April 13, 2020 

Cathryn W. Sacra 

Director, Labeling and Cosmetic Services 

EAS Consulting Group, LLC 

1700 Diagonal Road, Suite 750 

Alexandria, VA 22314 

Dear Ms. Sacra: 

Thank you for contacting FDA regarding Glanbia Nutritional (Glanbia)’s GRAS notice 

for the intended use of bovine lactoferrin (bLf). As our December 17, 2020 letter 

indicates, we declined to file your submission because Glanbia did not identify 

substantive differences from prior GRAS notices (i.e., GRNs 000465 and 000669) that 

would warrant a new notice. 

In your letter, you request the Office of Food Additive Safety to issue a statement that we 

do not object to Glanbia’s intended use of bLf at 600 mg/L in infant formula. We decline 

Glanbia’s request because, as we previously communicated to Glanbia, the Agency does 

have safety questions surrounding the intended use of bLf at levels higher than in GRNs 

000465 and 000669 (i.e., 150 mg/L). We communicated these concerns on the 

unsettled science surrounding bioactive ingredients in infant formula on multiple 

occasions in the context of meetings and emails with Glanbia, as well as in the 

documents Glanbia received under the Freedom of Information Act that we 

recommended. We wish to remind Glanbia that: 

1. The safe use of ingredients in infant formula that may functionally mimic 

constituents in human milk is an evolving scientific field. 

2. bLf is a bioactive protein and not a toxic chemical; therefore, traditional toxicological 

endpoints will not necessarily address long-term safety issues related to effects such 

as immunomodulation and altering iron homeostasis. 

3. Anticipated benefits cannot be used as evidence of safety, as these effects cannot 

compensate for potential risks under FDA’s food ingredient safety assessment 

paradigm. 

4. In arriving at a “no questions” conclusion for GRNs 000465 and 000669, FDA 

considered the widespread and longstanding exposure to roughly comparable 

quantities of bLf in bovine milk-based infant formulas. However, as the doseresponse curve for bLf is moved up and away from historical exposure patterns in 

infant populations, the potential mechanistic and physiological effects of bLf will 

have greater impact on the weight-of-evidence approach FDA typically uses to 

evaluate safety. At the present time, FDA continues to have questions regarding the 

use of bLf in infant formula at levels higher than 150 mg/L given the unsettled state 

U.S. Food and Drug Administration

Center for Food Safety & Applied Nutrition

5001 Campus Drive

College Park, MD 20740

www.fda.gov 
 

Page 2 – Ms. Sacra 

of the science. 

Regarding other infant formulas, we do not comment on the compliance status of 

products. We note that we have not evaluated a GRAS notice for the intended use of bLf 

at 600 mg/L in infant formula. As we previously communicated to Glanbia, GRAS is 

time-dependent and subject to the currently available science. The current state of the 

science has raised new questions about the safe use and use level of substances with the 

potential for effects in the developing infant. Until new data and information become 

available to address the issues outlined above and previously communicated to you, we 

would question any GRAS submission for bLf at use levels higher than 150 mg/L in 

infant formula. We trust this clarifies our position and reasons for declining Glanbia’s 

request. 

Sincerely, 

Digitally signed by Susan J. Susan J. Carlson -S 

Date: 2020.04.13 14:59:15 Carlson -S -04'00' 

Susan Carlson, Ph.D. 

Director 

Division of Food Ingredients 

Center for Food Safety 

and Applied Nutrition