[Federal Register Volume 87, Number 55 (Tuesday, March 22, 2022)]
[Notices]
[Pages 16212-16214]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[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 https://www.regulations.gov 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:
     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-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 https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. 
and 4 p.m., Monday through Friday, 240-402-7500.
     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

[[Page 16213]]

``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, 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, 
[email protected].

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 https://www.fda.gov/regulatory-information/search-fda-guidance-documents.
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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 https://www.fda.gov/media/101052/download.
    \3\ The IID is updated on a quarterly basis at https://www.accessdata.fda.gov/scripts/cder/iig/index.cfm.
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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