77222 Federal Register / Vol. 85, No. 231 / Tuesday, December 1, 2020 / Notices 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2020–D–1794] 

Evaluation of Gastric pH-Dependent 

Drug Interactions With Acid-Reducing 

Agents: Study Design, Data Analysis, 

and Clinical Implications; Draft 

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 draft 

guidance for industry entitled 

‘‘Evaluation of Gastric pH-Dependent 

Drug Interactions With Acid-Reducing 

Agents: Study Design, Data Analysis, 

and Clinical Implications.’’ This draft 

guidance focuses on specific 

recommendations pertinent to gastric 

pH-dependent drug-drug interaction 

(DDI) assessment and describes the 

FDA’s recommendations regarding 

when clinical DDI studies with acidreducing agents (ARAs) are needed; 

design of the clinical studies; 

interpretation of study results; and 

communicating findings and options for 

managing pH-dependent DDIs in 

product labeling. 

DATES: Submit either electronic or 

written comments on the draft guidance 

by March 1, 2021 to ensure that the 

Agency considers your comment on this 

draft guidance before it begins work on 

the final version of the guidance. 

ADDRESSES: You may submit comments 

on any guidance 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–1794 for ‘‘Evaluation of Gastric 

pH-Dependent Drug Interactions With 

Acid-Reducing Agents: Study Design, 

Data Analysis, and Clinical 

Implications.’’ 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. 

• 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. 

You may submit comments on any 

guidance at any time (see 21 CFR 

10.115(g)(5)). 

Submit written requests for single 

copies of the draft 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. Send one self-addressed adhesive 

label to assist that office in processing 

your requests. See the SUPPLEMENTARY

INFORMATION section for electronic 

access to the draft guidance document. 

FOR FURTHER INFORMATION CONTACT: 

Anuradha Ramamoorthy, Center for 

Drug Evaluation and Research, Food 

and Drug Administration, 10903 New 

Hampshire Ave., Bldg. 51, Rm. 3118, 

Silver Spring, MD 20993, 240–402– 

6426. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a draft guidance for industry entitled 

‘‘Evaluation of Gastric pH-Dependent 

Drug Interactions With Acid-Reducing 

Agents: Study Design, Data Analysis, 

and Clinical Implications.’’ ARAs such 

as antacids, histamine H2-receptor 

antagonists, and proton pump inhibitors 

are widely used, and many of these 

drugs are available over-the-counter. 

Because ARAs can elevate the gastric 

pH, concomitant administration of a 

drug with an ARA could alter the 

solubility, dissolution, and 

bioavailability of the drug, potentially 

resulting in a loss of efficacy for weakbase drugs or increased toxicity for 

weak-acid drugs. Therefore, it is 

important to assess the susceptibility of 

an investigational drug to gastric pH 

change-mediated DDIs early in drug 

development, characterize the DDI effect 

with clinical studies when needed, and 

communicate the findings in the drug 

product labeling. This draft guidance 

addresses when clinical DDI studies 

with ARAs should be conducted, the 

design and conduct of clinical pHVerDate Sep<11>2014 18:11 Nov 30, 2020 Jkt 253001 PO 00000 Frm 00084 Fmt 4703 Sfmt 4703 E:\FR\FM\01DEN1.SGM 01DEN1

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Federal Register / Vol. 85, No. 231 / Tuesday, December 1, 2020 / Notices 77223 

dependent DDI studies, alternative 

approaches for evaluating pHdependent DDIs, and extrapolating 

clinical DDI study results with drug 

classes of ARAs. 

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 ‘‘Evaluation of Gastric pH-Dependent 

Drug Interactions With Acid-Reducing 

Agents: Study Design, Data Analysis, 

and Clinical Implications.’’ 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. Therefore, clearance by the 

Office of Management and Budget 

(OMB) under the Paperwork Reduction 

Act of 1995 (PRA) (44 U.S.C. 3501– 

3521) is not required for this guidance. 

The previously approved collections of 

information are subject to review by 

OMB under the PRA. The collections of 

information for submissions of 

investigational new drug applications, 

new drug applications, and biologic 

license applications in 21 CFR parts 

312, 314, and 601 have been approved 

under OMB control numbers 0910– 

0014; 0910–0001; and 0910–0338, 

respectively. In addition, the 

submission of prescription drug labeling 

under 21 CFR 201.56 and 201.57 has 

been approved under OMB control 

number 0910–0572. 

