Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula (2025)

Chapter: Appendix C: Open Meeting Agendas

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Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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Appendix C

Open Meeting Agendas

This appendix contains the following:

  • C-1: April 3, 2024, public session agenda
  • C-2: April 3, 2024, public session presentation slides
  • C-3: July 9–10, 2024, public session workshop agenda
  • C-4: September 4, 2024, public session agenda
  • C-5: October 22, 2024, public session agenda

The presentation slides from the Meeting 7 public workshop are in the Public Access File, available by request via the National Academies. https://www.nationalacademies.org/our-work/protein-quality-and-growth-monitoring-studies-to-satisfy-quality-factor-requirements-for-in-fant-formula

Page 124 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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C-1: Meeting Agenda
Virtual
April 3, 2024
11:30 am–12:30 pm ET

Open Session

11:30 am Review of Committee’s Task
Patricia Hansen, U.S. Food and Drug Administration, Center for Food Safety and Applied Nutrition
11:50 am Q & A with Sponsor
Stephanie Atkinson
12:15 pm Closing Remarks
Stephanie Atkinson
12:30 pm Adjourn Open Session
Page 125 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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C-2: April 3, 2024
Open Session Presentation Slides

Title slide stating alternatives to protein efficiency ratio rat bioassay (per) and growth monitoring study (gms) to satisfy quality factor requirements for infant formula — NASEM consensus study. Presented by Patricia A. Hansen (deputy director, office of nutrition and food labelling) and FDA project advisory group on April 3rd 2024.

Page 126 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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Overview slide demonstrating the speaker will touch on background, statement of task, FDA’s goals for the study, infant formula quality factors and pivotal studies in FDA regulations and possibilities for alternatives, including sufficient biological quality of protein and normal physical growth, summary and key takeaways, and question and answers and discussion.

General background slide stating severe challenges in the US infant formula supply beginning in spring 2022 due to a major recall and facility shut-down by Abbott, actions took by the FDA and other federal partners to address the supply challenges and collaboration with infant formula manufacturers and other stakeholders, and congressional directions for further actions provided in the Food and Drug Omnibus Reform Act of 2022.

Page 127 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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Continued background slide on the ongoing NASEM study, stating the charge to examine and report on challenges in supply, market competition, and regulation of infant formula in the US. The report aimed to assess and evaluate infant formula marketed in the US, challenges in supply or market competition, and differences between the US and Europe. The report included recommendation on measures to address supply and market competition in the US.

Statement of Task slide, stating that the national academies will convene a committee to conduct a study to examine and report on the state of the science regarding methodologies for assessing biological quality of protein in an infant formula and the ability of an infant formula to support normal physical growth. The report will include a detailed evaluation of the state of the science or gaps in scientific knowledge. The committee will assess related information identified by FDA.

Page 128 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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FDA’s goals slide stating this study aims for an independent expert scientific evaluation that can help FDA consider whether and how changes to our regulations, guidance, or other tools regarding methods and study designs for satisfying the infant formula quality factors might be modified or supplemented. The report will also be used to inform FDA’s overall efforts to support a robust and resilient supply of safe and nutritionally adequate infant formula.

Quality factors slide defining quality factors as those factors necessary to demonstrate the safety of the infant formula and the bioavailability of its nutrients, as prepared for market and when fed as the sole source of nutrition, to ensure the healthy growth of infants. There is an emphasis on sufficient biological quality of protein and normal physical growth.

Page 129 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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New infant formula submission slide stating requirements as per 21 CFR 106.120 and 106.121 regulation. Which includes name and description of infant formula, quantitative formulation, processing and packaging information, assurances for quality factors requirements, compliance with nutrient content requirements, and basis for each ingredient meeting safety and suitability requirements of 21 CFR 106.40(a), and exemption requests (if applicable).

Quality factor of sufficient biological quality of protein as stated in regulations includes 106.96(e) an infant formula shall meet the quality factor of sufficient biological quality of protein and 106.96(f) manufacturer must demonstrate that an infant formula meets this quality factor by establishing the biological quality of protein in the infant formula matrix using an appropriate modification of the Protein Efficiency Ratio (PER) rat bioassay.

Page 130 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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Overview of PER rate bioassay slide states that the AOAC official method 960.48 describes a standardized rat bioassay that can be used to express the relative values of protein growth and provides a procedure for evaluating the quality of protein in an infant formula matrix compared to that of a reference protein (i.e., protein within the infant formula matrix vs. casein).

