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

Reflections on a Landmark Year for Medical Product Innovation and Public Health Advances and Looking Ahead to Policy in 2018

By: Scott Gottlieb, M.D.

Dr. Scott GottliebAs we look ahead to 2018, I’d like to take a moment to reflect on an inspiring year of advances in both medicine and public health for FDA — from groundbreaking medical products brought to market this year, to a record number of generic drug approvals that will promote competition, and to the agency’s ongoing efforts to advance policies that promote safe and effective product innovation, and keep Americans safe from food-related illnesses.

Today, new medical breakthroughs are profoundly altering how we view and treat disease in ways that seemed inconceivable just years ago. In this modern medical setting, FDA is evaluating all aspects of its policies to make sure we’re protecting consumers, while promoting beneficial innovation that has the potential to effectively treat disease for human and animal patients, and improve public health.

A Record Year for New Innovation

As scientific understanding of disease advances and the practice of medicine becomes more tailored to individual patient needs, we also are modernizing how we work with innovators throughout the development process to bring products to patients more efficiently, using the best available science.

For example, FDA recently coordinated the approval of a novel diagnostic device that can detect hundreds of genetic mutations in a single test with the Centers for Medicare & Medicaid Services’ proposed coverage of the test, thereby facilitating earlier access to this innovative product.

Also, in the rapidly advancing field of individualized medicine, the Agency advanced new draft guidance that addresses better ways to develop treatments that address the underlying molecular changes (e.g., genetic mutations) that often cause or contribute to diseases. This includes uncommon molecular changes that are present in only a small subset of patients. The guidance proposes an approach for drug developers to enroll patients into clinical trials for targeted therapies based on the identification of rare mutations,  when reasonable scientific evidence suggests the drug could be effective in patients with these genomic findings. The new guidance discusses the evidence needed to demonstrate effectiveness for a variety of molecular subsets within a particular disease. The framework could lead to more consistent development and approval of targeted therapies for patients who are likely to benefit from them.

This past August we also saw the practical advent of a whole new way to treat disease with the approval of the first gene therapy product in the United States. We have since approved two more gene therapy medicines. Innovations like these are creating a turning point in the treatment of serious illnesses. With this technology also comes greater potential to cure intractable and inherited diseases.

2017 saw a number of other similar, historic milestones with regard to new innovation. This collective progress reflects a fundamental shift in science that’s enabling us to attack more diseases with novel platforms. We’re increasingly able to identify patient benefit earlier in the development process because of the ability to better target medicines to the underlying mechanisms of disease. At the same time, in many cases these identical tools also allow us to surface safety issues earlier and more effectively.

pie chart of approvals

FDA approved a modern record number (56) of novel drugs and biologics in 2017.

Owing in part to these advances, FDA approved a modern record number (56) of novel drugs and biologics in 2017. Of these 56 novel approvals this past year, 46 were new molecular entities approved by our Center for Drug Evaluation and Research – of which 28 were approved using one or more of FDA’s expedited review programs. Ten of these 56 novel approvals were biological therapeutics that were approved by our Center for Biologics Evaluation and Research. We also had a record number of drugs with orphan indications approved. At the same time we eliminated the entire backlog of pending orphan drug designation requests. We also broke records, with the highest number of generic drugs approved in a single month multiple times in 2017, and we recorded the highest annual total of generic drug approvals (1,027) in the agency’s history. We believe that, if current trends continue, we’ll exceed this record number of generic drug approvals in 2018.

2017 generics approvals

Both full approvals and tentative approvals, which do not allow the applicant to market the generic drug product and postpones the final approval until all patents/exclusivity issues have expired.

Our science-based and patient-centered regulatory approach also extends to medical devices, where we’ve focused on a life-cycle approach to product development. This has allowed us to streamline clinical development protocols without compromising on our commitment to rely on rigorous evidence. By carefully considering when clinical data can be better gathered through post-market, as opposed to pre-market, studies, patients are waiting less time to access some breakthrough devices without conceding one bit FDA’s gold standard for demonstrating reasonable assurance of device safety and effectiveness.

Chart of device approvals

In 2017, the agency approved a record number of novel devices — 95. This was more than four times the number of novel devices that received market approval in 2009.

Our commitment to applying the “least burdensome standard” for generating information critical for device approval was strengthened and advanced by provisions in the 21st Century Cures Act. This policy approach is a hallmark of our efforts to help innovators generate high quality evidence that can support marketing approval as efficiently as possible. Our embrace of these principles has resulted in remarkable advances in access for patients. In 2017, the agency approved a record number of novel devices — 95. This was more than four times the number of novel devices that received market approval in 2009.

Modernizing FDA’s Regulatory Programs

These new advances also present new challenges. At FDA, we’re being confronted with the need to regulate highly novel areas of science like gene therapy, targeted medicine, cell-based regenerative medicine, and digital health; where our traditional approaches to product regulation may not be as well suited. To meet these new challenges, we’re taking a fresh look at how we can adapt our customary approaches to regulation. We need to make sure that we’re allowing beneficial new technologies to advance, while continuing to protect consumers as part of our product review processes.

To promote these efforts, we advanced a new policy framework allowing certain diagnostic tests to undergo review by accredited third parties. This new framework will reduce the burden on test developers and streamline the regulatory assessment of these types of innovative products. This approach more readily accommodates the highly iterative nature of these technologies, where tests often undergo routine modifications to improve their precision and clinical utility.

Over the past summer, we also launched a pilot program exploring a new way of regulating digital health devices so that these fast-evolving technologies can similarly undergo the rapid product evolution that’s the hallmark of software tools like medical apps, while FDA maintains the ability to make sure that these digital health tools are being reliably produced. We followed these actions with a suite of guidances that clarify how we intend to regulate certain digital health technologies in a way that encourages innovation.

More broadly, we provided more clarity for manufacturers of low- to moderate-risk medical devices which will reduce unnecessary submissions to FDA for minor modifications that could not significantly affect device safety or effectiveness. As a result, patients will benefit from upgraded products more quickly.

This effort to properly match our policies to the unique attributes of the new technologies we’re being asked to review was also evident in new steps we took across other programs; from our comprehensive policy on regenerative medicine aimed at spurring safe and effective innovation in these potentially transformative products, to our draft guidance for manufacturers of 3D printed medical devices.