III. Electronic Access 

Persons with access to the internet 

may obtain the draft guidance at either 

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

guidances-drugs or https://

www.regulations.gov. 

Dated: November 25, 2020. 

Lauren K. Roth, 

Acting Principal Associate Commissioner for 

Policy. 

[FR Doc. 2020–26510 Filed 11–30–20; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2011–N–0076] 

Agency Information Collection 

Activities; Submission for Office of 

Management and Budget Review; 

Comment Request; Electronic 

Records; Electronic Signatures 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing 

that a proposed collection of 

information has been submitted to the 

Office of Management and Budget 

(OMB) for review and clearance under 

the Paperwork Reduction Act of 1995. 

DATES: Submit written comments 

(including recommendations) on the 

collection of information by December 

31, 2020. 

ADDRESSES: To ensure that comments on 

the information collection are received, 

OMB recommends that written 

comments be submitted to https://

www.reginfo.gov/public/do/PRAMain. 

Find this particular information 

collection by selecting ‘‘Currently under 

Review—Open for Public Comments’’ or 

by using the search function. The OMB 

control number for this information 

collection is 0910–0303. Also include 

the FDA docket number found in 

brackets in the heading of this 

document. 

FOR FURTHER INFORMATION CONTACT: 

Domini Bean, Office of Operations, 

Food and Drug Administration, Three 

White Flint North, 10A–12M, 11601 

Landsdown St., North Bethesda, MD 

20852, 301–796–5733, PRAStaff@

fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: In 

compliance with 44 U.S.C. 3507, FDA 

has submitted the following proposed 

collection of information to OMB for 

review and clearance. 

Electronic Records; Electronic 

Signatures—21 CFR Part 11 

OMB Control Number 0910–0303— 

Extension 

This information collection supports 

FDA regulations in part 11 (21 CFR part 

11), which govern criteria for 

acceptance of electronic records, 

electronic signatures, and handwritten 

signatures executed to electronic 

records as equivalent to paper records. 

Under these regulations, records and 

reports may be submitted to us 

electronically provided that we have 

stated our ability to accept the records 

electronically in an Agency-established 

public docket and that the other 

requirements of part 11 are met. 

The recordkeeping provisions in 

§§ 11.10, 11.30, 11.50, and 11.300 (21 

CFR 11.10, 11.30, 11.50, and 11.300) 

require the following standard operating 

procedures to ensure appropriate use of 

and precautions for systems using 

electronic records and signatures: (1) 

§ 11.10 specifies procedures and 

controls for persons who use closed 

systems to create, modify, maintain, or 

transmit electronic records; (2) § 11.30 

specifies procedures and controls for 

persons who use open systems to create, 

modify, maintain, or transmit electronic 

records; (3) § 11.50 specifies procedures 

and controls for persons who use 

electronic signatures; and (4) § 11.300 

specifies controls to ensure the security 

and integrity of electronic signatures 

based upon use of identification codes 

in combination with passwords. The 

reporting provision (§ 11.100) requires 

persons to certify to us in writing that 

they will regard electronic signatures 

used in their systems as the legally 

binding equivalent of traditional 

handwritten signatures. 

The burden created by the 

information collection provision of this 

regulation is a one-time burden 

associated with the creation of standard 

operating procedures, validation, and 

certification. We anticipate that the use 

of electronic media will substantially 

reduce the paperwork burden associated 

with maintaining FDA-required records. 

The respondents are businesses and 

other for-profit organizations, State or 

local governments, Federal Agencies, 

and nonprofit institutions. 

To assist respondents with the 

information collection we have 

developed the guidance document 

entitled ‘‘Guidance for Industry: Part 11, 

Electronic Records; Electronic 

Signatures—Scope and Application,’’ 

available on our website at https://

www.fda.gov/media/75414/download. 

While we do not believe the guidance 

creates any attendant burden, it 

describes the Agency’s thinking 

regarding persons who, in fulfillment of 

a requirement in a statute or another 

part of FDA’s regulations to maintain 

records or submit information to FDA, 

have chosen to maintain the records or 

submit designated information 

electronically and, as a result, have 

become subject to part 11. Part 11 

applies to records in electronic form 

that are created, modified, maintained, 

archived, retrieved, or transmitted 

under any records requirements set 

forth in Agency regulations. Part 11 also 


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