Notice2026-10284
Protein Efficiency Ratio Rat Bioassay Studies To Demonstrate That a New Infant Formula Supports the Quality Factor of Sufficient Biological Quality of Protein; Guidance for Industry; Availability
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Published
May 22, 2026
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA or we) is announcing the availability of a guidance entitled "Protein Efficiency Ratio (PER) Rat Bioassay Studies to Demonstrate That a New Infant Formula Supports the Quality Factor of Sufficient Biological Quality of Protein." The guidance provides information for manufacturers and contract laboratories that perform PER studies to assist in designing, conducting, evaluating, and reporting PER studies. The guidance explains "appropriate modifications" of AOAC Official Method 960.48 (the AOAC Method) with the aim of supporting industry in successfully conducting PER studies that demonstrate that a new infant formula meets the quality factor of sufficient biological quality of protein when fed as the sole source of nutrition. The guidance finalizes the approach presented in the draft guidance issued in 2023.
Full Text
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<title>Federal Register, Volume 91 Issue 99 (Friday, May 22, 2026)</title>
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[Federal Register Volume 91, Number 99 (Friday, May 22, 2026)]
[Notices]
[Pages 30318-30319]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2026-10284]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2022-D-2424]
Protein Efficiency Ratio Rat Bioassay Studies To Demonstrate That
a New Infant Formula Supports the Quality Factor of Sufficient
Biological Quality of Protein; 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 we) is announcing the
availability of a guidance entitled ``Protein Efficiency Ratio (PER)
Rat Bioassay Studies to Demonstrate That a New Infant Formula Supports
the Quality Factor of Sufficient Biological Quality of Protein.'' The
guidance provides information for manufacturers and contract
laboratories that perform PER studies to assist in designing,
conducting, evaluating, and reporting PER studies. The guidance
explains ``appropriate modifications'' of AOAC Official Method 960.48
(the AOAC Method) with the aim of supporting industry in successfully
conducting PER studies that demonstrate that a new infant formula meets
the quality factor of sufficient biological quality of protein when fed
as the sole source of nutrition. The guidance finalizes the approach
presented in the draft guidance issued in 2023.
DATES: The announcement of the guidance is published in the Federal
Register on May 22, 2026.
ADDRESSES: You may submit either electronic or written 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-2424 for ``Protein Efficiency Ratio (PER) Rat Bioassay
Studies to Demonstrate That a New Infant Formula Supports the Quality
Factor of Sufficient Biological Quality of Protein.'' 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.'' We will review
this copy, including the claimed confidential information, in our
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 guidance to Office
of Critical Foods, Human Foods Program, Food and Drug Administration,
5001 Campus Dr., College Park, MD 20740. Send one self-addressed
adhesive label to assist that office in processing your request or
include a Fax number to which the guidance may be sent. See the
SUPPLEMENTARY INFORMATION section for information on electronic access
to the guidance.
FOR FURTHER INFORMATION CONTACT: With regard to the guidance: Ariel
Bourne, Office of Critical Foods, Human Foods Program, Food and Drug
Administration, 5001 Campus Dr., College Park, MD 20740, 240-402-1450,
email: <a href="/cdn-cgi/l/email-protection#40013229252c6e022f35322e25002624216e2828336e272f36"><span class="__cf_email__" data-cfemail="51102338343d7f133e24233f34113735307f3939227f363e27">[email protected]</span></a>; or Barbara Little, Office of Policy
and International Engagement, Human Foods Program, Food and Drug
Administration, 5001 Campus Dr., College Park, MD 20740, 240-402-8808.
With regard to the proposed collection of information: Michael
Ellison, Office of Operations, Food and Drug Administration, Three
White Flint North, 10A-12M, 11601 Landsdown St., North Bethesda, MD
20852, 240-402-2093, <a href="/cdn-cgi/l/email-protection#530301120027323535133537327d3b3b207d343c25"><span class="__cf_email__" data-cfemail="91c1c3d0c2e5f0f7f7d1f7f5f0bff9f9e2bff6fee7">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a guidance for industry
titled ``Protein
[[Page 30319]]
Efficiency Ratio (PER) Rat Bioassay Studies to Demonstrate That a New
Infant Formula Supports the Quality Factor of Sufficient Biological
Quality of Protein.'' Our regulations, at Sec. 106.96 (21 CFR 106.96),
establish requirements for quality factors for infant formulas,
including the quality factor of sufficient biological quality of
protein. Subject to a limited exception (see Sec. 106.96(g)), each
manufacturer of an infant formula that is not an eligible infant
formula must demonstrate that the formula meets the quality factor of
sufficient biological quality of protein by establishing the biological
quality of the protein in the infant formula when fed as the sole
source of nutrition using an appropriate modification of the AOAC
Official Method 960.48 (the AOAC Method) Protein Efficiency Ratio (PER)
Rat Bioassay (Sec. 106.96(f)).
