2017-23952. Determination That REVEX (Nalmefene Hydrochloride Injection), 0.1 Milligram Base/Milliliter and 1.0 Milligram Base/Milliliter, Was Not Withdrawn From Sale for Reasons of Safety or Effectiveness

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice.

SUMMARY:

The Food and Drug Administration (FDA or Agency) has determined that REVEX (nalmefene hydrochloride injection), 0.1 milligram (mg) base/milliliter (mL) and 1.0 mg base/mL, was not withdrawn from sale for reasons of safety or effectiveness. This determination will allow FDA to approve abbreviated new drug applications (ANDAs) for REVEX (nalmefene hydrochloride injection), 0.1 mg base/mL and 1.0 mg base/mL, if all other legal and regulatory requirements are met.

FOR FURTHER INFORMATION CONTACT:

Kelley Nduom, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 6221, Silver Spring, MD 20993-0002, 301-796-8597.

SUPPLEMENTARY INFORMATION:

In 1984, Congress enacted the Drug Price Competition and Patent Term Restoration Act of 1984 (Pub. L. 98-417) (the 1984 amendments), which authorized the approval of duplicate versions of drug products under an ANDA procedure. ANDA applicants must, with certain exceptions, show that the drug for which they are seeking approval contains the same active ingredient in the same strength and dosage form as the “listed drug,” which is a version of the drug that was previously approved. ANDA applicants do not have to repeat the extensive clinical testing otherwise necessary to gain approval of a new drug application (NDA).

The 1984 amendments include what is now section 505(j)(7) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(j)(7)), which requires FDA to publish a list of all approved drugs. FDA publishes this list as part of the “Approved Drug Products With Therapeutic Equivalence Evaluations,” which is known generally as the “Orange Book.” Under FDA regulations, a drug is removed from the list if the Agency withdraws or suspends approval of the drug's NDA or ANDA for reasons of safety or effectiveness or if FDA determines that the listed drug was withdrawn from sale for reasons of safety or effectiveness (21 CFR 314.162).

A person may petition the Agency to determine, or the Agency may determine on its own initiative, whether a listed drug was withdrawn from sale for reasons of safety or effectiveness. This determination may be made at any time after the drug has been withdrawn from sale, but must be made prior to approving an ANDA that refers to the listed drug (§ 314.161 (21 CFR 314.161)). FDA may not approve an ANDA that does not refer to a listed drug.

REVEX (nalmefene hydrochloride injection), 0.1 mg base/mL and 1.0 mg base/mL, is the subject of NDA 20-459, currently held by West-Ward Pharmaceuticals International Limited, and initially approved on April 17, 1995. REVEX is indicated for the complete or partial reversal of opioid drug effects, including respiratory depression, induced by either natural or synthetic opioids. REVEX is also indicated in the management of known or suspected opioid overdose.

In a letter dated June 5, 2009, Baxter Healthcare Corporation, the NDA holder at the time, notified FDA that the manufacturing and distribution of REVEX (nalmefene hydrochloride injection), 0.1 mg base/mL and 1.0 mg base/mL, had been discontinued on May 21, 2008, for business reasons. REVEX (nalmefene hydrochloride injection), 0.1 mg base/mL and 1.0 mg base/mL, is currently listed in the “Discontinued Drug Product List” section of the Orange Book.

Nirsum Pharmaceuticals, LLC, submitted a citizen petition dated March 31, 2017 (Docket No. FDA-2017-P-2044), under 21 CFR 10.30, requesting that the Agency determine whether REVEX (nalmefene hydrochloride injection), 0.1 mg base/mL and 1.0 mg base/mL, was withdrawn from sale for reasons of safety or effectiveness.

After considering the citizen petition (and comments submitted to the docket) and reviewing Agency records, and based on the information we have at this time, FDA has determined under § 314.161 that REVEX (nalmefene hydrochloride injection), 0.1 mg base/mL and 1.0 mg base/mL, was not withdrawn for reasons of safety or effectiveness. The petitioner has identified no data or other information suggesting that REVEX (nalmefene hydrochloride injection), 0.1 mg base/mL and 1.0 mg base/mL, was withdrawn for reasons of safety or effectiveness. We have carefully reviewed our files for records concerning the withdrawal of REVEX (nalmefene hydrochloride injection), 0.1 mg base/mL and 1.0 mg base/mL, from sale. We have also independently evaluated relevant literature and data for possible postmarketing adverse events. We have found no information that would indicate that this drug product was withdrawn from sale for reasons of safety or effectiveness.

Accordingly, the Agency will continue to list REVEX (nalmefene hydrochloride injection), 0.1 mg base/mL and 1.0 mg base/mL, in the “Discontinued Drug Product List” section of the Orange Book. The “Discontinued Drug Product List” delineates, among other items, drug products that have been discontinued from marketing for reasons other than safety or effectiveness. ANDAs that refer to this drug product may be approved by the Agency as long as they meet all other legal and regulatory requirements for the approval of ANDAs. If FDA determines that labeling for this drug product should be revised to meet current standards, the Agency will advise ANDA applicants to submit such labeling.

Dated: October 19, 2017.

Anna K. Abram,

Deputy Commissioner for Policy, Planning, Legislation, and Analysis.