Document ID: FDA-1975-N-0355-0007
Agency: fda
Document Type: Notice
Title: Drugs for Human Use; Drug Efficacy Study Implementation; Certain
Prescription Drugs Offered for Various Indications; Final Resolution of
Hearing Requests Under Dockets
Posted Date: 2014-01-10T05:00Z

[Federal Register Volume 79, Number 7 (Friday, January 10, 2014)]
[Notices]
[Pages 1875-1877]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2014-00256]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket Nos. FDA-1975-N-0355 (Formerly 75N-0185), FDA-1976-N-0272 
(Formerly 76N-0056), FDA-1976-N-0344 (Formerly 76N-0057), FDA-1978-N-
0701 (Formerly 78N-0070), FDA-1979-N-0224 (Formerly 79N-0169), and FDA-
1983-N-0297 (Formerly 83N-0030); DESI 1626, 3265, 12283, and 50213]

Drugs for Human Use; Drug Efficacy Study Implementation; Certain 
Prescription Drugs Offered for Various Indications; Final Resolution of 
Hearing Requests Under Dockets

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing that all 
outstanding hearing requests pertaining to Docket Nos. FDA-1975-N-0355 
(formerly 75N-0185) (DESI 3265); FDA-1976-N-0272 (formerly 76N-0056), 
FDA-1976-N-0344 (formerly 76N-0057), and FDA-1978-N-0701 (formerly 78N-
0070) (DESI 1626); FDA-1979-N-0224 (formerly 79N-0169) (DESI 12283); 
and FDA-1983-N-0297 (formerly 83N-0030) (DESI 50213) have been 
withdrawn. Shipment in interstate commerce of any of the products 
identified in these dockets, or any identical, related, or similar 
(IRS) product to the products in these dockets, that is not the subject 
of an approved new drug application (NDA) or abbreviated new drug 
application (ANDA) (other than an over-the-counter (OTC) product that 
complies with an applicable OTC monograph) is unlawful as of the 
effective date of this notice.

DATES: Effective Date: This notice is effective January 10, 2014.

ADDRESSES: All communications in response to this notice should be 
identified with the appropriate docket number and directed to Sakineh 
Walther, Division of Prescription Drugs, Center for Drug Evaluation and 
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 
51, Rm. 5242, Silver Spring,

[[Page 1876]]

MD 20993-0002, sakineh.walther@fda.hhs.gov.

FOR FURTHER INFORMATION CONTACT: Sakineh Walther, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 5242, Silver Spring, MD 20993-0002, 301-
796-3349, sakineh.walther@fda.hhs.gov.

SUPPLEMENTARY INFORMATION:

I. Background

    In a notice published in the Federal Register of July 24, 2012 (77 
FR 43337) (the July 24, 2012, notice), FDA described the outstanding 
hearing requests pertaining to, among others, Docket Nos. FDA-1975-N-
0355 (formerly 75N-0185) (DESI 3265); FDA-1976-N-0272 (formerly 76N-
0056), FDA-1976-N-0344 (formerly 76N-0057), and FDA-1978-N-0701 
(formerly 78N-0070) (DESI 1626); FDA-1979-N-0224 (formerly 79N-0169) 
(DESI 12283); and FDA-1983-N-0297 (formerly 83N-0030) (DESI 50213) 
established under the Agency's Drug Efficacy Study Implementation 
(DESI) program. In the July 24, 2012, notice, FDA offered an 
opportunity for companies with outstanding hearing requests under those 
dockets to withdraw or affirm their outstanding hearing requests.

A. Docket No. FDA-1975-N-0355 (Formerly 75N-0185) (DESI 3265)

    In 1971, FDA published DESI efficacy findings for single-ingredient 
anticholinergic drugs for oral or injectable use containing dicyclomine 
hydrochloride (HCl), among other ingredients (36 FR 11754, June 18, 
1971). In a notice published on November 11, 1975 (40 FR 52644), FDA 
determined that the June 18, 1971, Federal Register notice should not 
have included drugs containing certain specified ingredients, including 
dicyclomine HCl, because the drugs containing those ingredients were 
not anticholinergic drugs (40 FR 52644 at 52648). Elsewhere in the 
Federal Register of November 11, 1975 (40 FR 52649), FDA published a 
notice concluding that dicyclomine HCl products, among other products 
covered by the notice, were less than effective and offering an 
opportunity for hearing regarding these drugs.
    On June 22, 1984, in response to the submission of data, FDA 
published a followup notice regarding single entity dicyclomine HCl 
products (49 FR 25681). In that notice, FDA concluded that such 
products were effective for the treatment of functional bowel/irritable 
bowel syndrome (irritable colon, spastic colon, and mucous colitis) and 
established conditions for their marketing and labeling (49 FR 25681 at 
25683 and 25684). The Agency also found, however, that the products 
were lacking substantial evidence of effectiveness for use in the 
treatment of acute enterocolitis or infant colic (49 FR 25681 at 25684) 
and offered an opportunity for hearing.
    At the time of the July 24, 2012, notice, there was one outstanding 
hearing request under this docket filed by Merrell-National 
Laboratories, 110 Amity Rd., Cincinnati, OH 45215, regarding Bentyl 
Capsules (NDA 7-409), Bentyl Injection (NDA 8-370), Bentyl Syrup (NDA 
7-961), and Dactil Tablets (NDA 8-907). FDA believes Sanofi-Aventis 
U.S. to be the successor-in-interest to Merrell-National Laboratories, 
but received no response to its attempt to contact Sanofi-Aventis U.S. 
regarding this hearing request in September 2011. In the July 24, 2012, 
notice, FDA provided the company an opportunity to affirm or withdraw 
its hearing request. Requests that were not affirmed within 30 days of 
that notice were to be deemed by FDA to be withdrawn.

