to keep their food safe but still have questions about how to they can comply with the new requirements. The take-home lesson for us was the need to provide adequate education and training and clear guidance that will help these farmers comply with FSMA. Farmers are looking for this and we’re making sure that we can fill these needs.

There was also a lot of discussion about making sure that the information we provide can be understood by people working on farms who are not native English speakers. There is a great deal of diversity in these regions, including the Hmong-American farmers of California’s Central Valley.

So there’s a lot of work ahead of us, and together we will roll up our sleeves to get it done. We went to see farmers and other food producers, and met a lot of talented people who grow and process the food we eat. We found an incredible diversity in the food that is produced, but a shared commitment to having the safest possible food supply.

Stephen Ostroff, M.D. is FDA’s Deputy Commissioner for Foods and Veterinary Medicine

The Race to bring Penicillin to the Troops in WWII

By: John P. Swann, Ph.D.

John SwannThis Veterans Day we remember that nearly 75 years ago dozens of American academic, commercial, nonprofit, and governmental institutions – including FDA – joined together in a race to provide a promising but complex and unstable medicine to troops fighting in World War II — penicillin. Knowing that infection is the major killer in wars, not battle injuries, their goal was to help turn a British discovery into a crucial wartime medical contribution and what would become an indispensable therapeutic agent long after that conflict ended.

Many people are familiar with the story of Alexander Fleming’s 1928 discovery of a Penicillium mold that had contaminated — and surprisingly destroyed — his cultures of pathogenic organisms.

The strain of Penicillium notatum that Fleming discovered at St. Mary’s Hospital in London

The strain of Penicillium notatum that Fleming discovered at St. Mary’s Hospital in London.

Though Fleming and several others in the next decade studied the mold filtrate, known as penicillin, it was Howard Florey and his colleagues at Oxford who uncovered the drug’s chemotherapeutic potential. Their work began with studies in mice in May 1940 and transitioned to a handful of clinical cases nine months later. However, the drug was difficult to purify. Also, it presented an immense challenge to produce in sufficient quantities for study, and with Britain under siege firms there were too involved in other aspects of the war effort to offer much assistance. So Florey and a colleague came to the U. S. in the summer of 1941 for help.

Northern Regional Research Lab

A meeting of NRRL staff in the 1940s (courtesy of the American Institute of the History of Pharmacy).

Among the first sites they visited was the Department of Agriculture’s Northern Regional Research Laboratory (NRRL) in Illinois, which had extensive experience in fermentation work, and from there they contacted several drug and chemical companies to drum up support.  Americans quickly combined forces to tackle the challenge. The federal Office of Scientific Research and Development (OSRD), the federal entity that organized and facilitated investigations to support the war effort, arranged to act as a clearing-house for the latest research on chemical and other studies of penicillin, exchanging data with dozens of organizations in the U.S. and Britain. NRRL developed several production modifications that increased the yield of penicillin by 100 fold.

Penicillin Moisture Testing

An FDA analyst in the 1950s carries out part of the procedure in testing penicillin for moisture content.

FDA’s first experience with the potential wonder drug was around September 1942, when the NRRL Director approached FDA about testing the antibacterial effectiveness of a small quantity of penicillin. A year later, enough of the drug had been produced to confirm in 200 patients what the early results at Oxford had suggested, and penicillin was ready to enter the war. First, however, OSRD asked that FDA certify every lot produced by the half-dozen or so manufacturers, a task the agency also performed for insulin under statutory authority that began in 1941. Six FDA technicians certified samples for potency, absence of fever-producing contaminants, toxicity, sterility, and optimum moisture, which can affect the drug’s stability. So scarce was penicillin that companies always reconditioned the occasional rejected lot rather than destroying it.

By the end of the war, some of the participating firms had increased purity of the drug from the Oxford group’s one percent to about 85 percent. Penicillin was not only more potent, it was also more abundant, its production having increased by a factor of 500 from 1943 to 1945. In fact, by 1945 the output of penicillin, formerly under severe restriction outside of military and scientific use, was now available for most civilian needs as well. In a few years the cost of producing penicillin had decreased so much that the glass used to store ampules of the drug cost more than the drug itself. FDA’s wartime work was codified in the Penicillin Amendment of 1945, which mandated FDA’s certification of penicillin and, through subsequent laws, most other antibiotics — a responsibility that continued for nearly four decades, when the need for government testing no longer existed based on industry’s record of production.

