[Federal Register Volume 86, Number 10 (Friday, January 15, 2021)]
[Notices]
[Pages 4083-4084]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-00786]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration


FDA Drug Review Timeline Transparency; Statement of Policy

    The Department and its component agencies exist to serve the 
American people. Consistent with and in follow up to the Department's 
previous transparency efforts,\1\ and given the significant impact 
FDA's approval of drugs has on Americans, the Secretary believes the 
public would benefit from information regarding the timeline for FDA's 
review of drug product applications as provided in this document.
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    \1\ E.g., 85 FR 75893 (Nov. 27, 2020).
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    In 1962, Congress amended the Food, Drug, and Cosmetic Act (FD&C 
Act) to authorize the Food and Drug Administration (FDA) to review and 
approve ``new drugs'' for safety and efficacy.\2\ When Congress made 
this historic change to our nation's drug laws, it provided a timeframe 
for FDA's review. In section 104 of the Drug Amendments of 1962, 
codified at section 505(c) of the FD&C Act, 21 U.S.C. 355(c), Congress 
required that, for New Drug Applications (NDAs), ``[w]ithin one hundred 
eighty days after the filing of an application . . . , the Secretary 
shall either approve the application . . . or give the applicant notice 
of an opportunity for a hearing before the Secretary.'' As the Senate 
Judiciary Committee explained at the time, ``this provision strikes a 
balance between the need for governmental control to assure that new 
drugs are not placed on the market until they have passed the relevant 
tests and the need to insure that governmental control does not become 
so rigid that the flow of new drugs to the market, and the incentive to 
undergo the expense involved in preparing them for the market, become 
stifled.'' \3\
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    \2\ Drug Amendments of 1962, Pub. L. 87-781, 76 Stat. 780 (Oct. 
10, 1962).
    \3\ 1962 U.S.C.C.A.N. 2884, 2891.
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    At the time, the 180-day timeframe for review of ``new drugs'' was 
uncontroversial. At a 1963 public hearing, the Acting Director for 
FDA's Division of New Drugs stated that ``[a]pplications for drugs of 
questionable safety or effectiveness will continue to take more of 
every body's time.'' \4\ However, the Director ``pledge[d] action 
greatly short of the 180-day limit on all applications and supplements 
that present good scientific evidence of the safety and effectiveness 
of the drugs and that are properly informative to the physician or 
patient.'' \5\
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    \4\ Proceedings, FDA Conference on the Kefauver-Harris Drug 
Amendments and Proposed Regulations, at 7 (Feb. 15, 1963).
    \5\ Id. at 6.
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    When Congress made additional amendments to the FD&C Act in 1984, 
it borrowed from and applied the existing 180-day review framework to 
the review of Abbreviated New Drug Applications (ANDAs), the approval 
mechanism for generic drugs.\6\ Under section 505(j)(5)(A) of the FD&C 
Act, 21 U.S.C. 355(j)(5)(A), the Secretary ``shall approve or 
disapprove the [ANDA] application'' ``[w]ithin one hundred and eighty 
days of the initial receipt of an application.'' FDA promulgated 
regulations implementing the 180-day statutory provisions for review of 
NDAs and ANDAs. See 21 CFR 314.100, 314.101. While the Prescription 
Drug User Fee Act (PDUFA) and Generic Drug User Fee Act (GDUFA) in 
their iterative forms have provided FDA with additional resources to 
carry out its statutory mission, Congress did not do away with the 180-
day provisions in section 505 of the FD&C Act, 21 U.S.C. 355, in those 
laws.
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    \6\ Drug Price Competition and Patent Term Restoration Act of 
1984, Public Law 98-417, 98 Stat. 1585, 1588 (Sept. 24, 1984).
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    Though the agency has made strides over the years to expedite 
review in the face of limited resources, the total time elapsed between 
FDA's filing of an NDA or receipt of an ANDA to ultimate approval or 
disapproval of the application often exceeds 180 days. Even so, 
reporting on drug approvals, such as GAO's March 2020 report,\7\ 
focused primarily on agency compliance with PDUFA dates. The GAO report 
did not mention the 180-day benchmark or discuss the agency's approval 
timeframe in view of that requirement.
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    \7\ GAO, FDA Drug Approval, Application Review Times Largely 
Reflect Agency Goals (Mar. 2020), https://www.gao.gov/assets/710/705193.pdf.
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    Given this gap in reporting, the Department reviewed FDA's New Drug 
Therapy Approvals from 2019 \8\ in view of the 180-day timeframe. The 
Department's review considered 48 products listed by the agency as 
approved in 2019.\9\ The table below presents, among other things, the 
date of submission, date of approval, total days from submission to 
approval, and total days in excess of 180 days of submission for these 
drugs.
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    \8\ FDA, New Drug Therapy Approvals 2019, https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/new-drug-therapy-approvals-2019.
    \9\ In its review, the Department obtained the ``submission 
date'' (or, if available, ``filing date'') of the 48 drugs by 
searching documents available to the public on FDA's [email protected] 
website.

