[Federal Register Volume 83, Number 154 (Thursday, August 9, 2018)]
[Notices]
[Pages 39448-39449]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-17025]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2018-D-2614]


Dissolution Testing and Acceptance Criteria for Immediate-Release 
Solid Oral Dosage Form Drug Products Containing High Solubility Drug 
Substances; 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 final guidance for industry entitled 
``Dissolution Testing and Acceptance Criteria for Immediate-Release 
Solid Oral Dosage Form Drug Products Containing High Solubility Drug 
Substances.'' This guidance has been developed to provide manufacturers 
with recommendations for submission of new drug applications (NDAs), 
investigational new drug applications (INDs), or abbreviated new drug 
applications (ANDAs), as appropriate, for orally administered 
immediate-release (IR) drug products that contain highly soluble drug 
substances. The guidance is intended to describe when a standard 
release test and criteria may be used in lieu of extensive method 
development and acceptance criteria-setting exercises.

DATES: The announcement of the guidance is published in the Federal 
Register on August 9, 2018.

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:
    <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-2018-D-2614 for ``Dissolution Testing and Acceptance Criteria for 
Immediate-Release Solid Oral Dosage Form Drug Products Containing High 
Solubility Drug Substances.'' 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.gpo.gov/fdsys/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 this guidance to the 
Division of Drug Information, Center for Drug

[[Page 39449]]

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 guidance document.

FOR FURTHER INFORMATION CONTACT: Richard Lostritto, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Avenue, Bldg. 51, Rm. 4132, Silver Spring, MD 20993, 301-796-
1697.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Dissolution Testing and Acceptance Criteria for Immediate-
Release Solid Oral Dosage Form Drug Products Containing High Solubility 
Drug Substances.'' This guidance finalizes the draft guidance for 
industry entitled ``Dissolution Testing and Specification Criteria for 
Immediate-Release Solid Oral Dosage Forms Containing Biopharmaceutics 
Classification System Class 1 and 3 Drugs'' (August 2015) (FR 80 
46019), and the recommendations in this guidance clarify the 
recommendations in the guidance for industry entitled ``Dissolution 
Testing of Immediate Release Solid Oral Dosage Forms'' (August 1997) 
(FR 62 44974) for high solubility drug substances in IR drug products 
that meet the conditions described in section III of this guidance. For 
drug substances that do not meet the conditions in this guidance, 
sponsors/applicants should follow the recommendations provided in the 
August 1997 guidance.
    The title of this guidance has been revised to better reflect its 
focus on the solubility of the drug substance in the drug product. 
Therefore, a direct reference to biopharmaceutics classification system 
class 1 and class 3 is not necessary because permeability requirements 
are not within the focus of this guidance.
    Drug absorption from a solid dosage form after oral administration 
depends on the release of the drug substance from the drug product, the 
dissolution or solubilization of the drug under physiological 
conditions, and the permeation across the gastrointestinal membrane. 
NDAs and ANDAs submitted to FDA contain bioavailability (BA) or 
bioequivalence (BE) data and in vitro dissolution data that, together 
with chemistry, manufacturing, and controls data, characterize the 
quality and performance of the drug product. In vitro dissolution data 
are generally obtained from: (1) Batches used in pivotal clinical and/
or BA/BE studies, (2) batches used as stability registration batches, 
and (3) batches used in other human studies conducted during product 
development. In general, knowledge about the solubility, permeability, 
dissolution, and pharmacokinetics of a drug product is considered when 
defining dissolution acceptance criteria for the drug approval process.
    Immediate-release solid oral dosage form drug products containing 
high solubility drug substances are considered to be relatively low 
risk regarding the impact of dissolution on in vivo performance, 
provided the in vitro performance meets or exceeds the recommendations 
discussed within this guidance. This guidance establishes standard 
dissolution methodology and acceptance criteria that are appropriate 
for highly soluble drug substances that are formulated in IR dosage 
form. The availability of these standards will facilitate the rapid 
development of dissolution methodology and related acceptance criteria 
with no requirement to show discriminatory ability of the dissolution 
method for these products during drug product development. In addition, 
these standards will facilitate FDA's evaluation of the data submitted 
in the application.
    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 ``Dissolution Testing and Acceptance 
Criteria for Immediate-Release Solid Oral Dosage Form Drug Products 
Containing High Solubility Drug Substances.'' 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. This guidance is not subject to 
Executive Order 12866.

II. Paperwork Reduction Act of 1995

    This guidance refers to previously approved collections of 
information that are subject to review by the Office of Management and 
Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-
3520). The collections of information in 21 CFR parts 312 and 314 have 
been approved under OMB control numbers 0910-0014 and 0910-0001, 
respectively.

III. Electronic Access

    Persons with access to the internet may obtain the guidance at 
either https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or 
https://www.regulations.gov.

    Dated: August 3, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-17025 Filed 8-8-18; 8:45 am]
 BILLING CODE 4164-01-P