FDA Proposes Process Modernization to Support New Drug Development

By: Janet Woodcock, M.D.

The staff of the FDA’s Center for Drug Evaluation and Research (CDER) always tries to utilize cutting-edge science and up-to-date process management, befitting our stature as the global “gold standard” in drug regulation. Maintaining that standard requires us to keep up with evolving technology and the latest scientific, medical and regulatory advances. Current factors impacting drug development include the genomic revolution, the rise of targeted therapy, the availability of digital health data, the focus on patient involvement, complex drug-device combinations, globalization of drug development and harmonization of international standards. To be successful drug regulators, we reach well beyond the borders of the FDA. We collaborate with a wide variety of medical and scientific organizations such as those in biomedical research, the pharmaceutical industry, academia, global organizations and other regulatory agencies. Importantly, these collaborations also extend to patients and their caregivers and advocacy groups. All these interactions are critical to successful drug regulation.

Janet Woodcock

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

I have recently proposed changes to CDER’s new drug regulatory program. These changes are intended to free up resources so that our scientists and physicians have more time to focus on drug development, particularly for unmet medical needs, and on the multiple collaborations needed to make sure candidate drugs are developed and assessed properly, with appropriate input from external scientists, expert physicians and patient communities. The proposals include regulatory and review process changes, as well as organizational restructuring. We also intend to strengthen the support structures, including personnel and Information Technology (IT), that underpin the regulatory process.

As always, our goals are to expand access to safe and effective new drug therapies, conduct efficient and comprehensive safety surveillance, and ensure that accurate information about those drugs is available.

Here are some highlights of our proposal:

  • Recruiting the best and brightest individuals from many disciplines – Scientific leadership is vital for our ongoing success. After hiring talented scientists, we need to develop long-term career paths for them so they can become our next generation of seasoned leaders. Our recruitment efforts, strengthened by hiring incentives and other provisions in a new law called the 21st Century Cures Act, will help provide the staffing necessary for continued success in supporting the development and approval of innovative new therapies that meet previously unmet medical needs.
  • Enhancing our focus on multidisciplinary teams – Setting standards for approval and assessing innovative new drugs requires large and well-coordinated teams of highly trained professionals with many different types of expertise. CDER’s Office of New Drugs (OND) has a staff of more than 1,000 individuals who work together in many ways. New drug development and approval also requires coordination across many offices within CDER, including the Office of Translational Sciences (OTS), the Office of Surveillance and Epidemiology (OSE) and the Office of Pharmaceutical Quality (OPQ). A central component of our proposed changes involves stronger integration of our talented staff so they can better work together – within and across offices, a concept we refer to as “integrated assessment.” Previously, CDER reviewers would seek consults from specialists in other scientific disciplines (as issues were identified in the course of review). For greater collaboration, a cross-disciplinary team will be assigned to work on a new drug application at the outset.
  • Prioritizing operational excellence – Staff throughout CDER face a staggering pace of work, much of which involves attention to detailed administrative procedures. Our proposal would centralize project management functions within OND. CDER currently has 19 separate review divisions that regulate drugs. Over time, many divisions have developed procedures specific to their areas of review. We are proposing a single and consistent process: One organization with one process. Our aim is to enable our scientific and clinical experts to focus on what they know best – science and medicine – and our regulatory experts to manage the many processes we conduct.
  • Improving knowledge management – The information we process in our work is vast and diverse. Knowledge management is essential to control the data we receive from outside sources as well as what we generate from within the FDA. We plan to enhance our IT capabilities and access to information to better enable the storage and management of the collected experience of our scientific review staff. Accurate historic information from many past drug reviews is essential to informing current and future reviews – and to assure consistent regulatory decision-making. We want to make it easy for staff to find and use scientific and regulatory data, information and precedents. We’re also proposing changes that will increase the number of offices that oversee our review divisions from five to nine – and we’re envisioning 30 review divisions within those offices – up from our current 19. In addition to enabling greater efficiency, these envisioned changes will help us to better understand the diseases intended to be treated by the drugs we evaluate for approval – another way we aim to enhance our knowledge management.
  • Emphasizing the importance of safety across a drug’s lifecycle – Safety remains a key component of our new plans. We will work to establish a unified post-market safety surveillance framework to monitor the benefits and risks of drugs across their lifecycles, both before and after approval.
  •  Incorporating the patient voice – Patients are the FDA’s most important stakeholder and our vision includes incorporating the patient voice in modern patient-focused drug development. In fact, all the elements in our proposal have a common thread: they ultimately serve to improve health for patients.

Last year, CDER approved 46 novel drugs, 100% of which were reviewed on time – fulfilling our commitments under the Prescription Drug User Fee Act (PDUFA). Our system is effective, but we can always improve. Our new plan is designed to help us generate efficiencies so we can build stronger external collaboration capabilities and enhanced support for the scientific, clinical and technological innovation necessary for new drug therapies.

This proposal to modernize our new drug review processes will help us maintain and advance our global leadership, and better support our deeply committed staff. Both science and technology are changing at a blistering pace, and we need to keep up. Patients depend on the FDA to do what is necessary to provide access to safe and effective drug therapies. They take FDA-approved drugs because they trust us. While we have many steps to go before we can realize these changes, we feel confident that they will reinforce that trust and align us for ongoing success.

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

Statement from FDA Commissioner Scott Gottlieb, M.D., on proposed modernization of FDA’s drug review office

 

 

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

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

We’re Committed to Guarding Against the Intentional Adulteration of Food and Implementing the New Rule Efficiently

By: Scott Gottlieb, M.D.

The U.S. food supply is among the safest in the world. But to keep it safe we must recognize that our foods are vulnerable – not just from unintended contamination, but from those who would seek to deliberately do us harm.

Dr. Scott GottliebEnsuring that we’re prepared to minimize the risk of an intentional attack on our food supply is a goal that we share with the food industry and consumers.

The FDA Food Safety Modernization Act (FSMA) charges FDA with addressing the burden of foodborne illness by requiring that producers, importers and distributors of food take systematic steps to prevent contamination. Congress passed FSMA with a view of the unique risks posed by a global food supply. Six of FDA’s seven “foundational rules” for FSMA focus on the safe production, storage, and transport of human and animal food by addressing conventional food safety hazards

But a different reality shapes the seventh rule on Intentional Adulteration. This provision seeks to prevent acts of terrorism meant to harm and kill many people.

Food facilities covered by this rule (both domestic and foreign facilities that export to the United States) are required to implement — for the first time — a food defense plan that identifies vulnerabilities and ways to reduce the risk of intentional adulteration.

Congress directed FDA to focus its efforts to prevent intentional adulteration on the highest risks to the food supply. That’s why the Intentional Adulteration Rule primarily covers large food companies whose products reach many people.

Extensive analysis shows that some of the most significant risks are posed by an attack perpetrated by someone who has legitimate access to a facility, perhaps under the guise of an employee. This is why the new rule asks facilities to focus their efforts on processing activities that — if deliberately attacked by a rogue insider — could potentially result in widespread contamination of products.

FDA is committed to making the implementation of the Intentional Adulteration rule as practical and flexible as possible for the food industry. Even though the initial compliance date for the largest businesses is July 2019, more than a year away, I’m taking steps right now to fully understand stakeholder concerns and challenges, and address them.

As part of this fact-finding process, I recently visited the Nestlé Dreyer’s Grand Ice Cream facility in Laurel, Maryland. My FDA colleagues and I were taken on a tour of the facility, from the receiving dock to the production line to the packaging equipment. It was very helpful for me to see, first hand, the processes and practices that Nestlé has in place that could be used to guard against deliberate contamination.

Addressing Misconceptions

Having this kind of direct interaction with stakeholders is important. This is new regulatory territory for both FDA and industry. We need to make sure we implement these new requirements in a way that achieves its public health goal, without creating unnecessary burdens or costs on industry. From my interactions, I’ve come to believe that there may be misconceptions about how we’re expecting the food industry to implement this rule.

I want to use this opportunity to provide more transparency on our work.

Food facilities covered by the rule will be able to choose from a wide range of options to identify and reduce their vulnerabilities. They have the flexibility to tailor individual options that are cost-effective and make sense for each particular facility.

We recognize that many companies have already made significant efforts to reduce their vulnerability in response to terrorism concerns since the attacks of 9/11. These are important steps. And we believe these existing efforts can help food facilities meet many of the intentional adulteration rule requirements.

Existing measures may be in place for reasons related to business, food safety, and food defense. Many current steps companies take can become important parts of a food defense plan to meet the Intentional Adulteration requirements. However, we also know that there are some areas where additional measures will be needed.

We want to make sure these new measures can be implemented in a way that’s the least burdensome while achieving its intended, food protection purpose.

We agree with food companies that the “inherent characteristics” of food production equipment and processes should be considered when conducting a vulnerability assessment. At Nestlé, for example, vats of chocolate with hatches at the ground level can’t be opened without creating a flood of chocolate, which certainly wouldn’t escape notice. Our rules are meant to be practical. In this case, the inherent characteristics of chocolate vats make the ground-level hatches a low area of vulnerability. This means that mitigation steps may not be needed at this point of access.

During discussions with stakeholders, we’ve also heard that some people believe that plants might be required to construct vast enclosures for their equipment, invest in advanced computer systems, or reengineer whole processing lines.

That’s not the case. We want expectations to be clear to industry stakeholders.

We’ve also heard that some companies believe they’ll have to hire more workers for the sole purpose of observing other workers. We don’t believe that’s going to be the case.

Moreover, we’ve also heard concerns that implementing some food defense measures required under the rule may create conditions that negatively impact worker safety, food safety and food quality. During our extensive work with industry to develop the proposed rule, we’ve identified a variety of strategies that are very practical to implement and don’t impact food production or safety of any kind.

I want to be very clear about this point. Facilities will be given enough flexibility in selecting options for mitigation strategies that there should be no conflicts between food defense and food safety. We’ll work with any company that has those concerns.

And make no mistake, food safety is — and will remain — our first priority. In implementing the requirements of the intentional adulteration rule; we don’t want facilities to take any steps taken that could jeopardize food or worker safety.

I’ve also heard concerns expressed about the potential paperwork requirements associated with the rule and costs associated with monitoring the food defense protective measures required in the rule. We’ll provide examples of how to minimize paperwork and templates for recordkeeping so that costs are kept to a minimum.

We also expect that many of the options for monitoring can be incorporated into an employee’s existing responsibilities. And the frequency of monitoring for some strategies can also be kept to a minimum while still assuring the measures are working, thereby reducing costs.

Upcoming Guidance

Part of the feedback that we received during the Nestlé tour was the need for FDA to provide a guidance document to provide clarity on how firms can more easily meet the new requirements. That’s something we’re working on right now. We plan to publish this new guidance document well in advance of the initial compliance date in 2019.

We’ll soon be publishing the first chapters of this three-part draft guidance to focus on important questions that I’ve heard. Our hope is that this guidance will help manufacturers focus on those measures that have a meaningful impact on protecting food from intentional adulteration. We plan to publish the remaining two parts of the guidance this summer. The entire draft guidance will be available for public comment.

The first two installments of the guidance focus on the greatest concerns expressed by the food industry and the requirements that drive costs.

The first installment includes a simple, cost-effective way to identify the most vulnerable parts of the production process. It details numerous ways to guard against deliberate contamination, including some existing and cost-effective measures, as well as additional ways to monitor the operation to make sure that protections are working.

The second installment includes guidance on an additional, detailed, and flexible method to identify a facility’s most vulnerable points.

Finally, the third installment focuses on corrective actions, verifying that the system is working, how to reanalyze the plan and its parts, and record keeping.

Protecting Against an Inside Attacker

Importantly, the guidance will also address measures facilities can take to address the risk of an inside attacker. The rule identifies that the greatest risk comes from an inside attacker rather than from an outsider. The new measures require that the assessment of vulnerabilities must consider the potential threat from within a facility.

While the possibility of an inside attacker is hopefully not likely at a particular facility, we’re not talking about a theoretical danger. The threat landscape for intentional adulteration continues to grow regarding an inside attack even since the rule was finalized in 2016.

To take one vivid example: There was a recent report of a foiled terror plot in the United Kingdom that involved an employee at a food manufacturing plant who had been investigating ways to poison supermarket-ready foods.

FDA has worked on food defense assessments for more than a decade in collaboration with food manufacturers, universities, and government partners — including the intelligence and law enforcement communities. Our interactions with intelligence and law enforcement communities have repeatedly indicated that an inside attacker presents the greatest potential danger.

Some existing, protective measures in food facilities, such as perimeter fencing and general visitor protocols, are focused on thwarting an outside threat. These measures are also important. But they don’t address the full scope of risks, including an inside attacker, that must be considered when identifying a facility’s most vulnerable points.

The guidance document will provide examples of how to protect against an inside attacker using a range of measures that can be adapted to best meet individual facility needs. In many cases, food facilities will be able to leverage their existing protections.

