[Federal Register Volume 85, Number 134 (Monday, July 13, 2020)]
[Notices]
[Pages 42002-42003]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-15010]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2020-N-1253 (formerly FDA-1987-N-0054)]


Pentaerythritol Tetranitrate; Final Decision on Proposal To 
Withdraw Approval From New Drug Applications and Abbreviated New Drug 
Applications; Availability of Final Decision

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA) is announcing that the 
initial decision of the Administrative Law Judge (ALJ), to withdraw 
approval of new drug applications (NDAs) and abbreviated new drug 
applications (ANDAs) for pentaerythritol tetranitrate (PETN), is the 
final decision of the Commissioner of Food and Drugs (the Commissioner) 
by operation of law. In the initial decision, the ALJ found that PETN 
had not been shown to be supported by substantial evidence consisting 
of adequate and well-controlled studies to be effective for 
prophylactic treatment of angina pectoris and ordered the withdrawal of 
approval for all NDAs and ANDAs. Several parties to the hearing filed 
exceptions to the ALJ's initial decision; however, all parties who 
submitted exceptions have since voluntarily withdrawn them, or FDA has 
deemed them withdrawn after their associated NDA or ANDA was withdrawn. 
Consequently, the proceeding is in the same procedural position as if 
no exceptions to the ALJ's initial decision had been filed. Therefore, 
the ALJ's initial decision has become the final decision of the 
Commissioner by operation of law.
    Applicable Date: This notice is applicable July 13, 2020.

ADDRESSES: For access to the docket, go to https://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 Dockets Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, 
MD 20852 between 9 a.m. and 4 p.m., Monday

[[Page 42003]]

through Friday. Publicly available submissions may be seen in the 
docket.

FOR FURTHER INFORMATION CONTACT: Rachael Vieder Linowes, Office of the 
Chief Scientist, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 1, Rm. 4206, Silver Spring, MD 20993, 240-402-5931.

SUPPLEMENTARY INFORMATION:

I. Background

    In 1962, the Federal Food, Drug, and Cosmetic Act (FD&C Act) was 
amended by the Drug Amendments of 1962 (Pub. L. 87-781), and these 
amendments provided that new drugs could no longer be approved unless 
both safety and efficacy had been established for them. As amended, the 
FD&C Act also required FDA to evaluate drugs approved as safe between 
1938 and 1962 to determine whether such drugs were effective and to 
withdraw approval for any applications where there was not substantial 
evidence of the drug's effectiveness. The person contesting the 
withdrawal of the approval had the burden of coming forward with 
evidence of effectiveness for the drug. FDA's review of these pre-1962 
drugs is known as the Drug Efficacy Study Implementation program.
    In a notice published in the Federal Register of February 25, 1972 
(37 FR 4001) available at https://www.govinfo.gov/content/pkg/FR-1972-02-25/pdf/FR-1972-02-25.pdf), after evaluating reports received from 
the National Academy of Sciences/National Research Council, Drug 
Efficacy Study Group, and other available evidence, FDA classified 
certain coronary vasodilators containing PETN as ``possibly effective'' 
for the management, prophylaxis, or treatment of angina attacks. Parke-
Davis, a Division of Warner Lambert Co. (Parke-Davis) submitted data 
intended to support the effectiveness of single-entity coronary 
vasodilator drugs containing PETN in the treatment of angina pectoris.
    In a notice published in the Federal Register of October 15, 1984 
(49 FR 40213, available at https://www.govinfo.gov/content/pkg/FR-1984-10-15/pdf/FR-1984-10-15.pdf), the Center for Drugs and Biologics (the 
Center) concluded that, after reviewing all the data previously 
submitted to support the effectiveness of single-entity coronary 
vasodilator drugs containing PETN in the treatment of angina pectoris, 
the data did not constitute substantial evidence of effectiveness for 
the listed drug products in the treatment of angina pectoris. Further, 
the Center issued a notice of opportunity for hearing on a proposal to 
withdraw approval of 15 total NDAs and ANDAs for certain coronary 
vasodilators containing PETN.
    Multiple manufacturers responded to the notice for opportunity of 
hearing and submitted requests for hearings. By a notice published in 
the Federal Register of August 26, 1987 (52 FR 32170), available at 
https://www.govinfo.gov/content/pkg/FR-1987-08-26/pdf/FR-1987-08-26.pdf), the Office of the Commissioner granted requests for hearing 
with respect to seven NDAs and two ANDAs. Following the submission of 
written testimony and documentary evidence, an ALJ, Daniel J. Davidson, 
conducted a hearing from October 5-26, 1988. He issued his initial 
decision on May 10, 1989. The ALJ found that the effectiveness of PETN 
had not been shown to be supported by substantial evidence and, as a 
result, ordered that the approval of all affected NDAs and ANDAs be 
withdrawn.
    On July 10, 1989, three parties, Parke-Davis, Jones Medical 
Industries, Inc. (Jones Medical) (formerly Marion Laboratories, Inc.), 
and Bolar Pharmaceutical Co., Inc., appealed the ALJ's initial decision 
by filing exceptions with the Commissioner under 21 CFR 12.125. 
However, since the three parties submitted their exceptions, FDA has 
withdrawn approval of all applications held by the three parties, 
either through withdrawal requests or, after notice and opportunity for 
hearing, for failure to file annual reports.
    The Commissioner now finds that all exceptions have either been 
withdrawn upon the party's request or are deemed withdrawn. For these 
reasons, the Commissioner concludes that there are no pending appeals 
of the ALJ's initial decision. Parke-Davis, by a letter dated June 11, 
1996, requested withdrawal of its exceptions. Watson Laboratories 
(successor to Bolar Pharmaceutical Co.) also submitted a letter dated 
November 9, 1999, requesting the withdrawal of its exceptions as to its 
NDA. The letter did not reference its ANDA, but the ANDA was withdrawn 
under a plea agreement with the United States pursuant to which Bolar 
Pharmaceutical Co. pled guilty to fraud and admitted to falsifying drug 
testing records (see July 6, 2016, 56 FR 43928), available at https://www.govinfo.gov/content/pkg/FR-1991-09-05/pdf/FR-1991-09-05.pdf). In 
light of those circumstances, the Commissioner interprets Watson 
Laboratories' request to withdraw exceptions to apply to both the NDA 
and the ANDA. When the Center for Drug Evaluation and Research (CDER) 
withdrew approval of Jones Medical's NDAs, CDER notified Jones Medical 
that its appeal in this proceeding was also regarded as withdrawn (see 
62 FR 61338, available at https://www.govinfo.gov/content/pkg/FR-1997-11-17/pdf/97-30148.pdf#page=1). Given that Jones Medical has never 
filed an objection to CDER's determination that its appeal and 
exceptions are regarded as withdrawn, the Commissioner affirms that 
Jones Medical's appeal and exceptions are deemed withdrawn.

II. Conclusion and Order

    Given that the exceptions have all been withdrawn or deemed 
withdrawn, this proceeding is now in the same procedural posture as if 
no exceptions had ever been filed. When parties do not file exceptions 
to the ALJ's initial decision, and the Commissioner does not file a 
notice of review, the ALJ's initial decision becomes the final decision 
of the Commissioner (see 21 CFR 12.120(e)). FDA will publish a notice 
in the Federal Register when an initial decision becomes the final 
decision of the Commissioner without appeal to or review by the 
Commissioner (see 21 CFR 12.120(f)).
    Therefore, the ALJ's initial decision is the final decision of the 
Commissioner. Pursuant to the findings in the ALJ's initial decision, 
under section 505(e) of the FD&C Act (21 U.S.C. 355(e)) and under the 
authority delegated by the Secretary of Health and Human Services, 
there is a lack of substantial evidence that PETN will have the effect 
it purports or is represented to have under the conditions of use 
prescribed, recommended, or suggested in its labeling for prophylactic 
treatment of angina pectoris. Distribution of products subject to the 
initial decision in interstate commerce without an approved application 
is prohibited and subject to regulatory action (see, e.g., sections 
505(a) and 301(d) of the FD&C Act (21 U.S.C. 355(a) and 331(d)).
    The full text of the ALJ's initial decision may be seen in the 
Dockets Management Staff and in this docket (see ADDRESSES).

    Dated: July 7, 2020.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2020-15010 Filed 7-10-20; 8:45 am]
BILLING CODE 4164-01-P