B. Docket Nos. FDA-1976-N-0272 (Formerly 76N-0056), FDA-1976-N-0344 
(Formerly 76N-0057), and FDA-1978-N-0701 (Formerly 78N-0070) (DESI 
1626)

    In 1972, FDA classified certain combination drug products 
containing a xanthine derivative as lacking substantial evidence of 
effectiveness for some labeled indications and possibly effective for 
other labeled indications (37 FR 14895, July 26, 1972). As described in 
a Federal Register notice of February 29, 1984 (49 FR 7454), FDA 
subsequently handled these products in three groups:
    Group 1: Combinations containing 2 grains or less of a xanthine 
derivative, ephedrine, and 8 milligrams (mg) or less of phenobarbital 
(Docket No. FDA-1976-N-0344 (formerly 76N-0057));
    Group 2: Combinations containing more than 2 grains of xanthine 
derivative, more than 8 mg of phenobarbital, and/or an ingredient not 
considered as part of the OTC drug review (Docket No. FDA-1976-N-0272 
(formerly 76N-0056)); and
    Group 3: Combinations containing theophylline, ephedrine, and 
hydroxyzine HCl (Docket No. FDA-1978-N-0701 (formerly 78N-0070)).
    With respect to the products in Group 2, a notice of opportunity 
for hearing was published on April 9, 1976 (41 FR 15051). No hearing 
was requested, and approval of applications for products covered by 
Docket No. FDA-1976-N-0272 (formerly 76N-0056) (DESI 1626) were 
withdrawn by notice in the Federal Register published October 7, 1977 
(42 FR 54620).
    With respect to the products in Group 3, FDA granted a hearing in 
response to requests (49 FR 36443, September 17, 1984). The hearing 
requests were subsequently withdrawn, and approval of applications for 
products covered by Docket No. FDA-1078-N-0701 (formerly 78N-0070) 
(DESI 1626) were withdrawn by notice in the Federal Register published 
July 8, 1998 (63 FR 36923).
    With respect to the products in Group 1, in 1976, FDA granted 
temporary permission for the products to remain on the market because 
similar products had been marketed OTC in the past and were then 
undergoing review in the Over-the-Counter Drug Study (41 FR 15053, 
April 9, 1976). In 1984, FDA amended the April 1976 notice to include 
its analysis of new information regarding combination products 
containing a xanthine derivative (49 FR 7454, February 29, 1984). Based 
on its analysis of the new information, FDA concluded that there is a 
lack of substantial evidence: (1) That each ingredient contributes to 
the claimed effect of such combination drug products and (2) that the 
dosage of each component is such that the combinations are safe and 
effective for a significant patient population (49 FR 7454). Therefore, 
FDA proposed in the 1984 notice to withdraw approval of the 
applications for combination products containing a xanthine derivative 
and offered an opportunity for hearing regarding its proposal.
    At the time of the July 24, 2012, notice, there was one outstanding 
hearing request under Docket No. FDA-1976-N-0344 (formerly 76N-0057) 
filed by William P. Poythress & Co, Inc., 16 N. 22nd St., P.O. Box 
26946, Richmond, VA 23261, regarding an unidentified product containing 
a xanthine derivative, ephedrine, and 8 mg or less of phenobarbital. 
FDA was unable to find current contact information for William P. 
Poythress & Co, Inc. In the July 24, 2012, notice FDA provided this 
company an opportunity to withdraw or affirm its hearing request. 
Requests that were not affirmed within 30 days of that notice were to 
be deemed by FDA to be withdrawn.

C. Docket No. FDA-1979-N-0224 (Formerly 79N-0169) (DESI 12283)

    In 1979, FDA announced its DESI conclusions regarding the 
effectiveness of chlorthalidone for the treatment of hypertension and 
certain types of edema (44 FR 54124, September 18, 1979).

[[Page 1877]]

Specifically, FDA determined that there was substantial evidence to 
support the effectiveness of the 25- and 50-mg strengths for use in 
hypertension and edema, but that there was no longer justification for 
the 100-mg dosage form of chlorthalidone because of safety concerns at 
that dosage level (44 FR 54124 at 54126). In the 1979 notice, FDA 
proposed to withdraw approval of the 100-mg strength and offered an 
opportunity for hearing regarding its proposal.
    At the time of the July 24, 2012, notice, there was one outstanding 
hearing request under this docket filed by Generics International 
Division of Apotex, Inc., 2400 North Commerce Pkwy., Suite 400, Weston, 
FL 33326, regarding chlorthalidone. In the July 24, 2012, notice, FDA 
provided this company an opportunity to withdraw or affirm its hearing 
request. Requests that were not affirmed within 30 days of that notice 
were to be deemed by FDA to be withdrawn.

