Statement by FDA Commissioner on Agency's Work to Address Opioid Crisis

Over the past 17 months, we've set out to address the opioid crisis forcefully, using all the agency's tools and authorities. These steps have been part of a comprehensive approach that the Secretary of Health and Human Services has outlined. Our efforts at the U.S. Food and Drug Administration are part of these broader efforts and cut across three broad areas.

First, we set out to cut the rate of new addiction. We did this in part by taking new steps to rationalize the prescribing of opioids, and amounts dispensed, as a way to reduce exposure to the drugs in the medical setting.

Second, we've stepped up enforcement of the marketing and sale of illicit opioids. One way that we're doing this is by targeting online sites that enable the illegal sale of these drugs and their shipment through the mail.

Finally, we've undertaken new efforts to support novel product innovation. This includes innovation in treatments for opioid addiction, and efforts to promote their more widespread use. And it also includes steps to advance the development of non-addictive treatments for pain. We have great concern for the millions of Americans who live with chronic pain and for whom traditional treatment options have been exhausted.

I want to take this opportunity to provide an update on some of the work we are doing across each of these three areas and some of the new efforts we're going to pursue.

To pursue these goals, and many other commitments, in the last 17 months, we've taken a range of new steps.

We set out to extend our risk evaluation and mitigation strategy program to cover the immediate release formulations of opioid drugs, and we've updated our educational content for providers to include information on non-opioid alternatives. We also, for the first time, extended this training to non-physician prescribers.

And we've advanced a broad effort to develop evidence-based guidelines for opioid prescribing. We want to make sure that when opioids are used, the amount dispensed comports with the clinical reasons why these drugs are being used in the first place. No more 30-day prescriptions for a tooth extraction or an appendectomy.

We've also taken steps to protect children from unnecessary exposure to certain opioids in some common prescription cough and cold medicines.

We committed to look closely at the risks associated with the illicit use of these drugs as a factor in how we evaluate their pre- and post-market safety. We requested the market withdrawal of one drug – Opana ER – based on a consideration of risks that were manifest only when this drug was being misused and abused. We'll soon release new guidance outlining how we make these considerations of risks associated with illicit use a clear factor in our pre- and post-market regulatory decisions.

We also took enforcement actions, including work in collaboration with the Federal Trade Commission targeting the proliferation of products on websites that marketed unapproved treatments for pain and addiction. With additional actions that we took yesterday, we've brought to 70 the number of web sites that we've targeted this summer for marketing unapproved opioid drugs. More enforcement actions are on the way. We also formed a broad collaboration with legitimate internet sites – including leading social media platforms – to target the sale of opioids in ways that are visible to the public, and in some ways that are not apparent.

We sharply expanded our oversight of drugs being shipped illegally through international mail facilities, growing by nearly a factor of 10 the number of packages that the FDA is able to open and inspect. We have also increased our special agents doing criminal work at the ports of entry as well as cybercrime, strategic intelligence and strategic analysis units – all of whom are critical to effective enforcement. And we launched major operations with other federal partners to target these shipments and get an accurate estimate of how many opioids are coming in illegally through the mail. We'll soon announce the findings from this operation.

We expanded new pathways for the development of safe and effective treatments for addiction, lowering the barriers to innovation for treatments that meet our gold standard. New guidance we issued will expand the range of clinical endpoints that treatments for addiction can pursue, creating more opportunities for more efficient product development. And we undertook a broad campaign to promote Medication-Assisted Treatment (MAT), and address the inappropriate stigma that's sometimes associated with replacement therapy.

We developed new regulatory guidance to promote abuse-deterrent formulations of opioid drugs, including a new path for the development of generic versions of drugs with these features. And we've launched an effort to evaluate whether the nomenclature that we use to describe these drugs inappropriately promotes a view that these formulations are somehow less addictive.

