The FDA Issues Draft Guidance About the Absorption of Active Ingredients Being Considered for Inclusion in Over-the-Counter Drug Products Applied to the Skin and Marketed without Approved Applications

By: Theresa M. Michele, M.D.

All drugs have some risk — even over-the-counter (OTC) drugs available without a prescription — and the FDA is always taking steps to help ensure their safety. When you take a pill, you generally expect that some of the active ingredient gets into your body, but what about when you apply a topical product to the skin? How much of the product gets absorbed through the skin and enters the bloodstream, and is it safe? At the FDA, we’ve been working to better understand the absorption and safety profile of topical OTC products such as sunscreens and topical antiseptics. We are particularly interested in learning how these products affect vulnerable populations such as children, the elderly, and pregnant and breastfeeding women.

Theresa Michele, M.D.Until recently, there was little data available to demonstrate the extent to which topical OTC drugs are absorbed into the bloodstream after application, and whether there are any long-term consequences of this. In fact, many topical OTC products were first marketed when these products were thought not to be absorbed through the skin and when there were no effective methods available to measure absorption. Now, better measurement tools are available, and research indicates that topical drugs can indeed be absorbed into the body through the skin.

Consequently, the FDA has been generally encouraging manufacturers to collect data on the potential risks of a topical drug when used according to the maximum limits of the product’s instructions, what we call Maximal Usage Trials or MUsT studies. Most recently we included MUsT studies among the list of safety and efficacy studies recommended for sunscreen active ingredients being evaluated under a new marketing pathway established by the Sunscreen Innovation Act in a final guidance for industry in November 2016. Now we are issuing draft guidance that, when finalized, will provide recommendations to industry on how to design and conduct MUsT studies for topical active ingredients that are under consideration for inclusion in an OTC monograph.

The draft guidance includes discussions about how to study the topical active ingredient’s effects on specific subgroups of vulnerable patients like children and the elderly. The studies require a relatively small sample of patients for a short period of time and should not be overly burdensome. In fact, this draft guidance reflects the same safety and efficacy standards that have applied to all drug products marketed under the OTC Monograph System for more than 40 years.

Absorption studies have contributed significantly to the FDA’s knowledge of the safety of topical prescription products. Applying a similar level of safety research to active ingredients being considered for inclusion in an OTC monograph to that which currently exists for prescription products can help the FDA determine whether these ingredients should be included in OTC products marketed without approved applications.

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

Addressing Needs of Patients While Stemming the Tide of the Opioid Crisis

By: Scott Gottlieb, M.D.

The biggest public health crisis facing FDA is opioid addiction. Not a day goes by in my role at FDA without hearing stories of the emotional, physical, and financial toll this epidemic is taking on Americans.

Dr. Scott GottliebFDA is committed to making every possible effort to stem the tide of this crisis. A little over a year ago, I announced a redoubling of that commitment through the formation of the Opioid Policy Steering Committee (OPSC). This group, comprised of the agency’s most senior leaders, was tasked with developing new approaches to impacting this crisis. One overarching goal of the committee was to develop new policy solutions to reduce overall exposure to opioids, prevent new addictions, and support the development and use of better FDA-approved medications to treat those with opioid use disorder.

Part of this effort resulted in two important actions led by the OPSC. In September 2017, FDA solicited public input on how the agency’s authorities could be used to address the crisis. A meeting in 2018 was held to solicit specific input on how FDA’s actions could assist more appropriate prescribing.

These actions generated a wide range of feedback, and they included the important voices of the patients. The feedback we received affirmed for us that as we address this crisis, we wouldn’t lose sight of the needs of Americans living with chronic pain or coping with pain at the end of life.

We’ve heard the concerns expressed by these individuals about having continued access to necessary pain medication, the fear of being stigmatized as an addict, challenges in finding health care professionals willing to work with or even prescribe opioids, and sadly, for some patients, increased thoughts of or actual suicide because crushing pain was resulting in a loss of quality of life.

We’re focused on striking the right balance between reducing the rate of new addiction while providing appropriate access to those who need these medicines. In some medical circumstances, opioids are the only drugs that work for some patients. This might include patients with metastatic cancer or severe adhesive arachnoiditis. Today, to address these goals and challenges, we announced an upcoming meeting focused solely on the needs of those suffering from chronic pain.

This public meeting is an opportunity for FDA to hear directly from patients, including adult and pediatric patients. We want to hear their perspectives on the impacts of chronic pain, their views on treatment approaches for chronic pain, and the challenges or barriers they face accessing treatments. 

As FDA learns more about the types of chronic pain that are managed with analgesic medications such as opioids, acetaminophen, NSAIDs, antidepressants, other medications, and non-pharmacologic interventions or therapies, we gain valuable insight into strategies FDA can adopt to help strike the right balance between policies that allow appropriate prescribing for those in true need of these medicines and preventing unnecessary exposure to opioids that can increase the rate of new addiction.

For example, one idea FDA is considering is the development of a strategy for encouraging medical professional societies to develop evidence-based guidelines on appropriate prescribing for different acute medical indications, how to assess the scientific support for these guidelines and impact on prescribing behavior, and considering the possibility of incorporating new prescribing information in opioid analgesic labeling. We believe such guidelines could encourage the use of an appropriate dose and duration of an opioid for some common procedures and promote more rational prescribing, including that patients are not being under prescribed and patients in pain who need opioid analgesics are not caught in the cross hairs. In short, having sound, evidence-based information to inform prescribing can help ensure that patients aren’t over prescribed these drugs; while at the same time also making sure that patients with appropriate needs for short and, in some cases, longer-term use of these medicines are not denied access to necessary treatments. We will take the first steps toward developing this framework in the coming months, with the goal of providing standards that could inform the development of evidence based guidelines.