D. Docket No. FDA-1983-N-0297 (Formerly 83N-0030) (DESI 50213)

    Under Docket No. FDA-1983-N-0297 (formerly 83N-0030), FDA evaluated 
the evidence of effectiveness for certain fixed-combination drugs 
containing antibiotics and sulfonamides and determined that these 
products lacked substantial evidence of effectiveness (34 FR 6008, 
April 2, 1969). In the April 1969 Federal Register notice, FDA proposed 
to revoke provisions for certification of these products, and offered 
interested persons 30 days to submit data concerning the proposal. Data 
submitted in response to the April 1969 notice did not provide 
substantial evidence of effectiveness, so FDA amended the antibiotic 
regulations on June 30, 1970, by revoking provisions for the 
certification of these drugs (35 FR 10587, June 30, 1970). The order 
was to become effective in 40 days and allowed 30 days for interested 
persons to file objections and request a hearing. The time for 
responding to the June 1970 order was subsequently extended until 
August 17, 1970 (35 FR 12653, August 8, 1970).
    In response to the June 1970 order, Pfizer Inc. submitted data 
regarding its affected product, Urobiotic 250 Capsules, and requested a 
hearing. Despite the filing of timely objections, the amendments were 
inadvertently not stayed, and succeeding codifications of the 
antibiotic regulations did not explicitly provide for certification of 
Urobiotic 250 Capsules. However, FDA permitted Pfizer to continue 
distribution of its product pending resolution of the firm's hearing 
request. In July 2010, Pfizer voluntarily withdrew its application for 
Urobiotic (see 75 FR 42455, July 21, 2010).
    At the time of the July 24, 2012, notice, there was one outstanding 
hearing request under this docket filed by Pfizer, Inc., 235 East 42nd 
St., New York, NY 10017, regarding Urobiotic. As noted in the previous 
paragraph, the product itself was withdrawn, but FDA attempted to 
contact the company to verify that it no longer wished to pursue its 
hearing request. The company did not respond, and in the July 24, 2012, 
notice, FDA provided this company an opportunity to withdraw or affirm 
its hearing request. Requests that were not affirmed within 30 days of 
that notice were to be deemed by FDA to be withdrawn.

II. Resolution of Hearing Requests Pertaining to Dockets Subject to 
This Notice

    The time period for responding to the July 24, 2012, notice has 
elapsed, and no companies with outstanding hearing requests pertaining 
to the dockets listed in this document responded to the notice. Because 
no outstanding hearing requests relating to these dockets were affirmed 
in response to the July 24, 2012, notice (or in response to FDA's 
previous attempts to contact companies with outstanding hearing 
requests), all of the outstanding hearing requests pertaining to Docket 
Nos. FDA-1975-N-0355 (formerly 75N-0185) (DESI 3265); FDA-1976-N-0272 
(formerly 76N-0056), FDA-1976-N-0344 (formerly 76N-0057), and FDA-1978-
N-0701 (formerly 78N-0070) (DESI 1626); FDA-1979-N-0224 (formerly 79N-
0169) (DESI 12283); and FDA-1983-N-0297 (formerly 83N-0030) (DESI 
50213) are deemed to be withdrawn.
    Effective as of the date of this notice, it is unlawful to 
introduce into interstate commerce any of the products identified in 
any of the dockets included in this notice, or any IRS product to any 
product identified in these dockets, that is not the subject of an 
approved NDA or ANDA. Any person who wishes to determine whether a 
specific product is covered by this notice should write to the Center 
for Drug Evaluation and Research (see ADDRESSES).

III. Discontinued Products

    Some firms may have previously discontinued manufacturing or 
distributing products covered by this notice without removing them from 
the listing of their products under section 510(j) of the Federal Food, 
Drug, and Cosmetic Act (the FD&C Act) (21 U.S.C. 360(j)). Other firms 
may discontinue manufacturing or distributing listed products in 
response to this notice. Firms that wish to notify the Agency of 
product discontinuation should send a letter identifying the 
discontinued product(s), including the National Drug Code number(s), 
and stating that the manufacturing and/or distribution of the 
product(s) has (have) been discontinued. The letter should be sent 
electronically to Sakineh Walther (see ADDRESSES).
    Firms should also electronically update the listing of their 
products under section 510(j) of the FD&C Act to reflect 
discontinuation of products covered by this notice. Firms should be 
aware that, after the effective date of this notice, FDA intends to 
take enforcement action without further notice against any firm that 
manufactures or ships in interstate commerce any unapproved product 
covered by this notice.

    Dated: January 6, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-00256 Filed 1-9-14; 8:45 am]
BILLING CODE 4160-01-P