The AOAC Method provides a procedure by which the quality of a
protein in food can be evaluated and compared with those of other
proteins. Protein ``quality'' can be defined as the ability of a
protein to meet the essential amino acid needs of an animal. The AOAC
Method is a standardized bioassay with published collaborative study
data. The AOAC Method permits the calculation of a PER as the ratio of
the average animal body weight gain per gram of protein consumed of a
test protein versus casein after a 28-day feeding period. Typically,
the protein concentration of both the test and casein reference diet is
set at about 10 percent, a level that is below the estimated
requirement for growth of rats of 15 percent, to improve the
sensitivity of the method. While growth is slower at 10 percent protein
than at 15 percent protein, the lower protein level ensures that
available protein is efficiently utilized.
In the PER study described in the AOAC Method, a protein ingredient
was assayed at 10 percent and other potential variables were
standardized so that their numbers and potential effects were
minimized. Vitamin composition, moisture, ash, carbohydrates, fat, and
fiber were adjusted between the casein reference diet and the test
diet. Use of a test diet that contains an infant formula in its
entirety introduces matrices of high fat content and additional
vitamins, minerals, and other ingredients, as well as the low protein
source. A major challenge in analyzing infant formulas by the AOAC
Method is matching the casein reference diet and test diet to achieve
dietary groups with as few confounding variables as possible.
Since we promulgated Sec. 106.96, we have found that industry is
experiencing difficulties in consistently meeting its requirements.
Therefore, we are announcing the availability of a guidance for
industry titled ``Protein Efficiency Ratio (PER) Rat Bioassay Studies
to Demonstrate That a New Infant Formula Supports the Quality Factor of
Sufficient Biological Quality of Protein.'' This guidance will help
infant formula manufacturers and contract laboratories that perform PER
studies in designing, conducting, evaluating, and reporting PER
studies. The guidance explains ``appropriate modifications'' of the
AOAC Method to help manufacturers and contract laboratories conduct PER
studies that demonstrate to FDA that a new infant formula meets the
quality factor of sufficient biological quality of protein.
FDA's work on this guidance began prior to significant infant
formula supply chain concerns that arose in early 2022. Although this
guidance was not prepared specifically to alleviate supply chain
concerns, the guidance will help ensure that infant formula products
meet FDA's regulatory requirements and will contribute to ensuring a
more resilient infant formula supply.
We are issuing the guidance consistent with our good guidance
practices regulation (21 CFR 10.115). The guidance represents the
current thinking of FDA on this topic. It does not establish any rights
for any person and is not binding on FDA or the public. You can use an
alternate approach to make ``appropriate modifications'' if it
satisfies the requirements of the applicable statutes and regulations.
Topics discussed in the guidance include:
<bullet> Purpose of the AOAC Method;
<bullet> Overview of the AOAC Method as originally described;
<bullet> Need for ``appropriate modifications'' to update the AOAC
Method and for use of infant formulas in PER bioassays;
<bullet> Conduct and analysis of a PER study with ``appropriate
modifications'' (matching the reference and test diets);
<bullet> Protocols and reports;
<bullet> Reference guidelines; and
<bullet> Appendices: AOAC Official Method 960.48, composition of
vitamin and mineral mixtures, compositions of diets, and examples of an
approach for matching vitamin, mineral, and (methionine + cystine)
compositions of PER study diets.
We considered all comments on the draft guidance received during
the comment period in finalizing the guidance. Comments on the draft
guidance discussed the need for increased flexibility in formulating
diets; the need for clarification regarding addition of vitamins and
minerals to diets; the need for cellulose in diets; the lack of need
for an optional casein reference group with matched sulfur amino acid
concentrations; development of validation data to substantiate the
modifications in the PER bioassay; and replacement of the PER method
with alternative methods, including non-animal methods.
We made technical changes in the guidance in response to the
comments. While we generally maintain our recommendations for matching
the compositions of the test and reference diets to within 20 percent
above or below, we describe certain areas in which additional
flexibility may be needed. We are also recommending changes in specific
nutrients and deleting a recommendation for an optional casein
reference group with matched sulfur amino acid concentrations. We
anticipate future discussions regarding validation data for the
modifications and considering alternative methods besides the PER
method.
II. Paperwork Reduction Act of 1995
This guidance contains information collection provisions that are
subject to review by the Office of Management and Budget (OMB) under
the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3521). The
collections of information in the guidance have been approved under OMB
control number 0910-0256.
III. Electronic Access
Persons with access to the internet may obtain an electronic
version of the guidance at <a href="https://www.fda.gov/RegulatoryInformation/Guidances/default.html">https://www.fda.gov/RegulatoryInformation/Guidances/default.html</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>. Use the
FDA website listed in the previous sentence to find the most current
version of the guidance.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2026-10284 Filed 5-21-26; 8:45 am]
BILLING CODE 4164-01-P
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