We’re also going to be creating a new series of guidance documents focused on laying out an efficient, modern pathway for development of drugs targeted to the treatment of various types of pain. These will be up-to-date policies that focus on the treatment of specific areas of pain. This will allow us to tailor our requirements to the indications for which pain treatments are being developed. The aim will be to modernize FDA’s current guidance on analgesic drugs, to promote more new drug innovation.

As we address the opioid crisis with new approaches, and take more vigorous steps to confront addiction, we can’t lose sight of patients who have appropriate needs for these medicines. This meeting is one of many steps we’re taking to make sure we protect the needs of patients with chronic and acute pain even as we take new actions to reduce overall prescribing and dispensing of opioid medicines.

Scott Gottlieb, M.D., is Commissioner of the U.S. Food and Drug Administration

Follow Commissioner Gottlieb on Twitter @SGottliebFDA

Emerging issues of misuse and abuse of OTC loperamide challenge FDA to address a new turn in the opioid addiction crisis, while maintaining access for patients

By: Scott Gottlieb, M.D.

The opioid epidemic has reached tragic proportions. Yet it continues to take many new, and troubling turns. If there’s one lesson we’ve learned from this crisis, it has been the ability of the mounting abuse and misuse to evade our interventions. This history challenges us to deal more quickly and aggressively when new aspects of the addiction crisis emerge. For example, we’re seeing a crisis that began largely with the misuse of prescription opioids evolve into an epidemic that’s increasingly being driven by an influx of street drugs like illicit fentanyl and heroin. We must be alert to these new patterns of abuse and misuse of different drugs.

Dr. Scott GottliebOne such concern relates to the inappropriate use of loperamide – an FDA-approved drug to help control symptoms of diarrhea, including travelers’ diarrhea. Loperamide is sold under its over-the-counter (OTC) brand name Imodium A-D, as store brands and as a prescription drug. Loperamide is an opioid agonist, and it’s safe and effective at its approved doses. The drug acts locally, inside the gut, to treat the symptoms of diarrhea.

But when loperamide is abused and taken at extremely high doses, some of it can cross the gut lining, giving users an opioid like “high.” We’re aware that those suffering from opioid addiction see loperamide as a potential alternative to manage opioid withdrawal symptoms or to achieve euphoric effects. But at these very high doses, it’s also dangerous. We’ve received reports of serious heart problems and deaths, particularly among people who intentionally misuse or abuse high doses. Sometimes people are using as much as 100 times the recommended dose.

As with other new patterns of abuse and misuse related to the opioid crisis, the FDA acted with urgency to address the issues related to loperamide. We’ve issued a Drug Safety Communication and worked with sponsors to revise both prescription and OTC drug labeling to warn about serious heart problems associated with high doses of loperamide. We’re also encouraging changes to packaging of the OTC products to help deter abuse, such as the use of blister packs. And we’ve reached out to online sellers of these products to inform them of the public health risks and ask for their attention to the issue and their commitment to stop selling large quantities of the product.

At the same time, we’re very mindful of balancing benefit and risk and the needs of patients in our mission to promote and protect public health. We recognize that there are important and legitimate uses of loperamide, including for patients suffering from chronic diarrhea in adults associated with inflammatory bowel disease (IBD), including Crohn’s disease. We need to take the additional steps I outlined to address the abuse and misuse of loperamide. But preserving appropriate access to this treatment for patients who need it is something we take seriously. So we’re seeking input from the patient community on how best to strike this careful balance. In order to ensure that we don’t create access issues for such patients, we’re proceeding in a step-wise, deliberative fashion to ensure that the actions we take in relation to OTC loperamide use are reasonable and scientifically sound, and that these actions are necessary to achieve safe use of the drug and to address the issues of abuse and misuse.

It’s also the case that loperamide is available by prescription for patients who require maintenance therapy for chronic disease and are under the care of a health care provider.  We’ve also heard concerns that the changes to packaging could drive up the price. Affordability of medicines is one of my key concerns. We’re carefully evaluating the impact that our actions could have on the cost of this medicine. Based on our analysis to date, we don’t expect that the steps we’re taking will have much, if any, impact on cost, given that loperamide is available as a generic drug and manufactured by a range of competitors.

OTC loperamide is currently approved in packages of 8 to 200 tablets, which are often sold in multipacks of more than 1,000 tablets at a time. This is more than a three-year supply if the drug is taken according to the product label. Evidence suggests that reasonable packaging limitations and unit-of-dose packaging may reduce medication overdose and death.

Therefore, as we announced in January, the FDA has sent letters to the OTC brand manufacturers requesting that they implement packaging changes. We’re currently evaluating the maximal package size appropriate for OTC use, and plan to take into account data manufacturers provide on consumer use and needs; current OTC labeling and indications; the dose-response relationship of loperamide to cardiac events and known adverse event data; and importantly, the feedback of patients who rely on this medicine.

The agency is discussing implementation timeframes to ensure that manufacturers can continue to meet consumer need while package reconfiguration is taking place.

