Federal Register / Vol. 88, No. 168 / Thursday, August 31, 2023 / Notices 60215 

have not established a safe level for a 

residue from the extralabel use of any 

new animal drug and, therefore, have 

not required the development of 

analytical methodology, we believe that 

there may be instances when analytical 

methodology will be required. We are, 

therefore, estimating the reporting 

burden based on two methods being 

required annually. The requirement to 

establish an analytical method may be 

fulfilled by any interested person. We 

believe that the sponsor of the drug will 

be willing to develop the method in 

most cases. Alternatively, FDA, the 

sponsor, and perhaps a third party may 

cooperatively arrange for method 

development. The respondents may be 

sponsors of new animal drugs, State, or 

Federal and/or State Agencies, 

academia, or individuals. 

We estimate the burden of this 

collection of information as follows: 

TABLE 1—ESTIMATED ANNUAL REPORTING BURDEN 1

21 CFR Part; activity Number of 

respondents 

Number of 

responses per 

respondent 

Total 

annual 

responses 

Average 

burden per 

response 

Total 

hours 

530.22(b); Submission(s) of analytical method ................... 2 1 2 4,160 8,320 

1There are no capital costs or operating and maintenance costs associated with this collection of information. 

Based on a review of the information 

collection since our last request for 

OMB approval, we have made no 

adjustments to our burden estimate. 

Dated: August 28, 2023. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2023–18834 Filed 8–30–23; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2021–D–1214] 

Considerations for the Use of RealWorld Data and Real-World Evidence 

To Support Regulatory DecisionMaking for Drug and Biological 

Products; Guidance for Industry; 

Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice of availability. 

SUMMARY: The Food and Drug 

Administration (FDA or Agency) is 

announcing the availability of a final 

guidance for industry entitled 

‘‘Considerations for the Use of RealWorld Data and Real-World Evidence to 

Support Regulatory Decision-Making for 

Drug and Biological Products.’’ FDA is 

issuing this guidance as part of its RealWorld Evidence (RWE) Program for 

drugs and to satisfy, in part, the 

mandate under the Federal Food, Drug, 

and Cosmetic Act (FD&C Act) to issue 

guidance about the use of RWE in 

regulatory decision making. This 

guidance discusses the applicability of 

FDA’s investigational new drug 

application (IND) regulations to various 

clinical study designs that utilize realworld data (RWD) and clarifies the 

Agency’s expectations regarding clinical 

studies using RWD submitted to FDA in 

support of a regulatory decision 

regarding the effectiveness or safety of a 

drug that are not subject to the IND 

regulations. This guidance finalizes the 

draft guidance of the same title issued 

on December 9, 2021. 

DATES: The announcement of the 

guidance is published in the Federal 

Register on August 31, 2023. 

ADDRESSES: You may submit either 

electronic or written comments on 

Agency guidances at any time as 

follows: 

Electronic Submissions 

Submit electronic comments in the 

following way: 

• Federal eRulemaking Portal: 

https://www.regulations.gov. Follow the 

instructions for submitting comments. 

Comments submitted electronically, 

including attachments, to https://

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 https://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): Dockets 

Management Staff (HFA–305), Food and 

Drug Administration, 5630 Fishers 

Lane, Rm. 1061, Rockville, MD 20852. 

• For written/paper comments 

submitted to the Dockets Management 

Staff, 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– 

2021–D–1214 for ‘‘Considerations for 

the Use of Real-World Data and RealWorld Evidence to Support Regulatory 

Decision-Making for Drug and 

Biological Products.’’ Received 

comments will be placed in the docket 

and, except for those submitted as 

‘‘Confidential Submissions,’’ publicly 

viewable at https://www.regulations.gov 

or at the Dockets Management Staff 

between 9 a.m. and 4 p.m., Monday 

through Friday, 240–402–7500. 

• 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 

https://www.regulations.gov. Submit 

both copies to the Dockets Management 

Staff. 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 


ddrumheller on DSK120RN23PROD with NOTICES1
60216 Federal Register / Vol. 88, No. 168 / Thursday, August 31, 2023 / Notices 

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: https://

www.govinfo.gov/content/pkg/FR-2015- 

09-18/pdf/2015-23389.pdf. 

Docket: For access to the docket to 

read background documents or the 

electronic and written/paper comments 

received, 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, 240–402–7500. 

You may submit comments on any 

guidance at any time (see 21 CFR 

10.115(g)(5)). 

