64446 Federal Register / Vol. 88, No. 180 / Tuesday, September 19, 2023 / Notices 

Biological Products’’ issued on 

December 20, 2019 (84 FR 70196) and 

the 1998 guidance entitled ‘‘Providing 

Clinical Evidence of Effectiveness for 

Human Drug and Biological Products’’ 

issued on May 15, 1998 (63 FR 27093). 

In 1962, Congress required for the first 

time that new drugs be shown to be 

effective as well as safe. A new drug’s 

effectiveness must be established by 

substantial evidence. FDA has 

interpreted this substantial evidence 

requirement as generally requiring two 

adequate and well-controlled clinical 

investigations, each convincing on its 

own, to establish effectiveness. 

In 1997, Congress amended section 

505(d) of the Federal Food, Drug, and 

Cosmetic Act (FD&C Act) (21 U.S.C. 

355(d)) to make clear that FDA may 

consider data from one adequate and 

well-controlled investigation and 

confirmatory evidence to constitute 

substantial evidence if FDA determines 

that such data are sufficient to establish 

effectiveness. FDA issued the 1998 

Effectiveness guidance in response to 

this legislative change. In 2019, the 

Agency concluded that more guidance 

was needed on the flexibility in the 

amount and type of evidence needed to 

meet the substantial evidence standard 

and issued the 2019 Effectiveness draft 

guidance, which discussed a number of 

approaches that can yield evidence that 

meets the statutory standard for 

substantial evidence. 

Although both the 1998 Effectiveness 

guidance and the 2019 Effectiveness 

draft guidance provide examples of how 

a single adequate and well-controlled 

clinical investigation and confirmatory 

evidence can be used to support a 

marketing application, these guidances 

are not intended to provide a 

comprehensive discussion of meeting 

the substantial evidence standard based 

on one adequate and well-controlled 

clinical investigation and confirmatory 

evidence. Thus, there is a need for more 

Agency guidance to describe how one 

adequate and well-controlled clinical 

investigation and confirmatory evidence 

can be used to meet the substantial 

evidence requirement. 

When one adequate and wellcontrolled clinical investigation and 

confirmatory evidence are considered 

together to assess effectiveness, the 

quality and quantity of the confirmatory 

evidence are also important 

considerations. Confirmatory evidence 

should be evidence generated from 

quality data derived from an appropriate 

source. The quantity of confirmatory 

evidence needed in a development 

program will be impacted by the 

features of, and results from, the single 

adequate and well-controlled clinical 

investigation that the confirmatory 

evidence is intended to substantiate. 

This draft guidance describes these 

considerations in greater detail. It also 

provides examples of the types of 

evidence that could be considered 

confirmatory evidence that can be used 

with one adequate and well-controlled 

clinical investigation to demonstrate 

substantial evidence of effectiveness. 

Finally, the draft guidance includes 

recommendations for early engagement 

with the Agency for sponsors who 

intend to establish substantial evidence 

of effectiveness with one adequate and 

well-controlled clinical investigation 

and confirmatory evidence. 

This draft guidance is being issued 

consistent with FDA’s good guidance 

practices regulation (21 CFR 10.115). 

The draft guidance, when finalized, will 

represent the current thinking of FDA 

on ‘‘Demonstrating Substantial Evidence 

of Effectiveness Based on One Adequate 

and Well-Controlled Clinical 

Investigation and Confirmatory 

Evidence.’’ It does not establish any 

rights for any person and is not binding 

on FDA or the public. You can use an 

alternative approach if it satisfies the 

requirements of the applicable statutes 

and regulations. 

II. Paperwork Reduction Act of 1995 

While this guidance contains no new 

collection of information, it does refer to 

previously approved FDA collections of 

information. The previously approved 

collections of information are subject to 

review by the Office of Management and 

Budget (OMB) under the Paperwork 

Reduction Act of 1995 (PRA) (44 U.S.C. 

3501–3521). The collections of 

information in 21 CFR parts 58, 312, 

314, and 601 have been approved under 

OMB control numbers 0910–0119, 

0910–0014, 0910–0001, and 0910–0338, 

respectively. In addition, the collections 

of information pertaining to FDA’s 

guidance entitled ‘‘Formal Meetings 

Between the FDA and Sponsors or 

Applicants of PDUFA Products’’ have 

been approved under OMB control 

number 0910–0001. 

III. Electronic Access 

Persons with access to the internet 

may obtain the draft guidance at https:// 

www.fda.gov/drugs/guidancecompliance-regulatory-information/ 

guidances-drugs, https://www.fda.gov/ 

vaccines-blood-biologics/guidancecompliance-regulatory-informationbiologics, https://www.fda.gov/ 

regulatory-information/search-fdaguidance-documents, or https://

www.regulations.gov. 

Dated: September 14, 2023. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2023–20228 Filed 9–18–23; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

National Institute on Aging; Notice of 

Closed Meeting 

Pursuant to section 1009 of the 

Federal Advisory Committee Act, as 

amended, notice is hereby given of the 

following meeting. 

The meeting will be closed to the 

public in accordance with the 

provisions set forth in sections 

552b(c)(4) and 552b(c)(6), title 5 U.S.C., 

as amended. The grant applications and 

the discussions could disclose 

confidential trade secrets or commercial 

property such as patentable material, 

and personal information concerning 

individuals associated with the grant 

applications, the disclosure of which 

would constitute a clearly unwarranted 

invasion of personal privacy. 

Name of Committee: National Institute on 

Aging Special Emphasis Panel; Interorgan 

signal. 

Date: October 19–20, 2023. 

Time: 10:00 a.m. to 6:00 p.m. 

Agenda: To review and evaluate grant 

applications. 

Place: National Institute on Aging, 

Gateway Building, 7201 Wisconsin Avenue, 

Bethesda, MD 20892 (Virtual Meeting). 

Contact Person: Nijaguna Prasad, Ph.D., 

Scientific Review Officer, Scientific Review 

Branch, National Institutes of Health, 

National Institute on Aging, 7201 Wisconsin 

Avenue, Gateway Building, Suite 2W200, 

Bethesda, MD 20892, (301) 496–9667, 

prasadnb@nia.nih.gov. 

(Catalogue of Federal Domestic Assistance 

Program Nos. 93.866, Aging Research, 

National Institutes of Health, HHS) 

Dated: September 14, 2023. 

Miguelina Perez, 

Program Analyst, Office of Federal Advisory 

Committee Policy. 

[FR Doc. 2023–20239 Filed 9–18–23; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

National Institute of Diabetes and 

Digestive and Kidney Diseases; 

Amended Notice of Meeting 

Notice is hereby given of a change in 

the meeting of the Digestive Diseases 


ddrumheller on DSK120RN23PROD with NOTICES1