We launched an innovation challenge to spur the development of medical devices and mobile applications that can ultimately serve as alternatives to oral opioids to help combat the opioid crisis and prevent and treat opioid addiction. We also held two public meetings this year focused entirely on patients – one for Opioid Use Disorder and one for Chronic Pain. And we did many of these things under the direction of a new Opioid Policy Steering Committee that I formed when I arrived at the FDA that brings together senior leaders from our programs. That Steering Committee has helped generate and oversee some of the new ideas that drive our strategy.

We appreciate the support that Congress has given us in the pursuit of these goals, with new resources as well as the new authorities that have passed the House and that the Senate is now considering that will help us in this fight. Along the way, as we've embraced these challenges, we've learned some hard lessons. I've learned some hard lessons. And one sticks with me above others. It's this.

The reason that we find ourselves with a crisis of such proportion is that as a medical profession, we've been one step behind its sinister advance. Collectively, we didn't take all the steps we could, when we could, to stop the advance of this crisis. We shunned hard decisions. As a profession, providers were too liberal in our use of these drugs well past the point where there were signs of trouble, and the beginning of a crisis of addiction.

I'm committed to making sure that we don't perpetuate these mistakes of the past. And so, when we see this crisis taking new twists and turns, we've acted swiftly. For example, we've taken steps to address what we believe may be abuse of substances that contribute to the opioid crisis, like gabapentinoids and loperamide or kratom. And we're increasing our vigilance around the risk of addiction, and acting more quickly to warn the public when we identify harmful trends and emerging risks.

I don't want to look back ten years from now and wish there were more policies we had pursued, or more steps we had taken, to stop the advance of this crisis. We must all be able to say we did everything we could. That we acted as aggressively as needed. And that we succeeded.

So at the FDA, we've done all these things, and taken many other actions, with this promise in mind. We're going to be taking many additional steps to continue to pursue these goals. That includes additional steps to foster innovation. Part of our approach is focused on developing non-opioid, and non-addictive alternatives for the treatment of pain. We know that many Americans suffer from chronic and episodic acute pain. For these people, sometimes opioids are the only drugs that work. To address these medical needs, we're taking new steps to foster development of treatments for pain that don't rely on opioids and don't have their addictive features.

First, we intend to withdraw our existing, 2014 analgesic guidance document on developing new pain drugs. That guidance typically called for a large number of studies to get a general chronic pain indication and may have been difficult to implement because it was so broad. Instead, we've determined that a more focused approach would streamline drug development in specific areas.

To that end, we plan to issue at least four new guidance documents in place of this 2014 analgesic guidance document. We'll issue these guidances in a series over the next six to twelve months. These new policies will create a more efficient path for new product innovation.

The new guidance documents will recommend the study of one or two populations for innovators who wish to pursue a more limited indication for the treatment of specific kinds of pain. This will broaden the range of new drug development opportunities that are available. Our new approach should also help more novel products for the treatment of pain come to market more efficiently.

Among the forthcoming guidance documents that we plan to issue is a guidance, which will be out soon, and will address drugs that can spare the use of opioids in the treatment of acute pain. This guidance document will set forth the FDA's current thinking on how sponsors can demonstrate a clinically meaningful reduction in the use of opioid pain medications when used for acute pain.

In addition to this guidance, we also plan to issue a guidance to outline the information that the FDA will ask drug makers to provide to help assess the benefits and risks when new opioid pain drugs are put into development. This will include an updated framework for evaluating the risks associated with intentional or illicit misuse or abuse of drugs. As I noted, we're explicitly considering the risks associated with illicit use as a factor in how we assess risks and benefits.

In a third guidance, we'll outline a path for developing extended-release local anesthetics, which can serve as an alternative to the systemic use of oral opioid drugs. This guidance will address the clinical pharmacology, the proper evaluation of safety and efficacy, and the types of studies that may support approval of these products.