But it all started with an international effort to provide a lifesaving drug to the armed forces, bringing together all sorts of scientific and medical institutions, including FDA. Like so many others participating in this collaboration on a scale unseen up to that point, FDA played a small but critical role to support our troops at this time of global crisis.

John P. Swann, Ph.D., is an FDA Historian

Consumer expenditure on FDA regulated products: 20 cents of every dollar

By: Sheri Walker, Ph.D., and Clark Nardinelli

Sheri Walker

Sheri Walker, Ph.D., is an FDA Senior Economist

One of the much-cited statistics about FDA is this: that FDA-regulated products account for about 20 cents of every dollar of annual spending by U.S. consumers. Add up 20 cents of every dollar and it amounts to more than $2.4 trillion in annual consumption that includes medical products, food and tobacco.

Our staff of 34 economists comes up with this estimate of FDA’s impact every year. We think it helps the public put in perspective the sheer scope of FDA’s responsibilities, especially when you recognize that FDA is only one of dozens of governmental agencies.

We largely rely on personal consumption expenditure data collected by the Bureau of Economic Analysis (BEA) every year to calculate total consumer spending in each of the major FDA product categories. These product categories include food (except alcohol and meat products regulated by USDA), drugs, medical devices, cosmetics, dietary supplements, and (since 2009) tobacco products.

Clark Nardinelli

Clark Nardinelli is FDA’s Chief Economist

Some BEA expenditure categories include more than one FDA product area. For example, biologics and dietary supplements are included in the expenditure for pharmaceutical and medical products (although, legally, dietary supplements are food). Cosmetic products are captured under the BEA expenditure category for personal care products. Pet food and animal drugs are estimated as a percentage of the pet-related products category. The estimate for medical device products is derived using data from the therapeutic equipment products category from the BEA and data from the Annual Survey of Manufacturers collected by the U.S. Census Bureau.

Food products represent the largest share of spending on FDA products, accounting for approximately 11 cents of every dollar of consumer spending. Without the addition of tobacco products, spending on FDA-regulated products would be slightly less than 20 cents per dollar.

20 cents pie chartWe know that some people say FDA oversees 25 cents of every consumer dollar. Maybe it’s an urban legend – or maybe it harkens back to decades ago. The 20 cents (or 20 percent of spending on consumer goods and services) has held steady over the past 5 years. Americans used to spend a much higher proportion of their income on food – with over 25 cents of every dollar going to food during World War II. But since then the share of food and tobacco in total consumer spending has been falling steadily while the share of consumer spending devoted to medical products has been steadily climbing. Whether those trends will continue, and whether FDA’s 20 cents will hold steady for the next 5 or 50 years, is impossible to predict.

Sheri Walker, Ph.D., is an FDA Senior Economist, and Clark Nardinelli is FDA’s Chief Economist

Key Facts about “Abuse-Deterrent” Opioids

By: Douglas C. Throckmorton, M.D.

Here at FDA, we work diligently to be part of our nation’s solution to the opioid abuse epidemic. While there is no single solution to this complex problem, we continue to encourage efforts to develop new opioid formulations with abuse-deterrent properties that make it harder to abuse these powerful medications.

Douglas C. Throckmorton, M.D.Knowing there are some 100 million Americans with significant pain each year, we need to help ensure that patients in need continue to have appropriate access to pain medications, including opioids. At the same time we must work to ensure that these powerful medications are used as safely as possible.

To date, FDA has approved seven opioid formulations with abuse-deterrent properties consistent with FDA guidance, and there are more in the development pipeline.

What does it mean to be abuse-deterrent? Opioids with abuse-deterrent properties are tablets or capsules that are designed to deter abusers from crushing them into a powder for swallowing, snorting or injecting to create a faster, more intense high.

