[Federal Register Volume 85, Number 231 (Tuesday, December 1, 2020)]
[Notices]
[Pages 77222-77223]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-26510]



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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Implications; Draft Guidance for Industry; Availability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.

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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the availability of a draft guidance for industry entitled ``Evaluation 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 This draft 
guidance focuses on specific recommendations pertinent to gastric pH-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 acid-
reducing 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DATES: Submit either electronic or written comments on the draft 
guidance by March 1, 2021 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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:
    <bullet> 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.
    <bullet> 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:
    <bullet> 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.
    <bullet> 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.
    <bullet> 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 weak-base 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 pH-

[[Page 77223]]

dependent DDI studies, alternative approaches for evaluating pH-
dependent 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/guidance-compliance-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