2024-19233. Determination That DILTIAZEM HYDROCHLORIDE IN DEXTROSE 5% (Diltiazem Hydrochloride), 125 Milligrams/125 Milliliters (1 Milligram/Milliliter) and 250 Milligrams/250 Milliliters (1 Milligram/Milliliter), Was Not Withdrawn From Sale for ...

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Department of Health and Human Services

Food and Drug Administration

1. [Docket No. FDA-2024-P-1131]

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice.

SUMMARY:

The Food and Drug Administration (FDA or the Agency) has determined that DILTIAZEM HYDROCHLORIDE IN DEXTROSE 5% (diltiazem hydrochloride (HCl)), 125 milligrams (mg)/125 milliliters (mL) (1 mg/mL) and 250 mg/250 mL (1 mg/mL), was not withdrawn from sale for reasons of safety or effectiveness.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 diltiazem HCl, 125 mg/125 mL (1 mg/mL) and 250 mg/250 mL (1 mg/mL), if all other legal and regulatory requirements are met.

FOR FURTHER INFORMATION CONTACT:

Neerja Razdan, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 6217, Silver Spring, MD 20993-0002, [e-mail].

SUPPLEMENTARY INFORMATION:

Section 505(j) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355(j)) allows the submission of an ANDA to market a generic version of a previously approved drug product. To obtain approval, the ANDA applicant must show, among other things, that the generic drug product: (1) has the same active ingredient(s), dosage form, route of administration, strength, conditions of use, and (with certain exceptions) labeling as the listed drug, which is a version of the drug that was previously approved, and (2) is bioequivalent to the listed drug. ANDA applicants do not have to repeat the extensive clinical testing otherwise necessary to gain approval of a new drug application (NDA).

Section 505(j)(7) of the FD&C Act 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 ( print page 68625) regulations, drugs are 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approval of the drug's NDA or ANDA for reasons of safety or effectiveness or if FDA determines that the listed drug was withdrawn from sale for reasons of safety or effectiveness (§ 314.162 (21 CFR 314.162)).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.

DILTIAZEM HYDROCHLORIDE IN DEXTROSE 5% (diltiazem HCl), 125 mg/125 mL (1 mg/mL) and 250 mg/250 mL (1 mg/mL), is the subject of NDA 215252, held by Exela Pharma Sciences, LLC, and initially approved on October 28, 2021. DILTIAZEM HYDROCHLORIDE IN DEXTROSE 5% is indicated for the following: (1) temporary control of rapid ventricular rate in atrial fibrillation or atrial flutter; and (2) rapid conversion of paroxysmal supraventricular tachycardias to sinus rhythm.

DILTIAZEM HYDROCHLORIDE IN DEXTROSE 5% (diltiazem HCl), 125 mg/125 mL (1 mg/mL) and 250 mg/250 mL (1 mg/mL), is currently listed in the “Discontinued Drug Product List” section of the Orange Book. In previous instances (see, e.g.,72 FR 9763 (March 5, 2007), 61 FR 25497 (May 21, 1996)), the Agency has determined that, for purposes of §§ 314.161 and 314.162, never marketing an approved drug product is equivalent to withdrawing the drug from sale.

Fresenius Kabi USA, LLC submitted a citizen petition dated March 5, 2024 (Docket No. FDA-2024-P-1131), under 21 CFR 10.30, requesting that the Agency determine whether DILTIAZEM HYDROCHLORIDE IN DEXTROSE 5% (diltiazem HCl), 125 mg/125 mL (1 mg/mL) and 250 mg/250 mL (1 mg/mL), was withdrawn from sale for reasons of safety or effectiveness.

After considering the citizen petition and reviewing Agency records and based on the information we have at this time, FDA has determined under § 314.161 that DILTIAZEM HYDROCHLORIDE IN DEXTROSE 5% (diltiazem HCl), 125 mg/125 mL (1 mg/mL) and 250 mg/250 mL (1 mg/mL), was not withdrawn for reasons of safety or effectiveness. The petitioner has identified no data or other information suggesting that DILTIAZEM HYDROCHLORIDE IN DEXTROSE 5% (diltiazem HCl), 125 mg/125 mL (1 mg/mL) and 250 mg/250 mL (1 mg/mL), was withdrawn for reasons of safety or effectiveness. We have carefully reviewed our files for records concerning the withdrawal of DILTIAZEM HYDROCHLORIDE IN DEXTROSE 5% (diltiazem HCl), 125 mg/125 mL (1 mg/mL) and 250 mg/250 mL (1 mg/mL), from sale. We have also independently evaluated relevant literature and data for possible postmarketing adverse events. We have reviewed the available evidence and determined that this drug product was not withdrawn from sale for reasons of safety or effectiveness.

Accordingly, the Agency will continue to list DILTIAZEM HYDROCHLORIDE IN DEXTROSE 5% (diltiazem HCl), 125 mg/125 mL (1 mg/mL) and 250 mg/250 mL (1 mg/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. FDA will not begin procedures to withdraw approval of approved ANDAs that refer to this drug product. Additional ANDAs for this drug product may also 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: August 22, 2024.

Lauren K. Roth,

Associate Commissioner for Policy.