Each manufacturer has its own proprietary technology for deterring abuse. Some abuse-deterrent formulations consist of tablets with a hardened surface that is difficult to crush and some turn the crushed medicine into a gooey substance that is difficult to inject.  Other current approaches combine the opioid with naloxone or naltrexone, drugs that block the effects of the opioid in the body that are activated when the opioid is crushed.  Additional approaches are currently under development.

The manufacturers of the seven FDA-approved opioids with abuse-deterrent properties to date have all submitted study data demonstrating that the products are expected to deter abuse. This work was guided by the 2015 final guidance for industry, Abuse-Deterrent Opioids — Evaluation and Labeling. As a result of FDA’s review, FDA-approved product “labeling” (prescribing information) for these medications clearly states the product’s abuse-deterrent properties. Other manufacturers have chosen to add what they may intend as abuse-deterrent properties to their product, but FDA has not seen sufficient evidence that these properties are effective and therefore the FDA-approved labeling for these products does not identify them as having abuse-deterrent properties. Prescribers and patients can look to our web site for the list of FDA-approved products with abuse-deterrent properties in their labeling.

It’s important to recognize that FDA refers to these drugs as “abuse-deterrent” not abuse-proof. There will always be some potential for abuse of these products. For instance, a patient can orally ingest a quantity beyond what is prescribed. It’s also true that people intent on abusing an opioid may find ways to overcome the abuse-deterrent properties of the drug that were not identified during premarketing research. With this in mind, FDA requires that any drug approved as having abuse-deterrent properties be further evaluated by its manufacturer after it is marketed. The manufacturer is required to conduct studies to evaluate the impact of the product on abuse in the community. If necessary, we may approve updated product labeling that describes the drug’s abuse deterrent features after approval.

Still, abuse deterrent technology certainly helps. That’s why FDA is looking at ways to encourage the development of abuse-deterrent generic versions of an opioid since none currently exist. We released draft guidance for industry in March and we’re looking forward to an interesting public discussion of the topic next Monday and Tuesday.

The FDA opioid action plan we issued in February involves a multi-faceted approach to reducing opioid misuse and abuse. And we continue to look for ways to make a difference. We recently announced we would help fund the development of assessment tools to evaluate packaging, storage, delivery, and disposal solutions, as well as product formulations, designed to prevent or deter misuse and abuse of opioid analgesics.

Support for abuse deterrent formulations is one important part of a strategy to help prescribers and patients make the best possible choices about how to use these powerful drugs. Our goal is to find the balance between appropriate access to opioids for patients in pain and the need to reduce abuse and misuse of these medications.

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

National Cyber Security Awareness Month: Understanding the Interdependencies of Medical Devices and Cybersecurity

By: Suzanne B. Schwartz, M.D., M.B.A.

October is National Cybersecurity Awareness Month. Proclaimed by President Obama each year, Cybersecurity Awareness Month encourages the public and industry to understand the importance of cybersecurity and to be vigilant when it comes to the technology we rely on every day, including helping patients remain confident in the safety of their medical devices.

Suzanne SchwartzMany medical devices are “life critical systems”—meaning they play a crucial role in monitoring and protecting human life. As more and more of these systems use technology to interconnect, we must be dedicated to securing them from hackers and cyber-attacks.

Here at FDA, we work with hospitals, health care professionals, and patients to provide medical device manufacturers with guidance for monitoring, identifying, and addressing cybersecurity vulnerabilities in their devices before and after they have entered the market. To further counter threats, FDA has been making a deliberate effort to work with outside groups—including those we have previously not engaged with—such as security researchers.

This outreach has allowed our guidance to evolve. While manufacturers can incorporate controls in the design of a product to help prevent these risks, it is essential that manufacturers also be proactive and on guard for potential vulnerabilities and emerging threats throughout the lifecycle of devices, and be prepared to devise solutions—points made in FDA’s draft guidance on postmarket medical device cybersecurity, issued in January 2016.

