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 ( printed page 56655) 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 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approval of the drug's NDA or ANDA for reasons of safety or effectiveness or if FDA determines that the listed drug was withdrawn from sale for reasons of safety or effectiveness (21 CFR 314.162).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may petition the Agency to determine, or the Agency may determine on its own initiative, whether a listed drug was withdrawn from sale for reasons of safety or effectiveness. This determination may be made at any time after the drug has been withdrawn from sale but must be made prior to approving an ANDA that refers to the listed drug (§ 314.161 (21 CFR 314.161)).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.

PHENAPHEN WITH CODEINE NO. 3 (acetaminophen; codeine phosphate) oral capsules, 325 mg and 30 mg, and PHENAPHEN WITH CODEINE NO. 4 (acetaminophen; codeine phosphate) oral capsules, 325 mg and 60 mg, are the subject of ANDAs 084445 and 084446, held by Wyeth-Ayerst Laboratories, and both initially approved on July 22, 1975. PHENAPHEN WITH CODEINE NO. 3 and PHENAPHEN WITH CODEINE NO. 4 are indicated for the relief of mild to moderately severe pain.

In separate letters dated March 7, 2003, Wyeth-Ayerst requested withdrawal of ANDAs 084445 and 084446 for PHENAPHEN WITH CODEINE NO. 3 (acetaminophen; codeine phosphate) and PHENAPHEN WITH CODEINE NO. 4 (acetaminophen; codeine phosphate) in accordance with 21 CFR 314.150(c). In the Federal Register of May 5, 2004 (69 FR 25124), FDA announced that it was withdrawing approval of ANDAs 084445 and 084446, effective June 4, 2004.

LGM Pharma Solutions, LLC, submitted a citizen petition dated May 16, 2025 (Docket No. FDA-2025-P-1372), under 21 CFR 10.30, requesting that the Agency determine whether PHENAPHEN WITH CODEINE NO. 3 (acetaminophen; codeine phosphate) oral capsules, 325 mg and 30 mg, and PHENAPHEN W CODEINE NO. 4 (acetaminophen; codeine phosphate) oral capsules, 325 mg and 60 mg, were voluntarily 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 PHENAPHEN WITH CODEINE NO. 3 (acetaminophen; codeine phosphate) oral capsules, 325 mg and 30 mg, and PHENAPHEN W CODEINE NO. 4 (acetaminophen; codeine phosphate) oral capsules, 325 mg and 60 mg, were not withdrawn from sale for reasons of safety or effectiveness. The petitioner has identified no data or other information suggesting that PHENAPHEN WITH CODEINE NO. 3 (acetaminophen; codeine phosphate) oral capsules, 325 mg and 30 mg, and PHENAPHEN W CODEINE NO. 4 (acetaminophen; codeine phosphate) oral capsules, 325 mg and 60 mg, were withdrawn for reasons of safety or effectiveness. We have carefully reviewed our files for records concerning the withdrawal of PHENAPHEN WITH CODEINE NO. 3 (acetaminophen; codeine phosphate) oral capsules, 325 mg and 30 mg, and PHENAPHEN W CODEINE NO. 4 (acetaminophen; codeine phosphate) oral capsules, 325 mg and 60 mg, 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 these drug products were withdrawn from sale for reasons of safety or effectiveness.

Accordingly, the Agency will continue to list PHENAPHEN WITH CODEINE NO. 3 (acetaminophen; codeine phosphate) oral capsules, 325 mg and 30 mg, and PHENAPHEN W CODEINE NO. 4 (acetaminophen; codeine phosphate) oral capsules, 325 mg and 60 mg, 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 for these drug products 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 these drug products should be revised to meet current standards, the Agency will advise ANDA applicants to submit such labeling.