[Federal Register: April 9, 2007 (Volume 72, Number 67)]
[Notices]
[Page 17556-17558]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr09ap07-83]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 1978N-0224 (formerly Docket No. 78N-0224); DESI 11853]
Trimethobenzamide Hydrochloride Suppositories; Withdrawal of
Approval
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA) is announcing the
resolution of issues concerning trimethobenzamide hydrochloride
suppositories. This notice announces the withdrawal of approval of the
new drug application (NDA) for Tigan (trimethobenzamide hydrochloride)
Suppositories. The notice also declares that the marketing of
unapproved trimethobenzamide hydrochloride suppository products is
unlawful and subject to FDA regulatory action. FDA is taking these
actions because trimethobenzamide hydrochloride suppositories lack
substantial evidence of effectiveness.
ADDRESSES: Requests for an opinion on the applicability of this notice
to a specific trimethobenzamide hydrochloride suppository product
should be identified with Docket No. 1978N-0224 and reference number
DESI 11853 and directed to the Office of Compliance, Division of New
Drugs and Labeling Compliance (HFD-310), New Drugs and Labeling Team,
Center for Drug Evaluation and Research, Food and Drug Administration,
11919 Rockville Pike, Rockville, MD 20852.
DATE: Effective May 9, 2007.
FOR FURTHER INFORMATION CONTACT: Brian L. Pendleton, Center for Drug
Evaluation and Research (HFD-7), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857, 301-594-2041.
SUPPLEMENTARY INFORMATION:
I. Background
As part of its Drug Efficacy Study Implementation (DESI) program,
in a notice published in the Federal Register on February 24, 1971 (36
FR 3435) (the 1971 notice), FDA announced the following conclusions
regarding certain drug products that contain trimethobenzamide
hydrochloride: (1) The products were probably effective for nausea and
vomiting due to radiation therapy or travel sickness and for emesis
associated with operative procedures, labyrinthitis, or Meniere's
syndrome; (2) they were lacking substantial evidence
[[Page 17557]]
of effectiveness for the treatment of nausea and vomiting due to
infections, underlying disease processes, or drug administration; and
(3) they were possibly effective for all other labeled indications. The
1971 notice listed three trimethobenzamide hydrochloride products:
Tigan Solution for Injection (NDA 11-853), Tigan Capsules (NDA 11-854),
and Tigan Suppositories (NDA 11-855). Roche Laboratories held the NDAs
for these three products.
On January 9, 1979, we published a notice in the Federal Register
(44 FR 2021) (the 1979 suppository notice) announcing that we were
reclassifying trimethobenzamide hydrochloride suppositories to lacking
substantial evidence of effectiveness and proposing to withdraw
approval of the NDAs for trimethobenzamide hydrochloride suppositories.
The 1979 suppository notice stated that NDA 17-529 for Tigan
Suppositories, held by Beecham Laboratories (Beecham), had not been
included in the 1971 notice, but was affected by the new notice. (In
the same issue of the January 9, 1979, Federal Register (44 FR 2017)
(the 1979 injection and capsule notice), we published a notice
announcing that we were reclassifying trimethobenzamide hydrochloride
injection and capsules to effective for certain indications and to
lacking substantial evidence of effectiveness for their other
(previously designated) less-than-effective indications. On December
24, 2002, we published the final evaluation for trimethobenzamide
hydrochloride injection and capsules (67 FR 78476).)
In the 1979 suppository notice, we gave notice of an opportunity
for a hearing to the holders of the NDAs for trimethobenzamide
hydrochloride suppositories, and to all other interested persons,
stating that we proposed to issue an order under section 505(e) of the
Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 355(e))
withdrawing approval of the NDAs and all amendments and supplements
thereto (44 FR 2021 at 2021 to 2022). We stated that the notice of an
opportunity for a hearing encompassed all issues relating to the legal
status of the drug products subject to the notice, including identical,
related, or similar drug products as defined in Sec. 310.6 (21 CFR
310.6) of our regulations. In accordance with section 505 of the act
and parts 310 and 314 (21 CFR parts 310 and 314), we gave the holders
of the NDAs and all other persons who manufacture or distribute a drug
product that is identical, related, or similar to a drug product named
in the notice an opportunity for a hearing to show why approval of the
NDAs involved should not be withdrawn, and an opportunity to raise, for
administrative determination, all issues relating to the legal status
of a named drug product and all identical, related, or similar drug
products (44 FR 2021 at 2022).
The 1979 suppository notice stated that the failure of an applicant
or any other person subject to the notice to file a timely written
appearance and request for a hearing, as required by Sec. 314.200,
constituted an election by the person not to make use of the
opportunity for a hearing and a waiver of any contentions concerning
the legal status of any drug product subject to the notice. The notice
further stated that any such drug product could not thereafter lawfully
be marketed, and we would initiate appropriate regulatory action to
remove such drug products from the market (44 FR 2021 at 2022).