I also recently wrote to online distributors asking them to take two voluntary steps to help reduce the risks of loperamide abuse and misuse. First, I asked them not to sell bundled amounts of loperamide that contain more than one package of the drug. And second, I asked them to ensure that consumers can easily access and read the product labeling and warnings for drugs sold on shelves or on websites before purchase.

We appreciate the responsiveness from both the manufacturing and retail industry. Several companies are already committing to implement these packaging changes or purchasing safeguards. For example, Walmart has already taken a number of concrete steps to address the FDA’s request. These include ensuring that all loperamide products sold by Walmart/Sam’s Club have the product labeling clearly visible on the website; limiting purchase of 200 count tablet products in stores or online to a single bottle; and, moving the sale of bundled products at Sam’s Club behind the pharmacy counter and limiting sale to a single package. Walmart is also working to remove all loperamide “marketplace products” (i.e. products sold on their website by a third-party vendor) from their website. These vendors appear to be the primary source of bundled products and products that do not display product labeling on the Walmart site.

Amazon also has already taken some steps to address our recommendations and eBay has stated publicly that they also intend to follow our recommendations. We continue to work with other retailers to encourage them to take steps to help prevent abuse and misuse of loperamide.

All of us must do our part to address the public health challenges posed by the opioid addiction crisis.

The FDA will continue to assess the loperamide safety issue, and monitor adverse events, scientific literature, and data submitted by the public. We want to ensure that the steps we’re taking improve the safety of loperamide without limiting OTC access for consumers using the product according to labeling. The FDA’s actions to address drug misuse and abuse must be informed by an understanding of the complex social environment in which changing patterns of drug consumption occur. The agency is committed to addressing emerging issues of abuse and misuse while taking steps to safeguard the needs of patients who depend on these medicines.

Scott Gottlieb, M.D., is Commissioner of the U.S. Food and Drug Administration

Follow Commissioner Gottlieb on Twitter @SGottliebFDA

Spring Unified Agenda: FDA’s Anticipated Upcoming Regulatory Work

By: Scott Gottlieb, M.D.

Today, the federal government published the Spring 2018 “Unified Agenda of Federal Regulatory and Deregulatory Actions” (Unified Agenda), which provides federal agencies with the opportunity to update the American public on our government’s regulatory priorities.

Dr. Scott GottliebFor its part, the U.S. Food and Drug Administration (FDA) continues to make swift progress on our regulatory agenda, which reflects the key strategic priorities of the FDA and the Administration. Our regulatory agenda reflects our adherence to science based decision making and our commitment to our mission to protect and promote public health.

I provided a detailed overview of many of our proposed regulations for 2018 around the release of the Unified Agenda last fall – most of which we continue to take forward. I’d like to take this opportunity to highlight for you some of FDA’s new contributions to the Spring Unified Agenda.

Addressing the Nicotine Addiction Crisis

Smoking remains the leading cause of preventable death and disease. And too many young people are still being initiated on tobacco products, and becoming addicted to nicotine.

We’ve taken steps to address the morbidity and mortality associated with tobacco through the comprehensive plan that we announced last summer. We’re considering regulating the nicotine levels in combustible cigarettes, to render cigarettes minimally or non-addictive.

At the same time, we’re continuing to advance our framework for how we’ll regulate both novel nicotine delivery products, such as e-cigarettes, and traditional tobacco products. One goal of our efforts is to encourage innovation of less harmful products. We will ensure that all tobacco products, whatever their nicotine content or delivery mechanism, are put through an appropriate series of regulatory gates to maximize any public health benefits and minimize harms.

To that end, we will be proposing a new regulation to establish product standards for electronic nicotine delivery systems or ENDS. The proposed standard will, among other things, address the levels of toxicants and impurities found in nicotine, propylene glycol, and vegetable glycerin e-liquid, as these toxicants and impurities can cause death or other adverse health effects.

As part of our comprehensive plan, we’re also working hard to prevent access to products we believe are adulterated or misbranded. We recently joined with the Federal Trade Commission to issue 13 joint warning letters to companies that misleadingly labeled or advertised nicotine-containing e-liquids as kid-friendly food products (juice boxes, candies, and cookies).

As part of our comprehensive approach, we’ll also be proposing new regulations to establish requirements for the administrative detention of tobacco products encountered during an inspection that an officer or employee believes to be adulterated or misbranded. These steps will allow us to more effectively block the distribution and use of products that are ultimately found to be violative, including products that are misbranded because their labeling or advertising causes them to resemble kid-friendly foods.

Modernizing and Harmonizing Standards

As part of our efforts to continue to ensure efficiency of existing regulations, we will be taking another step to modernize medical device regulation, by proposing a new regulation to replace certain aspects of existing Quality System regulations with specifications of an international consensus standard for medical device manufactures (ISO). This rule, if finalized, will harmonize domestic and international requirements and modernize the regulation to make it more efficient for manufacturers of medical devices seeking to sell their products globally, while also continuing to ensure they adhere to high, internationally-accepted quality systems.

Enhancing Clinical Trial Processes

The Spring Unified Agenda also will propose rules to support the clinical trial process, for instance regarding the requirements for cooperative research. We’re proposing a new rule that would, in most cases, allow any institution located in the U.S. that is participating in a multisite cooperative research to be able to rely on approval from a single institutional review board.

We also will be issuing a proposed rule to update the agency’s investigational new drug application regulations to define and clarify the roles and responsibilities of the various persons engaged in clinical investigations to enhance protection of the rights, safety, and welfare of subjects and better ensure the integrity of clinical trials.

