Notice2025-09800
Replacing Color Additives in Approved or Marketed Drug Products; Draft Guidance for Industry; Availability
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Published
May 30, 2025
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The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled "Replacing Color Additives in Approved or Marketed Drug Products." This draft guidance provides recommendations for replacing color additives in approved or marketed drug products. If a color additive is replaced in a drug product, information to support the change should be retained and available at the manufacturing facility. Additionally, this draft guidance recommends that new drug application (NDA) and abbreviated new drug application (ANDA) holders submit information to support color additive replacements in changes being effected in 30 days (CBE-30) supplements. Although a qualitative or quantitative change to an inactive ingredient is generally considered a major change, in many cases, replacing a color additive with one that is listed in the color additive regulations is unlikely to adversely affect the identity, strength, quality, purity, or potency of the drug product. Therefore, this draft guidance recommends a CBE-30 for such a change.
Full Text
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<title>Federal Register, Volume 90 Issue 103 (Friday, May 30, 2025)</title>
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[Federal Register Volume 90, Number 103 (Friday, May 30, 2025)]
[Notices]
[Pages 23061-23063]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2025-09800]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2025-D-0507]
Replacing Color Additives in Approved or Marketed Drug Products;
Draft Guidance for Industry; Availability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the availability of a draft guidance for industry entitled ``Replacing
Color Additives in Approved or Marketed Drug Products.'' This draft
guidance provides recommendations for replacing color additives in
approved or marketed drug products. If a color additive is replaced in
a drug product, information to support the change should be retained
and available at the manufacturing facility. Additionally, this draft
guidance recommends that new drug application (NDA) and abbreviated new
drug application (ANDA) holders submit information to support color
additive replacements in changes being effected in 30 days (CBE-30)
supplements. Although a qualitative or quantitative change to an
inactive ingredient is generally considered a major change, in many
cases, replacing a color additive with one that is listed in the color
additive regulations is unlikely to adversely affect the identity,
strength, quality, purity, or potency of the drug product. Therefore,
this draft guidance recommends a CBE-30 for such a change.
DATES: Submit either electronic or written comments on the draft
guidance by July 29, 2025 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
[[Page 23062]]
information submitted, marked and identified, as confidential, if
submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-2025-D-0507 for ``Replacing Color Additives in Approved or Marketed
Drug Products.'' 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.
FOR FURTHER INFORMATION CONTACT: Ashley Boam, Center for Drug
Evaluation and Research (CDER), Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 4192, Silver Spring, MD 20993-0002, 301-
796-6341, <a href="/cdn-cgi/l/email-protection#96f5f2f3e4bbe7e3f7faffe2efbbe6f9fafff5efd6f0f2f7b8fefee5b8f1f9e0"><span class="__cf_email__" data-cfemail="ea898e8f98c79b9f8b86839e93c79a8586838993aa8c8e8bc4828299c48d859c">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a draft guidance for industry
entitled ``Replacing Color Additives in Approved or Marketed Drug
Products.'' This draft guidance provides recommendations for replacing
color additives in approved or marketed drug products. If a color
additive is used in a drug product, the color additive must conform to
FDA's color additive regulations. If FDA deems the color additive
unsafe and repeals the color additive regulation, the color additive
must be removed or replaced. Color additives can also be replaced for
other reasons (e.g., as a business decision).
This draft guidance describes considerations for replacing a color
additive, regardless of the reason for the change, including:
<bullet> Ensuring that the selected color additive conforms with
the color additive requirements (see section 721(a)-(b) of the Federal
Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 379e(a)-(b)) and
parts 70-71, 73-74, and 80-82 (21 CFR parts 70-71, 73-74, and 80-82))
<bullet> Updating information, including labeling, composition
statements, master batch records, and drug product specifications (as
applicable)
<bullet> Documenting information to support the change, including
maintaining appropriate records at the manufacturing site (see 21 CFR
211.180)
<bullet> Submitting information to support the change in a
supplement (for application products)
Although a qualitative or quantitative change in inactive
ingredients is generally considered a major change, in many cases,
replacing a color additive with one that is listed in the color
additive regulations (parts 73, 74 and 82) is unlikely to adversely
affect the identity, strength, quality, purity, or potency of the drug
product. Therefore, replacing a color additive can generally be
considered a moderate change that applicants can submit in a CBE-30.
The recommendations in this draft guidance apply to two groups:
applicants and manufacturers. In this draft guidance, the term
applicants refers to holders of approved NDAs or ANDAs for drug
products that are regulated by CDER. In this draft guidance, the term
manufacturers refers to manufacturers of:
<bullet> Drug products marketed under an NDA or ANDA (including
contract manufacturers)
<bullet> Drug products that are not marketed under a drug
application, including nonprescription drugs subject to section 505G of
the FD&C Act (21 U.S.C. 355h) (i.e., over-the-counter monograph drug
products)
<bullet> Compounded drug products subject to section 503B of the
FD&C Act (21 U.S.C. 353b)
<bullet> Other drug products that are subject to current good
manufacturing practice (CGMP) requirements
Some entities may be both applicants and manufacturers. These
entities should follow the appropriate recommendations for their roles
in each specific situation.
The recommendations in this draft guidance do not apply to drug
products in which a color additive is the active pharmaceutical
ingredient (e.g., methylene blue). The recommendations also do not
apply to drugs approved under section 505(b)(2) of the FD&C Act (21
U.S.C. 355(b)(2)) for which replacing a color additive would create a
different drug (see also 21 CFR 314.70(h)). Additionally, because
biological products rarely include color additives, the recommendations
in this draft guidance do not apply to products that have an approved
biologics license application. However, if a color additive is used as
an inactive ingredient in a biological product, the additive must be
listed in the color additive regulations and its use must conform to
the regulation (see section 721(a)-(b) of the FD&C Act and parts 70,
71, 73, 74, and 80 through 82).
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 ``Replacing
Color Additives in Approved or Marketed Drug Products.'' 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. As we develop
any final guidance on this topic, FDA will consider comments on the
applicability
[[Page 23063]]
of Executive Order 14192, per OMB guidance M-25-20, and in particular,
on any costs or cost savings.
II. Paperwork Reduction Act of 1995
While this draft guidance contains no collection of information, it
does refer to previously approved FDA collections of information. The
previously approved collections of information are subject to review by
the Office of Management and Budget (OMB) under the Paperwork Reduction
Act of 1995 (PRA) (44 U.S.C. 3501-3521). The collections of information
in Sec. Sec. 70.25 and 71.1 relating to the submission of color
additive petitions including labeling have been approved under OMB
control number 0910-0016. The collections of information in 21 CFR
201.56 and 201.57 relating to the submission of labeling for
prescription drug products and biological products have been approved
under OMB control number 0910-0572. The collections of information in
21 CFR parts 210 and 211 relating to CGMP requirements, including
manufacturing records, have been approved under OMB control number
0910-0139. The collections of information in 21 CFR part 314 relating
to the submission of NDAs and ANDAs, as well as related post approval
submissions (including annual reports) and drug master files, have been
approved under OMB control number 0910-0001. The collections of
information relating to labeling for certain over-the-counter products
have been approved under OMB control number 0910-0340.
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: May 27, 2025.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2025-09800 Filed 5-29-25; 8:45 am]
BILLING CODE 4164-01-P
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