[Federal Register Volume 84, Number 250 (Tuesday, December 31, 2019)]
[Notices]
[Pages 72366-72367]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-28270]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2019-P-3877]


Determination That GLUCOPHAGE (Metformin Hydrochloride) Oral 
Tablets, 500 Milligrams, 850 Milligrams, and 1 Gram, and GLUCOPHAGE XR 
(Metformin Hydrochloride) Oral Extended-Release Tablets, 500 Milligrams 
and 750 Milligrams, Were Not Withdrawn From Sale for Reasons of Safety 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, Agency, or we) has 
determined that, GLUCOPHAGE (metformin hydrochloride) oral tablets, 500 
milligrams (mg), 850 mg, and 1 gram (g), and GLUCOPHAGE XR (metformin 
hydrochloride) oral extended-release tablets, 500 mg and 750 mg, were 
not withdrawn from sale for reasons of safety or effectiveness.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 
these drug products, and it will allow FDA to continue to approve ANDAs 
that refer to these products as long as they meet relevant legal and 
regulatory requirements.

FOR FURTHER INFORMATION CONTACT: Carlarease Hunter, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6213, Silver Spring, MD 20993-0002, 301-
796-3702, Carlarease.Hunter@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 (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.'' 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

[[Page 72367]]

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.
    GLUCOPHAGE (metformin hydrochloride) oral tablets, 500 mg, 850 mg, 
and 1 g, are the subject of NDA 020357, held by EMD Serono Inc. and 
initially approved on March 3, 1995. GLUCOPHAGE is indicated as an 
adjunct to diet and exercise to improve glycemic control in adults and 
pediatric patients 10 years of age and older with type 2 diabetes 
mellitus. GLUCOPHAGE (metformin hydrochloride) oral tablets, 500 mg, 
850 mg, and 1 g, are currently listed in the ``Discontinued Drug 
Product List'' section of the Orange Book.
    GLUCOPHAGE XR (metformin hydrochloride) oral extended-release 
tablets, 500 mg and 750 mg, are the subject of NDA 021202, held by EMD 
Serono Inc. and initially approved on October 13, 2000. GLUCOPHAGE XR 
is indicated as an adjunct to diet and exercise to improve glycemic 
control in adults with type 2 diabetes mellitus. GLUCOPHAGE XR 
(metformin hydrochloride) oral extended-release tablets, 500 mg and 750 
mg, are currently listed in the ``Discontinued Drug Product List'' 
section of the Orange Book.
    Harman Finochem Ltd. submitted a citizen petition dated August 17, 
2019 (Docket No. FDA-2019-P-3877), under 21 CFR 10.30, requesting that 
FDA confirm that GLUCOPHAGE (metformin hydrochloride) oral tablets were 
not withdrawn from sale for reasons of safety or effectiveness. 
Although the citizen petition did not address the GLUCOPHAGE XR 
(metformin hydrochloride) oral extended-release tablets, 500 mg and 750 
mg, those products have also been discontinued. On our own initiative, 
we have also determined whether those products were withdrawn for 
safety or effectiveness reasons.
    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 GLUCOPHAGE (metformin hydrochloride) oral 
tablets, 500 mg, 850 mg, and 1 g, and GLUCOPHAGE XR (metformin 
hydrochloride) oral extended-release tablets, 500 mg and 750 mg, were 
not withdrawn for reasons of safety or effectiveness. The petitioner 
has identified no data or other information suggesting that GLUCOPHAGE 
(metformin hydrochloride) oral tablets were withdrawn for reasons of 
safety or effectiveness. We have carefully reviewed our files for 
records concerning the withdrawal of GLUCOPHAGE (metformin 
hydrochloride) oral tablets, 500 mg, 850 mg, and 1 g, and GLUCOPHAGE XR 
(metformin hydrochloride) oral extended-release tablets, 500 mg and 750 
mg, 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 these drug products were not 
withdrawn from sale for reasons of safety or effectiveness.
    Accordingly, the Agency will continue to list GLUCOPHAGE (metformin 
hydrochloride) oral tablets, 500 mg, 850 mg, and 1 g, and GLUCOPHAGE XR 
(metformin hydrochloride) oral extended-release tablets, 500 mg and 750 
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. FDA will not begin 
procedures to withdraw approval of approved ANDAs that refer to these 
drug products. Additional ANDAs for these drug products 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 these drug products should be revised to meet current 
standards, the Agency will advise ANDA applicants to submit such 
labeling.

    Dated: December 26, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-28270 Filed 12-30-19; 8:45 am]
 BILLING CODE 4164-01-P