A life cycle approach requires creating, evolving, and maintaining a comprehensive cybersecurity risk management program starting from early product development and extending throughout the product’s lifespan. A key component of such a program is what should be done after a product’s potential risks and vulnerabilities have been identified. A life cycle approach should include manufacturers collaborating with entities that discover threats or vulnerabilities to a medical device’s cybersecurity in order to understand and assess the identified risks. It should also include manufacturers developing appropriate solutions prior to the vulnerabilities being publicly disclosed, which is an added protection for patients.

But, our work alone won’t achieve safety if all stakeholders do not recognize and remain vigilant against potential threats. Medical device manufacturers, government agencies, health care delivery organizations, health care professionals, and patients all share this responsibility.

In recognition of this shared responsibility, FDA has entered into a partnership with the National Health Information Sharing and Analysis Center (NH-ISAC), and the Medical Device Innovation, Safety, and Security Consortium (MDISS) to foster rapid sharing of medical device vulnerabilities, threats, and mitigations within the hospital and health care ecosystem. Doing so will help to proactively address cybersecurity threats and vulnerabilities that may impact patient safety.

Digital connections provide great power to innovate—and security must keep pace with that innovation. Safeguarding our sector’s—Healthcare and Public Health (HPH)—critical infrastructure therefore includes first identifying, and then addressing previously unforeseen medical device cybersecurity vulnerabilities. As National Cybersecurity Awareness Month rolls on, we encourage everyone to be aware, vigilant, and committed to upholding and strengthening cybersecurity. Through a joint approach encompassing the public and several government agencies, we are beginning to see the necessary change in culture within the medical device ecosystem, accompanied by progress in the management of medical device cybersecurity. FDA’s January 2016 workshop “Moving Forward: Collaborative Approaches to Medical Device Cybersecurity” highlighted some of the progress that has been made. Moreover, recent examples of coordinated vulnerability disclosure between medical device manufacturers and security researchers demonstrate the promise of partnership in addressing medical device cybersecurity. But there is still work to be done, and we must remain committed to working collaboratively to address our goal of protecting the public health.

Learn More

For more information about National Cybersecurity Awareness Month including tips on cyber safety, visit the Stop.Think.Connect.™ campaign website. You can also find more information about medical device cybersecurity on FDA’s Center for Devices and Radiological Health web page.

Suzanne B. Schwartz, M.D., M.B.A., is Associate Director for Science and Strategic Partnerships at FDA’s Center for Devices and Radiological Health

SCORE at Six Months: Meeting the Challenge of Complex Recalls

By: Stephen Ostroff, M.D., and Howard Sklamberg, J.D.

When a potentially contaminated food is on the market, time is of the essence to keep people from becoming ill. Yet there are times when it is difficult to determine what actions should be taken. This can happen when we do not have enough information to reach a clear decision.

Stephen Ostroff, M.D.

Stephen Ostroff, M.D., is FDA’s Deputy Commissioner for Foods and Veterinary Medicine

To better address these situations, in April FDA established a team of senior leaders that is brought in to make decisions in the most challenging cases. The team is called SCORE, which originally stood for Strategic Coordinated Outbreak Response and Evaluation, but it soon became clear that the scope of its work is broader than outbreaks. The team looks at cases in which recalls and other actions may be needed, even when there are no reports that people have fallen ill. So SCORE now stands for Strategic Coordinated Oversight of Recall Execution.

And we’re happy to report that SCORE is already making a difference, helping to overcome obstacles and streamlining processes to get potentially harmful foods off the market as soon as possible to reduce further consumer exposure.

In the last six months, SCORE has reviewed and directed operations in cases that include flour contaminated with peanut protein, (a major food allergen), facilities contaminated with Listeria monocytogenes, pistachios in which Salmonella was detected, and baby food that was not manufactured in compliance with infant formula regulations. All of these cases resulted in recalls and announcements issued by the firms and FDA.

Howard Sklamberg

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

SCORE was launched, in part, in response to concerns raised by the Department of Health and Human Services’ Office of the Inspector General about FDA’s ability to ensure that companies initiate voluntary recalls in a prompt and effective manner. While FDA staff were already helping to facilitate thousands of prompt and successful voluntary recalls, we recognized the need for an enhanced response in certain, more complex cases.