Finally, we also plan to issue a guidance document to assist sponsors with the development of new non-opioid pain medications for chronic pain that can provide therapeutic alternatives to the use of opioids.

These are just some of the new steps we're taking to promote innovation for alternatives to opioid drugs for those who need treatment for acute and chronic pain. And today, I outlined just some of the overall steps we're taking to address the crisis of addiction to opioids. We have many other actions underway. This is an all-of-the-above approach. Everything is on the table.

We needed to broaden our approach as this crisis continues to evolve. The epidemic is turning from one that was largely dominated by addiction formed in the medical setting, involving prescription drugs, to one that increasingly implicates the use of illicit drugs, including highly potent fentanyls. These drugs are obtained illegally, often through purchases made on-line, and in many cases shipped through the international mail.

A recent FDA analysis of commercially available data showed steep drops in dispensing of opioid analgesics in retail outpatient settings. In the first six months of 2018, the volume of opioid analgesics dispensed was 74.1 metric tons of oral morphine equivalent, down more than 16 percent from the first half of 2017, when the volume dispensed was 88.8 metric tons. Earlier declines were there, but smaller. The volumes of opioid analgesics dispensed in the first half of 2017 and 2016 were about 10.4 percent and 3.4 percent less than comparable values 12 months earlier. These trends seem to suggest that the policy efforts that we've taken are working as providers, payers and patients are collectively reducing some of their use of prescription opioid analgesic drugs.

But the public health impact from these reductions in prescription opioid use could be offset by the rising availability of illicit opioids, and principally fentanyl, that's coming into America. The growing use of fentanyl is contributing to a rise in overdose deaths. It isn't necessarily the case that more people are suddenly switching from prescription opioids to these illicit drugs. The idea of people switching to illicit drugs isn't new as an addiction expands, and some people have a harder time maintaining a supply of prescription drugs from doctors. Many heroin users switched from prescription drugs. What's new is that more people are now switching to highly potent drugs that are far deadlier. That's driven largely by the growing availability of the illicit fentanyls.

At the FDA, we're taking steps right now to accurately estimate the flow of these illicit drugs. But our current estimates are largely based on the fentanyl seized by our colleagues and partners at Customs and Border Protection (CBP). Based off of publicly available information, seizures of fentanyl by our CBP colleagues were reported as two pounds in fiscal year 2013, rising to 440 pounds in FY16, and 1,377 pounds in FY17. CBP reported 1,640 pounds seized during the first 10 months of fiscal year 2018. During these same periods, reported heroin seizures also increased, from 4,790 pounds in 2016, to 4,878 pounds in fiscal year 2017 and an estimated 5,472 pounds in fiscal year 2018 if we were to extrapolate seizures through July to the full fiscal year.

If we assume that the seizures effected by our colleagues at CBP represent some fraction of the overall illegal flows that are being smuggled into the U.S. through different routes and despite our best efforts; then we should worry that the public health impact of a decline in prescription opioid use in the medical setting could be offset by the rise in highly potent, illicit opioids like fentanyl. The FDA has garnered a strong partner with CBP in our efforts to combat these trends, whether it be our joint scientific or operational work. Our two teams are collaborating closely on solutions to this problem. We're taking new steps to confront this dangerous turn.

We have additional enforcement operations underway. We're taking new steps to promote innovation in the development of alternative treatments for pain that may not be as addictive as opioids. At the same time, we're advancing new policies to rationalize the legal use of prescription opioid drugs in the medical setting. To address this goal we are also developing an approach on the use of blister packs for opioid drugs as a way to better control prescription dispensing and reduce exposure.

And we're actively considering other new policy options, like novel steps to better manage the use of high-dose opioid formulations. More FDA action is on the way.

I made a commitment 17 months ago, when I first joined the FDA as the agency's Commissioner, that we'd do everything in our scope to address this opioid crisis. I've made this promise a cornerstone of my efforts at the agency, and a foundation of my obligation to Americans.

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