83 FR 39448 - Dissolution Testing and Acceptance Criteria for Immediate-Release Solid Oral Dosage Form Drug Products Containing High Solubility Drug Substances; Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 83, Issue 154 (August 9, 2018)

Page Range		39448-39449
FR Document		2018-17025

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.

Federal Register, Volume 83 Issue 154 (Thursday, August 9, 2018)

[Federal Register Volume 83, Number 154 (Thursday, August 9, 2018)]
[Notices]
[Pages 39448-39449]
From the Federal Register Online [www.thefederalregister.org]
[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:
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-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.
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.thefederalregister.org/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

Federal Register / Vol. 83, No. 154 / Thursday, August 9, 2018 / Notices 39449

Evaluation and Research, Food and characterize the quality and https://www.fda.gov/Drugs/Guidance
Drug Administration, 10001 New performance of the drug product. In ComplianceRegulatoryInformation/
Hampshire Ave., Hillandale Building, vitro dissolution data are generally Guidances/default.htm or https://
4th Floor, Silver Spring, MD 20993– obtained from: (1) Batches used in www.regulations.gov.
0002. Send one self-addressed adhesive pivotal clinical and/or BA/BE studies, Dated: August 3, 2018.
label to assist that office in processing (2) batches used as stability registration
Leslie Kux,
your requests. See the SUPPLEMENTARY batches, and (3) batches used in other
Associate Commissioner for Policy.
INFORMATION section for electronic human studies conducted during
product development. In general, [FR Doc. 2018–17025 Filed 8–8–18; 8:45 am]
access to the guidance document.
FOR FURTHER INFORMATION CONTACT: knowledge about the solubility, BILLING CODE 4164–01–P

Richard Lostritto, Center for Drug permeability, dissolution, and
Evaluation and Research, Food and pharmacokinetics of a drug product is
considered when defining dissolution DEPARTMENT OF HEALTH AND
Drug Administration, 10903 New HUMAN SERVICES
Hampshire Avenue, Bldg. 51, Rm. 4132, acceptance criteria for the drug approval
Silver Spring, MD 20993, 301–796– process.
Immediate-release solid oral dosage Food and Drug Administration
1697.
form drug products containing high
SUPPLEMENTARY INFORMATION: solubility drug substances are [Docket No. FDA–2018–N–0180]
I. Background considered to be relatively low risk
regarding the impact of dissolution on Agency Information Collection
FDA is announcing the availability of in vivo performance, provided the in Activities; Submission for Office of
a guidance for industry entitled vitro performance meets or exceeds the Management and Budget Review;
‘‘Dissolution Testing and Acceptance recommendations discussed within this Comment Request; Generic Clearance
Criteria for Immediate-Release Solid guidance. This guidance establishes for the Collection of Quantitative Data
Oral Dosage Form Drug Products standard dissolution methodology and on Tobacco Products and
Containing High Solubility Drug acceptance criteria that are appropriate Communications
Substances.’’ This guidance finalizes the for highly soluble drug substances that
draft guidance for industry entitled are formulated in IR dosage form. The AGENCY: Food and Drug Administration,
‘‘Dissolution Testing and Specification availability of these standards will HHS.
Criteria for Immediate-Release Solid facilitate the rapid development of ACTION: Notice.
Oral Dosage Forms Containing dissolution methodology and related
Biopharmaceutics Classification System acceptance criteria with no requirement SUMMARY: The Food and Drug
Class 1 and 3 Drugs’’ (August 2015) (FR to show discriminatory ability of the Administration (FDA) is announcing
80 46019), and the recommendations in dissolution method for these products that a proposed collection of
this guidance clarify the during drug product development. In information has been submitted to the
recommendations in the guidance for addition, these standards will facilitate Office of Management and Budget
industry entitled ‘‘Dissolution Testing of FDA’s evaluation of the data submitted (OMB) for review and clearance under
Immediate Release Solid Oral Dosage in the application. the Paperwork Reduction Act of 1995.
Forms’’ (August 1997) (FR 62 44974) for This guidance is being issued
high solubility drug substances in IR consistent with FDA’s good guidance DATES: Fax written comments on the
drug products that meet the conditions practices regulation (21 CFR 10.115). collection of information by September
described in section III of this guidance. The guidance represents the current 10, 2018.
For drug substances that do not meet the thinking of FDA on ‘‘Dissolution Testing ADDRESSES: To ensure that comments on
conditions in this guidance, sponsors/ and Acceptance Criteria for Immediate- the information collection are received,
applicants should follow the Release Solid Oral Dosage Form Drug OMB recommends that written
recommendations provided in the Products Containing High Solubility comments be faxed to the Office of
August 1997 guidance. Drug Substances.’’ It does not establish Information and Regulatory Affairs,
The title of this guidance has been any rights for any person and is not OMB, Attn: FDA Desk Officer, Fax: 202–
revised to better reflect its focus on the binding on FDA or the public. You can 395–7285, or emailed to oira_
solubility of the drug substance in the use an alternative approach if it satisfies submission@omb.eop.gov. All
drug product. Therefore, a direct the requirements of the applicable comments should be identified with the
reference to biopharmaceutics statutes and regulations. This guidance OMB control number 0910–0810. Also
classification system class 1 and class 3 is not subject to Executive Order 12866. include the FDA docket number found
is not necessary because permeability
II. Paperwork Reduction Act of 1995 in brackets in the heading of this
requirements are not within the focus of
document.
this guidance. This guidance refers to previously
Drug absorption from a solid dosage approved collections of information that FOR FURTHER INFORMATION CONTACT:
form after oral administration depends are subject to review by the Office of Amber Sanford, Office of Operations,
on the release of the drug substance Management and Budget (OMB) under Food and Drug Administration, Three
from the drug product, the dissolution the Paperwork Reduction Act of 1995 White Flint North, 10A–12M, 11601
or solubilization of the drug under (44 U.S.C. 3501–3520). The collections Landsdown St., North Bethesda, MD
physiological conditions, and the
sradovich on DSK3GMQ082PROD with NOTICES

of information in 21 CFR parts 312 and 20852, 301–796–8867, PRAStaff@
permeation across the gastrointestinal 314 have been approved under OMB fda.hhs.gov.
membrane. NDAs and ANDAs control numbers 0910–0014 and 0910–
submitted to FDA contain 0001, respectively. SUPPLEMENTARY INFORMATION: In
bioavailability (BA) or bioequivalence compliance with 44 U.S.C. 3507, FDA
(BE) data and in vitro dissolution data III. Electronic Access has submitted the following proposed
that, together with chemistry, Persons with access to the internet collection of information to OMB for
manufacturing, and controls data, may obtain the guidance at either review and clearance.

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Document Created: 2018-08-09 01:10:56
Document Modified: 2018-08-09 01:10:56

Category		Regulatory Information
Collection		Federal Register
sudoc Class		AE 2.7: GS 4.107: AE 2.106:
Publisher		Office of the Federal Register, National Archives and Records Administration
Section		Notices
Action		Notice of availability.
Dates		The announcement of the guidance is published in the Federal Register on August 9, 2018.
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.
FR Citation		83 FR 39448

83 FR 39448 - Dissolution Testing and Acceptance Criteria for Immediate-Release Solid Oral Dosage Form Drug Products Containing High Solubility Drug Substances; Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration

Federal Register Volume 83, Issue 154 (August 9, 2018)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration