Budget Matters: Infrastructure to Support Robust Generic Drug Competition

By: Scott Gottlieb, M.D.

The FDA launched its Drug Competition Action Plan more than a year ago, with the aim of advancing policies that would promote robust generic drug entry as a way to foster competition and lower drug prices. Access to drugs is a matter of public health. And among the best ways to help consumers get broader access to medicines is through policies that help ensure branded drugs are subject to timely generic competition.

Dr. Scott GottliebOur work is far from finished. But the policies we’ve advanced are already showing benefits toward these goals. The benefits we’ve seen reinforce the fact that policy can be used as a vehicle to advance these purposes.

New resources have also helped advance our work. Owing in large measure to the FDA’s implementation of the Generic Drug User Fee Amendments of 2012 (GDUFA), which funded critical enhancements to FDA’s generic drugs program, our staff eliminated the backlog of generic drug applications. In 2017, we also approved the largest number of generic drugs in the FDA’s history.

As part of GDUFA, as well as through our own new efforts, the FDA also has put policies in place to promote generic drug development in areas where there’s inadequate competition. This includes a focus on developing new guidance aimed at promoting development of generic versions of complex drugs. These are drugs that are often harder to copy. By advancing clear, objective, science-based guidance for developing generic copies of complex drugs, we hope to foster more competition.

And the FDA also has improved the efficiency and predictability of the generic drug review process to help promote more robust generic drug competition. For example, we’re prioritizing the review of generic drug applications for which there are no blocking patents or exclusivities. The aim is to promote competition so that there are at least four approved applications for each product (including the brand drug). Our data shows that there are significant price decreases once there are at least three generic drugs on the market. Our new policy will help ensure that there is robust competition across the market that will drive down drug costs to consumers.

In addition, we’re taking other new steps to curtail various forms of “gaming” by brand companies, where some sponsors sometimes adopt tactics that seek to delay entry of generic competition.

But we know that we need to do even more to promote access and competition. And so we’ve put forward a broader plan, as part of the President’s Budget, to achieve these aims.

Toward these goals, the President’s fiscal year 2019 Budget Request included $37.6 million to fund two initiatives that will help modernize aspects of our generic drug review process.

The first initiative will create a new review platform — the Knowledge-aided Assessment & Structured Application (KASA) platform — to modernize generic drug review from a text-based to a data-based assessment. The KASA will enable a structured review that will make the application review process more efficient, and allow deficiencies to be spotted earlier. This will allow the FDA to provide earlier feedback to generic drug makers that will, in turn, help to reduce multiple cycles of application review, one of our key aims and a primary focus of our overall efforts to speed market access to new generic medicines. Going through multiple review cycles is one of the primary reasons why the approval of generic drug applications is sometimes delayed many years. The new KASA system will help sponsors submit high-quality and more complete applications on the first submission. It will decrease the risk that applications will be refused for receipt and reduce the number of review cycles that applications undergo.

We anticipate that the new platform will allow more generic applications to be approved after the first cycle. This will promote timely generic entry and increase overall competition.

The new platform will also enable more efficient and robust knowledge management across different aspects of the FDA’s review process, helping reviewers capture and manage all of the information about products allowing for more seamless and effective product surveillance based upon quality and risk. This system will benefit both the agency and generic drug sponsors by increasing overall speed and efficiency of the pre- and post-market processes.

Having a structured template that completely replaces the current largely narrative-based review will allow for more consistent and predictable entry and analysis of data. Current assessments require manual review of the entire application. KASA will enable automated analysis of some portions of the application, which will save time, and ensure consistency.

The second initiative is aimed at promoting the more widespread use of existing generic drugs by looking for ways to keep generic drug labeling up-to-date with the latest information about each medicine’s risks and benefits. Generic drugs are generally required to have the same labeling as the brand drug they reference. And the burden to update the labeling with new safety and effectiveness information is typically born by the brand company.

However, when brand reference drug companies voluntarily withdraw their marketing applications, they also stop updating their labeling. When this happens, the FDA loses a key mechanism that the agency relies on as a way to update generic labeling. This can stymie the ability to modernize generic labels. In turn, when labels become out-of-date, providers may not have complete information about the full range of benefits and risks of the product. This can serve to diminish the use of these lower cost alternatives.

Consistent with our current authorities, which allow for certain types of labeling changes to continue to be made for generic drugs after the brand drug is withdrawn, this budget request will provide the funding to allow the FDA to assume more responsibility to help bring these drug labels up to date. We intend to launch this initiative initially for oncology products.

Our goal is to help ensure that doctors and patients have up-to-date information for these products. This will better inform clinical decisions regarding these medicines, and help promote more widespread use of low-cost, generic alternatives. By ensuring generic product labels are up to date, we’ll promote wider and more clinically optimal use of these drugs, which can save patients money.

We appreciate that the appropriations committees of both chambers of Congress supported this budget request in their appropriations bills. Congress has long recognized the need for — and importance of – investments in our generic drug program and efforts to promote generic drug use. The benefits of these initiatives are significant to the FDA’s modernization and efficiency. They’ll help advance a robust generic drug market that drives product competition and lowers drug prices.

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

Follow Commissioner Gottlieb on Twitter @SGottliebFDA

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

 

 

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.

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