We know that the public health benefits derived from our efforts to modernize our regulatory approaches are not confined to the pre-market review process. Advances in our post-market tools and policies can yield meaningful advances for patients in the form of safer products, better information to guide medical decisions, and more opportunity to more efficiently move products to market – if we can have confidence in our post-market oversight. This is why we’re always looking for ways to reform and improve this oversight, and advance the ways that we share this information with patients and providers.

For example, last fall we launched a new searchable database to better inform patients and health care professionals of adverse events reported with drug and biologic products. We’ll be taking other steps soon to improve on the ways that we share important clinical information with patients and providers. These goals also include new efforts to step up our post-market oversight of potentially risky products, and warn consumers earlier of potential problems we find. As an example, we’ve taken decisive action to protect the public from risky stem cell products offered by unscrupulous clinics. We’ll pursue similar actions in 2018.

In 2017, we also took new steps to warn companies making false claims that their unapproved products can treat or cure life-threatening diseases; we advanced a new draft guidance describing FDA’s approach to regulating homeopathic products based on the risk they can pose to consumers; and we took steps to alert the public to the dangers of other unproven and untested products, such as certain body-building products, contaminated dietary supplements and kratom. Among other efforts, we also took new steps to facilitate faster patient access to needed compounded medicines, while protecting the public from poorly compounded drugs. There will be additional enforcement steps in 2018. And we continue to promote work that will enable FDA to use real world data to better inform our regulatory decision-making.

Promoting Drug Competition

Many say that FDA has no role in drug pricing, but I disagree. While we don’t have the authority to regulate prices, we do have the authority — and the responsibility — to ensure that the agency’s policies are not impeding competition that could ultimately be a check to rising drug prices and patient access.

Our role as gatekeeper of cost-effective, high-quality generic drug products is a foundational part of fostering human and animal drug competition. We’re advancing new ways that FDA can help enable patients to get access to more affordable medications. We shared some of the steps the agency is taking with our launch in June 2017 of the Drug Competition Action Plan — from prioritizing our review of generic drug applications, to working to stop companies from finding loopholes in the system that delay the entry of generic drugs to market, to making substantial progress on the generic drug review backlog, to ensuring that low cost drugs get to the patients who can benefit from their effectiveness and more affordable price.

New Steps to Combat Addiction

I’ve noted many times that among my highest priorities as Commissioner is addressing addiction crises facing the nation, principally with respect to nicotine and opioids. In 2017 we announced new plans for how we address these crises. In July, we announced a comprehensive plan that proposes to lower nicotine in combustible cigarettes to minimally or non-addictive levels. At the same time, we took new steps to enable development of innovative delivery systems that could be potentially less harmful than cigarettes for adults who still want to get access to satisfying levels of nicotine. As part of that plan, we formed a new Nicotine Steering Committee. It’s charged with modernizing FDA’s approach to development and regulation of nicotine replacement therapy products that can help smokers quit and stay quit

FDA also unveiled new actions to confront the staggering human and economic toll created by opioid abuse and addiction, starting with my first major action as commissioner to establish an Opioids Policy Steering Committee. Under the leadership of this committee, FDA is reevaluating how drugs that are already on the market are used, both for legitimate purposes and misuse and abuse.

The committee will recommend new policy steps to address this crisis. FDA also is taking immediate action where needed, as we did with FDA’s first-of-its-kind request to remove a currently marketed opioid pain drug from sale due to the public health consequences associated with the product’s abuse and misuse. We’ve also worked to identify ways to decrease exposure to opioids, prevent new addiction, and support the treatment of those with opioid use disorder; for example, through new Risk Evaluation and Mitigation Strategy requirements for makers of immediate-release opioids, and requiring labeling changes to add important clarifying information regarding the use of medication-assisted treatments for patients suffering from opioid use disorder. We’re continuing to pursue other creative ways to address the crisis, such as leveraging different forms of packaging, storage and disposal of opioid medications.

Protecting and Empowering Consumers

It’s not only medical products and policies where FDA can innovate to better serve the public – we’ve also made much progress in the implementation of the Food Safety Modernization Act, which was designed to keep the American public safe from food-related illness. Implementing the most comprehensive food safety reform in 70 years requires a massive commitment from federal, state and local governments to food producers, farmers and other stakeholders that are working to protect the public health in new and innovative ways. That’s why in July we announced more than $30 million in funding for states to help implement new produce safety requirements. We also launched an innovative software tool called the Food Safety Plan Builder that assists food manufacturers in creating a food safety plan to help prevent foodborne contamination and ultimately protect public health. And we’re looking at other ways to empower farmers and producers to ensure the law’s modernized requirements are effectively fulfilled.

I also believe in empowering people to make better choices. This is reflected in our continued efforts to pursue the practical implementation of the menu-labeling rule. We listened to public feedback and have proposed practical solutions to make it easier for industry to meet obligations in these important public health endeavors, while ensuring restaurant patrons have access to the nutrition information they need.

Empowerment also is critical for patients facing life-threatening or debilitating illness. This year we held our first-ever patient engagement advisory committee meeting. This is a pioneering effort that seeks to strengthen our engagement with patients and secure the patient voice in our regulatory decision-making.

We also understand that in many serious diseases, patients want earlier access to experimental treatments. We’ve taken new steps to improve the expanded access resources we have to serve patients, including enhancing our online Expanded Access Navigator Tool and simplifying the process for approving a patient’s request for access to an investigational treatment. Last month, as part of our commitment to expediting drug development for rare diseases, we issued draft guidance that describes a possible new approach for companies to collaborate and test multiple drug products in the same clinical trials for a specific ultra-rare pediatric disease, thereby reducing the number of patients that need to be treated with placebo. This framework can be applied more widely to other ultra-rare diseases.

In everything we do at FDA, our top priority is to protect the public health. Perhaps nowhere was this more evident in 2017 than in the areas of the United States that were impacted by last year’s hurricanes.

The devastation caused by Hurricanes Harvey, Maria and Irma brought to public view some of the critical work FDA does in overseeing the safety of the food and medical products. We worked around the clock to ensure that farmers in Texas and Florida could safely handle their crops affected by flooding. We remain deeply committed to the recovery in Puerto Rico and that island’s long-term success. We worked closely with drug and medical device manufacturers in Puerto Rico to take steps to address potential and apparent shortages of medical products that resulted from the devastation left by Hurricane Maria.

Although we’re seeing progress in Puerto Rico owing to the hard work of federal and local authorities — and primarily because of the resilience of the American people who are affected — our work and commitment to hurricane victims and patients in need of critical medical products will continue into 2018.

