
[Federal Register Volume 79, Number 137 (Thursday, July 17, 2014)]
[Notices]
[Pages 41699-41700]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2014-16820]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2011-N-0021]


AbbVie Inc., et al.; Withdrawal of Approval of Abbreviated New 
Drug Applications for Prescription Pain Medications Containing More 
Than 325 Milligrams of Acetaminophen

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is withdrawing approval 
of 7 abbreviated new drug applications (ANDAs) for prescription drug 
products containing more than 325 milligrams (mg) of acetaminophen. The 
holders of these ANDAs have waived their opportunity for a hearing.

DATES: Effective July 17, 2014.

FOR FURTHER INFORMATION CONTACT: Rachel Turow, Center for Drug 
Evaluation and Research (CDER), Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6236, Silver Spring, MD 20993-0002, 301-
796-5094.

SUPPLEMENTARY INFORMATION: In the Federal Register of January 14, 2011 
(76 FR 2691), FDA announced its plans to reduce the maximum dosage unit 
strength of acetaminophen in prescription drug products. The notice 
announced FDA's conclusion that, based on a reevaluation of the 
relative risks and benefits of prescription acetaminophen products, 
fixed-combination prescription drugs containing more than 325 mg of 
acetaminophen per dosage unit (tablet, capsule, or liquid) do not 
provide a sufficient margin of safety to protect the public against the 
serious risk of acetaminophen-induced liver injury. Accordingly, we 
asked product sponsors to limit the maximum amount of acetaminophen per 
dosage unit to 325 mg and, for those products containing more than 325 
mg of acetaminophen per dosage unit, to submit requests that FDA 
withdraw approval of their applications under Sec.  314.150(d) (21 CFR 
314.150(d)). FDA asked that all such requests be made before January 
14, 2014, after which date the Agency planned to initiate proceedings 
under section 505(e) of the Federal Food, Drug, and Cosmetic Act (the 
FD&C Act) (21 U.S.C. 355(e)) to withdraw approval of any prescription 
drug products containing more than 325 mg of acetaminophen per dosage 
unit that remained on the market.
    FDA did not receive a request for withdrawal of approval of an 
application containing more than 325 mg of acetaminophen per dosage 
unit from one sponsor. In addition, FDA received requests for 
withdrawal of approval of five applications for products containing 
more than 325 mg of acetaminophen per dosage unit for which sponsors 
either submitted requests under Sec.  314.150(c) or failed to cite a 
relevant regulatory provision. FDA contacted all of these sponsors on 
multiple occasions to ask that they submit a request that FDA withdraw 
approval of their applications under Sec.  314.150(d), but they failed 
to respond.
    With respect to the application for which FDA received no request 
for withdrawal, FDA initiated proceedings under Sec.  314.150(a) and 
(b) to withdraw approval. With respect to the requests for withdrawal 
of approval submitted under Sec.  314.150(c), the Agency notes that 
because FDA has made a determination under Sec.  314.150(a) that 
approval of these applications should be withdrawn for reasons of 
safety, application holders may not withdraw their applications under 
Sec.  314.150(c). The text of Sec.  314.150(c) expressly precludes 
withdrawal of an application under the subsection if FDA has made a 
safety determination under Sec.  314.150(a). Similarly, when a request 
for withdrawal is made without a citation to any regulation, FDA does 
not consider it to be appropriately notified that an application holder 
has voluntarily waived the opportunity for a hearing. Accordingly, FDA 
decided to proceed with withdrawal of approval of applications for 
which sponsors either submitted requests under Sec.  314.150(c) or 
failed to cite a relevant regulatory provision under the withdrawal 
procedures outlined in Sec.  314.150 (a) and (b).
    Thus, in a notice published in the Federal Register on March 27, 
2014 (79 FR 17156), the Director of CDER offered an opportunity for a 
hearing on a proposal to issue an order, under section 505(e) of the 
FD&C Act and 21 CFR 314.150(a), withdrawing approval of 6 ANDAs for 
products containing more than 325 mg of acetaminophen for which the 
ANDA holders did not voluntarily request to withdraw their applications 
under Sec.  314.150(d). The ANDA holders were provided an opportunity 
to request a hearing to show why approval of their ANDAs should not be 
withdrawn. None of the ANDA holders requested a hearing in response to 
the notice.
    The ANDAs listed in table 1, other than ANDA 040148, were the 
subject of the March 27, 2014, Federal Register notice. Because the 
holders of these ANDAs failed to request a hearing by April 28, 2014, 
they are considered to have waived their opportunity for a hearing 
under Sec.  314.200(a)(2) and FDA is now withdrawing approval of their 
applications.
    In addition, table 1 includes ANDA 040148 for which the ANDA holder 
submitted a timely voluntary request for withdrawal under 314.150(d) 
and waived its opportunity for a hearing. However, ANDA 040148 was 
erroneously omitted from the March 27, 2014, Federal Register notice 
(79 FR 17163) announcing withdrawal of approval of 108 ANDAs. FDA is 
now withdrawing approval of ANDA 040148 as well.