In addition to the new proposed regulations I’m highlighting here, FDA will continue to pursue a multitude of other important rules across the Agency, such as taking forward our compounding policy priorities and advancing food and drug safety initiatives. Moreover, we continue to remove outdated rules or reconsider proposed rules in light of our evolving policy priorities. I want to note, however, that some previously identified regulations that weren’t included in this Unified Agenda may still remain FDA priorities. Just because you don’t see them here, doesn’t mean that we don’t intend to continue advancing some prior policy proposals.

While we continue to have a robust regulatory agenda for the coming year, regulation is only one way in which we can foster our mission and improve public health. We’ll continue to tackle many additional priority areas through guidance documents and other policy efforts. These areas will include efforts to reduce the cost of drugs by encouraging competition – including in biosimilars; spurring innovation across medical products; battling obesity through our various nutrition initiatives; and, continuing to attack the opioid addiction crisis facing our country.

I look forward to keeping you updated as we progress toward these goals.

Scott Gottlieb, M.D., is Commissioner of the U.S. Food and Drug Administration

Follow Commissioner Gottlieb on Twitter @SGottliebFDA

The FDA is Asking for More Information on Application Forms — Here’s Why That’s Good for Innovation and Improving Health

By: Christopher Leptak, M.D., Ph.D.

To be most effective, electronic health records (EHRs) use a systematized and standardized nomenclature for the hundreds of thousands of clinical terms that characterize patient care. This helps to ensure consistency from EHR to EHR and allows these records to be usable from healthcare entity to health care entity, a concept known as interoperability. This nomenclature, used by both industry and the federal government, is called SNOMED CT.

Christopher LeptakRecognizing the value of such a comprehensive and standard clinical healthcare terminology, the FDA is also embracing the use of SNOMED CT to characterize disease names for its drug development pipeline and for FDA-approved products. The forms drug developers submit in their product applications now request use of this nomenclature. Forms for Investigational New Drugs (INDs) (FDA Form 1571) and New Drug Applications (NDAs), Biologic License Applications (BLAs) and Abbreviated New Drug Applications (ANDAs) (FDA Form 356h) have been revised to request additional supplemental systematized information using the SNOMED CT nomenclature to state for what disease or diseases the drug in the application is indicated.

Here’s why the new nomenclature is good for innovation and improved health: By clearly identifying the intended uses or indications for a potential new drug, SNOMED CT enabled metrics will better inform review activities and aid in consistency in the FDA advice for applications with similar indications. Newly systematized indication information will allow the FDA to better identify areas of unmet medical need for future drug development. This information will also help inform policy development, and with it, allow FDA to become more proactive about developing guidances and gathering public feedback. Additionally, using SNOMED CT will make it possible for the FDA to link its internal data with other data sources coded to SNOMED CT (e.g., EHRs).

To help industry understand what to do, we just released an online tutorial for industry explaining the newly revised forms in detail.

We look forward to working closely with industry to make sure applicants understand the revised forms and how to fill them out. We encourage industry to watch the tutorial, learn the coding system, and partner with the FDA on improving public health.

Christopher Leptak, M.D., Ph.D., is Director, Office of New Drug’s Regulatory Science Program in the FDA’s Center for Drug Evaluation and Research.

Food Information That’s Pro Market and Pro Consumer

By: Scott Gottlieb, M.D.

Information about how healthy our food is gives us the chance to make better choices about our diets. This same information also inspires competition among producers to formulate food in ways that make it more healthful.

Dr. Scott GottliebThese core principles are at the heart of FDA’s recent initiative to expand opportunities for food manufacturers to make voluntary claims on food products about the healthy attributes of their merchandise. Easier access to this information is something both consumers and manufactures want. More Americans are looking for healthier food options. At the same time, food producers should be able to compete on the ability to develop foods that are healthier, and make reliable, science-based claims about these attributes to consumers.

So at FDA, we’re reforming our policies to make it more efficient to develop these claims. This clarity may encourage more manufacturers to invest in making foods healthier.

These same principles also underlie our efforts to promote the disclosure of basic information about calories on chain restaurant menus. Americans drink or eat about one-third of their daily calories outside the home. While we all want to be able to share a good meal with our families, our hectic lives often have us looking to chain restaurants or take-out meals for convenience and value. Food options aren’t always healthy. But there’s no reason that convenient, affordable food can’t also be wholesome.

America is the world’s breadbasket, with some of the most innovative manufacturers. Whether companies are formulating food to be sold at grocery stores for meals we prepare ourselves — or served in restaurants or grab-and-go establishments — they should have the same incentives to compete on delivering healthy, inexpensive food options that are also tasteful. And food producers and retailers should have the same ability to make claims about the healthy attributes of their products.

Driving this “healthy” competition depends on transparency and a level playing field.

This is why FDA is implementing efficient rules to make sure that consumers are provided with some basic information about the nutritional features of food provided both through our nutrition facts label that consumers see on food sold in stores, as well as through the new restaurant menu label rule that goes into effect next week.

Over the past year we’ve worked hard to make sure this new rule can be implemented in a way where the information will be maximally beneficial to consumers and the new requirements will be minimally burdensome to restaurants and retail establishments.

National menu labeling could help make a big difference in America’s obesity rates, one of our most vexing public health challenges. Today, about 40 percent of all Americans are obese, and obesity increases the chances of developing heart disease, diabetes, and some types of cancer. Weight-related diseases and conditions reduce productivity and shorten lives due to decades of metabolic damage. Obesity also is a big driver of chronic disease.

