Notice2022-06031
Prioritizing the Addition of Maximum Daily Exposure Information and Removing Dosage Form Information From the Inactive Ingredient Database; Establishment of a Public Docket; Request for Comments
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Published
March 22, 2022
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA, we, or Agency) is announcing the establishment of a docket to solicit comments that will assist the Agency in determining how best to prioritize the addition of maximum daily exposure (MDE) information for inactive ingredients that do not currently include MDE information in the Center for Drug Evaluation and Research's Inactive Ingredient Database (IID) and whether to restructure the IID by removing dosage form information.
Full Text
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<title>Federal Register, Volume 87 Issue 55 (Tuesday, March 22, 2022)</title>
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[Federal Register Volume 87, Number 55 (Tuesday, March 22, 2022)]
[Notices]
[Pages 16212-16214]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2022-06031]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2022-N-0236]
Prioritizing the Addition of Maximum Daily Exposure Information
and Removing Dosage Form Information From the Inactive Ingredient
Database; Establishment of a Public Docket; Request for Comments
AGENCY: Food and Drug Administration, Department of Health and Human
Services (HHS).
ACTION: Notice; establishment of a public docket; request for comments.
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SUMMARY: The Food and Drug Administration (FDA, we, or Agency) is
announcing the establishment of a docket to solicit comments that will
assist the Agency in determining how best to prioritize the addition of
maximum daily exposure (MDE) information for inactive ingredients that
do not currently include MDE information in the Center for Drug
Evaluation and Research's Inactive Ingredient Database (IID) and
whether to restructure the IID by removing dosage form information.
DATES: Submit either electronic or written comments on the notice by
June 21, 2022.
ADDRESSES: You may submit comments as follows. Please note that late,
untimely filed comments will not be considered. The <a href="https://www.regulations.gov">https://www.regulations.gov</a> electronic filing system will accept comments until
11:59 p.m. Eastern Time at the end of June 21, 2022. Comments received
by mail/hand delivery/courier (for written/paper submissions) will be
considered timely if they are postmarked or the delivery service
acceptance receipt is on or before that date.
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-N-0236 for ``Prioritizing the Addition of Maximum Daily
Exposure Information and Removing Dosage Form Information From the
Inactive Ingredient Database; Establishment of a Public Docket; Request
for Comments.'' Received comments, those filed in a timely manner (see
ADDRESSES), 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
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``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.
FOR FURTHER INFORMATION CONTACT: Susan Zuk, Center for Drug Evaluation
and Research, Food and Drug Administration, 10903 New Hampshire Ave.,
Bldg. 75, Rm. 6684, Silver Spring, MD 20993-0002, 240-402-9133,
<a href="/cdn-cgi/l/email-protection#471432342629691d322c07212326692f2f3469202831"><span class="__cf_email__" data-cfemail="3c6f494f5d52126649577c5a585d1254544f125b534a">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
The IID provides information on inactive ingredients in FDA-
approved drug products.\1\ An inactive ingredient, or excipient, is any
component of a drug product other than an active ingredient (21 CFR
210.3(b)(8) and 314.3(b)). Generally, the IID identifies excipients
that appear in approved drug products for a particular dosage form and
route of administration. This information in the IID has been used by
all segments of industry as an aid in developing new drug products,
including new generic drug products. For example, excipients used in
drug products submitted in an abbreviated new drug application are
required to be safe at the levels proposed and under the conditions
prescribed, recommended, or suggested in the labeling proposed for the
drug (see sections 505(j)(4)(H)(i) and (ii) of the Federal Food, Drug,
and Cosmetic Act (21 U.S.C. 355(j)(4)(H)(i) and (ii))). The IID
provides evidence that a particular excipient was previously permitted
by FDA in specific levels, routes of administration, and dosage forms
in FDA-approved products. FDA may consult the IID when performing
regulatory filing reviews and technical reviews of applications as part
of an evaluation of whether the proposed levels of excipients in drug
product formulations are acceptable or require additional documentation
to support their use.
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\1\ For more information on the IID, see the draft guidance for
industry entitled ``Using the Inactive Ingredient Database'' (July
2019). When final, this guidance will represent FDA's current
thinking on this topic. For the most recent version of a guidance,
check the FDA guidance web page at <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents">https://www.fda.gov/regulatory-information/search-fda-guidance-documents</a>.