Improving our Stewardship of Vital Drugs

Antimicrobial resistance continues to be a major public health challenge. Addressing this problem requires adoption of a “one health” approach that involves new efforts to use antibiotics more responsibly in both human and animal medicine. To better manage antibiotic usage in food animals, in 2017 FDA completed its implementation of a groundbreaking Guidance for Industry (GFI #213). This new guidance document eliminates the use of medically important antimicrobials for food production purposes and brings the remaining therapeutic uses of antibiotics in animals under veterinary oversight.

A total of 292 approved drug applications were impacted by this new guidance; with 84 drug applications withdrawn, 93 applications for oral dosage form products intended for use in water converted from over-the counter (OTC) to prescription, and another 115 applications for products intended for use in feed converted from OTC to Veterinary Feed Directive. This is a major accomplishment. It represents a milestone in our efforts to promote judicious use of antibiotics in animal health. We will take additional steps in 2018 to build on these successes, and improve stewardship over medically important antibiotics.

A look ahead to 2018

When I look back at my eight months as Commissioner, since coming aboard at FDA in May, I’m humbled by the many accomplishments of the agency’s dedicated professional staff.

We’ve achieved a great deal in 2017. We’re committed to making even more progress this year. 2018 holds promise in even more areas where the agency will take steps to advance beneficial innovation by adopting new measures to make sure our processes are efficient, human and animal products are safe, and practical solutions are implemented that protect and promote the public health. The launch of our Unified Agenda highlights some of our priorities. These include advancing biosimilar policies, modernizing how we advance over-the-counter products, and better informing women about health issues and risk factors.

Nobody innovates in a silo. Advancements in medicine, biotechnology, food science, and the whole of public health are possible only because of the collaboration of the public health community. FDA is in a unique position to bring together stakeholders from across the sector — patients, industry, academics, providers, other government agencies — to ensure innovation translates into successful outcomes that protect and benefit the public. That’s what drives us at FDA. It’s what we’ll pursue in the year ahead.

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

Follow Commissioner Gottlieb on Twitter @SGottliebFDA

FDA Takes Important Steps to Stem the Tide of Opioid Misuse and Abuse

By Scott Gottlieb, M.D.

 America is awash in immediate-release (IR) opioids. About 90 percent of all opioid pain medications prescribed – or 160 million prescriptions a year – are for IR formulations like hydrocodone and acetaminophen or oxycodone and acetaminophen combinations. Many people who are currently addicted to opioids became medically addicted. Their first exposure to opioids was from a legal prescription, and for many, that prescription was written for an IR formulation of these drugs. Many addicted patients may then move on to higher dose formulations or more accessible illegal street drugs.

At FDA, we believe it’s necessary to continue to take steps to address both ends of this continuum, the potential gateway to addiction that is often the IR formulations, and the higher dose, extended-release formulations, both of which carry a significant risk of overdose and mortality. We are taking several actions to address these challenges. This week, we issued letters notifying 74 manufacturers of IR opioid analgesics intended for use in the outpatient setting that their drugs will now be subject to a more stringent set of requirements under a Risk Evaluation and Mitigation Strategy (REMS). The REMS requires that training be made available to health care providers who prescribe IR opioids, including training on safe prescribing practices and consideration of non-opioid alternatives.

Dr. Scott GottliebFDA also will soon issue a final guidance document that will assist potential applicants who plan to develop, and submit to FDA, an application to seek approval of a generic version of abuse-deterrent formulations (ADFs) of opioid drugs. Most of the currently approved opioids with labeling describing abuse-deterrent properties are extended release/long-acting (ER/LA) formulations of opioids. These drugs are generally formulated to be more resistant to the sort of manipulation that would otherwise make them amenable to snorting and/or injecting. Addicted patients who start by using the IR drugs will sometimes migrate onto the ER/LA formulations, and then try to manipulate those higher-dose formulations in ways that can provide a more immediate “high” through injection or snorting. But there are currently only brand name ADF formulations. These steps that FDA is taking are aimed at addressing each end of the spectrum of abuse and addiction.

With respect to the new REMS measures to address the safer use of the IR opioid pain medications, these short-acting drugs will now be subject to the same regulatory requirements as the ER/LA opioid analgesic formulations. Since 2012, manufacturers of ER/LA opioid analgesics have been subject to a REMS, which requires, as its primary component, that training be made available to prescribers of those products. To meet this requirement, the sponsors of the ER/LA opioid analgesics have been providing unrestricted grants to accredited continuing education providers for the development of education courses for health care professionals based on content outlined by FDA, which the agency calls the “Blueprint.” FDA is now extending these REMS requirements to the IR manufacturers.

While some of the ER/LA manufacturers also make IR opioids, today’s action will greatly expand the number of products covered by the REMS. The existing REMS currently includes 64 ER/LA opioid analgesic products. Once the action is finalized, an additional 277 IR opioid analgesics will be subject to these REMS requirements.

In addition to expanding the REMS to include IR products, FDA is modifying the content of the educational “Blueprint” required under the REMS. The agency is adding content on pain management, including non-opioid alternatives. This includes principles related to the acute and chronic pain management; non-pharmacologic treatments for pain; and pharmacologic treatments for pain (both non-opioid analgesic and opioid analgesic). The revised Blueprint will also cover information about the safe use of opioids, and basic information about addiction medicine and opioid use disorders.

For the first time, this training will also be made available to other health care professionals who are involved in the management of patients with pain, including nurses and pharmacists, which is in addition to prescribers of opioid analgesics. FDA believes that all health care professionals involved in the management of patients with pain should be educated about the safe use of opioids so that when they write or dispense a prescription for an opioid analgesic, or monitor patients receiving an opioid analgesic, they can help ensure that the product is properly indicated for the patient and used under appropriate clinical care.

FDA’s new Opioid Policy Steering Committee is also considering whether there are circumstances when FDA should require some form of mandatory education for health care professionals, and how the agency would pursue such a goal. The agency’s purpose is to reduce overall exposure to opioids by making certain that prescribing doctors are properly informed about appropriate prescribing recommendations, that providers understand how to identify the risk of abuse in individual patients, and know how to get addicted patients into treatment. In fact, today, the agency issued a public notice to solicit input on a detailed series of questions related to these goals. FDA has also been scheduling meetings with provider organizations and sponsors engaged in dispensing drugs – including health systems and pharmacy chains, in an effort to solicit additional input on new strategies.