Rationale for PER rat bioassay slide explains that the PER rat bioassay is currently the only method that accounts for protein digestibility and absorption in a living animal system; with chemical measures of protein composition (e.g., nitrogen measurements, amino acid patterns) do not address the bioavailability of the protein, and assessment of protein quality using an animal model will permit determination of a formula’s protein quality before infants are exposed to the formula.

Page 131 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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Exemptions from the requirement to conduct PER Study include regulation 106.96(g)(3) that to request an exemption, one must provide assurances, as per 106.121(i), that shows that an alternative method to the PER that is based on sound scientific principles is available to demonstrate that the formula supports the quality factor for the biological quality of protein, with 106.121(i) requiring an explanation of the alternative method and data ensuring biological quality of the protein.

Alternatives to PER slide, states that while showing significant promise, alternatives have yet to reach wide acceptability and standardization for use with infant formula. It includes indicator amino acid oxidation technique, net post-prandial protein utilization, dual stable isotope approaches, and in vitro gastrointestinal models. Might some of these studies be used in combination or with supplemental data, in accordance with sound scientific principles to meet our quality factor requirement?

Page 132 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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Quality factor of normal physical growth slide shows regulations 106.96(a) “An infant formula shall meet the quality factor of normal physical growth” and 106.96(b) “Manufacturer must demonstrate that an infant formula supports normal physical growth in infants when fed as a sole source of nutrition by conducting, in accordance with good clinical practice, an adequate and well-controlled growth monitoring study of the infant formula”.

According to regulation 106.96(b), growth monitoring studies should be at least 15 weeks long and infants no more than 2 weeks old at time of entry into study; have collection and maintenance of data on formula intake and anthropometric measures of physical growth, with collection at specific time intervals and data comparison between study groups and for each infant in each study group to 2009 CDC growth charts (anthropometric) and to a scientifically appropriate reference (formula intake).

Page 133 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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Evaluation of the GMS in a new infant formula submission slide depicts the requirements, including IRB-approved study protocol and statistical analysis plan, clinical study report, individual adverse event tables, plotted individual male/female CDC growth charts, and locked raw data sets and statistical analysis files.

Alternative study designs for normal physical growth may be accepted due to unique and/or extenuating circumstances. For example, the COVID-19 pandemic allowed for extended visit windows and use of anthropometric measurements collected at well baby visits and at home caregivers, or in a case of a required major reformulation after starting the GMS, which would require to divide the GMS study into two parts and combining the control groups from both parts into one.

Page 134 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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Alternative study design consideration for GMS include use of concurrent vs. historical control group, infant age at enrollment to be no more than two weeks of age at time of study entry, study duration no less than 15 weeks, and number and frequency of anthropometric measurements at least six total measurements with three measurements collected within the first four weeks of the study.

Consideration by the Committee include quality factor (QF) of sufficient biological quality of protein such as benefits and limitations of the PER design, alternative methods for determining protein quality, and gaps in research related to PER and alternative methods. Consideration for QF of normal physical growth include benefits and limitations of the GMS design, alternative methods and/or study designs, and gaps in research related to GMS and alternative methods.

Page 135 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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Key Takeaway slide states that FDA is interested in an independent and broad examination of the state of the science relevant to studies or combination of study types that could potentially be used to satisfy the infant formula quality factors, in the identification of scientific gaps and research needs, and to consider whether FDA, other federal agencies, industry, or other institutions are best positioned to potentially address specific gaps and needs identified.

U.S. Food and Drug Administration logo.

Page 136 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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C-3: Meeting Agenda
Advances in the Science to Assess Quality Factors for Infant Formulas in United States
July 9–10, 2024
The National Academies’ Keck Center
Washington, DC

The goal of this workshop is to gather information on current global perspectives on the rationale for use of protein quality assessment measures, the applicability of animal model research, and challenges of assessing protein quality using infant growth in clinical studies for the purpose of approving new infant formulas for market.

Objectives:

  • Provide a critical review of the state of the science on current methods for assessment of protein quality and their use/limitations as measures of protein quality of infant formula.
  • Explore the approaches considered by other countries in establishing regulations for protein quality in infant formula and growth in infants fed a new infant formula.
  • Obtain a global perspective of the variation in requirements for the conduct of clinical trials in infants for the purpose of regulatory approval locally/internationally and the challenges experienced.

