[Federal Register Volume 80, Number 220 (Monday, November 16, 2015)]
[Notices]
[Pages 70822-70825]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-28853]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-1977-N-0356 (Formerly 77N-0240); DESI 1786]
Drugs for Human Use; Drug Efficacy Study Implementation;
Nitroglycerin Transdermal Systems; Withdrawal of Hearing Request;
Withdrawal of Applications; Final Resolution of Hearing Requests
Regarding Transdermal Systems Under Docket
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
that all outstanding hearing requests regarding nitroglycerin drug
[[Page 70823]]
products in transdermal systems under Docket No. FDA-1977-N-0356
(formerly 77N-0240) (DESI 1786) have been withdrawn. Therefore,
shipment in interstate commerce of any nitroglycerin drug product in a
transdermal system identified in this docket, or any identical,
related, or similar (IRS) product, that is not the subject of an
approved new drug application (NDA) or abbreviated new drug application
(ANDA) is unlawful as of the effective date of this notice.
DATES: Effective Date: This notice is effective November 16, 2015.
ADDRESSES: You may submit comments as follows:
Electronic Submissions
Submit electronic comments in the following way:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to http://www.regulations.gov
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on http://www.regulations.gov.
If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').
Written/Paper Submissions
Submit written/paper submissions as follows:
Mail/Hand delivery/Courier (for written/paper
submissions): Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
For written/paper comments submitted to the Division of
Dockets Management, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-1977-N-0356 for ``Drugs for Human Use; Drug Efficacy Study
Implementation; Nitroglycerin Transdermal Systems; Withdrawal of
Hearing Request; Withdrawal of Applications; Final Resolution of
Hearing Requests Regarding Transdermal Systems Under Docket.'' Received
comments will be placed in the docket and, except for those submitted
as ``Confidential Submissions,'' publicly viewable at http://www.regulations.gov or at the Division of Dockets Management between 9
a.m. and 4 p.m., Monday through Friday.
Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on http://www.regulations.gov.
Submit both copies to the Division of Dockets Management. If you do not
wish your name and contact information to be made publicly available,
you can provide this information on the cover sheet and not in the body
of your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law. For more information about FDA's posting of
comments to public dockets, see 80 FR 56469, September 18, 2015, or
access the information at: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to http://www.regulations.gov and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Division of Dockets Management, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Barbara Wise, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 5160, Silver Spring, MD 20993-0002, 301-
796-2089, email: [email protected].
SUPPLEMENTARY INFORMATION:
I. Background
When enacted in 1938, the Federal Food, Drug, and Cosmetic Act (the
FD&C Act) required that ``new drugs'' (21 U.S.C. 321(p)) be approved
for safety by FDA before they could legally be sold in interstate
commerce. Between 1938 and 1962, if a drug obtained approval, FDA
considered drugs that were IRS (see 21 CFR 310.6(b)(1)) to the approved
drug to be covered by that approval, and allowed those IRS drugs to be
marketed without independent approval.
In 1962, Congress amended the FD&C Act to require that new drugs be
proven effective for their labeled indications, as well as safe, in
order to obtain FDA approval. This amendment also required FDA to
conduct a retrospective evaluation of the effectiveness of the drug
products that FDA had approved as safe between 1938 and 1962. FDA
contracted with the National Academy of Science/National Research
Council (NAS/NRC) to make an initial evaluation of the effectiveness of
over 3,400 products that had been approved only for safety between 1938
and 1962. The NAS/NRC reports for these drug products were submitted to
FDA in the late 1960s and early 1970s. The Agency reviewed and
reevaluated the reports and published its findings in Federal Register
notices. FDA's administrative implementation of the NAS/NRC reports was
called the Drug Efficacy Study Implementation (DESI). DESI covered the
approximately 3,400 products specifically reviewed by the NAS/NRC, as
well as the even larger number of IRS products that entered the market
without FDA approval.
All drugs reviewed under DESI are ``new drugs'' under the FD&C Act.