Sending out the manufacturer notification letters is the first step in extending the REMS to the IR drugs. This process could take about a year to finalize. The modified REMS will continue to include a requirement for patient Medication Guides, patient-counseling documents, and plans for assessing the effectiveness of the revised REMS. The crisis of opioid addiction is a public health tragedy of enormous proportions. By putting in place safety measures for IR opioid analgesics, and creating a more robust path to converting the high dose opioids to formulations that are more resistant to manipulation, we are addressing both ends of this crisis. Our hope is that we can help prevent new patients from becoming addicted, and keep some individuals from experiencing the serious adverse effects associated with these medications.

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

Follow Commissioner Gottlieb on Twitter @SGottliebFDA

Working Together to Reduce the Devastating Effects of Opioid Misuse

By Robert M. Califf, M.D.

The public health crisis of opioid misuse, addiction and overdose is one of the most challenging issues the U.S. Food and Drug Administration has faced during my time as FDA commissioner.  Solving this issue is critical to our future.

The issues cut across every socioeconomic level and geographic boundary. It would be difficult to identify any community in America that has not been touched by friends, family members or colleagues suffering from addiction, and far too often, losing their lives to it. As I leave the agency as part of the presidential transition, I have reflected on what I have seen, how far the nation has come, and the important work that remains for both the public and private sectors.

Robert CaliffI’ve made it a point to see affected communities, first-hand, because interventions and national policy solutions work best when they are well informed by what communities actually need. Just last week, I visited Baltimore to better understand how our cities are being affected – in this case, by an inflow of illicit fentanyl, a synthetic opioid that is about 100 times more potent than many other prescription opioids, and can be deadly on its first use. I have also visited the neonatal intensive care unit, or “NICU” of a Tennessee hospital where babies were screaming and shaking in the pain of withdrawal because they were born with Neonatal Opioid Withdrawal Syndrome. I have met people in West Virginia who did back-breaking work in power plants or in coal mines; after suffering on-the-job injuries they were first afflicted with pain, then by addiction. They got prescription pain relief but, too often, it wasn’t accompanied by the proper support and counseling. In Kentucky, I spoke to spouses and families whose lives have been forever changed by addiction, even as the community rallied together to fight it. And, much closer to home, I have heard personal stories from FDA employees and providers in local health care facilities, whose families and friends are not immune.

We have taken a number of actions at the FDA over the past several years to help reduce the number of people who become addicted, or who ultimately overdose from prescription opioids. We’ve improved product labeling, pushed for prescriber education, and encouraged the development of abuse-deterrent formulations. In addition, we have approved new intranasal and auto-injector forms of naloxone — products to reverse opioid overdoses, which can be administered by laypersons and are, therefore, better available able to save lives.

I’m also proud of the partnerships we have formed with other federal Agencies and the work that has resulted from them. But the latest data, including data from the Centers for Disease Control and Prevention (CDC) remind us that while some progress is being made, there is more to do. For example, it is promising to see that the nationally estimated number of outpatient prescriptions dispensed for Schedule II opioids decreased by 10 percent in 2015 compared to the previous year, according to IMS Health. However, the CDC reports that while the rate of overdose deaths associated with prescription opioid use increased by just 4 percent instead of by 9 percent the previous year, deaths associated with heroin use have skyrocketed. Clearly, more work needs to be done.

As I prepare to turn over the awesome responsibility of FDA commissioner to the next Administration, I feel compelled to point out that public and private sector efforts in this area must be continued and strengthened. In particular, I want to call on the pharmaceutical companies that manufacture and sell these drugs to dig deeper into their expertise and resources to prioritize finding solutions to this public health problem. I have consistently been impressed that the motivation to cure disease and improve quality of life for patients is shared across the spectrum of federal agencies, public health workers, health care providers and scientists within the pharmaceutical industry. However, the financial incentives in the industry can lead to a focus on short-term profits instead of patient well-being.This is the time for both branded and generic drug companies  to go beyond marketing and distribution plans and instead commit their expertise and resources to  confronting  the devastating negative consequences of a class of drugs that brings much needed pain relief, when used appropriately.

Specifically, I urge us all to focus on the following priorities:

  1. Encouraging appropriate prescribing by healthcare practitioners. Too many people become addicted from unnecessary prescriptions for minor pain or injury. And even appropriately prescribed opioids can lead to addiction, so careful monitoring of patients prescribed these powerful drugs is needed. While there are situations where opioids are appropriate, there are also situations where other alternatives can be effective. Therefore, conversations between provider and patient about the pain treatment plan are imperative. If an opioid is appropriate, CDC guidelines and FDA labeling emphasize the need to start on the lowest dose and minimum time necessary, and carefully monitoring patients for signs of addiction and inadequate pain control.
  1. Considering the family as well as the patient. Pain treatment, and use of opioid drugs, will be more successful when the family is involved. It will result in fewer drugs diverted from the medicine chest, fewer babies born addicted to opioids and better treatment of pain. Women who use or abuse opioids, or who are in treatment for opioid addiction, should talk to their health care provider before considering pregnancy.
  1. Finding better ways to treat pain with new medications and with more holistic pain management. It’s time to put more resources into the development of non-opioid, non-addictive medications to help people who are in serious, debilitating pain. We need more research to define the most effective non-medication approaches to pain and how to deliver them in a complex and financially constrained healthcare system.
  1. Improving how companies, professional societies and academics communicate about their activities in this area. I urge companies to commit to transparent and appropriate company communications and to work with government and others in the community to do a better job in educating the medical professionals responsible for treating our nation’s pain, as part of the overarching effort to do everything possible to help prevent addiction. Professional societies and academic medical centers also need to continue their efforts at educating their members and examining their practices to find ways to improve. For example, the education of the next generation of physicians about how best to manage pain is critical.
  1. Finding new ways to curb diversion and misuse of opioids. In addition to our continuing efforts to help support the development of abuse-deterrent formulations, the FDA is exploring potential packaging, storage, delivery, and disposal solutions that companies and other stakeholders might consider that would prevent opioids from being diverted to those without a legitimate prescription for these powerful drugs. I implore companies to conduct research and offer their creative ideas and resources to innovate in this area.
  1. Increasing pragmatic research to better understand how to implement appropriate pain therapy in general and use of opioids in particular. Post-market requirements from FDA that mandate industry-funded studies and recent pragmatic research efforts by the Patient-Centered Outcomes Research Institute and the NIH and Department of Defense are expected to provide important data, but we need more robust evidence to better guide practice. Pain is a vexing issue that seems to fall between the cracks in research funding; we need to keep the pressure on funding entities to move pain to the forefront as a research issue.
  1. Treating addiction as a disease, not as criminal behavior. We have the tools to treat addiction and reverse overdose from opioids and are working to develop more of them. But there’s a lot we don’t know about the drivers for drug abuse, and scientific knowledge will help us make better decisions. This is one reason why we need companies with products on the market to monitor the safety of those drugs and make their data public. We have mandated post-market studies to define major questions about chronic use of opioids, and it is essential that industry fulfills these requirements.

