[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and 8 Milligrams/2 Milligrams, Were Not Withdrawn From Sale for Reasons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withdrawn from sale for reasons of safety or effectiveness.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.
[[Page 34109]]
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