If FDA's final DESI determination classifies a drug product as lacking
substantial evidence of effectiveness for one or more indications, that
drug product and those IRS to it may no longer be marketed for such
indications and are subject to enforcement action as unapproved new
drugs. If FDA's final DESI determination classifies the drug product as
effective for one or more of its labeled indications, the drug can be
marketed for such indications, provided it is the subject of an
application approved for safety and effectiveness. Sponsors of drug
products that have been found to be effective for one or more
indications through the DESI process may rely on FDA's effectiveness
[[Page 70824]]
determinations, but typically must update their labeling to conform to
the indication(s) found to be effective by FDA and include any
additional safety information required by FDA. Those drug products with
NDAs approved before 1962 for safety therefore require approved
supplements to their original applications if one or more indications
are found to be effective under DESI; IRS drug products require an
approved NDA or ANDA, as appropriate. Furthermore, labeling for drug
products classified as effective may contain only those indications for
which the review found the product effective unless the firm marketing
the product has received an approval for the additional indication(s).
II. Final Resolution of Hearing Requests Regarding Nitroglycerin
Transdermal Systems Under Docket No. FDA-1977-N-0356 (formerly 77N-
0240); DESI 1786
In a Federal Register notice published in February 1972, FDA
announced its evaluation of reports received from NAS/NRC regarding
certain single-entity coronary vasodilators, including controlled-
release nitroglycerin tablets, for indications relating to the
management, prophylaxis, and treatment of angina attacks (37 FR 4001,
February 25, 1972). In a Federal Register notice published in December
1972, FDA temporarily exempted specified single-entity coronary
vasodilators covered by DESI from the time limits established for
completing DESI (37 FR 26623 at 26624, December 14, 1972). The December
1972 notice did not initially include controlled-release forms of the
drugs, but a notice published in July 1973 allowed the case-by-case
addition of controlled-release dosage forms, pending the completion of
scientific studies that showed a drug was released in a defined manner
which would permit well-controlled clinical trials to determine
effectiveness (38 FR 18477, 18478, July 11, 1973; corrected by 38 FR
19920, July 25, 1973).
The December 1972 notice was amended again in August 1977, to
announce the addition of controlled-release forms of specified coronary
vasodilators, and the availability of guidelines and methods for
determining the bioavailability of coronary vasodilators (42 FR 43127,
August 26, 1977). The August 1977 notice specifically added
nitroglycerin (topical ointment forms, conventional oral forms, and
controlled release forms) to the list of drugs allowed to remain on the
market while efficacy studies were conducted (42 FR 43127 at 43128).
The December 1972 notice was further amended in October 1977, to extend
the deadlines for submission of data and applications required for the
coronary vasodilator products, and to announce the availability of
guidelines for alternative methods of determining bioavailability for
these products (42 FR 56156, October 21, 1977). Controlled-release
transdermal nitroglycerin patches were included among the types of
drugs permitted to remain on the market pending completion of efficacy
studies based on their similarity to nitroglycerin ointment products
(58 FR 38129 at 38130, July 15, 1993).
In July 1993, FDA revoked the temporary exemption for single-entity
coronary vasodilator products containing nitroglycerin in a transdermal
delivery system, which had allowed the products to stay on the market
beyond the time limit scheduled for the implementation of DESI (58 FR
38129). FDA found the products to be effective for prevention of angina
pectoris caused by coronary artery disease, and required sponsors to
submit bioavailability/bioequivalence studies within 1 year (see 58 FR
38129 at 38130 to 38131). In March 1999, FDA reclassified one NDA and
five ANDAs for nitroglycerin transdermal systems to lacking substantial
evidence of effectiveness, based on the sponsors' failure to submit the
required bioavailability/bioequivalence data (64 FR 14451, March 25,
1999). In the March 1999 notice, FDA proposed to withdraw approval of
the applications and offered an opportunity for a hearing on the
proposal to withdraw the applications.