In the cases brought to the team, we believe that SCORE has helped determine the right course of action and shorten recall timeframes, getting the products off the market faster. SCORE has helped improve tactical planning, leading to additional inspections and sampling assignments, and to getting the word out to more consumers about potentially dangerous products. In one case, FDA suspended a food facility’s registration after a reinspection and additional sampling requested by SCORE showed continued contamination. Suspension of registration effectively shuts a facility down until FDA determines that there is no longer a reasonable probability that foods produced there will cause serious illnesses or death.

We set individual deadlines and got prompt results in these, and other, instances. FDA staff are seeing these actions as a model for their efforts going forward.

FDA has been evolving over the past few years into an agency that speaks with one voice in its oversight of food safety. SCORE’s membership includes leaders from within the directorates of Foods and Veterinary Medicine and Global Regulatory Operations and Policy, in addition to the Office of the Chief Counsel. The spectrum of expertise covers inspections and investigations, compliance and enforcement, policy, legal, communications, outbreak response and, most important, science.

This team is in its infancy but the results it has achieved thus far signal an integrated approach to food recalls that will help ensure a swift response no matter what obstacles arise. The arrival of the compliance dates for the FDA Food Safety Modernization Act rules overseeing the safety of domestic and imported foods are putting additional food safety controls in place to help reduce food contamination. And the work of SCORE and its colleagues will continue.

SCORE’s goals for the next year include identifying and closing gaps that slow the process of determining whether a food is a threat to public health or interfere with identifying the right actions to take in response to potential contamination. Our ultimate goal is to continue to improve our ability to protect consumers from contaminated food.

Stephen Ostroff, M.D., is FDA’s Deputy Commissioner for Foods and Veterinary Medicine, and Howard Sklamberg, J.D., is FDA’s Deputy Commissioner for Global Regulatory Operations and Policy.

FDA’s Opioids Action Plan: A Midyear Checkup

By: Robert M. Califf, M.D.

As FDA works to address the opioid epidemic of abuse, misuse and addiction, it’s valuable to see firsthand some of the ways the crisis is affecting our communities.

This summer, I toured areas hard-hit by the opioid crisis in Tennessee, West Virginia, and Kentucky, visiting  with survivors of opioid addiction and overdose as well as community activists, government officials, and health care providers, all of whom are working diligently and creatively to address and overcome this crisis.

Robert Califf

Robert Califf, M.D., is Commissioner of the U.S. Food and Drug Administration

My visit to the nationally-recognized neonatal intensive care unit at East Tennessee Children’s Hospital was deeply moving and set the stage for the rest of my tour and underscored the urgency of fighting this epidemic. More than a third of the babies admitted to the NICU have neonatal opioid withdrawal syndrome (NOWS), a condition which can be life-threatening if not recognized and treated

Watching a nurse treat a fretful baby suffering from NOWS underscored the complexity of the opioid problem.  Many women taking opioids haven’t planned their pregnancy, don’t immediately know they are pregnant and may not be aware of the risk that opioids pose to their unborn child. This includes those women who are taking medication as part of medication-assisted treatment (MAT) which also includes counseling and behavioral therapies. For women on MAT, the risk of NOWS must be balanced against the additional dangers of untreated opioid addiction during pregnancy.

How best to prevent NOWS and treat opioids use disorder was a continued theme of my trip, and among the issues we grappled with during a roundtable at the University of Tennessee’s Medical Center hosted by Surgeon General Vivek Murthy, who is traveling the country to discuss solutions to opioid abuse as part of his TurnTheTideRx campaign. I’m pleased that expanding access to and the use of evidence-based MAT is a key focus area for the Administration, is a part of the HHS-wide opioid initiative, and is an approach supported by a recent FDA advisory committee.

In Charleston, WV, I met with several patients who are reclaiming their lives with the use of MAT including “Dave.” Like so many others, Dave became addicted to opioid pain medication after being treated for an injury. As a result of his addiction, his marriage failed and he lost contact with his children. But with treatment, he has reunited with his family and next spring will graduate from college and hopes to taper off of his treatment.

