Notice2022-08012
Considerations for Waiver Requests for pH Adjusters in Generic Drug Products Intended for Parenteral, Ophthalmic, or Otic Use; Draft Guidance for Industry; Availability
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Published
April 14, 2022
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled "Considerations for Waiver Requests for pH Adjusters in Generic Drug Products Intended for Parenteral, Ophthalmic, or Otic Use." This guidance is intended to assist abbreviated new drug application (ANDA) applicants that reference a drug product intended for parenteral, ophthalmic, or otic use in seeking approval of a drug that is qualitatively (Q1) different or quantitatively (Q2) different from the reference listed drug (RLD) with respect to the pH adjuster(s). This draft guidance describes how FDA intends to evaluate a request for a waiver of Agency requirements for a Q1 or Q2 difference in pH adjuster, including recommendations on the type of information to provide in support of such a waiver request. This draft guidance also includes recommendations on the timing and process for submitting such waiver requests.
Full Text
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<title>Federal Register, Volume 87 Issue 72 (Thursday, April 14, 2022)</title>
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[Federal Register Volume 87, Number 72 (Thursday, April 14, 2022)]
[Notices]
[Pages 22217-22218]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2022-08012]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2022-D-0108]
Considerations for Waiver Requests for pH Adjusters in Generic
Drug Products Intended for Parenteral, Ophthalmic, or Otic Use; Draft
Guidance for Industry; Availability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the availability of a draft guidance for industry entitled
``Considerations for Waiver Requests for pH Adjusters in Generic Drug
Products Intended for Parenteral, Ophthalmic, or Otic Use.'' This
guidance is intended to assist abbreviated new drug application (ANDA)
applicants that reference a drug product intended for parenteral,
ophthalmic, or otic use in seeking approval of a drug that is
qualitatively (Q1) different or quantitatively (Q2) different from the
reference listed drug (RLD) with respect to the pH adjuster(s). This
draft guidance describes how FDA intends to evaluate a request for a
waiver of Agency requirements for a Q1 or Q2 difference in pH adjuster,
including recommendations on the type of information to provide in
support of such a waiver request. This draft guidance also includes
recommendations on the timing and process for submitting such waiver
requests.
DATES: Submit either electronic or written comments on the draft
guidance by June 13, 2022 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: <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to <a href="https://www.regulations.gov">https://www.regulations.gov</a>
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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
<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-2022-D-0108 for ``Considerations for Waiver Requests for pH
Adjusters in Generic Drug Products Intended for Parenteral, Ophthalmic,
or Otic Use.'' Received comments will be placed in the docket and,
except for those submitted as ``Confidential Submissions,'' publicly
viewable at <a href="https://www.regulations.gov">https://www.regulations.gov</a> or at the Dockets Management
Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-402-7500.
<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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
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: <a href="https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf">https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf</a>.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> 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 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: Melissa Mannion, Center for Drug
[[Page 22218]]
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 75, Rm. 1611, Silver Spring, MD 20993-0002, 301-
796-2747.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a draft guidance for industry
entitled ``Considerations for Waiver Requests for pH Adjusters in
Generic Drug Products Intended for Parenteral, Ophthalmic, or Otic
Use.'' 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
``Considerations for Waiver Requests for pH Adjusters in Generic Drug
Products Intended for Parenteral, Ophthalmic, or Otic Use.'' 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.
The Federal Food, Drug, and Cosmetic Act (FD&C Act) does not
require an ANDA to have the same inactive ingredients as the RLD.\1\
Section 505(j)(4)(H) of the FD&C Act (21 U.S.C. 355(j)(4)(H)) does,
however, state that an ANDA shall not be approved if information
submitted in the application (or other information available) shows (1)
the inactive ingredients of the drug are unsafe for use under the
conditions prescribed, recommended, or suggested in the labeling
proposed for the drug, or (2) the type or quantity of inactive
ingredients included or the manner in which the inactive ingredients
are included is unsafe under such conditions.\2\
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\1\ See section 505(j)(2)(A) of the FD&C Act (setting forth the
required contents of an ANDA).
