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 Department of Health and Human Services Food and Drug Administration
 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. 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] 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] 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. 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. 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. Drug brand name
Summary of FDA-approved use on approval date
Submission date
Approval date
Days
                             submission 
                             to approval
Days in
                             excess of 
                             180 daysAccrufer
Iron deficiency anemia
9/27/2018
7/25/2019
301
121Adakveo
Reduce vasoocclusive crises in sickle cell disease
5/16/2019
11/15/2019
183
3Aklief
Acne vulgaris
10/4/2018
10/4/2019
365
185Balversa
Locally advanced or metastatic bladder cancer
9/18/2018
4/12/2019
206
26Beovu
Wet age-related macular degeneration
2/7/2019
10/7/2019
242
62Brukinsa
Mantle cell lymphoma
6/27/2019
11/14/2019
140
N/ACablivi
Acquired thrombotic thrombocytopenic purpura
6/6/2018
2/6/2019
245
65Caplyta
Schizophrenia
9/27/2018
12/20/2019
449
269Dayvigo
Insomnia
12/27/2018
12/20/2019
358
178Egaten
Fascioliasis
6/14/2018
2/13/2019
244
64Enhertu
Metastatic breast cancer
8/29/2019
12/20/2019
113
N/AEvenity
Osteoporosis
7/9/2018
4/9/2019
274
94ExEm Foam
Diagnostic agent for fallopian tube assessment
10/9/2018
11/7/2019
394
214Fetroja
Complicated urinary tract infection
12/14/2018
11/14/2019
335
155fluorodopa F 18
Diagnostic agent for Parkinsonian syndromes
4/10/2019
10/10/2019
183
3( print page 4084)Ga 68 DOTATOC
Diagnostic agent for neuroendocrine tumors
5/23/2018
8/21/2019
455
275Givlaari
Acute hepatic porphyria
6/4/2019
11/20/2019
169
N/AIbsrela
Irritable bowel syndrome with constipation
9/12/2018
9/12/2019
365
185Inrebic
Certain types of myelofibrosis
1/4/2019
8/16/2019
224
44Jeuveau
Improve appearance of glabellar lines (lines between eyebrows)
5/15/2017
2/1/2019
627
447Mayzent
Relapsing forms of multiple sclerosis
6/28/2018
3/26/2019
271
91Nourianz
Parkinson's disease “off” episodes
7/27/2019
8/27/2019
31
N/ANubeqa
Non-metastatic prostate cancer
2/26/2019
7/30/2019
154
N/AOxbryta
Sickle cell disease
6/26/2019
11/25/2019
152
N/APadcev
Refractory bladder cancer
7/15/2019
12/18/2019
146
N/APiqray
Advanced or metastatic breast cancer
12/18/2018
5/24/2019
157
N/APolivy
Relapsed or refractory diffuse large B-cell lymphoma
12/19/2018
6/10/2019
173
N/Apretomanid
Treatment-resistant forms of tuberculosis
12/14/2018
8/14/2019
243
63Reblozyl
Anemia associated with beta thalassemia
4/4/2019
11/8/2019
218
38Recarbrio
Complicated urinary tract infections and complicated intra-abdominal infections
11/16/2018
7/16/2019
242
62Reyvow
Migraine with or without aura
10/11/2018
10/11/2019
365
185Rinvoq
Moderately to severely active rheumatoid arthritis
12/18/2018
8/16/2019
241
61Rozlytrek
Metastatic non-small cell lung cancer and locally advanced or metastatic solid tumors with a specific genetic defect
12/18/2018
8/15/2019
240
60Scenesse
Increase pain-free light exposure in patients with erythropoietic protoporphyria
11/8/2018
10/8/2019
334
154Skyrizi
Moderate-to-severe plaque psoriasis
4/3/2018
4/23/2019
385
205Sunosi
Excessive daytime sleepiness in patients with narcolepsy or obstructive sleep apnea
12/20/2017
3/20/2019
455
275TissueBlue
Dye used in eye surgery
4/29/2019
12/20/2019
235
55Trikafta
Cystic Fibrosis
7/19/2019
10/21/2019
94
N/ATuralio
Symptomatic tenosynovial giant cell tumor
12/3/2018
8/2/2019
242
62Ubrelvy
Migraine
12/26/2018
12/23/2019
362
182Vyleesi
Hypoactive sexual desire disorder in premenopausal women
3/23/2018
6/21/2019
455
275Vyndaqel
Cardiomyopathy caused by transthyretin-mediated amyloidosis
11/2/2018
5/3/2019
182
2Vyondys 53
Duchenne muscular dystrophy
12/19/2018
12/12/2019
358
178Wakix
Excessive daytime sleepiness in patients with narcolepsy
12/14/2018
8/14/2019
243
63Xcopri
Partial-onset seizures
11/21/2018
11/21/2019
365
185Xenleta
Community-acquired bacterial pneumonia
12/19/2018
8/19/2019
243
63Xpovio
Relapsed or refractory multiple myeloma
8/6/2018
7/3/2019
331
151Zulresso
Postpartum depression
4/9/2018
3/19/2019
344
164
 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.


# Footnotes

1.
    
                         E.g., 85 FR 75893 (Nov. 27, 2020). Back to Citation
 2.
    
                         Drug Amendments of 1962, Pub. L. 87-781, 76 Stat. 780 (Oct. 10, 1962). Back to Citation
 3.
    
                         1962 U.S.C.C.A.N. 2884, 2891. Back to Citation
 4.
    
                         Proceedings, FDA Conference on the Kefauver-Harris Drug Amendments and Proposed Regulations, at 7 (Feb. 15, 1963). Back to Citation
 5.
    
                         
                        *Id.*
                         at 6. Back to Citation
 6.
    
                         Drug Price Competition and Patent Term Restoration Act of 1984, Public Law 98-417, 98 Stat. 1585, 1588 (Sept. 24, 1984). Back to Citation
 7.
    
                         GAO, 
                        *FDA Drug Approval, Application Review Times Largely Reflect Agency Goals*
                         (Mar. 2020), 
                        *https://www.gao.gov/​assets/​710/​705193.pdf.* Back to Citation
 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.* Back to Citation
 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 Drugs@FDA website. Back to Citation


[FR Doc. 2021-00786 Filed 1-14-21; 8:45 am] BILLING CODE 4150-26-P