In response to the March 1999 notice, Schwarz Pharma, Inc. (Schwarz
Pharma), now a subsidiary of UCB, S.A., which was the sponsor of two of
the five ANDAs, and Hercon Laboratories Corp. (Hercon), which was the
sponsor of the remaining three ANDAs, requested hearings.\1\ G.D.
Searle & Co., which was the sponsor of the identified NDA, did not
submit a hearing request.
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\1\ The March 1999 notice incorrectly referred to Hercon as
``Hercon Pharmaceutical Company, Inc.''
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At the request of Hercon, in the Federal Register of March 4, 2005
(70 FR 10651 at 10656), FDA withdrew approval of Hercon's three ANDAs
that were the subject of the 1999 notice of opportunity for a hearing.
On January 10, 2011, FDA sent a letter to Hercon to determine whether
it remained interested in pursuing its hearing request. On February 9,
2011, Hercon responded by withdrawing its hearing request. On July 17,
2002, Schwarz Pharma withdrew its hearing request and requested
withdrawal of its ANDAs that were the subject of the 1999 notice of
opportunity for a hearing.
There are no longer outstanding hearing requests for nitroglycerin
drug products in transdermal systems under this docket. Therefore, as
proposed in the March 1999 notice of opportunity for hearing, FDA finds
that the following applications lack substantial evidence of
effectiveness and hereby withdraws approval of the applications under
section 505(e) of the FD&C Act (21 U.S.C. 355): ANDA 88-727, DEPONIT
(release rate of 0.2 mg of nitroglycerin per hour), held by Schwarz
Pharma; ANDA 89-022, DEPONIT (release rate of 0.4 mg of nitroglycerin
per hour), held by Schwarz Pharma; and NDA 20-146, NITRODISC, held by
G.D. Searle & Co. Shipment in interstate commerce of any nitroglycerin
drug product in a transdermal system identified in this docket, or any
IRS product, that is not the subject of an approved NDA or ANDA is
unlawful as of the effective date of this notice (see DATES). Any
person who wishes to determine whether a specific product is covered by
this notice should write to Barbara Wise at the Center for Drug
Evaluation and Research (see FOR FURTHER INFORMATION CONTACT). Firms
should be aware that, after the effective date of this notice (see
DATES), 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.
III. Discontinued Products
Firms must notify the Agency of certain product discontinuations in
writing under section 506C(a) of the FD&C Act (21 U.S.C. 356c). See
http://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm142398.htm. Some
firms may have previously discontinued manufacturing or distributing
products covered by this notice without discontinuing the listing as
required under section 510(j) of the FD&C Act (21 U.S.C. 360(j)). Other
firms may discontinue manufacturing or distributing listed products in
response to this notice. All firms are required to electronically
update the listing of their products under section 510(j) of the FD&C
Act to reflect discontinuation of unapproved products covered by this
notice (21 CFR 207.21(b)). Questions on electronic drug listing updates
should be sent to [email protected]. In addition to the required
update, firms can also notify the Agency of product discontinuation by
sending a letter, signed by the firm's chief executive officer and
fully identifying the
[[Page 70825]]
discontinued product(s), including the product NDC number(s), and
stating that the manufacturing and/or distribution of the product(s)
have been discontinued. The letter should be sent electronically to
Barbara Wise (see FOR FURTHER INFORMATION CONTACT). FDA plans to rely
on its existing records, including its drug listing records, the
results of any future inspections, or other available information, when
it targets violative products for enforcement action.
IV. Reformulated Products
FDA cautions firms against reformulating products into unapproved
new drugs and marketing under the same name or substantially the same
name (including a new name that contains the old name). Reformulated
products marketed under a name previously identified with a different
active ingredient or combinations of active ingredients have the
potential to confuse health care practitioners and harm patients.
Dated: November 9, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-28853 Filed 11-13-15; 8:45 am]
BILLING CODE 4164-01-P