[Federal Register Volume 84, Number 24 (Tuesday, February 5, 2019)]
[Notices]
[Pages 1746-1747]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-01131]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-1987-D-0240 (formerly 87D-0315)]


Neomycin Sulfate for Prescription Compounding; Withdrawal of 
Approval of One Abbreviated New Drug Application

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is 
withdrawing approval of abbreviated new drug application (ANDA) 061579 
for nonsterile neomycin sulfate powder for prescription compounding. 
The basis for the withdrawal is that the product is no longer 
considered safe as labeled due to clinical evidence that systemic 
exposure to neomycin sulfate can induce significant toxicity, including 
ototoxicity (manifested as sensorineural hearing loss), nephrotoxicity, 
and neuromuscular blockade. The holder of this ANDA has waived its 
opportunity for a hearing.

DATES: Approval is withdrawn as of February 5, 2019.

FOR FURTHER INFORMATION CONTACT: Kate Greenwood, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6286, Silver Spring, MD 20993-0002, 240-
402-1748.

SUPPLEMENTARY INFORMATION: In the Federal Register of April 15, 1988, 
FDA published four documents arising out of the Agency's finding that 
systemic absorption of neomycin sulfate can induce significant 
toxicity, including ototoxicity (manifested as sensorineural hearing 
loss), nephrotoxicity, and neuromuscular blockade (see generally 53 FR 
12644; 53 FR 12658; 53 FR 12662; and 53 FR 12664 (April 15, 1988)). Two 
of the four documents were issued under docket numbers FDA-1979-N-0220 
and FDA-1987-D-0240 and related to nonsterile neomycin sulfate for 
prescription compounding.\1\
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    \1\ These documents were originally assigned docket numbers 79N-
0155, and 87D-0315. The numbers were changed to FDA-1979-N-0220 and 
FDA-1987-D-0240, respectively, as a result of FDA's transition to 
its new docketing system (Regulations.gov) in January 2008. The 
other two documents were issued under docket number FDA-1979-N-0256 
(formerly 79N-0151) and related to neomycin sulfate in sterile vials 
for parenteral use.
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    Under docket number FDA-1979-N-0220, FDA published a final rule 
amending the antibiotic drug

[[Page 1747]]

regulations governing the certification of nonsterile neomycin sulfate 
powder for prescription compounding (53 FR 12644). Based on its 
evaluation of the written and oral comments received on the proposed 
rule (44 FR 44180 (July 27, 1979)), and based on other information, FDA 
concluded that there was a favorable risk:benefit profile for orally 
administered neomycin sulfate preparations as adjunctive therapy for 
preoperative suppression of intestinal bacteria and for the treatment 
of hepatic coma. However, consistent with the findings published in the 
proposed rule, FDA concluded in the final rule that the risks of 
adverse reactions from the use of the product for wound irrigation 
resulted in systemic absorption and a resultant risk of adverse 
reactions that significantly outweighed any demonstrated benefits. 
Accordingly, the final rule amended the antibiotic drug regulations by 
changing the product name from ``neomycin sulfate for prescription 
compounding'' to ``neomycin sulfate for compounding oral products'' and 
by requiring package insert labeling to provide information concerning 
the appropriate uses of the product and to warn about the risks 
associated with inappropriate use.
    Under docket number FDA-1987-D-0240, FDA proposed to issue an order 
under section 505(e) of the Federal Food, Drug, and Cosmetic Act (FD&C 
Act) (21 U.S.C. 355(e)) withdrawing approval of six antibiotic drug 
applications and abbreviated antibiotic drug applications (AADAs) \2\ 
for nonsterile neomycin sulfate for prescription compounding products 
unless the application holders submitted supplemental applications 
providing for a product name and labeling consistent with the revised 
name and labeling requirements described in the newly amended 
antibiotic certification regulations (53 FR 12662).\3\ In the document, 
FDA announced the availability of guideline labeling for nonsterile 
neomycin sulfate for prescription compounding products that 
manufacturers could adopt to ensure that their labeling would be 
consistent with the labeling required by the revised antibiotic 
certification regulations. The proposed order was based on clinical or 
other experience, tests, or other scientific data that showed 
nonsterile neomycin sulfate was unsafe for use except when named 
``Neomycin Sulfate for Compounding Oral Products'' and used in 
accordance with package insert labeling that provides information 
concerning appropriate uses and that warns about risks associated with 
inappropriate use. Under section 505 and the regulations promulgated at 
21 CFR parts 310 and 314, the holders of the applications were given 
the opportunity for a hearing to show why approval should not be 
withdrawn. One application holder, Pharma-Tek, Inc. (Pharma-Tek), 
requested a hearing to challenge FDA's proposal to withdraw approval of 
its application, AADA 61-579. On December 6, 1988, FDA announced the 
withdrawal of approval of five of the six applications for nonsterile 
neomycin sulfate for prescription compounding for which the holders had 
not requested a hearing (53 FR 49231). The AADA for neomycin sulfate 
for prescription compounding, AADA 61-579, held by Pharma-Tek, was not 
withdrawn at that time because of the sponsor's pending hearing 
request. Today, this application corresponds to ANDA 061579 held by X-
Gen Pharmaceuticals, Inc. (X-Gen).
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    \2\ The terms ``antibiotic drug applications'' and ``abbreviated 
antibiotic drug applications'' are no longer used. AADAs approved 
under section 507 of the FD&C Act on or before November 20, 1997, 
are deemed to have been approved under section 505(j) of the FD&C 
Act.
    \3\ This proposed regulatory action was necessary because the 
antibiotic drug certification regulations did not apply to products 
with applications in which FDA had approved alternative labeling.
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    X-Gen informed FDA by letter dated October 9, 2015, that it was 
withdrawing the hearing request previously filed on behalf of its 
predecessor Pharma-Tek concerning ANDA 061579. X-Gen also informed FDA 
that it waived the opportunity for a hearing and, under 21 CFR 
314.150(d), X-Gen permitted the Agency to withdraw approval of ANDA 
061579 for neomycin sulfate for prescription compounding.
    For the reasons discussed in the document published in the Federal 
Register on April 15, 1988, under docket number FDA-1987-D-0240, the 
Director of FDA's Center for Drug Evaluation and Research finds that 
ANDA 061579 was withdrawn from sale for safety and effectiveness 
reasons (21 CFR 314.161(c)). The Director, under section 505(e) of the 
FD&C Act and under authority delegated to her by the Commissioner, also 
finds that new evidence of clinical experience, not contained in ANDA 
061579 and not available at the time the application was approved, 
evaluated together with the evidence available to the Secretary when 
the application was approved, shows that nonsterile neomycin sulfate 
for prescription compounding is not shown to be safe for use under the 
conditions of use upon the basis of which the application was approved 
(21 U.S.C. 355(e)). Therefore, approval of ANDA 061579 is hereby 
withdrawn.
    Under 21 CFR 314.161(e) and 314.162(a)(2), FDA will remove ANDA 
061579 from the list of drug products with effective approvals 
published in FDA's ``Approved Drug Products With Therapeutic 
Equivalence Evaluations.''

    Dated: January 23, 2019.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2019-01131 Filed 2-4-19; 8:45 am]
 BILLING CODE 4164-01-P