[Federal Register Volume 89, Number 50 (Wednesday, March 13, 2024)]
[Notices]
[Pages 18420-18421]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-05298]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2023-P-2874]


Determination That Romidepsin Injection, 10 Milligrams/2 
Milliliters (5 Milligrams/Milliliter) and 27.5 Milligrams/5.5 
Milliliters (5 Milligrams/Milliliter), Were Not Withdrawn From Sale for 
Reasons of Safety or Effectiveness

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA or Agency) has 
determined that Romidepsin Injection, 10 milligrams (mg)/2 milliliters 
(mL) (5 mg/mL) and 27.5 mg/5.5 mL (5 mg/mL), were not withdrawn from 
sale for reasons of safety or effectiveness. This determination will 
allow FDA to approve abbreviated new drug applications (ANDAs) for 
romidepsin solution, 10 mg/2 mL (5 mg/mL) and 27.5 mg/5.5 mL (5 mg/mL), 
that refer to these drugs as long as they meet relevant legal and 
regulatory requirements.

FOR FURTHER INFORMATION CONTACT: Veniqua Stewart, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6219, Silver Spring, MD 20993-0002, 301-
796-3267, [email protected].

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 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 (Sec.  314.161 (21 CFR 314.161)). FDA may not approve an ANDA that 
does not refer to a listed drug.
    Romidepsin Injection, 10 mg/2 mL (5 mg/mL) and 27.5 mg/5.5 mL (5 
mg/mL), are the subject of NDA 208574, held by Teva Pharmaceuticals 
USA, Inc. (Teva), and initially approved on March 13, 2020. Romidepsin 
Injection is currently indicated only for the treatment of cutaneous T-
cell lymphoma (CTCL) in adult patients who have received at least one 
prior systemic therapy.
    Romidepsin Injection, 10 mg/2 mL (5 mg/mL) and 27.5 mg/5.5 mL (5 
mg/mL), are currently listed in the ``Discontinued Drug Product List'' 
section of the Orange Book.
    E. Rust Consulting, LLC submitted a citizen petition dated July 11, 
2023 (Docket No. FDA-2023-P-2874), under 21 CFR 10.30, requesting that 
the Agency determine whether Romidepsin Injection, 10 mg/2 mL (5 mg/mL) 
and 27.5 mg/5.5 mL (5 mg/mL), were 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 Sec.  314.161 that Romidepsin Injection, 10 mg/2 mL (5 mg/mL) and 
27.5 mg/5.5 mL (5 mg/mL), were not withdrawn for reasons of safety or 
effectiveness. The petitioner has identified no data or other 
information suggesting that Romidepsin Injection, 10 mg/2 mL (5 mg/mL) 
and 27.5 mg/5.5 mL (5 mg/mL), were withdrawn for reasons of safety or 
effectiveness. We have carefully reviewed our files for records 
concerning the withdrawal of Romidepsin Injection, 10 mg/2 mL (5 mg/mL) 
and 27.5 mg/5.5 mL (5 mg/mL), from sale. We have also independently 
evaluated relevant literature and data for possible postmarketing 
adverse events.
    We note that Romidepsin Injection, 10 mg/2 mL (5 mg/mL) and 27.5 
mg/5.5 mL (5 mg/mL), previously were approved with an indication for 
treatment of peripheral T-cell lymphoma (PTCL) in adult patients who 
have received at least one prior therapy, under the Agency's 
accelerated approval regulations, 21 CFR part 314, subpart H. The 
accelerated approval of Teva's Romidepsin Injection for PTCL included a 
required postmarketing clinical trial intended to verify the clinical 
benefit of romidepsin (the Ro-CHOP study) for PTCL. Teva's Romidepsin 
Injection product was approved under the 505(b)(2) approval pathway, 
and the listed drug relied upon is Celgene Corp.'s (Celgene) NDA 
022393, ISTODAX (romidepsin) for injection, 10 mg/vial. Celgene was 
acquired by Bristol-Meyers Squib Co. which is

[[Page 18421]]

currently listed as the NDA holder in the Orange Book.
    On August 6, 2020, Celgene submitted high level results from the 
Ro-CHOP study to FDA, which indicated the study failed to meet its 
primary endpoint of progression-free survival. On May 14, 2021, Celgene 
informed FDA that after careful consideration, Celgene decided to 
voluntarily withdraw the PTCL indication from ISTODAX (romidepsin) for 
injection, 10 mg/vial. On June 17, 2021, Celgene submitted a 
supplemental NDA proposing to remove the PTCL indication. On July 14, 
2021, Celgene submitted a letter asking FDA to withdraw approval of the 
PTCL indication pursuant to Sec.  314.150(d) (21 CFR 314.150(d)) and 
waiving its opportunity for a hearing.
    On August 27, 2021, Teva submitted a labeling supplement proposing 
to remove the PTCL indication. On September 12, 2021, the Agency 
requested Teva voluntarily request withdrawal of the PTCL indication 
pursuant to Sec.  314.150(d) and waive its opportunity for a hearing. 
On September 14, 2021, Teva amended its supplement by submitting a 
cover letter requesting withdrawal of approval of the PTCL indication 
pursuant to Sec.  314.150(d) and waiving its opportunity for a hearing. 
On December 8, 2021, FDA approved the supplemental NDA to revise the 
labeling to remove the PTCL indication. In the Federal Register of May 
9, 2022 (87 FR 27644), FDA announced that it was withdrawing approval 
of the PTCL indications for ISTODAX (romidepsin) for injection, 10 mg/
vial, and Romidepsin Injection. Therefore, Romidepsin Injection is only 
indicated for the treatment of CTCL in adult patients who have received 
at least one prior systemic therapy.
    The Agency will continue to list Teva's Romidepsin Injection, 10 
mg/2 mL (5 mg/mL) and 27.5 mg/5.5 mL (5 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 accept and, where appropriate, approve ANDAs 
that refer to these drug products, but does not intend to do so if they 
propose to include the PTCL indication (see, e.g., section 
505(j)(2)(A)(v) and (j)(4)(G) of the FD&C Act and 21 CFR 
314.94(a)(8)(iv) and 314.127(a)(7)). 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.

    Dated: March 8, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2024-05298 Filed 3-12-24; 8:45 am]
BILLING CODE 4164-01-P