[Federal Register Volume 86, Number 30 (Wednesday, February 17, 2021)]
[Notices]
[Pages 9944-9945]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-03083]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket Nos. FDA-2020-P-1511 and FDA-2020-P-1549]


Determination That NYMALIZE (nimodipine), Oral Solution, 3 
Milligrams/Milliliter, Was Not Withdrawn From Sale for Reasons of 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, the Agency, or we) has 
determined that NYMALIZE (nimodipine), oral solution, 3 milligrams 
(mg)/milliliter (mL), was not withdrawn from sale for reasons of safety 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 nimodipine, oral 
solution, 3 mg/mL, if all other legal and regulatory requirements are 
met.

FOR FURTHER INFORMATION CONTACT: Ayako Sato, Center for Drug Evaluation 
and Research, Food and Drug Administration, 10903 New Hampshire Ave., 
Bldg. 51, Rm. 6206, Silver Spring, MD 20993-0002, 240-402-4191, 
Ayako.sato@fda.hhs.gov.

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 (FD&C 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.'' 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; section 505(j)(7) of the FD&C Act).
    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 (Sec.  314.161 (21 CFR 
314.161)). 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. FDA may not approve an ANDA that 
does not refer to a listed drug (see section 505(j)(4) of the FD&C 
Act).
    NYMALIZE (nimodipine), oral solution, 3 mg/mL, is the subject of 
NDA 203340, held by Arbor Pharmaceuticals, LLC (Arbor), and initially 
approved on May 10, 2013. NYMALIZE is indicated for the improvement of 
neurological outcome by reducing the incidence and severity of ischemic 
deficits in adult patients with subarachnoid hemorrhage from ruptured 
intracranial berry aneurysms regardless of their post-ictus

[[Page 9945]]

neurological condition (i.e., Hunt and Hess Grades I through V).
    In a letter dated May 4, 2020, Arbor notified FDA that NYMALIZE 
(nimodipine), oral solution, 3 mg/mL was being discontinued, and FDA 
moved the drug product to the ``Discontinued Drug Product List'' 
section of the Orange Book. As indicated in the Orange Book, Arbor 
markets a 6 mg/mL strength of NYMALIZE (nimodipine) oral solution, 
which was approved through NDA 203340/S-011 on April 8, 2020.
    Annora Pharma Private Limited submitted a citizen petition dated 
June 6, 2020 (Docket No. FDA-2020-P-1511) and Windels Marx Lane & 
Mittendorf, LLC submitted a citizen petition dated June 10, 2020 
(Docket No. FDA-2020-P-1549), both under 21 CFR 10.30, requesting that 
the Agency determine whether NYMALIZE (nimodipine), oral solution, 3 
mg/mL was withdrawn from sale for reasons of safety or effectiveness.
    After considering the citizen petitions and comments submitted to 
the dockets and reviewing Agency records and based on the information 
we have at this time, FDA has determined under Sec.  314.161 that 
NYMALIZE (nimodipine), oral solution, 3 mg/mL, was not withdrawn for 
reasons of safety or effectiveness. The petitioner has identified no 
data or other information suggesting that NYMALIZE (nimodipine), oral 
solution, 3 mg/mL, was withdrawn for reasons of safety or 
effectiveness. We have carefully reviewed our files for records 
concerning the withdrawal of NYMALIZE (nimodipine), oral solution, 3 
mg/mL, from sale. We have also independently evaluated relevant 
literature and data for possible postmarketing adverse events.
    A comment submitted by Arbor suggests that it was necessary to 
discontinue marketing the 3 mg/mL strength to mitigate potential 
confusion between the 3 mg/mL and 6 mg/mL strengths of NYMALIZE 
(nimodipine), oral solution. FDA disagrees. While discontinuation of 
the 3 mg/mL strength is one way to reduce the risk of confusion between 
the two strengths, there are other (often-used) mitigation strategies 
that may be employed to reduce the risk of confusion among multiple 
marketed strengths of a drug that could have been used by Arbor. 
Arbor's comment also states that FDA should find that the 3 mg/mL 
strength was discontinued for safety reasons because the Agency made 
similar determinations for BREVIBLOC (esmolol hydrochloride) injection, 
250 mg/mL, 10-mL ampule, and the original formulation of PROTONIX I.V. 
(pantoprazole sodium) for injection. Our finding that the 3 mg/mL 
strength for NYMALIZE was not withdrawn from sale for reasons of safety 
is factually distinguishable from BREVIBLOC and PROTONIX I.V.
    Based on a thorough evaluation of the information we have available 
to us and the latest version of the approved labeling for NYMALIZE 
(nimodipine), oral solution, 3 mg/mL, we have determined that this drug 
product would be considered safe and effective if it were reintroduced 
to the market today. Certain labeling changes should be considered to 
prevent future medication errors due to the presence of two different 
strengths of NYMALIZE (nimodipine), oral solution, on the market (i.e., 
NYMALIZE (nimodipine), oral solution, 3 mg/mL and NYMALIZE 
(nimodipine), oral solution, 6 mg/mL), but no existing safety signals 
or efficacy concerns make labeling changes necessary.
    Accordingly, the Agency will continue to list NYMALIZE 
(nimodipine), oral solution, 3 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. ANDAs that refer to NYMALIZE (nimodipine), oral 
solution, 3 mg/mL, 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: February 10, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2021-03083 Filed 2-16-21; 8:45 am]
BILLING CODE 4164-01-P


