Key Dates

Related Announcements

PA-20-183- NIH Research Project Grant (Parent R01 Clinical Trial Required)

PA-20-185- NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

PA-20-194 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Required)

PA-20-195 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)

PA-21-221- NIH Small Research Grant Program (Parent R03 Clinical Trial Required)

PA-21-200- NIH Small Research Grant Program (Parent R03 Clinical Trial Not Allowed)

PA-20-227 - Administrative Supplements for Research on Dietary Supplements (Admin Supp Clinical Trial Not Allowed)

PA-22-176 - PHS 2022-2 Omnibus Solicitation of the NIH, CDC and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed)

PA-22-177 - PHS 2022-2 Omnibus Solicitation of the NIH and CDC for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Required)

PA-22-178 - PHS 2022-2 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42] Clinical Trial Not Allowed)

PA-22-179 - PHS 2022-2 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42] Clinical Trial Required)

Issued by

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Office of The Director, National Institutes of Health (OD)

All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers. The following NIH Offices may co-fund applications assigned to those Institutes/Centers.

Office of Dietary Supplements (ODS)

Purpose

The purpose of this NOSI is to invite investigator-initiated applications addressing major research gaps in the evidence base to support regulation of biologically active substances, components and molecules that are intended for use in infant formula.

Background

Human milk research has brought to the attention of researchers, infant formula companies and families alike the possibility that new biologically active (bioactive) substances found in human milk could be added to infant formula as ingredients to improve child health. While research on the function and safety of most of these bioactive substances is scarce, the FDA is still required to make decisions on whether these ingredients can be included in infant formulas in a timely fashion. Further, children who consume infant formula are at higher risk for some diseases than those that consume human milk, making this group of children especially vulnerable. A recent joint NICHD-led NIH-FDA workshop (https://www.nichd.nih.gov/about/meetings/2021/092321;  https://web.cvent.com/event/ec019daf-1ecf-4ff5-b84c-92e7bf5c3949/summary) on this topic revealed several areas of research related to infant formula bioactive ingredients that are needed to make informed public health regulations but are not regularly studied in academic or industry labs. NIH was urged by attendees to act to support this research.

The goal of this Notice is to catalyze research on bioactive ingredients intended for use in infant formulas (e.g., lactoferrin, Milk Fat Globule Membrane (MFGM), Osteopontin, bioactive proteins, and others)¹ but is needed for public health regulation of infant formulas in the following areas:

1) Improved model systems, particularly non-rodent animal models, to test the effects and safety of new bioactive ingredients for use in infant formula

a. May also include testing to standardize model systems or testing of novel model systems

b. Particular interest is noted in model systems that pursue outcomes beyond usual infant growth measures and evaluate the gastrointestinal, immune and neurocognitive effects, if any, of bioactive ingredients

c. May include model systems that allow comparisons of the function and safety of bioactive ingredients delivered via different matrices (infant formula varieties, cow’s milk, human milk) and bioactive ingredients from different sources (human, bovine, other)

2) Improved methods for evaluating function (or activity) and safety of proposed bioactive ingredients for use in infant formulas alone, in the infant formula matrix and with other ingredients used in infant formulas

a. May also include testing to standardize methods or testing of novel methodologies

b. Particular interest is noted in methodologies that evaluate the gastrointestinal fate and bioavailability of proposed bioactive ingredients, and that pursue outcomes beyond usual infant growth measures

c. May include methodologies that allow comparisons of the function and safety of bioactive ingredients delivered via different matrices (infant formula varieties, cow’s milk, human milk) and bioactive ingredients from different sources (human, bovine, other)

3) Determination of adequate endpoints and timing for human studies that evaluate the function and safety of proposed bioactive ingredients for use in infant formulas.

a. Particular interest is noted in endpoints that move beyond usual infant growth measures and pursue measures of gastrointestinal, immune, endocrine and neurocognitive development or function.

b. May include model systems that allow comparisons of the function and safety of bioactive ingredients delivered via different matrices (infant formula varieties, milk from ruminants, human milk) and bioactive ingredients from different sources (human, animal, other)

4) Comparison of exposure levels and function of bioactive ingredients from infant formula vs exposure levels and function when the bioactive ingredients are delivered as usual components from human milk

¹ Almeida, et al. “Bioactive Compounds in Infant Formula and Their Effects on Infant Nutrition and Health: A Systematic Literature Review” Int J Food Sci (2021) PMID: 34095293

NIH Institute, Center and Office-specific Interests

The Office of Dietary Supplements: Dietary supplement ingredients are defined as including vitamins, minerals, herbs and other botanicals, amino acids, and other dietary or bioactive substances, consumed as dietary supplement or added to foods to promote health, prevent disease and other outcomes. The Office of Dietary Supplements is particularly interested in the study of docosahexaenoic acid (DHA), lactoferrin, bioactive proteins, prebiotics and probiotics (or living microorganisms) added to infant formulas. Particular interest is also in filling in knowledge gaps in mechanisms and a variety of developmental outcomes.

The Office of Nutrition Research is particularly interested in areas 1), 2) and 4) above, and applications from Minority Serving Institutions (Historically Black Colleges and Universities, Hispanic-Serving Institutions, Tribal Colleges and Universities, and Asian American and Pacific Islander Serving Institutions).

Responsiveness

The following types of research are not responsive to the intent of this NOSI:

• Discovery of new substances in human milk or other milk sources
• Testing the function of human milk substances solely being delivered via human milk or cow’s milk, without comparison to infant formula delivery

Application and Submission Information

This notice applies to due dates on or after June 5, 2022 and subsequent receipt dates through May 8, 2023. 

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcement through the expiration date of this notice.

• PA-20-183- NIH Research Project Grant (Parent R01 Clinical Trial Required)

• PA-20-185- NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

• PA-20-194 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Required)

• PA-20-195 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)

• PA-21-221- NIH Small Research Grant Program (Parent R03 Clinical Trial Required)

• PA-21-200- NIH Small Research Grant Program (Parent R03 Clinical Trial Not Allowed)

• PA-20-227 - Administrative Supplements for Research on Dietary Supplements (Admin Supp Clinical Trial Not Allowed)

• PA-22-176 - PHS 2022-2 Omnibus Solicitation of the NIH, CDC and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed)
• PA-22-177 - PHS 2022-2 Omnibus Solicitation of the NIH and CDC for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Required)
• PA-22-178 - PHS 2022-2 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42] Clinical Trial Not Allowed)
• PA-22-179 - PHS 2022-2 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42] Clinical Trial Required)

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

• For funding consideration, applicants must include “NOT-HD-22-016” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.
• Applicants must select the IC and associated FOA to use for submission of an application in response to the NOSI. The selection must align with the IC requirements listed in order to be considered responsive to that FOA. Non-responsive applications will be withdrawn from consideration for this initiative.

In addition, applicants using NIH Parent announcements (listed below) will be assigned to those ICs on this NOSI that have indicated those FOAs are acceptable and based on usual application-IC assignment practices.

• PA-20-183- NIH Research Project Grant (Parent R01 Clinical Trial Required)
• PA-20-185- NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

Applications nonresponsive to terms of this NOSI will be withdrawn from consideration for this initiative.

Inquiries

Scientific/Research Contact(s)

Ashley Vargas, PhD, MPH, RDN
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-827-6030
Email: ashley.vargas@nih.gov