Submit written requests for single 

copies of this guidance to the Division 

of Drug Information, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10001 New 

Hampshire Ave., Hillandale Building, 

4th Floor, Silver Spring, MD 20993– 

0002; or to the Office of 

Communication, Outreach and 

Development, Center for Biologics 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 71, Rm. 3128, 

Silver Spring, MD 20993–0002. Send 

one self-addressed adhesive label to 

assist that office in processing your 

requests. See the SUPPLEMENTARY

INFORMATION section for electronic 

access to the guidance document. 

FOR FURTHER INFORMATION CONTACT: 

Dianne Paraoan, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 51, Rm. 3226, 

Silver Spring, MD 20993–0002, 301– 

796–3161, Dianne.Paraoan@

fda.hhs.gov; or Anne Taylor, Center for 

Biologics Evaluation and Research, 

Food and Drug Administration, 10903 

New Hampshire Ave., Bldg. 71, Rm. 

7301, Silver Spring, MD 20993–0002, 

240–402–7911, Anne.Taylor@

fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a guidance for industry entitled 

‘‘Considerations for the Use of RealWorld Data and Real-World Evidence to 

Support Regulatory Decision-Making for 

Drug and Biological Products.’’ The 

guidance discusses the following major 

topics: (1) applicability of 21 CFR part 

312 to studies using RWD and (2) 

regulatory considerations for noninterventional (observational) studies 

involving the use of RWD. Regulatory 

considerations addressed by the 

guidance include the following: (1) 

transparency for data collection and 

analysis, (2) access to RWD, (3) study 

monitoring, (4) safety reporting, (5) 

other sponsor responsibilities, and (6) 

the analysis of RWD generated from the 

use of a product under an emergency 

use authorization (EUA) in routine 

practice. 

Section 3022 of the 21st Century 

Cures Act (Cures Act) of 2016 amended 

the FD&C Act to add section 505F, 

Utilizing Real World Evidence (21 

U.S.C. 355g), which requires FDA to 

issue guidance about the use of RWE in 

regulatory decision-making. In addition, 

under the Prescription Drug User Fee 

Amendments of 2017 (PDUFA VI), FDA 

is committed to publish draft guidance 

on how RWE can contribute to the 

assessment of safety and effectiveness in 

regulatory submissions. In 2018, FDA 

created an RWE Framework and an 

RWE Program to evaluate the potential 

use of RWE to help support the approval 

of a new indication for a drug already 

approved under the FD&C Act or to help 

support or satisfy postapproval study 

requirements. In late 2021, FDA utilized 

the RWE Program to issue draft 

guidances outlining considerations for 

the use of RWD and RWE in regulatory 

decision making to satisfy the Cures Act 

mandate and the PDUFA VI 

commitment. 

This guidance finalizes the draft 

guidance of the same title issued on 

December 9, 2021 (86 FR 70131). FDA 

considered comments received on the 

draft guidance as the guidance was 

finalized. Changes from the draft to the 

final guidance include transfer of 

relevant definitions from the glossary to 

the text as well as additional language 

about data generated in clinical practice 

for products used under an EUA 

consistent with a mandate under the 

Food and Drug Omnibus Reform Act of 

2022. Clarifying information was also 

added, including the use of existing 

regulatory pathways for third parties to 

provide patient-level data to FDA when 

a sponsor cannot submit such data to 

FDA through traditional channels. In 

addition, editorial changes were made 

to improve clarity. 

This guidance is being issued 

consistent with FDA’s good guidance 

practices regulation (21 CFR 10.115). 

The guidance represents the current 

thinking of FDA on ‘‘Considerations for 

the Use of Real-World Data and RealWorld Evidence to Support Regulatory 

Decision-Making for Drug and 

Biological Products.’’ 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 

collection of information, it does refer to 

previously approved FDA collections of 

information. The previously approved 

collections of information are subject to 

review by 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 part 11 

pertaining to electronic records and 

signatures have been approved under 

OMB control number 0910–0303. The 

collections of information in 21 CFR 

parts 50 and 56 relating to protection of 

human subjects and Institutional 

Review Boards have been approved 

under OMB control number 0910–0130. 

The collections of information in 21 

CFR part 310 relating to postmarketing 

adverse drug experience reporting have 

been approved under OMB control 

number 0910–0230. The collections of 

information in 21 CFR part 600 for 

general records and postmarketing 

adverse experience reporting pertaining 

to biological products have been 

approved under OMB control number 

0910–0308. The collections of 

information in 21 CFR parts 310, 314, 

and 600 pertaining to adverse event and 

product experience reporting have been 

approved under OMB control number 

0910–0291. The collections of 

information in 21 CFR part 312 have 

been approved under OMB control 

number 0910–0014. The collections of 

information in 21 CFR part 314 have 

been approved under OMB control 

number 0910–0001. The collections of 

information in 21 CFR part 601 have 

been approved under OMB control 

number 0910–0338. The collections of 

information in 21 CFR part 600 have 

been approved under OMB control 

number 0910–0458. 