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                                 Summary of FDA-                                       Days
        Drug brand name          approved use on    Submission     Approval date   submission to  Days in excess
                                  approval date        date                          approval       of 180 days
----------------------------------------------------------------------------------------------------------------
Accrufer......................  Iron deficiency        9/27/2018       7/25/2019             301             121
                                 anemia.
Adakveo.......................  Reduce                 5/16/2019      11/15/2019             183               3
                                 vasoocclusive
                                 crises in
                                 sickle cell
                                 disease.
Aklief........................  Acne vulgaris...       10/4/2018       10/4/2019             365             185
Balversa......................  Locally advanced       9/18/2018       4/12/2019             206              26
                                 or metastatic
                                 bladder cancer.
Beovu.........................  Wet age-related         2/7/2019       10/7/2019             242              62
                                 macular
                                 degeneration.
Brukinsa......................  Mantle cell            6/27/2019      11/14/2019             140             N/A
                                 lymphoma.
Cablivi.......................  Acquired                6/6/2018        2/6/2019             245              65
                                 thrombotic
                                 thrombocytopeni
                                 c purpura.
Caplyta.......................  Schizophrenia...       9/27/2018      12/20/2019             449             269
Dayvigo.......................  Insomnia........      12/27/2018      12/20/2019             358             178
Egaten........................  Fascioliasis....       6/14/2018       2/13/2019             244              64
Enhertu.......................  Metastatic             8/29/2019      12/20/2019             113             N/A
                                 breast cancer.
Evenity.......................  Osteoporosis....        7/9/2018        4/9/2019             274              94
ExEm Foam.....................  Diagnostic agent       10/9/2018       11/7/2019             394             214
                                 for fallopian
                                 tube assessment.
Fetroja.......................  Complicated           12/14/2018      11/14/2019             335             155
                                 urinary tract
                                 infection.
fluorodopa F 18...............  Diagnostic agent       4/10/2019      10/10/2019             183               3
                                 for
                                 Parkinsonian
                                 syndromes.

[[Page 4084]]

 
Ga 68 DOTATOC.................  Diagnostic agent       5/23/2018       8/21/2019             455             275
                                 for
                                 neuroendocrine
                                 tumors.
Givlaari......................  Acute hepatic           6/4/2019      11/20/2019             169             N/A
                                 porphyria.
Ibsrela.......................  Irritable bowel        9/12/2018       9/12/2019             365             185
                                 syndrome with
                                 constipation.
Inrebic.......................  Certain types of        1/4/2019       8/16/2019             224              44
                                 myelofibrosis.
Jeuveau.......................  Improve                5/15/2017        2/1/2019             627             447
                                 appearance of
                                 glabellar lines
                                 (lines between
                                 eyebrows).
Mayzent.......................  Relapsing forms        6/28/2018       3/26/2019             271              91
                                 of multiple
                                 sclerosis.
Nourianz......................  Parkinson's            7/27/2019       8/27/2019              31             N/A
                                 disease ``off''
                                 episodes.
Nubeqa........................  Non-metastatic         2/26/2019       7/30/2019             154             N/A
                                 prostate cancer.
Oxbryta.......................  Sickle cell            6/26/2019      11/25/2019             152             N/A
                                 disease.
Padcev........................  Refractory             7/15/2019      12/18/2019             146             N/A
                                 bladder cancer.
Piqray........................  Advanced or           12/18/2018       5/24/2019             157             N/A
                                 metastatic
                                 breast cancer.
Polivy........................  Relapsed or           12/19/2018       6/10/2019             173             N/A
                                 refractory
                                 diffuse large B-
                                 cell lymphoma.
pretomanid....................  Treatment-            12/14/2018       8/14/2019             243              63
                                 resistant forms
                                 of tuberculosis.
Reblozyl......................  Anemia                  4/4/2019       11/8/2019             218              38
                                 associated with
                                 beta
                                 thalassemia.
Recarbrio.....................  Complicated           11/16/2018       7/16/2019             242              62
                                 urinary tract
                                 infections and
                                 complicated
                                 intra-abdominal
                                 infections
Reyvow........................  Migraine with or      10/11/2018      10/11/2019             365             185
                                 without aura.
Rinvoq........................  Moderately to         12/18/2018       8/16/2019             241              61
                                 severely active
                                 rheumatoid
                                 arthritis.
Rozlytrek.....................  Metastatic non-       12/18/2018       8/15/2019             240              60
                                 small cell lung
                                 cancer and
                                 locally
                                 advanced or
                                 metastatic
                                 solid tumors
                                 with a specific
                                 genetic defect.
Scenesse......................  Increase pain-         11/8/2018       10/8/2019             334             154
                                 free light
                                 exposure in
                                 patients with
                                 erythropoietic
                                 protoporphyria.
Skyrizi.......................  Moderate-to-            4/3/2018       4/23/2019             385             205
                                 severe plaque
                                 psoriasis.
Sunosi........................  Excessive             12/20/2017       3/20/2019             455             275
                                 daytime
                                 sleepiness in
                                 patients with
                                 narcolepsy or
                                 obstructive
                                 sleep apnea.
TissueBlue....................  Dye used in eye        4/29/2019      12/20/2019             235              55
                                 surgery.
Trikafta......................  Cystic Fibrosis.       7/19/2019      10/21/2019              94             N/A
Turalio.......................  Symptomatic            12/3/2018        8/2/2019             242              62
                                 tenosynovial
                                 giant cell
                                 tumor.
Ubrelvy.......................  Migraine........      12/26/2018      12/23/2019             362             182
Vyleesi.......................  Hypoactive             3/23/2018       6/21/2019             455             275
                                 sexual desire
                                 disorder in
                                 premenopausal
                                 women.
Vyndaqel......................  Cardiomyopathy         11/2/2018        5/3/2019             182               2
                                 caused by
                                 transthyretin-
                                 mediated
                                 amyloidosis.
Vyondys 53....................  Duchenne              12/19/2018      12/12/2019             358             178
                                 muscular
                                 dystrophy.
Wakix.........................  Excessive             12/14/2018       8/14/2019             243              63
                                 daytime
                                 sleepiness in
                                 patients with
                                 narcolepsy.
Xcopri........................  Partial-onset         11/21/2018      11/21/2019             365             185
                                 seizures.
Xenleta.......................  Community-            12/19/2018       8/19/2019             243              63
                                 acquired
                                 bacterial
                                 pneumonia.
Xpovio........................  Relapsed or             8/6/2018        7/3/2019             331             151
                                 refractory
                                 multiple
                                 myeloma.
Zulresso......................  Postpartum              4/9/2018       3/19/2019             344             164
                                 depression.
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    The Department found that 38 of the 48 drugs (79.1%) were approved 
more than 180 days after submission of an application. The average time 
from submission to approval for the 48 drugs in the table above was 
273.8 days. It should be noted that in many instances the failure to 
meet the 180-day statutory benchmark may have been justified and in 
such cases, was frequently the result of questions by the agency and 
responses by the applicant.
    Because FDA's approval of drugs affects the health and financial 
well-being of all Americans, the Department believes the public is 
entitled to information like the data provided in the table above 
regarding the amount of the time required for FDA review and approval 
of new and generic drugs. To that end, effective upon publication of 
this Notice, for all NDA and ANDA approvals, FDA must take the 
following action.
    FDA shall publish annually on its website, for each approved NDA 
and ANDA approved after the date of this publication, (a) the date on 
which FDA ``filed,'' in the case of an NDA, or ``received,'' in the 
case of an ANDA, such application; (b) the date on which FDA approved 
the NDA or ANDA; (c) the total days elapsed between the dates in (a) 
and (b); and (d) the total days in excess of 180-days the date of (c). 
For example, if an NDA was ``filed'' on January 25, 2021 and approved 
on December 27, 2021, then the total days elapsed for review would be 
336 days, and the days in excess of 180 days would be 156 days.
    Members of the public can use this information to further study the 
health and economic impacts of FDA review timelines. This reporting is 
also consistent with FDA's mission to ``promote the public health by 
promptly and efficiently reviewing clinical research and taking 
appropriate action on the marketing of regulated products in a timely 
manner.'' 21 U.S.C. 393(b)(1). In addition to educating the public, the 
Department believes this information will inform Congress as to whether 
to provide FDA with additional resources to carry out the agency's 
review obligations within the timeframe prescribed by Congress.

    Dated: January 8, 2021.
Alex M. Azar II,
Secretary, Department of Health and Human Services.
[FR Doc. 2021-00786 Filed 1-14-21; 8:45 am]
BILLING CODE 4150-26-P


