[Federal Register Volume 88, Number 44 (Tuesday, March 7, 2023)]
[Notices]
[Pages 14169-14170]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-04560]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket Nos. FDA-2022-P-2752 and FDA-2022-P-3125]


Determination That Lithium Citrate Oral Solution, 8 
Milliequivalents/5 Milliliters, Was Not Withdrawn From Sale for Reasons 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 lithium citrate oral solution, 8 milliequivalents 
(mEq)/5 milliliters (mL), was not withdrawn from sale for reasons of 
safety or effectiveness. This determination means that FDA will not 
begin procedures to withdraw approval of abbreviated new drug 
applications (ANDAs) that refer to this drug product, and it will allow 
FDA to continue to approve ANDAs that refer to the product as long as 
they meet relevant legal and regulatory requirements.

FOR FURTHER INFORMATION CONTACT: Caitlin Callahan, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6240, Silver Spring, MD 20993-0002, 240-
402-4318, [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.
    Lithium citrate oral solution, 8 mEq/5 mL, is the subject of NDA 
018421, held by Hikma Pharmaceuticals USA Inc., and initially approved 
on December 23, 1980.\1\ Lithium citrate oral

[[Page 14170]]

solution is a mood-stabilizing agent indicated as monotherapy for the 
following treatment of bipolar I disorder: treatment of acute manic and 
mixed episodes in patients 7 years and older; and maintenance treatment 
in patients 7 years and older.
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    \1\ In their citizen petitions, petitioners Saptalis 
Pharmaceuticals LLC, and Hyman, Phelps & McNamara, P.C., refer to 
this drug product, respectively, as ``Lithium Citrate Syrup EQ 300 
mg Carbonate/5mL'' and ``Lithium Citrate Oral Syrup, 300 mg 
Carbonate/5mL.'' The currently approved labeling refers to this drug 
product as ``Lithium Oral Solution USP, 8 mEq per 5 mL'' and 
provides that the dosage strength for Lithium Oral Solution in terms 
of lithium content, 8 mEq/5mL, is equivalent to 300 mg lithium 
carbonate/5 mL. For purposes of this determination, we use the 
current label's description, ``Lithium Oral Solution USP, 8 mEq per 
5 mL.''
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    Lithium citrate oral solution, 8 mEq/5 mL, is currently listed in 
the ``Discontinued Drug Product List'' section of the Orange Book. 
Saptalis Pharmaceuticals, LLC submitted a citizen petition dated 
November 2, 2022 (Docket No. FDA-2022-P-2752), under Sec.  10.30 (21 
CFR 10.30), requesting that the Agency determine whether lithium 
citrate oral solution, 8 mEq/5 mL, was withdrawn from sale for reasons 
of safety or effectiveness. Hyman, Phelps & McNamara, P.C. separately 
submitted a citizen petition dated December 6, 2022 (Docket No. FDA-
2022-P-3125), under Sec.  10.30, requesting that the Agency make the 
same determination.
    After considering the citizen petitions and reviewing Agency 
records and based on the information we have at this time, FDA has 
determined under Sec.  314.161 that lithium citrate oral solution, 8 
mEq/5 mL, was not withdrawn for reasons of safety or effectiveness. The 
Petitioners have identified no data or other information suggesting 
that lithium citrate oral solution, 8 mEq/5 mL, was withdrawn for 
reasons of safety or effectiveness. We have carefully reviewed our 
files for records concerning the withdrawal of lithium citrate oral 
solution, 8 mEq/5 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 lithium citrate oral 
solution, 8 mEq/5 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: March 1, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-04560 Filed 3-6-23; 8:45 am]
BILLING CODE 4164-01-P