11/2/2018 Press Announcements > Statement from FDA Commissioner Scott Gottlieb, M.D.

M.D., on agency’s approval of Dsuvia and the FDA’s future c…

FDA Statement

Statement from FDA Commissioner Scott

Gottlieb, M.D., on agency’s approval of
Dsuvia and the FDA’s future consideration
of new opioids
For Immediate Release
November 2, 2018

Statement

The crisis of opioid addiction is an issue of great concern for our nation. Addressing it is a public health priority for
the FDA. The agency is taking new steps to more actively confront this crisis, while also paying careful attention to
the needs of patients and physicians managing pain. As part of these considerations, there’s been an important and
robust public debate leading up to the regulatory decision on Dsuvia that merits a response. I want to take this
opportunity to address some of the concerns that were raised, and more broadly, how I believe the FDA should
consider the approval of new opioid pain medications that can help fill targeted medical needs.

Looking beyond this particular drug approval, I believe that we should consider whether we should be doing more to
evaluate each candidate opioid, not just as an independent review decision, but rather also to consider each novel
opioid drug in the context of the overall therapeutic armamentarium that’s available to patients and providers. As we
look at the public health implications of each new approval, we should evaluate whether we need to take additional
steps to systematically consider new opioids relative to the comparative benefit and risks of other opioids already
on the market. We should consider whether we could do more in weighing approvals to ensure that new opioids are
sufficiently better than existing drugs to justify their addition to the market in the context of the current crisis of
abuse.

In this particular case, Dsuvia is a sublingual (under the tongue) formulation of sufentanil that’s delivered through a
disposable, pre-filled, single-dose applicator. The medicine is restricted to use in certified medically-supervised
health care settings ‒ such as hospitals, surgical centers and emergency departments ‒ for administration by a
health care professional. Dsuvia, which was previously approved by the European Medicines Agency in July under
the brand name Dzuveo, has some unique features in that the drug is delivered in a stable form that makes it
ideally suited for certain special circumstances where patients may not be able to swallow oral medication, and
where access to intravenous pain relief is not possible. This includes potential uses on the battlefield. For this
reason, the Department of Defense (DoD) worked closely with the sponsor on the development of this new
medicine. This opioid formulation, along with Dsuvia’s unique delivery device, was a priority medical product for the

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Pentagon because it fills a specific and important, but limited, unmet medical need in treating our nation’s soldiers
on the battlefield. The involvement and needs of the DoD in treating soldiers on the battlefield were discussed by
the advisory committee.

There are very tight restrictions being placed on the distribution and use of this product. We’ve learned much from
the harmful impact that other oral opioid products can have in the context of the opioid crisis. We’ve applied those
hard lessons as part of the steps we’re taking to address safety concerns for Dsuvia, including requiring a Risk
Evaluation and Mitigation Strategy (REMS) to accompany this drug. The REMS reflects the potential risks
associated with this product and will tightly control its distribution and use. Importantly, the distribution system will
restrict Dsuvia’s use to certified medically-supervised health care settings, an important step to help prevent misuse
and abuse of Dsuvia. The FDA will continue to carefully monitor the implementation of the REMS associated with
Dsuvia and compliance with its requirements, and we’ll work to quickly make regulatory adjustments if problems
arise.

But underlying the debate surrounding this approval is a broader issue that must be addressed head on: why do we
need an oral formulation of sufentanil – a more potent form of fentanyl that’s been approved for intravenous and
epidural use in the U.S. since 1984 – on the market?

This question is especially critical in the context of the crisis of opioid addiction and evidence that opioids continue
to be inappropriately prescribed, marketed, diverted and abused. Given this context, we need to address the
question that I believe underlies the criticism raised in advance of this approval: to what extent should we evaluate
each opioid solely on its own merits, and how should we also consider, within the broader context of our public
health mission including the overall therapeutic armamentarium that we have available for addressing pain, the
other opioid analgesics that are already on the market, the epidemic of opioid misuse and abuse that’s gripping our
nation and the risk for illicit diversion and abuse?

I’m committed to considering these key questions as part of a comprehensive process that the FDA has underway
to develop a formal benefit and risk framework for how the agency evaluates the safety and efficacy of opioid
medicines.

Currently, in applying our statute and regulations, we generally consider each new drug approval – and each new
opioid drug approval – largely on its own merits. As part of our review, we ask whether the individual drug meets the
standard for safety and effectiveness, and whether additional controls are needed to ensure safe use of that
specific drug.

But opioids are a unique class of medicines. Congress recently directed us to think differently about opioids as a
drug class in enacting novel and specific authorities that enable the FDA to, among other things, require post-
market studies to evaluate efficacy of opioids if we have concerns that these products may not be as effective as
previously thought; to consider the risks associated with the misuse and abuse of opioids as a factor in how we
make pre- and post-market regulatory decisions; to require opioids to be sold in unit dose packaging; and to require
that certain opioids be dispensed with packaging or systems that enable the drugs to be safely disposed.

The FDA has already begun implementing these new authorities. And, even before Congress granted the FDA
these new authorities, we have started to take a different approach to the benefit-risk evaluation of opioids. In the
post-market setting, we’ve taken strong actions where appropriate, such as requesting the withdrawal of
reformulated Opana ER (/NewsEvents/Newsroom/PressAnnouncements/ucm562401.htm) from the market. In
the pre-market setting, we routinely seek advisory committee input on new opioid product approvals. For example,
at an October 2018 meeting (/AdvisoryCommittees/Calendar/ucm620163.htm) of the Anesthetic and Analgesic
Drug Products Advisory Committee, the committee recommended 10-3 that Dsuvia be approved. Committee
members in attendance for the meeting included experts on pain management, medication safety, human factors
and critical care nursing, who are anesthesiologists, pain specialists and pharmacists.