Starting next Monday, consumers will be able to walk into any large chain restaurant and other chain establishments in the country and know, at a glance, how many calories are in the foods a restaurant offers. Surveys show consumers overwhelmingly want this information. And many use it to improve their diets and health.

Studies show that menu labeling can make an important difference in every day food choices that add up over time. Recent research shows that smart menu labeling reduces the average number of calories ordered by 30 to 50 calories per visit.

That may sound like a small amount. It comes out to less than a cookie a day. But over a year, based on that sort of reduction, you could end up consuming 10,000 to 20,000 fewer calories, making you three to five pounds slimmer. Consuming just 64 fewer calories per day, on average, would help the nation meet the government’s goal of reducing youth obesity by 2020. Better information that prompts people to cut 50 calories a day out of their diets can go a long way. And, over time, this can drive population-wide changes.

Creating a level playing field for menu labeling is only one of the steps FDA is pursuing to leverage diet as a way to help Americans reduce their burden of chronic disease.

We’re also taking final steps to implement the new Nutrition Facts label. This is the first overhaul of food labeling in more than 20 years. Consumers will soon have access to an updated food label that’s based on current science. It provides more easily understandable information to help Americans to build healthy, home-cooked menus when they’re shopping in grocery stores.

And FDA is taking new steps to modernize our approach to food claims. Claims can show that a food component may reduce the risk of a health-related condition, such as the relationship between folate and the reduction in risk of a child being born with certain birth defects, or high fiber and low fat diets reducing the risk of developing some types of cancer. Claims can also help consumers quickly identify foods that are lower in a food component that they are trying to avoid like sodium.

Combining food claims and enhanced labels can allow families to mix and match foods and meals that contain essential nutrients, while staying within caloric guidelines. Consumers also will have an easy to use and consistent baseline for the nutrition information that they need to better manage their health. These efforts were outlined in a nutrition initiative that I announced last month. Our goal is to leverage diet as a way to reduce death from chronic disease.

Consumers already are demanding more information about their diets, becoming smarter shoppers, and seeking out healthier options. In a 2016 survey of more than 1,500 consumers, virtually all responded that it’s important that the brands and manufacturers they buy from are transparent about what is in their food and how it is made. It’s in everyone’s interest to have meaningful nutrition information and claims that consumers can understand and trust.

We’ve already seen healthy changes in the restaurant market supported by consumers, like coffee chains shifting their recipes from whole milk to two percent milk. You can still order whole milk, but now the default option is better for your health and your waistline. Many kid’s meals now come with the option of apple slices instead of fries. These are changes for the better without taking away anyone’s choices. This is how information drives competition by producers to make food more healthful, and also make consumers more discerning. Armed with reliable information, consumers are making these choices.

I know not everyone has supported restaurant menu labels. Not every chain wants to display calorie information. But consumers want this data. And FDA has taken steps to make it easy for manufacturers and restaurants to provide this information in cost effective ways already found in many chains. In addition, firms won’t need to deal with a patchwork of different requirements for calorie labeling across the country.

In the guidance we’ll soon release, we took the concerns of the industry to heart, particularly that it could be costly to display calorie information. So, we lay out flexible options for complying with the requirements ranging from low-tech paper menu handouts to utilizing the electronic kiosks that are becoming commonplace in food establishments around the country. These options won’t require costly changes to existing infrastructure.

Further, we’ve made clear that materials used for marketing don’t have to have calorie counts on them. That picture of a delicious cheeseburger doesn’t require a calorie declaration. And when it comes to build-your-own foods, like choose-your-topping pizzas, calorie ranges can be used to make the various combinations fit on a standard-size menu board. We also provide more flexibility when it comes to the calories information that restaurants need to disclose. We know that prepared food can diverge from one entree to the next. So we allow room for that variability.

Pizza makers don’t need to worry about that extra slice of pepperoni.

America’s food industry is ripe for innovation. Consumers want healthier options and food producers want to develop these choices and make claims about these attributes. We support those innovations. And science-based regulations and transparent labels make it easier for consumers to understand the impact that day-to-day food choices have on their long-term health. They also make it practical for producers to compete on these features.

Consumers also want to have the chance to make informed choices about the meals they eat out based on access to nutritional information. Our goal is to establish a menu labeling framework that allows our broad food industry to meet these desires in an efficient and cost-effective manner that also accommodates the industry’s diverse business models.

Scott Gottlieb, M.D., is Commissioner of the U.S. Food and Drug Administration

Follow Commissioner Gottlieb on Twitter @SGottliebFDA

Mission Possible: Moving the Needle Forward to Advance Health Equity

By: CAPT Richardae Araojo

Every April our country observes National Minority Health Month to spotlight what we’re doing to eliminate health disparities among minority populations. A health disparity is a particular type of health difference that is closely linked with social and economic disadvantage, discrimination, or exclusion. We strive for what we call health equity―the attainment of the highest level of health for all people―by enlisting a range of approaches to remove the social and economic obstacles to health faced by racial and ethnic groups.