Tuesday, July 9, 2024

Open Session

8:45 am Welcome and Chair’s Statement

Stephanie Atkinson, Committee Chair

Session 1: Models for Assessment of Protein Quality in Infant Formula

Moderated by: Rajavel Elango
9:00

Critical Analysis of PER Method to Assess Protein Quality in Infant Formula

Robert Burns, Ph.D., Indiana University Bloomington
9:20

PDCAAS and DIAAS as an Assessment of Amino Acid Score and Use of Human Milk Pattern as a Reference

Paul Moughan, Ph.D., D.Sc., Hon D.Sc., FRSNZ, FRSC, Massey University, New Zealand
9:40 Q&A
Page 137 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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10:00

Models of Ileal Digestion and Amino Acid Composition of Breast Milk in Protein Quality Studies

Daniel Tomé, Ph.D., AgroParisTech, Université Paris-Saclay, France
10:30 Q&A
10:45 Break
11:00

Session 2: Global Perspectives on Guidance for Measures and Regulation of Quality Factors in Assessing Infant Formula—Panel Discussion

Moderated by: John C. Wallingford
11:00

Perspectives from the European Union

Brian Kineman, Ph.D., Regulatory Affairs, Danone

Perspectives from Multinational Corporations

Robert DiGregorio, D.O., Harmony Baby Nutrition

Perspectives from the United States

Russell Merritt, M.D., Ph.D., Division of Gastroenterology, Hepatology and Nutrition, University of Southern California, Los Angeles
11:30 Questions and Discussion
12:00 pm Adjourn Open Session
1:00 pm Closed Session
4:30 pm Adjourn

Wednesday, July 10, 2024

Open Session

8:30 am

Welcome and Chair’s Statement

Stephanie Atkinson, Committee Chair

Session 3: Challenges in the Conduct and Interpretation of Clinical Trials for Regulatory Approval for a New Infant Formula

Moderated by: Steven Abrams
8:40

Body Composition as a Measure of Quality of Growth in Infants

Shane Norris, Ph.D., MASSAF, FAAS, University of Southampton, U.K.
9:00

Challenges in Conduct of Clinical Trials Assessing Quality Factors for Infant Formula: Methods, Cost, and Options

Michael B Montalto, Ph.D., Principal, Montalto Consulting Services in Health Sciences
9:20

Optimizing Clinical Trial Design for Studies in Infants

Deborah O’Connor, Ph.D., RD, Department of Nutritional Sciences, University of Toronto
Page 138 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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9:40 Q&A
10:10 Closing Remarks

Stephanie Atkinson, Committee Chair
10:30 Adjourn Open Session
11:00 am Closed Session
1:00 pm Adjourn Meeting

C-4: Meeting Agenda
September 4, 20241

C-5: Meeting Agenda
October 22, 2024
11:00 am–12:00 pm Eastern

Open Session

10:00 am Welcome and Introductions

Stephanie Atkinson, Chair
10:35 am Panel Discussion

Moderated by Stephanie Atkinson, Chair

  • Robert DiGregorio, D.O., Harmony Baby Nutrition
  • Brian Kineman, Ph.D., Regulatory Affairs, Danone
12:00 pm Adjourn Meeting

___________________

1 There was no printed agenda for this open public meeting with sponsors. The video recording is available at: https://www.nationalacademies.org/event/43605_09-2024_protein-quality-and-growth-monitoring-studies-to-satisfy-quality-factor-requirements-for-in-fant-formula-meeting-with-sponsor (accessed January 20, 2025).

Page 123 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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Page 124 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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Page 125 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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Page 126 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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Page 127 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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Page 128 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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Page 129 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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Page 130 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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Page 131 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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Page 132 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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Page 133 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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Page 134 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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Page 135 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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Page 136 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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Page 137 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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Page 138 Cite
Suggested Citation: "Appendix C: Open Meeting Agendas." National Academies of Sciences, Engineering, and Medicine. 2025. Protein Quality and Growth Monitoring Studies: Quality Factor Requirements for Infant Formula. Washington, DC: The National Academies Press. doi: 10.17226/29065.
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Page 138
Next Chapter: Appendix D: Protein Quality in Infant Formula: A Scoping Review
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