I am proud to have been part of the effort that’s changing the tide on this epidemic, but the nation has a long way to go.Government, companies, healthcare systems and healthcare providers all have important roles to play. The most recent data reminds us it’s time to double down on these efforts. While I won’t have the good fortune of leading this fight in an official capacity, I’m proud of the work the FDA and others have done so far. I leave FDA’s efforts to the many leaders at the agency who have been working tirelessly on this issue — and will continue doing so — and look forward to supporting public and private efforts to bring this epidemic to an end.

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

FDA’s Opioids Action Plan: A Midyear Checkup

By: Robert M. Califf, M.D.

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

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

Robert Califf

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

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

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

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

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

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

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

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

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

Our milestones so far include:

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

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

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

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

 

National Drug Take Back Day: A Great Time to Dispose of Prescription Medications Cluttering Your Cabinets

By: Douglas C. Throckmorton, M.D

On Wednesday, April 27, FDA staff can bring in their unwanted, unused, or expired prescription drugs to the FDA campus for safe disposal as part of the Drug Enforcement Administration’s (DEA) National Prescription Drug Take Back Initiative. In past years, we’ve collected more than 200 pounds of unused medications that would have otherwise lingered in medicine chests and kitchen cabinets. FDA’s event is in advance of National Drug Take Back Day, marked on April 30.

Douglas C. Throckmorton, M.D.Medicines no longer being used may pose grave and unnecessary dangers to families and the people visiting their homes. For example, in the last two decades, FDA has received more than 30 reports of accidental exposure to the powerful pain medication in fentanyl patches – most of them in children under two years old. Tragically, 12 of these incidents required hospitalization and another 12 were deadly. Drug Take Back programs are the preferred method for fentanyl patch disposal and frequent drug take back programs run by local communities are a big step toward preventing unnecessary deaths due to accidental medication exposure.

Another important effect of National Take Back Day is that it helps to divert medicines from entering the environment. We share the public’s concerns regarding the potential environmental impact of disposing unused medicines in household trash, or by flushing. We are working with other agencies, including the U.S. Environmental Protection Agency (EPA), to better understand the human health and ecological risks from medicines in our water and have a shared overall goal of reducing medicine levels in our water.

FDA has strongly supported work to expand the availability of take back programs for several years. We will continue to work with manufacturers to develop new formulations with reduced risk for accidental harm and with our federal partners to develop alternative, safe disposal systems. We look forward to a time when effective disposal alternatives are more widely available.

The importance is underscored when you think about the epidemic this country is facing with opioid medications. Many people who misuse medications, such as opioids, get their first dose by using medications prescribed to other people. FDA is deeply concerned about the growing epidemic of abuse, misuse, dependence, and overdose of opioids in the United States. In response to this crisis, FDA has developed a comprehensive action plan to take concrete steps toward reducing the impact of opioid abuse on American families and communities.

So if your prescription medications have expired or you are no longer taking them, Drug Take Back Day is a way to make sure they are disposed of properly. April 30 marks the eleventh nationwide opportunity since 2010 for Americans across the country to do what we’re doing at FDA this week and get rid of all unused drugs in the home. It’s simple and easy. Gather them up and take them to a disposal site near you. The service is available from 10 a.m. to 2 p.m. It’s free and anonymous, no questions asked. Past drug take-back days have been highly successful. Cumulatively, previous events have collected well over 5 million pounds of unwanted, unused, or expired drugs.

Safe disposal of medicine is a year-round activity. FDA’s Disposal of Unused Medicine site offers valuable “do-it-yourself” safety information when there isn’t a take back site available.

Together, we can make difference.

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

Changing course: A new approach to opioid pain medication at FDA

By: Robert M. Califf, M.D.

As a doctor, I have a first-hand understanding of the important and legitimate need for powerful medication to help people deal with chronic or severe pain. If you have had a family member or loved one touched by a serious illness or injury, you understand it too. You know how tough it can be to see them try to endure pain that can’t be touched by anything you can get over the counter.

Robert M. Califf, M.D., MACC, FDA's Commissioner of Food and Drugs

But as all of you know, more Americans now die every year from drug overdoses than they do in motor vehicle crashes. Opioids were involved in 28,648 deaths in 2014, according to the CDC.

The FDA is deeply concerned about this growing epidemic, and I am personally disturbed by the toll it has taken in communities across the country. It’s an issue I’ve been involved with for years as an academic, having overseen the NIH’s National Institute on Drug Abuse Clinical Trial Network, which was involved in some of the early medication assisted treatment studies.

After seeing the dependence and mortality numbers continue to rise and hearing from voices who care about this issue, I asked our folks to take a hard look at whether we’re doing everything we can to ensure that we’re appropriately taking into account the public health crisis that confronts us in the context of the role we play in ensuring the safety and efficacy of drugs.

The conclusion of that comprehensive assessment was that we can do more.

So we are announcing a change in course in how our agency approaches opioids – their approval, their labeling and their prescribing. We are going to fundamentally re-examine the risk-benefit paradigm for opioids and ensure that we consider their wider public health effects.

To that end, we have developed a comprehensive action plan to take concrete steps toward reducing the impact of opioid abuse on American families and communities.

There are four main pillars to the plan.

First, we’re going to be more transparent and open in the approval process for this category of drugs. Starting today, the FDA will convene an expert advisory committee before approving any new drug application for an opioid that is not in an abuse-deterrent formulation (ADF).

Additionally, we’re going to engage the Pediatric Advisory Committee to make recommendations on pediatric opioid labeling before any new labeling is approved.

Importantly, the advisory committee process is going to provide opportunity for public input, which is going to help us better understand and answer the concerns people have about these drugs.