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We’re also re-evaluating how we consider both the individual and public health impacts of new opioids as they are
reviewed for approval. To that end, I’ve asked the professional staff at the FDA to evaluate a new framework for
opioid analgesic approvals; one that provides a transparent process to delineate clearly, eventually in new
guidance, how we intend to consider the benefits and risks of these products in the context of this crisis. As part of
this process, we need to closely consider how we evaluate questions such as:

How does the availability of an additional opioid drug benefit the public health through its ability to, for example,
provide therapeutic differentiation, promote more appropriate access, or advance safer use of these medicines?
Does the approval of an additional opioid drug create added risks for diversion, accidental overdose, abuse and
misuse, or other concerns?
If the approval of an additional opioid will create such added risks, will the new drug provide sufficient clinical
differentiation that can benefit certain groups of patients, or offer other important clinical benefit, such that the
benefits to patients of introducing the additional opioid outweigh the risks? And can the implementation of REMS
help mitigate some of these risks?

Such a framework also would need to address the potential hurdles to product innovation. So, if we develop such a
framework that takes into closer consideration the overall therapeutic armamentarium as we consider new opioid
product approvals, and weighs new opioid approvals against the benefits and risks of existing drugs for the
treatment of pain; then we’d also need to describe how we intend to characterize the benefits and risks of opioids,
and what we believe the unmet medical needs are. In this way, innovators would know up front where the
opportunities are for developing new drugs that meet the FDA’s standards for safety and effectiveness.

As part of the effort to consider and apply a more holistic approach, I will also be taking these questions, and a
consideration of such a framework, to my Opioid Policy Steering Committee
(/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/ucm587929.htm) to evaluate what additional
steps we may want to take within our own authority to consider these goals and the development of such a
framework. There could also be other places where we would seek additional input, as well as help from Congress.
We know now that our evaluation of opioids is different than how we assess drugs in other therapeutic classes. And
Congress agreed with us that opioids are different. I believe that there are population-based considerations when it
comes to drugs that are subject to such widespread abuse and misuse that warrant us considering each approval
within a broad public health context.

This brings us back to discussion around today’s approval.

I believe that the unique aspects of Dsuvia, including those that make this drug a high priority for the Pentagon,
differentiate this new formulation of sufentanil from other sufentanil products in a way that is consistent with
population-based considerations for how it fits into the overall drug armamentarium. The FDA has made it a high
priority to make sure our soldiers have access to treatments that meet the unique needs of the battlefield, including
when intravenous administration is not possible for the treatment of acute pain related to battlefield wounds. The
military application for this new medicine was carefully considered in this case. We understand the concerns about
the availability of a high potency formulation of sufentanil and the associated risks. The FDA has implemented a
REMS that reflects the potential risks associated with this product and mandates that Dsuvia will only be made
available for use in a certified medically-supervised heath care setting, including its use on the battlefield.

To address concerns about the potential risks associated with Dsuvia, this product will have strong limitations on its
use. It can’t be dispensed to patients for home use and should not be used for more than 72 hours. And it should
only be administered by a health care provider using a single-dose applicator. That means it won’t be available at
retail pharmacies for patients to take home. These measures to restrict the use of this product only within a
supervised health care setting, and not for home use, are important steps to help prevent misuse and abuse of
Dsuvia, as well reduce the potential for diversion. Because of the risks of addiction, abuse and misuse with opioids;

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Dsuvia is also to be reserved for use in patients for whom alternative pain treatment options have not been
tolerated, or are not expected to be tolerated, where existing treatment options have not provided adequate
analgesia, or where these alternatives are not expected to provide adequate analgesia. Like all opioids, Dsuvia will
also carry a boxed warning about the serious risks of misuse and abuse, which can lead to addiction, overdose and
death. It also includes a boxed warning about the serious risks, including extreme sleepiness, respiratory
depression, coma and death, side effects that may be potentiated by the combined use with central nervous system
depressants such as drugs called benzodiazepines. Common side effects of Dsuvia include nausea, headache,
vomiting, dizziness and hypotension.

But I recognize that the debate goes beyond the characteristics of this particular product or the actions that we’re
taking to mitigate this drug’s risks and preserve its differentiated benefits. We won’t sidestep what I believe is the
real underlying source of discontent among the critics of this approval – the question of whether or not America
needs another powerful opioid while in the throes of a massive crisis of addiction.

It’s an important question that has surfaced in past approval decisions and will come up again in the future. As a
public health agency, we have an obligation to address this question openly and directly. As a physician and
regulator, I won’t bypass legitimate questions and concerns related to our role in addressing the opioid crisis.

We owe an answer to those who support us in these decisions, and to those who may disagree. We owe an answer
to patients with medical pain, and the innovators who take risks to develop products to help address their needs.
We owe it to Americans who want the FDA to do our part to help end one of the biggest addiction crises of modern
times, while we carefully balance these grave risks against patient needs.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by
assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological
products for human use, and medical devices. The agency also is responsible for the safety and security of our
nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating
tobacco products.

###

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