Throughout my tour, I heard that opioid education – including training during medical school and residency and greater public awareness far and wide – is a key component in fighting the opioid epidemic. At a roundtable in Charleston, Gov. Earl Ray Tomblin and U.S. Sen. Joe Manchin singled out their state’s model mandatory education program for prescribers and they told me the state is leading an effort to implement the CDC’s Guideline for Prescribing Opioids for Chronic Pain as a best practice for their state-run Medicaid program.

At a firehouse in the town of Williamson, WV, I met with those on the frontlines of the opioid epidemic – the firefighters and first responders who carry life-saving naloxone to help reverse an overdose. They told me more education about naloxone was needed and told me that they appreciate our efforts to help make naloxone more available to the general public.

My last stop this summer was to Kentucky where I toured the emergency room at the Pikeville Medical Center and participated in a roundtable with physicians, pharmacists, and state policy and community leaders brought together with the help of the regional organization Operation UNITE. UNITE coordinates treatment for those with substance use disorder as well as support for their families and friends, and educates the public about the dangers of drug use. These measures, combined with a recent state law requiring prescribers to register with a prescription drug monitoring program are working, we were told.

Throughout my travels, I listened and learned more about how FDA can help end this crisis. I also had the chance to share what FDA has been doing this year to implement a multipart plan to address the opioid epidemic.

Our milestones so far include:

  • Developing warning and safety information for immediate release opioids and requiring that prescription opioid analgesics and opioid-containing cough product labels include strengthened warnings about the risk of using benzodiazepines at the same time.
  • Working to better understand the long-term safety of using extended release/long acting opioids. Sponsors must now conduct a number of studies to generate postmarket data on these products.
  • Issuing draft guidance for industry to support the development of generic versions of approved opioids with abuse-deterrent formulations.
  • Seeking advice from the National Academy of Science Engineering and Medicine on how to balance both the needs of patients with pain and the need to address opioid misuse and abuse.
  • Supporting increased access to naloxone; for instance, by awarding a contract to conduct consumer behavior studies based on model product labeling for a potential OTC version of the antidote and by launching a competition to create a mobile app that could help find the closest available naloxone treatment in an emergency.
  • Approving the first implantable treatment for the maintenance treatment of opioid dependence.

The community-based successes I observed on my three-state tour reinforced my view that we are making important progress in addressing this crisis.  But continued hard work, creative ideas, and collaboration — across government, with the medical profession, health care providers, industry, and, most importantly, patients and their families, is still required.

We at FDA will continue to work with all of these groups, using all the resources at our disposal, to improve the judicious and responsible use of opioids and to help bring an end to this epidemic.

Robert M. Califf, M.D., is Commissioner of the U.S. Food and Drug Administration

 

FDA is working with hospitals to modernize data collection about medical devices

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

By: Jeffrey Shuren, M.D., J.D.

America’s hospitals and their dedicated staff helps us fight disease and suffering by delivering life-saving and life-enhancing care every day in an astounding variety of ways.

From helping set a broken leg or responding to an emerging viral threat, to assisting and performing delicate heart surgeries on tiny newborns, these hospital personnel are the front line of surveillance, vigilance, and intervention.

Throughout their work day, hospital staff use a variety of medical devices: imaging machines, EKGs and in vitro tests to make diagnoses; infusion pumps, ventilators and robotics to provide treatment, and an array of implants to replace diseased joints and organs. And, as the nation’s hubs for real-time health care data, hospitals are uniquely positioned to help identify new safety problems with devices as well as changes in the frequency of already known safety problems because they use these technologies in the real-world setting of clinical practice, outside of the more controlled setting  of a clinical trial.

FDA is looking to improve the way we work with hospitals to modernize and streamline data collection about medical devices.

Jeffrey Shuren

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

Given the greater diversity and complexity of medical devices today; the rapid technological advances and iterative nature of medical device product development; the interface between the technology and the user – including the learning curve associated with adopting new technology; and, in some cases, a relatively short product life cycle that can be measured in months, not years; FDA’s evaluation of medical device safety presents unique challenges not seen with drugs and biologics. Therefore, assuring the safety of medical devices depends on many factors and should a problem arise, it could be due to a variety of causes.