In a letter dated January 30, 1979, Beecham requested a hearing on
the proposed withdrawal of NDA 17-529 for Tigan Suppositories. In a
letter dated March 5, 1979, Beecham submitted data in support of its
request for a hearing. Beecham was the only party to request a hearing.
On April 13, 1979, we published a notice in the Federal Register
announcing that we were withdrawing the approval of NDA 11-8550 (the
only other NDA named in the 1979 suppository notice), effective April
23, 1979 (44 FR 22199).
On November 12, 1999, King Pharmaceuticals, Inc., 501 Fifth St.,
Bristol, TN 37620 (King), purchased from Roberts Pharmaceutical Corp.
the NDAs for the Tigan products previously held by Beecham: NDA 17-529
(suppositories), NDA 17-530 (injection), and NDA 17-531 (capsules). We
subsequently initiated discussions with King on bringing the Tigan
products into compliance with the 1979 notices on trimethobenzamide
hydrochloride drugs.
In an agreement that became effective on August 16, 2001 (the
Agreement), FDA and King agreed to take several actions to resolve the
matter of the compliance of Tigan products with the 1979 notices. Among
other things, King agreed to withdraw the request for a hearing
(originally submitted by Beecham) on matters related to NDAs 17-529
(Tigan Suppositories), 17-530 (Tigan Injection), and 17-531 (Tigan
Capsules), and all amendments and supplements thereto, within 10 days
of the effective date of the Agreement. In a letter dated August 24,
2001, King withdrew its request for a hearing on these matters in
accordance with the Agreement. The issues relating to Tigan Capsules
and Injection were resolved in 2001 and 2002, and on December 24, 2002,
we published a notice in the Federal Register announcing our final
evaluation of these products (67 FR 78476).
II. Resolution of Issues Concerning Tigan Suppositories
King notified us in a letter dated March 21, 2005, that it had
decided not to pursue additional studies for Tigan Suppositories. In a
letter dated August 19, 2005, we asked King, in accordance with the
Agreement, to request the withdrawal of NDA 17-529 for Tigan
Suppositories. In a letter dated September 6, 2005, King requested that
we withdraw NDA 17-529.
As stated in section I of this document, King has withdrawn its
request for a hearing on matters related to NDA 17-529. No party other
than Beecham (a previous holder of NDA 17-529) submitted a request for
a hearing in response to the 1979 suppository notice. Therefore, all
other parties waived any possible contentions regarding the legal
status of their trimethobenzamide hydrochloride suppository products.
III. Withdrawal of Approval of NDA 17-529 for Tigan Suppositories
As a result of the events described in section II of this document,
we have concluded that Tigan Suppositories have not been shown to be
effective. Therefore, we are withdrawing approval of the NDA for this
product.
Under Sec. 310.6, this notice applies to any drug product that is
identical, related, or similar to Tigan Suppositories and is not the
subject of an approved NDA. Any person who wishes to determine whether
a specific product is covered by this notice should write to the
Division of New Drugs and Labeling Compliance (see ADDRESSES).
The Director of the Center for Drug Evaluation and Research, under
section 505(e) of the act and under the authority delegated to him,
finds that, on the basis of the information in this docket on Tigan
Suppositories (NDA 17-529), evaluated together with the evidence
available to FDA when the application for this product was approved,
there is a lack of substantial evidence that this product has the
effect it purports or is represented to have under the conditions of
use prescribed, recommended, or suggested in its labeling.
Therefore, based on the foregoing finding, the approval of NDA 17-
529, including all amendments and supplements thereto, is withdrawn
effective May 9, 2007. Shipment in interstate commerce of Tigan
Suppositories or any identical, related, or similar trimethobenzamide
[[Page 17558]]
hydrochloride suppository product that is not the subject of an
approved NDA will then be unlawful.
We note that under enforcement policies regarding drugs marketed
without required applications described in the agency's guidance
entitled Marketed Unapproved Drugs--Compliance Policy Guide, it is a
high priority for the agency to take enforcement action against those
unapproved drug products that lack evidence of effectiveness. Firms
should be aware that we intend to take enforcement action without
further notice against any firm that manufactures or ships in
interstate commerce any unapproved product covered by this notice after
May 9, 2007. Firms that discontinue or have already discontinued
manufacturing products covered by this notice may want to notify us
that they are no longer manufacturing those products. A firm that
wishes to notify us of product discontinuation should send a letter,
signed by the firm's chief executive officer, fully identifying the
discontinued product, including its National Drug Code (NDC) number.
The firm should send the letter to the Division of New Drugs and
Labeling Compliance, New Drugs and Labeling Team (see ADDRESSES). Firms
should also update the listing of their products under section 510(j)
of the act (21 U.S.C. 360(j)) to reflect discontinuation of unapproved
or otherwise discontinued products. We plan to rely on our existing
records, the results of a subsequent inspection, or other available
information when we evaluate whether to take enforcement action.
Dated: March 14, 2007.
Douglas C. Throckmorton,
Deputy Director, Center for Drug Evaluation and Research.
[FR Doc. E7-6593 Filed 4-6-07; 8:45 am]
BILLING CODE 4160-01-S