Everything You Should Know about FDA’s Draft Guidance on Abuse-Deterrent Generic Opioids, Part One

March 30, 2016

Evaluating the Abuse Deterrence of Generic Opioid Drug Products

FDA Draft Guidance on Abuse-Deterrent Generic Opioids

As we recently reported, the prevalence of opioid abuse and overdose have reached epidemic levels in the U.S. over the past decade. In response to this increasingly important issue, the FDA has taken and continues to take a number of steps to help reverse the impact of this widespread problem.

The Agency’s latest effort in the fight against opioid abuse came on Thursday, March 24th when the FDA issued a draft guidance entitled “General Principles for Evaluating the Abuse Deterrence of Generic Solid Oral Opioid Drug Products.” The document “recommends studies, including comparative in vitro studies, which should be conducted to demonstrate that a proposed generic solid oral opioid drug product is no less abuse-deterrent than its reference listed drug.”

Generic Opioids

Although the abuse and misuse of opioid pain medications has created a serious epidemic in the U.S., prescription opioid analgesics are still an important aspect of modern pain management. As such, developing products that have abuse-deterrent properties is critical for the FDA to ensure that safer opioids are created, which they have stated is a high public health priority. The Agency has also expressed that it is essential for generic versions of these abuse-deterrent opioids to be developed as well to help ensure the availability of analgesics for patients who need them.

General ANDA Requirements

In order for an abbreviated new drug application (ANDA) to be approved, the sponsor must provide the FDA with sufficient information to show that the proposed product is bioequivalent to the reference listed drug (RLD), and that it has the same:

  • Active ingredient(s)
  • Dosage form
  • Route of administration
  • Strength
  • Labeling (with limitations)

Furthermore, the sponsor must also prove “that the methods used in, or the facilities and controls used for, the manufacture, processing, and packing of the drug are adequate to assure and preserve its identity, strength, quality, and purity; and that the inactive ingredients and composition of the generic drug are not unsafe for use under the conditions prescribed, recommended, or suggested in the labeling.”

If products are bioequivalent and meeting the following criteria, they are considered to be “therapeutically equivalent” and can be substituted for one another:

  1. They are approved as safe and effective.
  2. They are pharmaceutical equivalents in that they:
    1. Contain identical amounts of the same active ingredient in the same dosage form and route of administration.
    2. Meet compendial or other applicable standards of strength, quality, purity, and identity.
  3. They are bioequivalent.
  4. They are adequately labeled.
  5. They are manufactured in compliance with current good manufacturing practices (cGMP) regulations.

Evaluating Abuse Deterrence of Generic Opioids

FDA states that if the RLD’s label does not describe any abuse-deterrent properties, the recommendations provided in the draft guidance are not applicable and thus irrelevant. However, if the RLD does have abuse-deterrent properties listed on its labeling, the generic product should have the same properties. When the labeling of the RLD does include abuse-deterrent properties, the sponsor should evaluate the abuse deterrence of the generic product vs. the RLD. In such situations, the FDA recommends that the comparison be conducted according to the following guidelines:

  • Use of a tier-based approach to testing
  • Evaluation of abuse deterrence
  • Use of control
  • Identification of discriminatory study conditions
  • Comparison of the reference and proposed generic products

Details on the Agency’s guidelines for conducting a comparative evaluation are available in the draft guidance. The document also includes information regarding routes of abuse, provides sponsors with recommendations for conducting comparative in vitro studies, and a number of other considerations.

FDA is seeking public feedback on the draft guidance and is asking interested parties to submit comments electronically or by mail no later than May 24, 2016.

Part two is available now!  More details on the other topics addressed in the draft guidance are available in our FDA News article entitled "Everything You Should Know about FDA’s Draft Guidance on Abuse-Deterrent Generic Opioids, Part Two"


Are you developing a generic version of an opioid or other FDA approved product? We can help you obtain FDA approval for your product. To learn more about our services and how we can help you, contact us today.


March 6, 2017

2016 was Record-Setting Year for Generic Drug Approvals, Reports FDA

In a recent post on the FDA Voice blog, the Agency reported that its generic drug program hit record highs in 2016. In the blog post, Kathleen “Cook” Uhl, M.D., Director of FDA’s Office of Generic...

March 31, 2016

Everything You Should Know about FDA’s Draft Guidance on Abuse-Deterrent Generic Opioids, Part Two

FDA Touches on Routes of Abuse, Comparative In Vitro Studies, and Various Other Factors to Consider Regarding Abuse-Deterrent Generic Opioids Due to recent increases in the prevalence of opioid abuse...

November 3, 2015

Draft Guidance for Microbial Vectors Used for Gene Therapy Outlines FDA Safety Concerns

Issues for Sponsors with INDs and CMC concerns FDA recently released a draft guidance entitled “Recommendations for Microbial Vectors Used for Gene Therapy” as a supplemental guidance to “Guidance...