CAPT AraojoAs the Director of FDA’s Office of Minority Health (OMH), I lead cross-agency efforts with my team to protect, promote, and advance the public health of our country’s most vulnerable and underrepresented populations. OMH does this in many ways. For example, we:

  • Conduct and fund research on diseases that disproportionately affect minorities, like HIV/AIDS, diabetes, and heart disease.
  • Work to diversify the public health workforce by training principal investigators and pharmacists from diverse backgrounds, such as African Americans, Hispanics, American Indians/Alaska Natives, and Asian Americans and other Pacific Islanders, who can relate to research volunteers and patients from underserved communities. Research shows that people want their health professionals to look like them, so a workforce that reflects the demographics of the community it serves is vital.
  • Help minorities make better informed health decisions by creating culturally and linguistically tailored health education materials for use across different social media platforms.
  • Engage with minority-serving institutions of higher learning to protect and improve the health of the populations they serve.
  • Serve as a voice for those in need by encouraging all our constituents to participate in the work that we do. One example is the inaugural FDA Rural Health Symposium, a cross-Agency effort among OMH, the Office of Health and Constituent Affairs, and the Center for Tobacco Products, with participation from other FDA product centers. The symposium offered stakeholders from rural and tribal communities a forum to discuss how we can work together to address rural health challenges that range from the opioid crisis and tobacco use among youth to the need for telemedicine.

In the spirit of this year’s theme for National Minority Health Month, Partnering for Health Equity, I’d like to share a couple of other ways we’ve been partnering with private- and public-sector organizations to further equity on all fronts.

Getting culturally sensitive messages out to minority communities

My office conducts robust communications and outreach activities to share research and information on FDA-regulated products and to promote public health. For instance, Asian Americans, African Americans, and Latinos have lower immunization rates for adult vaccinations like herpes zoster, whooping cough, hepatitis B, and influenza. To better understand these disparities, OMH is supporting a study to assess the impact of advertising and promotional labeling as it relates to vaccine health disparities. OMH has message-tested FDA’s communications with consumer panels, among others, and we’re using the information from this research to shape FDA’s health education materials and outreach to minority communities.

Ensuring minority representation in clinical trials

Ensuring minority representation in clinical trials is crucial to improving minority health because we need to understand how different racial and ethnic groups respond to medical products before they are approved for use in the broad population. To that end, FDA developed guidance for industry and FDA staff. This guidance provides recommendations on using a standardized approach for collecting and reporting race and ethnicity data used to support marketing applications for FDA-regulated medical products.

OMH also works collaboratively with organizations whose mission includes encouraging more minorities to participate in clinical trials. We’ve partnered with the Veteran Health Administration’s Office of Health Equity to launch two videos featuring veterans talking about why diverse representation is so important. These veterans will also appear in the first installment of our new podcast series on health equity and disparities to share their experiences as participants in clinical trials.

Another important partnership involves our newly formed memorandum of understanding (MOU) with Yale University. Under this MOU, we’ll be working to advance scientific collaborations, outreach, and educational initiatives. Especially exciting is the cultural ambassador’s program, which will engage community members to get more involved in clinical research.

In sum, to create a world where health equity is a reality for all we must involve all stakeholders in new ways of thinking and working. And that requires the kind of teamwork, partnerships, and collaboration across disciplines, experiences, and sectors that I’ve shared with you here.

Visit www.fda.gov/minorityhealth for more information on FDA’s Office of Minority Health, and follow us on Twitter @FDAOMH for updates.

CAPT Richardae Araojo is FDA’s Associate Commissioner for Minority Health

New CDER Report Highlights Ongoing Drug Safety Initiatives and Priorities

By: Janet Woodcock, M.D.

At FDA’s Center for Drug Evaluation and Research (CDER), drug safety is among our highest priorities. Before we approve a drug, we make every effort to ensure its benefits outweigh its risks. After approval, we keep a careful watch for new safety issues that can arise once new therapies are prescribed for a broad population of patients.

Janet WoodcockIt’s a complex and ever-changing responsibility. As drug therapies become increasingly advanced, so too must our methods to prevent and/or manage risks related to their use. These risks come in many forms – including adverse events (side effects), problems arising from inappropriate or incorrect use, manufacturing issues related to sophisticated new production techniques, criminal tampering or counterfeiting, and the devastating effects of addiction, like that of the opioid epidemic. And, as innovative study methods provide new information, new safety issues can emerge for drugs that have been on the market and widely used for decades. For these reasons, we focus our efforts both on newly approved drug therapies and those already on the market.

Our annual report, Drug Safety Priorities 2017, provides updates on our ongoing initiatives, discusses new work, and highlights last year’s safety-related milestones and achievements.

Protecting the American public from risks associated with medications requires teamwork from many scientific and medical specialists at FDA working together to inform decisive regulatory action. Key efforts include the Safe Use Initiative to reduce preventable harm from medications; the FDA Adverse Event Reporting System (FAERS), which collects vast amounts of data about side effects and medication errors from medical products reported by patients, health care professionals, and manufacturers; and the Sentinel System, our state-of-the-art electronic drug safety surveillance system. We also collaborate with health care professionals, academia, researchers, and other health and science agencies in studying the effects of medications before and after approval to help ensure that the benefits of these therapies outweigh their risks.