We have also engaged the National Academies of Sciences, Engineering, and Medicine on how to take into account our evolving understanding of the risks of opioids, not only to the patient but also the risks of misuse by other persons who obtain them. The goal is to formally incorporate the broader public health impact of opioid abuse in approval decisions. And in March, we will seek advice from the Agency’s Science Board to reassess the risk-benefit approval framework for opioid use. The results of these efforts will be made public.

Second, we’re going to improve our communication with the medical community about these drugs. That starts with enhancing safety labeling. Our goal is to provide better information to doctors about the risks of these drugs and how to safely prescribe them. We’re developing changes to immediate release opioid labeling that will bring it more in line with the extended-release/long-acting labeling that occurred in 2013.

After reviewing the existing requirements and hearing recommendations from an advisory committee, we’re also going to update our Risk Evaluation and Mitigation Strategy (REMS) program requirements for opioids. We need to increase the number of prescribers who receive training on pain management and improve the safe prescribing of opioids to decrease inappropriate prescribing.

That effort will complement work being done at the Department level and at the CDC to help ensure that opioids are prescribed appropriately. We believe that this is a key component of ending this public health crisis. The more than 250 million prescriptions for these types of pain killers in 2012 – enough for every adult in the U.S. to have a bottle of pills – is clear evidence of the work ahead of us.

Third, we’re going to work to improve the information that’s available about opioid use. We’re going to require drugmakers to strengthen post-market analysis of these drugs. Today, that information, especially about long-term use, is lacking. We need more and better evidence on the risks of misuse and abuse associated with long-term opioid use and to better understand predictors of addiction, among other issues.

Finally, we’re going to focus efforts on approving drugs that have the potential to help mitigate the crisis. That means spurring the development of promising generics with abuse deterrent formulations. The FDA will issue draft guidance with its recommendations for the approval standards for generic abuse-deterrent formulations. We believe the availability of less costly generic products should accelerate prescribers’ update of abuse deterrent formulations.

And we’re going to work to improve access to naloxone, which is effective at treating overdoses. The FDA is reviewing options, including over-the-counter availability, to make naloxone more accessible. That work builds on FDA’s recent approval of intranasal naloxone.

What I’ve just described is a change in course – a framework for how FDA can better do its part to confront the opioids epidemic. In the coming weeks and months, we’re going to further develop these plans and continue to fill in the details for each initiative I’ve described.

But it’s time for us to act – to take the first steps toward changing how we do business and addressing this problem.

Robert M. Califf, M.D., previously FDA’s Deputy Commissioner for Medical Products and Tobacco, became FDA’s Commissioner of Food and Drugs on Feb. 25, 2016

FDA 2015: A Look Back (and Ahead) – Part 2: Medical Product Safety and Oversight

By: Stephen M. Ostroff, M.D.

In my first look back on FDA’s 2015 accomplishments, I focused on our achievements in medical product innovation and our constant drive to make safe, effective and innovative products available. Because FDA’s responsibility covers the entire life cycle of products, in this second year-end blog post, I will review FDA’s impact on medical product safety and oversight.

Acting FDA Commissioner, Stephen Ostroff, M.D.Responding to Ebola

In a world where disease knows no borders FDA’s response to the Ebola epidemic in West Africa demonstrates how we use our scientific expertise and regulatory authorities to the fullest extent possible to address a tragic public health crisis of global impact. Our response involved collaborating with partners across government, pharmaceutical and diagnostic companies, international organizations like the World Health Organization, and our international regulatory counterparts. We played a key role in expediting the availability of diagnostic tests and investigational therapeutics and vaccines, as well as investigating fraudulent products marketed to diagnose, prevent and treat Ebola. And many FDA commissioned corps officers of the U.S. Public Health Service served on the front lines, deployed in a humanitarian mission to provide care to patients at the Monrovia Medical Unit in Liberia, one of the West African nations that were hard hit by the outbreak.

Addressing Transmission of Infections from Duodenoscopes

This year we took steps to help protect the public from the risk of transmitted infections, including antibiotic-resistant infections, from duodenoscopes. Duodenoscopes are complex devices used during endoscopic retrograde cholangiopancreatography (ERCP), a potentially life-saving procedure to diagnose and treat blockages in the pancreas and bile ducts. In the United States, duodenoscopes are used in more than 500,000 ERCP procedures each year.

Last February, the FDA issued a safety communication to raise awareness about the risk of transmitted infections from duodenoscopes, after it determined that the design of these devices may impede effective reprocessing, even when the manufacturer’s reprocessing instructions are followed correctly. Reports also indicated that some healthcare facilities may not have adequately followed the manufacturer’s reprocessing instructions. To address these concerns, the FDA has been working with the device manufacturers to ensure that the reprocessing instructions for their duodenoscopes are put through the most rigorous testing. The Agency held a public advisory committee meeting in May to discuss the scientific challenges, and it incorporated recommendations for enhancing the safety margin of reprocessing duodenoscopes into a safety communication in August. Also in August, FDA issued Warning Letters to all three duodenoscope manufacturers citing violations found during recent inspections. In October, the FDA ordered the manufacturers to develop postmarket surveillance studies of how the devices are reprocessed in real-world clinical settings.

Our foremost concern is protecting patients, and we are committed to taking steps to assure that duodenoscopes – and all reprocessed medical devices — are safe to use.

Compounding

We continue to respond effectively to the 2012 outbreak of fungal meningitis linked to contaminated compounded drugs. We are implementing the Drug Quality and Security Act and continuing our inspection and enforcement efforts at compounding facilities nationwide. To that end we have issued numerous policy documents regarding compounding and related activities to provide guidance to industry as we implement the new law. We’ve also held meetings with stakeholders, including pharmacy, physician, and consumer groups, and we have continued our active and successful collaborations with state governments.

Addressing the Opioid Abuse Crisis

Over the last year, we’ve been very focused on the growing epidemic of opioid abuse and addiction and its devastating impact on public health. This focus has required us to strike a delicate balance: ensuring medical treatments are available for patients who are in pain, while addressing the often tragic consequences of abuse and misuse, which all too often overwhelm individuals, families, friends and communities. Our approach is multi-pronged, from encouraging scientific investigation to improving the training of practitioners who prescribe these powerful medicines.

We believe it is vitally important to encourage the development of abuse-deterrent formulations of opioids and to support options for medication-assisted treatment of opioid-dependence. Final guidance for industry regarding the development of abuse-deterrent formulations was issued in April and several abuse-deterrent products have been approved. We are also making strides to treat the consequences of overdoses. In November, FDA approved the first nasal spray version of naloxone hydrochloride, to provide a route of delivery in addition to injection for this life-saving medication that can stop or reverse an opioid overdose. And we are working with our federal partners to improve access to naloxone.