[[Page 41700]]



          Table 1--ANDAs for Which FDA Is Withdrawing Approval
------------------------------------------------------------------------
       Application No.           Drug product(s)     Applicant or holder
------------------------------------------------------------------------
ANDA 40117..................  Vicodin HP            AbbVie Inc., 1 N.
                               (Acetaminophen and    Waukegan Rd., North
                               Hydrocodone           Chicago, IL 60064.
                               Bitartrate
                               Tablets), 660 mg/10
                               mg.
ANDA 88058..................  Vicodin               AbbVie Inc.
                               (Acetaminophen and
                               Hydrocodone
                               Bitartrate
                               Tablets), 500 mg/5
                               mg.
ANDA 89736..................  Vicodin ES            AbbVie Inc.
                               (Acetaminophen and
                               Hydrocodone
                               Bitartrate
                               Tablets), 750 mg/
                               7.5 mg.
ANDA 89166..................  SYNALGOS-DC-A         Leitner
                               (Acetaminophen,       Pharmaceuticals
                               Caffeine, and         LLC, 340 Edgemont
                               Dihydrocodeine        Ave., Bristol, TN
                               Bitartrate            37620.
                               Capsules), 356.4 mg/
                               30 mg/16 mg.
ANDA 40366..................  Acetaminophen and     Nesher
                               Hydrocodone           Pharmaceuticals USA
                               Bitartrate Oral       LLC, 13910 St.
                               Solution, 500 mg/15   Charles Rock Rd.,
                               milliliters (mL);     Bridgeton, MO
                               7.5 mg/15 mL.         63044.
ANDA 040148.................  Acetaminophen and     Watson Laboratories,
                               Hydrocodone           311 Bonnie Circle,
                               Bitartrate Tablets,   Corona, CA 92880.
                               500 mg/10 mg.
ANDA 040637.................  Acetaminophen,        West-Ward
                               Caffeine, and         Pharmaceutical
                               Dihydrocodeine        Corp., 435
                               Bitartrate Tablets,   Industrial Way
                               712.8 mg/60 mg/32     West, Eatontown, NJ
                               mg.                   07724.
------------------------------------------------------------------------

    With respect to the ANDAs listed in table 1 (with the exception of 
ANDA 040148), for the reasons discussed in the January 14, 2011, and 
March 27, 2014, notices, the Director of CDER, under section 505(e)(2) 
of the FD&C Act and under authority delegated to her by the 
Commissioner of Food and Drugs (the Commissioner), finds that new 
evidence of clinical experience, not contained in the applications 
listed in table 1 and not available at the time the applications were 
approved, shows that prescription drugs containing more than 325 mg of 
acetaminophen per dosage unit are not safe for use under the conditions 
of use that formed the basis upon which the applications were approved 
(21 U.S.C. 355(e)(2)). Therefore, approval of the applications for the 
drug products listed in table 1 of this document (with the exception of 
ANDA 040148), and all amendments and supplements thereto, is withdrawn 
(see DATES). Distribution of these products in interstate commerce 
without an approved application is illegal and subject to regulatory 
action (see sections 505(a) and 301(d) of the FD&C Act (21 U.S.C. 
355(a) and 331(d)).
    With respect to ANDA 040148 listed in table 1, under Sec.  
314.150(d), and under authority delegated to the Director of CDER by 
the Commissioner, approval of ANDA 040148 and all amendments and 
supplements thereto, is withdrawn (see DATES).
    The safety issue discussed in this document and the March 27, 2014, 
and January 14, 2011, Federal Register notices is limited to products 
containing more than 325 mg of acetaminophen per dosage unit. Thus, the 
withdrawal of approval of products containing more than 325 mg of 
acetaminophen per dosage unit listed in table 1 does not change the 
approval status of any products with 325 mg or less of acetaminophen 
per dosage unit that were approved under the same application. In 
addition, the withdrawal of approval of products containing more than 
325 mg of acetaminophen per dosage unit does not change the approval 
status of products with 325 mg or less of acetaminophen per dosage unit 
that refer to or rely on the withdrawn products. For example, this 
withdrawal action will not affect the approval status of an ANDA for a 
product that contains 325 mg or less per dosage unit that references a 
product listed in table 1, but for which FDA approved a suitability 
petition for a lower strength under section 505(j)(2)(C) of the FD&C 
Act and Sec.  314.93 (21 CFR 314.93)).

    Dated: July 14, 2014.
Peter Lurie,
Associate Commissioner for Policy and Planning.
[FR Doc. 2014-16820 Filed 7-16-14; 8:45 am]
BILLING CODE 4164-01-P