Next Steps

Industry has also asked about the availability of training on these new requirements, both for food facilities and regulators. We’re working on both fronts to create training and technical assistance for food facilities that’s consistent with other FSMA-related training. And we’ll be training both federal and state regulators as well.

I was grateful to meet and learn from the professionals at Nestlé. I’m impressed by their commitment to food safety and food defense. I know that their efforts, and their commitment, reflect the ethic that’s in place at a lot of leading food companies.

We’ll continue to work through the issues raised by food manufacturers covered by the Intentional Adulteration rule. We need to make sure we implement these requirements in a way that’s cost-effective and efficient. Safeguards that are too costly to put into place, or are too hard for firms to adhere to, don’t work. They don’t meet their purpose.

I look forward to continuing to engage personally in this dialogue. Keeping food safe from contamination during production, storage and transport remains a primary focus of the FSMA rules. And food defense is an important component of achieving that goal.

While intentional adulteration is unlikely, a successful attack could have devastating public health consequences. FDA and the food industry are committed to the overarching goal of protecting consumers from these and other risks. I look forward to partnering with industry to ensure that appropriate measures are in place to give us all confidence that the food supply is as safe as possible from hazards of all kinds.

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

FDA’s New Pilot Program Aims for More Transparency about New Drug Approvals

By: Janet Woodcock, M.D.

When FDA approves a new drug, it has been found safe and effective when used under the conditions described in the label. Although this concept seems simple, the execution can be complex. Many factors are involved in weighing the benefits a drug can provide against the risks associated with its use. To that end, after we approve a new drug, we also want to make sure the scientific community and the public can understand why we approved it. This can help inform future drug development and, in turn, may facilitate the approval of additional safe and effective medicines.

Janet Woodcock, M.D.One way we explain the “why” behind a drug approval is by sharing information from the clinical trials that supported the approval decision. This information is usually discussed in FDA review documents authored by our physicians and other scientists. But often there is no complete description of the important efficacy trials, including the trial protocols, descriptions of any modifications made during the trial itself, and an explanation of all of the results. That’s why we launched the Clinical Data Summary Pilot in January. During the pilot, we will post key portions of the Clinical Study Reports (CSRs) – documents that sponsors create for FDA on each of their clinical studies. These portions would contain complete summaries of the study results, the protocol and protocol amendments, and the statistical plan. FDA plans to release these portions of the CSRs for the pivotal studies that supported the approval. The reports will be redacted by FDA to exclude confidential commercial information, trade secrets, and personal privacy information. FDA will not release patient-level data. Our goal is to share more directly complete summaries of the clinical trial information we have evaluated to determine whether a drug is safe and effective.

Currently FDA posts its review documents on line – material we call drug approval action packages. While the action packages include a significant amount of information pulled in from the sponsor’s application, that information is frequently separated into different sections and does not provide a complete summary of the results of any given study. This makes it difficult for academic researchers, regulators in other agencies, and other stakeholders to gain an in-depth understanding of the studies supporting approval. By providing the CSRs we hope to:

  • Enhance the accuracy of information used in scientific publications;
  • Increase stakeholders’ understanding of the basis for FDA’s approval decisions; and,
  • Inform physicians and other healthcare providers about the detailed results that regulatory decisions were based on.

The pilot will post the CSRs from up to 9 approved new drug applications of participating sponsors. We hope that reviewing the CSRs will help the scientific community better understand the information FDA used to evaluate an application and make an approval decision. At the end of the pilot we plan to seek comment from the public through a Federal Register notice to hear first-hand how the information was accessed and used. We hope to hear from a wide variety of stakeholders!

Our first pilot participant is Janssen Biotech for the approval of Erleada (apalutamide), the first FDA-approved treatment for non-metastatic, castration-resistant prostate cancer, as well the first to use the clinical trial result, or endpoint, of metastasis-free survival. Today we posted the CSR of the pivotal study with the regular action package. It’s a novel drug and we believe the CSR information, together with the FDA review, label, and other supporting documents, will facilitate a deeper understanding of how we reached our approval decision.

As an added benefit, our pilot program can help with global alignment, as our counterparts at the European Medicines Agency are similarly working to make information about their approvals more accessible and easier to understand.

The Clinical Summary Pilot is one of many efforts underway that require FDA working with industry to advance science. Now that it’s launched, we look forward to collaborating with sponsors who have an active or forthcoming NDA at FDA and who wish to participate in the pilot. For more information, visit the Center for Drug Evaluation and Research’s new pilot program page on our website.

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