Our report describes many ways CDER worked in 2017 to enhance drug safety for the American public. These include:

  • Safety surveillance and oversight of marketed drug products: In 2017, CDER’s Office of Surveillance and Epidemiology (OSE) conducted 7,446 safety reviews. Of those, 2,860 were initiated as a result of ongoing OSE surveillance.
  • The importance of real-world evidence to help advance drug safety science: Although randomized clinical trials (RCTs) are the gold standard for medical and scientific evidence needed to support FDA drug product approval decisions, they are often conducted in specialized and controlled research settings and are time-consuming and costly. And at the end of a drug development program, RCTs can leave critical questions unanswered, particularly about the effects or impacts of a drug after it gets into the “real world,” and is used by hundreds of thousands of people over an extended period. CDER safety scientists are using powerful new scientific computing and data storage technologies to enhance our capabilities of gaining valuable information from “real world evidence.”
  • New tools and new approaches for fighting our Nation’s opioid crisis: Our report emphasizes that in 2016, an estimated 11.5 million people misused prescription opioids — and that each day of that year, an estimated 116 people died from an opioid-related overdose. FDA actions taken in 2017 in response to the opioid epidemic align with our current four key priorities in this area: 1) decreasing exposure and preventing new addiction, 2) safely treating those with opioid addiction, 3) developing safe and effective novel alternative therapies to opioids, and, 4) improving enforcement of safety measures and assessing benefit-risk ratios.
  • Safety oversight for generic drugs: The report explains how we evaluate generic drugs to ensure they meet quality standards and deliver the necessary amount of active ingredient, and how we monitor generic drug use in the marketplace to flag early safety concerns. CDER’s Clinical Safety Surveillance Staff (CSSS) is addressing post-marketing safety concerns related to complex generic drug-device combination products. In 2017 a generic drug had two intravenous (IV) bag ports (rather than a single IV bag port used by the brand name drug). This difference raised concerns for potential confusion, risk of incompatibility issues, and potential adverse events in patients. The CSSS’s collaboration activities led to the development of a new process for managing review of similar IV bags with different port configurations.
  • Efforts to reduce preventable harm from medications: More than a million Americans are injured or killed each year due to preventable medication errors. FDA’s Safe Use Initiative works to reduce preventable medication-related errors, such as medicines dispensed in error, medicines taken for too long or not long enough, or medicines inappropriately mixed with other medicines or with foods that can increase risks of side effects. Among many other efforts, our work through the Safe Use Initiative in 2017 included making recommendations to enhance the safety of fluoroquinolone antibiotics, identifying “high-risk” prescribers (those who write prescriptions for high doses or co-prescribe with medications which increase the risk of adverse events) and educating them about safer prescribing practices, and identifying which diabetic patients may be at high risk of hypoglycemia (low blood sugar).
  • Compounded drugs – continuing regulatory and oversight efforts: FDA has taken many steps to strengthen safety measures for compounded medications since the 2012 outbreak of fungal meningitis associated with contaminated compounded drugs. Among other actions, the agency conducted 140 inspections, sent 55 warning letters, and issued 40 recalls related to compounding.
  • Diverse strategies, tools, and services for communicating drug safety: Effectively communicating what we do is an essential component of our work to protect the public. In 2017, we responded to 57,094 inquiries from the public (39,883 by phone, 16,269 by e-mail, and 942 via written letters), each an opportunity to help a patient ensure they are safely using their medication. Our Drug Safety Podcasts reached an estimated 350,000 listeners each week. These and many other communication efforts, such as our Drug Safety Communications that alert consumers and health care professionals about new or potential safety issues, serve to keep the public informed of important drug safety concerns that may impact them.

The report also details a variety of ways we keep pace with the rapid evolution of technology. For instance, we are evaluating the use of technologies, such as machine learning methods and other advanced computation techniques, to help our analytics systems contribute to more predictive safety and risk data. We are also exploring ways to leverage mobile apps, social media, and electronic prescribing data while ensuring patient privacy. As we pursue a wide-ranging safety agenda, CDER Drug Safety Priorities 2017 offers a deeper dive into FDA’s drug safety research, surveillance, and regulatory activities. We hope this report serves to demonstrate CDER’s ongoing commitment to protect the American public.

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

Ironed Out

By: Vanessa Burrows, Ph.D.

During the early part of the 20th century, the growing scientific knowledge that certain diseases were caused by vitamin and mineral deficiencies sparked public interest in products that touted these substances. But the public had little understanding of this emerging health care field and, as a result, was often easy prey for unscrupulous marketers who used phony claims that their products had therapeutic value.

Vanessa BurrowsOne such charlatan was a man named E. Virgil Neal, whose past schemes included palm-reading and hypnotism performed under the name Xenophon LaMotte Sage; a mail-order health and self-improvement program, which earned him a conviction for mail fraud; and a French cosmetics company that marketed false hair regenerators and bust enhancers.

Operating at the dawn of the modern advertising age, Neal employed a sophisticated and misleading marketing campaign to sell Nuxated Iron pills, which included iron and nux vomica, a derivative of the strychnine tree, which is highly toxic to humans and other animals. Beginning in 1917, Neal’s advertisements used celebrity endorsements that touted the product’s invigorating and strength-building qualities, promising to alleviate “that tired feeling.” However, the pills contained so little iron that their health impact was questionable, and so much strychnine that, in at least one case, they caused the fatal poisoning of a young boy.

Neal’s fraudulence was exposed by the American Medical Association and journalists in the early 1920s, but FDA was unable to prosecute him because the misbranding provisions of the 1906 Pure Food and Drugs Act did not outlaw misleading promotional material of the type that Neal distributed. Neal’s product actually contained some iron, albeit negligible amounts, and only made therapeutic claims in promotional materials. It wasn’t until 1944, after the passage of the 1938 Federal Food, Drug, and Cosmetic Act, when FDA was able to take action against the product on new types of misbranding grounds, which forbid, among other things, misrepresenting the quantity of ingredients contained in the product.

