[Federal Register Volume 78, Number 109 (Thursday, June 6, 2013)]
[Notices]
[Pages 34108-34109]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-13446]



[[Page 34108]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2012-P-1034]


Determination That SUBOXONE (Buprenorphine Hydrochloride and 
Naloxone Hydrochloride) Sublingual Tablets, 2 Milligrams/0.5 Milligrams 
and 8 Milligrams/2 Milligrams, Were Not Withdrawn From Sale for Reasons 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) has determined that 
SUBOXONE (buprenorphine hydrochloride (HCl) and naloxone HCl) 
sublingual tablets, 2 milligrams (mg)/0.5 mg and 8 mg/2 mg, were not 
withdrawn from sale for reasons of safety or effectiveness. This 
determination will allow FDA to approve abbreviated new drug 
applications (ANDAs) for buprenorphine HCl and naloxone HCl sublingual 
tablets, 2 mg/0.5 mg and 8 mg/2 mg, if all other legal and regulatory 
requirements are met.

FOR FURTHER INFORMATION CONTACT: David E. Markert, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6248, Silver Spring, MD 20993-0002, 301-
796-3602.

SUPPLEMENTARY INFORMATION:

I. Background

    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 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.
    SUBOXONE (buprenorphine HCl and naloxone HCl) sublingual tablets, 2 
mg/0.5 mg and 8 mg/2 mg, are the subject of NDA 20-733, held by Reckitt 
Benckiser Pharmaceuticals, Inc. (Reckitt), and initially approved on 
October 8, 2002. SUBOXONE is indicated for maintenance treatment of 
opioid dependence.
    In a letter dated September 18, 2012, Reckitt notified FDA that 
SUBOXONE (buprenorphine HCl and naloxone HCl) sublingual tablets, 2 mg/
0.5 mg and 8 mg/2 mg, were being discontinued. Shortly thereafter, 
Reckitt publicly announced that it was discontinuing this product for 
safety reasons and that it had submitted a citizen petition requesting 
that FDA require all manufacturers of buprenorphine-containing products 
for the treatment of opioid dependence to implement certain public 
health safeguards (Ref. 1).\1\ Reckitt later informed the Agency that 
it ceased distributing SUBOXONE sublingual tablets in March 2013, at 
which time FDA moved the product to the ``Discontinued Drug Product 
List'' section of the Orange Book.
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    \1\ The citizen petition (Docket No. FDA-2012-P-1028), which was 
submitted on September 25, 2012, also requested that FDA refuse to 
approve any ANDAs for buprenorphine HCl and naloxone HCl products 
for opioid dependence until the Agency determined whether SUBOXONE 
sublingual tablets were discontinued for safety reasons. In its 
February 22, 2013, response to the citizen petition, FDA concluded 
that this request was premature because Reckitt had not yet 
withdrawn SUBOXONE sublingual tablets from sale. Nonetheless, the 
Agency conducted a full review and analysis of the safety issues 
raised in Reckitt's citizen petition and determined, on the basis of 
the data available at that time, that withdrawal of SUBOXONE 
sublingual tablets from sale was not necessary for reasons of 
safety.
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    Lachman Consultant Services, Inc. (Lachman), submitted a citizen 
petition dated September 27, 2012 (Docket No. FDA-2012-P-1034), under 
21 CFR 10.30, requesting that the Agency determine whether SUBOXONE 
(buprenorphine HCl and naloxone HCl) sublingual tablets, 2 mg/0.5 mg 
and 8 mg/2 mg, were withdrawn from sale for reasons of safety or 
effectiveness. The petitioner noted that Reckitt had publicly announced 
that it was discontinuing this product.
    After considering Lachman's citizen petition and reviewing our 
records, including the safety analysis that the Agency prepared in 
connection with Reckitt's citizen petition, FDA has determined under 
Sec.  314.161 that SUBOXONE (buprenorphine HCl and naloxone HCl) 
sublingual tablets, 2 mg/0.5 mg and 8 mg/2 mg, were not withdrawn for 
reasons of safety. We described the basis for this determination in our 
letter response to Reckitt's citizen petition (available at http://www.regulations.gov under Docket No. FDA-2012-P-1028). Since the 
issuance of that response, we have updated our reviews of relevant 
literature and data on this product. We found no additional information 
during this process that would indicate that SUBOXONE (buprenorphine 
HCl and naloxone HCl) sublingual tablets, 2 mg/0.5 mg and 8 mg/2 mg, 
were, or should have been, withdrawn from sale for reasons of safety.
    FDA has also determined under Sec.  314.161 that SUBOXONE 
(buprenorphine HCl and naloxone HCl) sublingual tablets, 2 mg/0.5 mg 
and 8 mg/2 mg, were not withdrawn for reasons of effectiveness. We have 
reviewed our records and other relevant data sources, and have found no 
information that would indicate that this product was ineffective as a 
maintenance treatment of opioid dependence.
    Accordingly, the Agency will continue to list SUBOXONE 
(buprenorphine HCl and naloxone HCl) sublingual tablets, 2 mg/0.5 mg 
and 8 mg/2 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. ANDAs that refer to 
SUBOXONE (buprenorphine HCl and naloxone HCl) sublingual tablets, 2 mg/
0.5 mg and 8 mg/2 mg, 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.

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II. References

    The following reference has been placed on display in the Division 
of Dockets Management (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, Rm. 1061, Rockville, MD 20852, and may be seen by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday, 
and is available electronically at http://www.regulations.gov. (FDA has 
verified the Web site address in this reference section, but FDA is not 
responsible for any subsequent changes to the Web site after this 
document publishes in the Federal Register.)

1. ``Further US RB Pharmaceuticals Announcement,'' http://www.rb.com/site/rkbr/templates/mediainvestorsgeneral2.aspx?pageid=1332&cc=GB, Reckitt Benckiser 
Group plc, September 25, 2012. Web. May 17, 2013.

    Dated: May 31, 2013.
Janet Woodcock,
Director, Center for Drug Evaluation and Research.
[FR Doc. 2013-13446 Filed 6-5-13; 8:45 am]
BILLING CODE 4160-01-P