While we cannot solve this complex problem alone, we remain committed to making the best use of our regulatory authorities and working with our partners both in and outside government to reduce the risks associated with opioids. To continue to achieve that, we have been engaging in a comprehensive review of our many current activities related to opioids and identifying which measures can and should be strengthened and what further measures are needed to address this crisis during 2016.

Ensuring the safety of the medical products we regulate requires us to manage a wide-range of issues across multiple scientific disciplines; and to employ scientists with the knowledge to solve today’s complex regulatory challenges. The last year brought many challenges, and just as many solutions.

In my final post, I will address some of our accomplishments in the area of food, tobacco product regulation, and antimicrobial resistance.

Stephen M. Ostroff, M.D., is Acting Commissioner of Food and Drugs

A Year of Significant Progress in Public Health

By: Margaret A. Hamburg, M.D.

Margaret Hamburg, M.D.A new year offers both an opportunity to look forward and an opportunity to reflect on the achievements of the previous year. And, in 2014, FDA’s accomplishments were substantial, touching on many of the agency’s broad responsibilities to protect and promote the public health.

Whether our achievements involved medical product safety and innovation, food safety and nutrition, tobacco control, or other areas of our important work, all were accomplished thanks in large part to our ability to respond to evolving needs and opportunities including the embrace of new approvals, technologies and cutting-edge science.

Consider these highlights:

Drug Approvals: This past calendar year, FDA approved 51 novel drugs and biologics (41 by CDER and 10 by CBER), the most in almost 20 years. Among CDER’s 2014 approvals are treatments for cancer, hepatitis C and type-2 diabetes, as well as the most new drugs for “orphan” diseases since Congress enacted the Orphan Drug Act over 30 years ago. Seventeen of these new approvals are “first in class” therapies, which represent new approaches in the treatment of disease. In addition, CBER approved many important biological products in 2014, including a number of groundbreaking vaccines for meningitis B, the flu, and certain types of Human Papillomavirus, the latter of which is expected to prevent approximately 90 percent of the cervical, vulvar, vaginal and anal cancers caused by HPV.

These developments are a testament not just to our expanding understanding of human biology, the biology of disease and the molecular mechanisms that drive the disease process, but also to FDA’s innovative approaches to help expedite development and review of medical products that target unmet medical needs, while adhering to the established standards for safety and efficacy. These include enhanced guidance to shape the research and development agenda, early input on clinical study needs and design, expedited review programs, targeted regulatory advice and other tools and incentives that spur investment and innovation in new medical products to address unmet medical needs.

Opioids: This past year FDA took several actions to address the abuse of opioid drugs. First, we approved abuse deterrent labeling for three opioid products that are designed to deter prescription drug abuse. These drugs used different technologies to combat the abuse problem in different ways, such as by making the product resistant to crushing or dissolving or using “aversive technology” to discourage users from taking more than the approved dosage of the drug. To help encourage the development of more drugs in abuse-deterrent forms, we are also working to provide additional advice to manufacturers. Although abuse-deterrent opioid drugs are not a silver bullet to prevent opioid abuse, we believe that our work in this area will give physicians effective new treatment options with less risk of abuse.

FDA also worked to improve the treatment of patients who overdose on opioids. We approved a new dosage form of naloxone, with an autoinjector to enable a caregiver to administer the drug in the emergency treatment of opioid overdose (as it rapidly reverses the effects of an overdose). While we continue to support development in this area, this approval offers a new valuable tool to help prevent the tragedy of opioid drug overdose.

Antibiotic Resistance: We made important strides in confronting the growing resistance of some bacteria to antimicrobial drugs. Our efforts, which are a critical part of the recently unveiled National Strategy on Combating Antibiotic Resistant Bacteria, offer a multi-pronged approach that recognizes that to effectively address this challenge means simultaneously addressing the many different causes for increasing antibiotic resistance. One important response has been efforts to expand the pipeline of new medical products, including therapeutics to treat and cure infection, diagnostics to aid in the identification of the cause of infection and of resistant infections, and vaccines to help prevent infection with bacteria in the first place.

These efforts are already having an impact. In 2014, FDA approved four novel systemic antibiotics. In contrast, only five new antibiotics had been approved in the previous ten year period.

In addition to working on the human medical product side, we also developed and, over the next two years will be implementing, an important complementary strategy to eliminate the use of medically important antibiotics for growth promotion in food-producing animals. This strategy, once fully implemented, also will bring the remaining uses of such drugs to treat, control or prevent disease in these animals under the oversight of veterinarians. All 26 animal health companies who produce those drugs have committed to participate, and 31 products already have been withdrawn from the market.

Pharmacy Compounding: We continued to respond effectively to the 2012 outbreak of fungal meningitis that was linked to contaminated compounded drugs. This included conducting more than 90 inspections of compounding facilities across the nation in the past year. As a result, numerous firms that engaged in poor sterile practices stopped making sterile drugs, and many firms recalled drugs that have been made under substandard conditions. Where appropriate, we have worked with the Department of Justice to pursue enforcement action against some of these facilities.

We also have continued to implement the compounding provisions of the Drug Quality and Security Act (DQSA), and to develop and implement policies to address compounding by state-licensed pharmacies and the new category of registered outsourcing facilities.

Food Safety: Over the past year, the Agency has made great strides in implementing the landmark FDA Food Safety Modernization Act (FSMA). Through our proposed rules for preventive controls requirements for both human and animal food, standards for produce safety, foreign supplier verification programs, third party auditor accreditation, focused mitigation strategies to prevent intentional adulteration of food aimed at causing large-scale public health harm, and requirements for sanitary transportation practices to ensure the safe transport of food, we are working to ensure the safety of American consumers related to the foods they eat.

Nutrition: Good health depends not just on food safety, but also on what we choose to eat. FDA plays an important role in promoting good nutrition and healthy food choices by helping consumers understand the importance and benefits of good nutrition – and of being able to make informed choices about what we eat.

New rules in 2014 to finalize requiring calorie information on restaurant menus and vending machines give our citizens information they need to make healthy food choices and hopefully help reduce the epidemic of obesity in the United States. We also proposed changes to the familiar “Nutrition Facts” label on packaged foods which, when finalized, will give our citizens updated nutrition information, reflecting the most current nutrition science, to help them make healthy choices when purchasing packaged foods.