\2\ Section 505(j)(4)(H) of the FD&C Act.
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The Agency has interpreted section 505(j)(4)(H) of the FD&C Act as
permitting the Agency to deny approval of an ANDA ``if there is a
reasonable basis to conclude that its inactive ingredients or
composition raise serious questions about the drug's safety.'' \3\
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\3\ 21 CFR 314.127(a)(8)(ii); 54 FR 28871 at 28903 (July 10,
1989).
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The regulations at Sec. 314.94(a)(9)(iii) and (iv) (21 CFR
314.94(a)(9)(iii) and (iv)), with parallel provisions in the approval
regulations at Sec. 314.127(a)(8)(ii)(B) and (C) (21 CFR
314.127(a)(8)(ii)(B) and (C)), specify that FDA will consider an
inactive ingredient in, or the composition of, a generic drug product
intended for parenteral, ophthalmic, or otic use to be unsafe and will
refuse to approve the ANDA unless the generic drug product contains the
same inactive ingredients (with certain listed exceptions) in the same
concentration as the RLD. These regulations also identify permissible
differences in certain inactive ingredients for drug products intended
for parenteral, ophthalmic, or otic use, commonly referred to as
``exception excipients,'' if the ANDA contains sufficient information
to demonstrate that any such differences do not affect the safety or
efficacy of the drug. The regulations do not, however, expressly
identify pH adjusters as one of these ``exception excipients,'' and, as
such, the inactive ingredient requirements in Sec. 314.94(a)(9)(iii)
and (iv) apply to pH adjusters.
Under Sec. 314.99(b) (21 CFR 314.99(b)), however, an applicant may
ask FDA to waive any requirement that applies to the applicant under
Sec. Sec. 314.92 through 314.99 (21 CFR 314.92 through 314.99). Such a
request under Sec. 314.99(b) must comply with the requirements at 21
CFR 314.90. FDA may grant a Sec. 314.99(b) waiver if the Agency finds
one of the following: (1) The applicant's compliance with the
requirement is unnecessary for the Agency to evaluate the ANDA or
compliance cannot be achieved; (2) the applicant's alternative
submission satisfies the requirement; or (3) the applicant's submission
otherwise justifies a waiver. Even if FDA grants a waiver of a
requirement in Sec. Sec. 314.92 through 314.99 in a particular
application, the application still must meet all applicable statutory
requirements for approval. If FDA grants the applicant's waiver request
with respect to a requirement under Sec. Sec. 314.92 through 314.99,
the waived requirement will not constitute a basis for refusal to
approve an ANDA under Sec. 314.127. Thus, an ANDA applicant for a drug
product intended for parenteral, ophthalmic, or otic use who seeks to
use a pH adjuster(s) that is Q1 or Q2 different from the RLD may ask
the Agency to waive the inactive ingredient requirements at Sec.
314.94(a)(9)(iii) or (iv) for the pH adjuster(s). This draft guidance
document provides recommendations on (1) the type of information that
applicants should consider submitting with a Sec. 314.99(b) waiver
request when an ANDA applicant asks the Agency to waive the inactive
ingredient requirements for pH adjusters and (2) the format and process
for submitting such waiver requests.
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 in 21 CFR part 314 have been approved under OMB control
number 0910-0001; the collections of information in 21 CFR part 320
been approved under OMB control numbers 0910-0014 and 0910-0291; and
the collections of information for the submission of controlled
correspondence related to generic drug development and FDA approval
have been approved under OMB control number 0910-0797.
III. Electronic Access
Persons with access to the internet may obtain the draft guidance
at <a href="https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs">https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs</a>, <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents">https://www.fda.gov/regulatory-information/search-fda-guidance-documents</a>, or <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Dated: April 11, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-08012 Filed 4-13-22; 8:45 am]
BILLING CODE 4164-01-P
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