At the time of premarket evaluation, however, it is not feasible to identify all possible risks or to have absolute certainty regarding a technology’s benefit-risk profile. Among other reasons, studies required to do so would likely be prohibitively large in order to capture less frequent and more unpredictable effects or consequences. In addition, such larger studies still may not reflect the true benefit-risk profile of the device. Once a device is on the market, for example, doctors may use it beyond the FDA cleared intended use. In addition, subsequent modifications to the device or changes in how the device is used in practice can result in new safety risks or greater frequency of known risks.

FDA has several tools for watching devices once they are on the market, also called postmarket surveillance, all of which have inherent limitations. For one thing, we can require that a manufacturer conduct a post-approval or postmarket surveillance study that focuses on identifying potential longer-term issues noted at the time of clearance or approval or specific safety concerns that may arise after clearance or approval. However, conducting studies on a product after it’s already on the market can be challenging because patients often have little incentive to enroll in a study when the device is already available to them.

Likely the most well-known of FDA’s postmarket surveillance tools is medical device reporting, which FDA requires from certain entities, including device manufacturers and device user facilities, such as hospitals. Federal law requires hospitals and other user facilities to report when they become aware of information reasonably suggesting that a medical device has or may have caused or contributed to a death or serious injury to a patient.  They must report these medical device-related deaths to both FDA and the manufacturer, if known; and device-related serious injuries to the manufacturer, or to FDA, if the manufacturer is not known.  Such passive surveillance has important limitations because it relies on people to identify that a harm occurred or a risk is present, recognize that the harm or risk is associated with the use of a particular device, and take the time to report it.

Congress mandated this reporting by user facilities in 1990 to complement similar adverse event reporting by manufacturers. But then, in 1997, Congress required that FDA establish a reporting program that could limit user facility reporting to a subset of representative user facilities. As part of our efforts to develop this  reporting program, FDA set up a large-scale network of about 300 hospitals, called MedSun (the Medical Product Safety Network), with whom we work interactively to better understand and report on device use in the real-world environment. Even with MedSun, all hospitals were required to continue reporting until FDA implements by regulation a program limiting user facility reporting to a subset of facilities.

Although FDA has recognized that requiring all hospitals and other user facilities to report may provide limited added value and could entail unnecessary costs that take away from patient care, we have not yet established the program limiting reporting to a subset of user facilities. In the past, we have not enforced universal reporting requirements for hospitals and other user facilities.

In light of several high-profile device safety issues occurring in hospitals, FDA, in December 2015, initiated inspections at 17 hospitals, chosen because there were reports of events at these facilities related to the spread of uterine cancer from the use of morcellators or the spread of infections associated with contaminated duodenoscopes. While these events appeared to be the kind that would have fallen under our current medical device reporting requirements, we did not see corresponding adverse event reports in our adverse event (MAUDE) database. From those inspections, we learned three important lessons:

  • First, some hospitals didn’t submit required reports for deaths or serious injuries related to devices used at their facilities, and in some cases, they did not have adequate procedures in place for reporting device-related death or serious injury events to FDA or to the manufacturers.  Based on the number of user facilities in the United States and the number of reports we receive, we believe that these hospitals are not unique in that there is limited to no reporting to FDA or to the manufacturers at some hospitals.  We want to work with all hospitals to address these issues.
  • Second, hospital staff often were not aware of nor trained to comply with all of FDA’s medical device reporting requirements.
  • Third, we feel certain there is a better way to work with hospitals to get the real-world information we need, and we should work with the hospital community to find that right path, especially in light of developments in the creation and evaluation of electronic health information.

In order to effectively address these issues, we will work with the hospital community on what role they should play in assuring the safe use of medical devices. This work will include how they can effectively participate in  the National Evaluation System for health Technology (NEST), and whether or not current reporting requirements should remain, be modified, or eliminated in light of more effective modern tools, such as software tools to conduct active surveillance of electronic health information that contains unique device identifiers.  In many cases, our inspections of these 17 hospitals turned up violations of FDA’s medical device reporting regulation. For some hospitals with significant violations of the regulation, FDA received a response that we determined was not adequate to address those violations, and we engaged with these facilities to facilitate an effective path to compliance. These hospitals indicated their willingness to work with us and address the violations, and at this time, we do not believe any additional action with regard to these hospitals is necessary.  Some hospitals also expressed willingness to work with us on more efficient and effective ways to collect the information we need.

On December 5, FDA will hold a public workshop to solicit input and advice on improving hospital-based surveillance systems and the broader role of using hospitals to evaluate how well devices work in the clinical setting. We encourage all hospital stakeholders—from clinicians to IT system managers—to attend and discuss current hospital-based surveillance efforts, the role of hospitals in evidence generation and future opportunities for hospital-based surveillance. We’d also like their input on the incorporation of unique device identifiers (UDIs) into electronic health records to aid in the future development of evidence generation efforts, including the support of better device development, surveillance and health care delivery.

We are already working directly with the Association of American Medical Colleges and the American Hospital Association to prepare for this workshop and help develop improvements to our systems.

Hospitals are our partners in building the infrastructure for NEST. Together we can build a state-of-the-art system that not only quickly identifies life-threatening problems caused by medical devices but also expedites patient access to crucial life-saving devices. Armed with such information, health care providers can help patients make more informed medical decisions that improve their health.

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

Introducing FDA’s Emerging Sciences Idea Portal: Please Help Us Predict the Future

By: Donna L. Mendrick, Ph.D.

Gazing into the future to predict the next new things in science and technology is not just the work of a science fiction writer.

Donna MendrickGovernment and business engage in this forward thinking too– it’s called “horizon scanning,” a fairly recent practice that involves systematically gathering a broad range of information about emerging trends to help organizations develop the capabilities they need to deal better with an uncertain and complex future.

FDA set up its own intra-agency horizon scanning group in April 2015 called the Emerging Sciences Working Group, which I chair. Our 15-member group meets regularly and includes representatives from FDA product and research centers as well as relevant offices.

With the mission of leveraging scientific expertise and resources to conduct long-range horizon scanning, we advise Agency and product center leadership on how emerging issues and cross-cutting scientific advances may affect FDA preparedness and activities across government agencies.

The fact is, FDA’s ability to achieve its mission relies on awareness and preparing pro-actively to address emerging issues and scientific advances that will affect the products FDA regulates five or more years in the future – well in advance of formal FDA regulatory submissions.

What kinds of new science and technology will alter the way FDA does its work? We are not focused on evolving areas such as nanotoxicology, since nanoparticles are already in some approved products even though the field is still being developed and understood.  Our goal is to identify areas not yet addressed in current products like hibernation for surgery and brain-computer interfaces.

Once we have such information it can be used for science-based planning, programs, policies, reporting, and communication within and outside FDA.

It’s no surprise that FDA can’t possibly employ experts in every subcategory of scientific and technological knowledge. To cast a wide net, we are also seeking the advice of other government agencies that fund research, evaluate patent submissions, and develop scientific policy for the U.S. government — and that process has begun.

But it is clear that to fully horizon scan we must turn to experts in the private sector. That’s why today we are issuing a Federal Register notice asking science and technology experts outside of the government to submit their predictions on the next new things in their field of specialization.

To be clear, we’re not looking for advances that are already under discussion. We’re seeking information about scientific and technological advances that are so unknown they don’t show up – or barely show up – on a web search.

Your electronic submissions to our Emerging Sciences Idea Portal will be public so all confidential information should be submitted in writing. And there is no guarantee we’ll get back to you with a response – but we might if we’re sufficiently intrigued and want more information.

We look forward to your submissions. With your help, FDA will be ready to provide advice and to promptly review applications for products that truly represent the next new thing.

Donna L. Mendrick, Ph.D., is FDA’s Associate Director for Regulatory Activities at the National Center for Toxicological Research