Tobacco Control: There are few areas that have as profound an impact on public health as tobacco products, which is why, five years ago, Congress gave FDA the responsibility to oversee the manufacture, marketing, distribution, and sale of tobacco products.

Over the past year, we worked with state authorities to conduct more than 124,000 inspections of retailers to enforce the ban on the sale of tobacco products to children. We unveiled the first of its kind national public education campaign—The Real Cost—to reduce youth smoking. And we took the first steps towards extending the agency’s tobacco product authority over additional products such as electronic cigarettes (e-cigarettes), cigars, pipe tobacco, nicotine gels, waterpipe (hookah) tobacco, and dissolvables not already subject to such authority through our proposed “Deeming Rule.” In addition, as part of ongoing work on product review decisions, eleven tobacco products that were allowed to enter the market during a provisional period established by the Tobacco Control Act were found “not substantially equivalent” to a predicate tobacco product. As a result of this finding, these products can no longer be sold or distributed in interstate commerce or imported into the United States.

Ebola: The tragic Ebola epidemic in West Africa demonstrates that we do not have the luxury of closing our eyes – or our borders – to the public health problems that exist in the rest of the world. I’m proud that FDA has played an important role in the response to this disease, working closely with colleagues in our government as well as the scientific community, industry and a range of other organizations and nations. We have helped facilitate the development, testing, manufacture, and availability of investigational products for use in diagnosing, treating and preventing Ebola, and worked with sponsors and health care providers to facilitate access to these products as clinical circumstances warrant. In August 2014, FDA designated the drug Z-Mapp as an orphan drug for Ebola, with the hope that this would incentivize further development and study.

And I’m very pleased to report that FDA is represented on the ground in West Africa by dedicated officers of the Commissioned Corps of the Public Health Service who continue to staff and operate the Monrovia Medical Unit in Liberia that was built to treat the health workers who became ill responding to the outbreak. Like everything FDA does, both at home and abroad, our actions on Ebola represent our agency’s continuing commitment to health and safety, and the use of science to advance these important goals.

I am extremely proud of our accomplishments in 2014, and I am confident that FDA will have a successful 2015, as we continue our work to protect and promote the public health.

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

Opioid Auto-Injector Can Help Prevent Overdose Deaths

By: Dr. Douglas C. Throckmorton

The Food and Drug Administration has today made an important advance in helping to save lives when overdoses from drugs known as opioids occur: the approval of a drug that can actually reverse that overdose.

Douglas C. Throckmorton, M.D.Opioids include legal prescription drugs, such as OxyContin (oxycodone) and Vicodin (hydrocodone with acetaminophen), used to treat pain, as well as illegal street drugs, such as heroin. In 2010, overdoses of prescription opioids were linked to 16,651 deaths and heroin was linked to 3,036 deaths in the United States.

Whether opioids are used by patients as prescribed by their health care professional or are misused or abused, these drugs have one important thing in common: They can all cause rapid and fatal overdose.

FDA, along with other organizations, has been working diligently on ways to address this major public health issue. That’s why FDA has approved a drug-device combination product that delivers the medication known as naloxone, which is the standard treatment for a drug overdose. This product is potentially easier to use than existing technology and thus could save lives.

Overcoming an Obstacle

Naloxone reverses the effects of opioids. Most significantly, it reverses the severely slowed breathing that can lead to death during an overdose. When naloxone works, the results can be dramatic: Comatose patients can wake up in minutes.

Over the years, emergency health care professionals and others with special training have saved thousands of lives by giving injections of naloxone to people suffering from opioid overdoses. Although effective, this requires expertise – to be able to draw the naloxone up from a vial and then inject it with a needle and syringe. In some cases, the injectable form is adapted so it can be administered through the nose, but there is currently no intranasal form of naloxone approved by FDA.

FDA has now approved  the first naloxone product that is given using an auto-injector, without having to use a separate needle and syringe.  Available via prescription, the product enables anyone – even the general public – to inject naloxone from a pre-filled, single-use device into a person who is overdosing. This is similar to devices used by laypeople to administer epinephrine in cases of severe allergy. In addition, the auto-injector gives recorded instructions to the user describing how to deliver the medication. The instructions also reinforce the need to seek emergency medical attention immediately because while naloxone works rapidly, it only temporarily reverses the effects of opioid overdose. The patient still needs immediate medical care.

The product’s brand name is Evzio, and information on its safe use is available by clicking this hyperlink.

This approval is the culmination of concerted efforts at FDA and throughout the Department of Health and Human Services (HHS) to spur research into alternative forms of naloxone and to expand its availability. On April 12, 2012, FDA co-sponsored a meeting that highlighted the impact of community-based naloxone distribution programs and explained to sponsors the path to FDA approval.

FDA Working on Other Fronts to Combat Opioid Misuse and Abuse

FDA has a responsibility to demand the best science and data to uphold its high standards to ensure a proper benefit/risk profile for drugs that treat pain. We also foster discussion and research that leads to a better understanding of pain and pain drugs. Because we are concerned about the public health issue, the agency has taken a number of actions to help reduce the devastating consequences of opioid misuse, abuse, and fatal overdoses. We are targeting key drivers of the problem with efforts that include:

  • Changing the labeling of certain opioids to help improve their safe use.
  • Requiring that manufacturers conduct studies of the safety of long-term use of certain prescription opioids.
  • Requiring that manufacturers  of certain opioids make training available to practitioners (physicians, dentists and others authorized to prescribe opioids) on responsible prescribing practices and assessing and addressing signs of abuse and/or dependence.
  • Strengthening our surveillance efforts to actively monitor the changing nature of prescription opioid abuse and identify emerging issues.
  • Working with the Drug Enforcement Administration on opioid controls.
  • Encouraging the development of new forms of opioids that are resistant to abuse.
  • Supporting the development of new pain treatments, especially non-addictive treatments.

While FDA plays an important role in mitigating the risks of addiction, abuse and misuse of prescription opioids, we cannot fix the problem alone. A comprehensive approach must be taken by federal and state governments, public health officials, opioid prescribers, addiction experts, researchers, industry, patient organizations, and others. That is why FDA is working closely with our HHS counterparts, including CDC, NIDA, SAMHSA, and throughout the US government.

There’s much work to be done, but today’s approval of the opioid auto-injector could save thousands of lives. FDA will continue to work to prevent the consequences of misuse and abuse of opioids, including preventing fatal overdoses.

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