GRAS Notice (GRN) No.

980
https://www.fda.gov/food/generally-recognized-safe-gras/gras-notice-inventory

JHeimbach LLC

November 16, 2020 NOV 2 0 2020

OFFICE OF
FOOD ADDITIVE SAFETY

Susan J. Carlson, Ph.D., Director

Office of Food Additive Safety (HFS-200),
Center for Food Safety and Applied Nutrition
Food and Drug Administration
5001 Campus Dr., College Park, MD 20740

Dear Dr. Carlson:

Pursuant to 21 CFR Part 170, Subpart E, ByHeart, Inc., through me as its agent,
hereby provides notice of a claim that the addition of dry whole milk to nonexempt infant
formula intended for consumption by healthy term infants from the first day of life is
exempt from the premarket approval requirement of the Federal Food, Drug, and
Cosmetic Act because ByHeart, Inc., has determined that the intended use is generally
recognized as safe (GRAS) based on scientific procedures.
A CD is enclosed containing Form 3667, the GRAS monograph, and the
signatures of members of the GRAS panel in a zip directory produced through COSM.
If you have any questions regarding this notification, please feel free to contact
me at 202-320-3063 or [email protected].
Sincerely_[
- - -"- -

James T. Heimbach, Ph.D., F.A.C.N.

President
Encl.

1205 Prince Edward Street, Fredericl:?sburg Virginia 22535, USA

tel. (+1) 804-742-5548 cell (+1) 202-320-3063 [email protected]
 Generally Recognized as Safe (GRAS) Determination for the
Intended Use of Dry Whole Milk in Nonexempt Infant Formula

Prepared for:
ByHeart, Inc.
New York, NY

Prepared by:
JHeimbach LLC
Port Royal Virginia

November, 2020

Dry Whole Milk GRAS 1 JHEIMBACH LLC

 Table of Contents
Table of Contents.........................................................................................................................................2
List of Tables ...............................................................................................................................................3
Part 1: Signed Statements and Certification ................................................................................................4
1.1. GRAS Notice Submission ............................................................................................................... 4
1.2. Name and Address of Notifier ......................................................................................................... 4
1.3. Name of Notified Substance ............................................................................................................ 4
1.4. Intended Conditions of Use ............................................................................................................. 4
1.5. Statutory Basis for GRAS Status ..................................................................................................... 4
1.6. Premarket Exempt Status................................................................................................................. 5
1.7. Data Availability.............................................................................................................................. 5
1.8. Freedom of Information Act Statement ........................................................................................... 5
1.9. Certification ..................................................................................................................................... 5
1.10. FSIS Statement .............................................................................................................................. 5
1.11. Name, Position, and Signature of Notifier..................................................................................... 5
Part 2: Identity, Methods of Manufacture, Specifications, and Physical and Technical Effects .................6
2.1. Name of the GRAS Substance......................................................................................................... 6
2.2. Source, Description, Manufacture, and Specifications .................................................................... 6
2.2.1. Source and Description..........................................................................................................6
2.2.2. Manufacture...........................................................................................................................8
2.2.3. Specifications.........................................................................................................................9
2.3. Stability.......................................................................................................................................... 11
2.4. Technical Effect............................................................................................................................. 12
Part 3: Dietary Exposure............................................................................................................................13
3.1. Intended Conditions of Use ........................................................................................................... 13
3.2. Estimated Daily Exposure ............................................................................................................. 13
3.2.1. Phospholipids and Other Lipids...........................................................................................14
3.2.2. Nutrients with Maximum Allowable Levels........................................................................15
Part 4: Self-limiting Levels of Use ............................................................................................................17
Part 5: Experience Based on Common Use in Food..................................................................................18
Part 6: Narrative.........................................................................................................................................19
6.1. Regulatory Status of Whole Milk and Dry Whole Milk................................................................ 19
6.2. Past Use of Whole Milk or Dry Whole Milk in Infant Feeding..................................................... 20
6.3. Studies in Animals......................................................................................................................... 20
6.4. Studies in Infants and Toddlers ..................................................................................................... 21
6.5. Safety Assessment and GRAS Determination ............................................................................... 28
6.5.1. Evidence of Safety...............................................................................................................28
6.5.2. Conclusion of the GRAS Panel ...........................................................................................29
6.6. Statement Regarding Information Inconsistent with GRAS.......................................................... 29
6.7. Statement of the GRAS Panel........................................................................................................ 30
Part 7: List of Supporting Data and Information .......................................................................................31