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FDA made certain enhancements to the IID in 2020 consistent with
the Generic Drug User Fee Amendments (GDUFA) Reauthorization
Performance Goals and Program Enhancements Fiscal Years 2018-2022
(GDUFA II commitment letter).\2\ One of these enhancements permits
users to perform electronic queries to obtain accurate maximum daily
intake (MDI) and MDE information for each route of administration for
which data are available. MDE is defined as the total amount of the
excipient that would be taken in a day based on the maximum daily dose
of the drug products in which it is used. MDE can also be referred to
as MDI for oral drug products. FDA has steadily increased the number of
excipient records that display MDE with each publication of the IID,\3\
but not all excipients in the IID have MDE information. The inclusion
of such information could enhance the ability of applicants to
reference IID information in support of proposed levels of excipients
in their drug products. In meetings with FDA, stakeholders have asked
about FDA's plan to prioritize the addition of MDE information and have
suggested that FDA focus on specific excipients that the stakeholders
consider to be of high priority.
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\2\ See the GDUFA II commitment letter, p.17, at <a href="https://www.fda.gov/media/101052/download">https://www.fda.gov/media/101052/download</a>.
\3\ The IID is updated on a quarterly basis at <a href="https://www.accessdata.fda.gov/scripts/cder/iig/index.cfm">https://www.accessdata.fda.gov/scripts/cder/iig/index.cfm</a>.
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Further, some stakeholders have expressed that the numerous records
in the IID for each excipient can be confusing. Each IID record
includes the excipient, its route of administration, and its dosage
form. An excipient search can yield a lengthy list of dosage forms for
each route of administration, which could make finding the most
appropriate IID record to reference challenging. Some stakeholders have
suggested that FDA could remove dosage form information from the IID to
simplify searches. We believe such an approach would be consistent with
the GDUFA II commitment letter, which describes upgrades to the IID to
provide excipient MDE information associated with particular routes of
administration. However, we recognize that some stakeholders may find
the IID's dosage form information helpful for drug product development.
For example, applicants may refer to this information to confirm that
FDA has approved drug products in certain dosage forms that contain an
excipient at a particular level. For these applicants, removal of
dosage form information from the IID could hinder their drug
development program.
II. Other Issues for Consideration
FDA is considering how best to prioritize the addition of MDE
information and plans to target those excipients deemed to be high
priority by various stakeholders. Under such a plan, individual
excipients could be designated for prioritization from those currently
listed in the IID without MDE information. Alternatively, priority
excipients could be designated based on a category of drug products in
which they are used (e.g., excipients used in oral or topical
products), and then FDA would prioritize adding MDE information for
those excipients included in that category of drug products. FDA
intends to develop a priority list based on feedback to this Federal
Register notice. FDA will consider those excipients that are a high
priority for multiple stakeholders and will also consider stakeholders'
rationale for inclusion of specific excipients in developing the
priority list. FDA is also considering how to post information about
recent updates to the IID based on efforts related to this Federal
Register notice.
FDA intends also to explore the feasibility of modifying the IID
structure to eliminate dosage form information if feedback to this
Federal Register notice indicates that such action would benefit drug
developers and other stakeholders.
Interested persons are invited to provide detailed comments on all
aspects described in this notice. To facilitate this input, FDA has
developed the following list of questions. These questions are not
meant to be exhaustive, and FDA is also interested in other pertinent
information
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stakeholders would like to share on this topic. In all cases, FDA
encourages stakeholders to provide the specific rationale and basis for
their comments, including available supporting information.
1. Should FDA focus on adding MDE information for certain
excipients? If so, which excipients should be prioritized for inclusion
of MDE information and why?
2. Should FDA focus on prioritizing excipients used in certain
categories of drug products (e.g., oral or topical products)? If so,
which categories and which specific excipients used in those categories
should be prioritized and why?
3. Is dosage form information in the IID helpful to your drug
development program? If so, please explain how dosage form information
in the IID is used in your drug development program.
4. Is the current structure or format of the IID difficult to
navigate? If so, how can it be improved?
Dated: March 15, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-06031 Filed 3-21-22; 8:45 am]
BILLING CODE 4164-01-P
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