III. Electronic Access 

Persons with access to the internet 

may obtain the guidance at: https://

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

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

vaccines-blood-biologics/guidancecompliance-regulatory-informationbiologics/biologics-guidances, https://

www.fda.gov/regulatory-information/ 

search-fda-guidance-documents, or 

https://www.regulations.gov. 


ddrumheller on DSK120RN23PROD with NOTICES1
Federal Register / Vol. 88, No. 168 / Thursday, August 31, 2023 / Notices 60217 

Dated: August 28, 2023. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2023–18841 Filed 8–30–23; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2020–D–2024] 

Enhanced Drug Distribution Security at 

the Package Level Under the Drug 

Supply Chain Security Act; Guidance 

for Industry; Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice of availability. 

SUMMARY: The Food and Drug 

Administration (FDA or Agency) is 

announcing the availability of a final 

guidance for industry entitled 

‘‘Enhanced Drug Distribution Security at 

the Package Level Under the Drug 

Supply Chain Security Act.’’ This 

guidance clarifies the enhanced drug 

distribution security requirements listed 

in the Federal Food, Drug, and Cosmetic 

Act (FD&C Act). In addition, this 

guidance outlines and makes 

recommendations on the system 

attributes necessary to enable secure 

tracing of product at the package level, 

including allowing for the use of 

verification, inference, and aggregation, 

as necessary. This guidance finalizes the 

draft guidance of the same title issued 

on June 4, 2021. 

DATES: The announcement of the 

guidance is published in the Federal 

Register on August 31, 2023. 

ADDRESSES: You may submit either 

electronic or written comments on 

Agency guidances at any time as 

follows: 

Electronic Submissions 

Submit electronic comments in the 

following way: 

• Federal eRulemaking Portal: 

https://www.regulations.gov. Follow the 

instructions for submitting comments. 

Comments submitted electronically, 

including attachments, to https://

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 https://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): Dockets 

Management Staff (HFA–305), Food and 

Drug Administration, 5630 Fishers 

Lane, Rm. 1061, Rockville, MD 20852. 

• For written/paper comments 

submitted to the Dockets Management 

Staff, 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– 

2020–D–2024 for ‘‘Enhanced Drug 

Distribution Security at the Package 

Level Under the Drug Supply Chain 

Security Act.’’ Received comments will 

be placed in the docket and, except for 

those submitted as ‘‘Confidential 

Submissions,’’ publicly viewable at 

https://www.regulations.gov or at the 

Dockets Management Staff between 9 

a.m. and 4 p.m., Monday through 

Friday, 240–402–7500. 

• 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 

https://www.regulations.gov. Submit 

both copies to the Dockets Management 

Staff. 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: https://

www.govinfo.gov/content/pkg/FR-2015- 

09-18/pdf/2015-23389.pdf. 

Docket: For access to the docket to 

read background documents or the 

electronic and written/paper comments 

received, 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, 240–402–7500. 

You may submit comments on any 

guidance at any time (see 21 CFR 

10.115(g)(5)). 

Submit written requests for single 

copies of this guidance to the Division 

of Drug Information, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10001 New 

Hampshire Ave., Hillandale Building, 

4th Floor, Silver Spring, MD 20993– 

0002, or to the Office of 

Communication, Outreach and 

Development, Center for Biologics 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 71, Rm. 3128, 

Silver Spring, MD 20993–0002. Send 

one self-addressed adhesive label to 

assist that office in processing your 

requests. See the SUPPLEMENTARY

INFORMATION section for electronic 

access to the guidance document. 

FOR FURTHER INFORMATION CONTACT: 

Abha Kundi, Center for Drug Evaluation 

and Research, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Silver Spring, MD 20993–0002, 

301–796–3130, drugtrackandtrace@

fda.hhs.gov; or Anne Taylor, Center for 

Biologics Evaluation and Research, 

Food and Drug Administration, 10903 

New Hampshire Ave., Bldg. 71, Rm. 

7301, Silver Spring, MD 20993–0002, 

240–402–7911. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a guidance for industry entitled 

‘‘Enhanced Drug Distribution Security at 

the Package Level Under the Drug 

Supply Chain Security Act.’’ The Drug 

Supply Chain Security Act (DSCSA) 

(Title II of Pub. L. 113–54) was signed 

into law on November 27, 2013. 

The DSCSA outlines critical steps to 

achieve electronic pharmaceutical 

supply chain interoperability by 

November 27, 2023, that will enhance 


ddrumheller on DSK120RN23PROD with NOTICES1