Today, FDA continues to play a critical role in protecting consumers from fraudulent, adulterated, and misbranded products like Nuxated Iron.

We hope you enjoy your visit to the History Vault.

Vanessa Burrows, Ph.D., is an FDA Historian

In Forum and On Farms, FDA and Partners Work to Harvest Agreement on Water Issues

By: Samir Assar, Ph.D.

A two-day summit on the topic of agricultural water, followed by farm tours organized by FDA’s Produce Safety Network (PSN), illustrate FDA’s collaborative approach to implementing provisions of the FDA Food Safety Modernization Act (FSMA).

The Produce Safety Rule under FSMA includes standards for the microbial quality and testing of agricultural water that comes in direct contact with the harvestable portion of produce. In response to stakeholder concerns that these standards may be too complex to understand and implement, FDA is exploring ways to simplify them while still protecting public health.

That exploration recently took shape in two different ways. My team and I attended an agricultural water summit on February 27 and 28 with hundreds of participants in Covington, Kentucky, and 28 satellite locations across the country to discuss ways to simplify the agricultural water standards. And after the summit, a handful of FDA produce safety experts embarked on a different kind of fact-finding mission – an educational tour of two South Florida farms covered by new FDA regulations.

Both the summit and the farm tours included representatives from government agencies, academia, and the produce industry, along with farmers who must implement the produce rule provisions. Many of the participants know each other and have been working together to leverage strengths and trade knowledge as they cross territory that’s new for all of us.

There was a consensus at the summit that it’s time to agree on next steps. Some want the water standards to be redone; others want to stay with the standards as written but with a lot more interpretive guidance on how to meet them. There were frank discussions during breakout sessions about the challenges presented by the current requirements, specific on-farm hazards of concern and how they translate into food safety risks, and alternate water management strategies that could be used to control these hazards. Outcomes from these group discussions will help inform the decisions that FDA makes on these important issues.

I spoke at the summit about our need for more information about on-farm conditions and water systems. Ongoing dialogue with stakeholders will be crucial as we move forward.

We received feedback that additional clarity on how we arrived at the current agricultural water requirements in the final rule would be helpful, as would be increased communications on the research FDA is funding, particularly for projects involving cooperative monitoring programs. There was also a push for FDA to establish partnerships with other federal agencies that have water quality databases and tools that might be used to alleviate some compliance challenges. Throughout this process, we have been engaging with people who have technical expertise on a variety of relevant issues (for example, produce safety, water microbiology, and water systems). During the summit, we were able to establish connections with more technical experts, and we plan to continue engaging with all of these experts as we consider ways to simplify the standards.

Farm photo

Canals bring water from Lake Okeechobee to the Duda fields, where it reaches the crops through seep irrigation.

These conversations continued as my colleagues in FDA’s Division of Produce Safety joined their counterparts in the public and private sectors on the two Palm Beach County farms on March 1 and 2. In addition to the produce team and colleagues from the agency, those on the tours included representatives of the Florida Fruit and Vegetable Association, the University of Florida/Institute of Food and Agricultural Science Extension, and state partners from the Florida Department of Agriculture and Consumer Services and the Florida Department of Health.

FDA has been putting these educational farm tours together for about a year, having done 117 in 2017 alone. Trevor Gilbert, the PSN representative whose region includes Florida, organized tours of the J&J Family of Farms and the Duda Farm Fresh Foods Facility, both of which began as family farms and grew to become national suppliers of produce. Both use a kind of irrigation unique to Florida’s high water table called the seepage method. The growing fields are intersected by canals that supply the water that is pulled up through a below-surface bed of sand to reach the crop roots. And both farms have staff specifically dedicated to food safety.

At J&J, the visitors were taken through fields of peppers and squash, the latter being cleaned and packed right in the field—in equipment invented on this farm—because of the crop’s sturdiness. The peppers are cleaned and packed in an off-farm facility. As the J&J food safety staff outlined the steps taken there to prevent the contamination of their crops, the main concern expressed about FSMA is a desire that the standards provide enough flexibility to allow room for innovative methods to ensure adequate supplies of water.

Farm photo

Perry Yance, Duda’s Farm Manager, talks to visitors from FDA about the farm’s use of water resources.

The next day, the team traveled to the Duda Farms, which started as a celery farm in 1926 and has staff members who have worked there for decades. Duda’s fields are fed by water that flows down from Lake Okeechobee, its fields laced with canals and pumps to control the water levels. The visitors were taken through fields of celery and radishes, marked by the occasional alligator sunning itself on the edge of a canal. As at J&J, some of the crops—celery in this case—are packed in the field using equipment invented by these farmers. The sentiment expressed here by the food safety team was one that I heard from others at the water summit: It’s time to reach agreement on the water standards and move forward.

Both farms follow food safety standards that preceded FSMA, ones shaped by audits required by retailers. The need to harmonize the requirements of such audits with FSMA is another challenge that has surfaced in discussions with the produce industry.

One of the calls for action that came out of the agricultural water summit was a need for more transparency and communications. That call will be answered in multiple ways, including building new connections through more of these educational farm tours. And the PSN’s team members are based all over the country to provide information and technical assistance.

FDA will continue working with dedicated teams of produce experts to find the right path forward, one that, where possible, makes the standards easier to understand and follow while still producing safe fruits and vegetables for consumers across America and throughout the world.

Samir Assar, Ph.D., is the Director of FDA’s Division of Produce Safety