Dry Whole Milk GRAS 2 JHEIMBACH LLC

 List of Tables
Table 1. Composition in 100 g Dry Whole Milk Without Added Vitamin D (USDA 2020)....................................6
Table 2. Analyses of Three Non-Consecutive Lots of Dry Whole Milk Against Specifications............................10
Table 3. Stability of Dry Whole Milk over 10 Months. ..........................................................................................11
Table 4. Stability of Dry Whole Milk over 4 Months. ............................................................................................11
Table 5. Nutrient Specifications for Milk-Based Infant Formula (from 21 CFR §107.100)...................................13
Table 6. Phospholipids Provided by Dry Whole Milk vs. Breast Milk and Current US Commercial Formula......15
Table 7. Other Lipids Provided by Dry Whole Milk vs. Breast Milk and Current US Commercial Formula. .......15
Table 8. Nutrients Provided by Dry Whole Milk and Maximum Allowable Levels...............................................16
Table 9. Published Research on Bovine Whole Milk..............................................................................................22

List of Figures
Figure 1. Process Flow Diagram of ByHeart’s Dry Whole Milk. .............................................................................9

Dry Whole Milk GRAS 3 JHEIMBACH LLC

Part 1: Signed Statements and Certification
1.1. GRAS Notice Submission
ByHeart, Inc., submits this GRAS notification through its agent James T. Heimbach,
president of JHeimbach LLC, in accordance with the requirements of 21 CFR Part 170, Subpart E.

1.2. Name and Address of Notifier

ByHeart, Inc.
689 5th Avenue
14th Floor
New York NY 10022
Notifier Contact
Gyan Rai, Ph.D.
Director, Regulatory
ByHeart, Inc.
689 5th Avenue
14th Floor
New York NY 10022
[email protected]
+1 (978) 400-9668
Agent Contact
James T. Heimbach, Ph.D., F.A.C.N.
President
JHeimbach LLC
923 Water Street #66
Port Royal VA 22535
[email protected]
+1 (804) 742-5543

1.3. Name of Notified Substance

The subject of this Generally Recognized as Safe (GRAS) notice is dry whole milk as
defined in 21 CFR §131.147, produced under current Good Manufacturing Practice (cGMP).

1.4. Intended Conditions of Use

As described in Section 3.1, the intended use of dry whole milk is as a component of non-
exempt infant formula intended for consumption by healthy term infants from the first day of life.
The addition level, allowing for manufacturing variability under cGMP, will not exceed 16% (w/w)
of the powdered infant formula.

1.5. Statutory Basis for GRAS Status

ByHeart’s GRAS determination for the intended use of dry whole milk in infant formula is
based on scientific procedures in accordance with 21 CFR §170.30(b).
Determination of the safety and GRAS status of the intended use of dry whole milk has
been made through the deliberations of a GRAS Panel consisting of Ronald Kleinman, M.D.,
Berthold V. Koletzko, M.D., Ph.D., and Robert J. Nicolosi, Ph.D. These individuals are qualified
by scientific training and experience to evaluate the safety of food ingredients intended for addition

Dry Whole Milk GRAS 4 JHEIMBACH LLC

to infant formula. They independently critically reviewed and evaluated the publicly available
information and the potential human exposure to dry whole milk anticipated to result from its
intended use, and individually and collectively determined that no evidence exists in the available
information on whole milk that demonstrates, or suggests reasonable grounds to suspect, a hazard
to infants or toddlers under the intended conditions of use of dry whole milk.
It is the GRAS Panel’s opinion that other qualified scientists reviewing the same publicly
available information would reach a similar conclusion regarding the safety of the substance under
its intended conditions of use. Therefore, the intended use of dry whole milk in non-exempt infant
formula intended for consumption by healthy term infants from the first day of life is GRAS by
scientific procedures.

1.6. Premarket Exempt Status

The intended use of dry whole milk is not subject to the premarket approval requirements of
the Federal Food, Drug and Cosmetic Act based on ByHeart’s determination that it is GRAS.

1.7. Data Availability

The data and information that serve as the basis for the conclusion that dry whole milk is
GRAS for its intended use will be made available to the FDA upon request. At FDA’s option, a
complete copy of the information will be sent to FDA in either paper or electronic format, or the
information will be available for review at the home office of JHeimbach LLC, located at 923
Water Street, Port Royal VA 22535, during normal business hours.

1.8. Freedom of Information Act Statement

None of the information in this GRAS notice is exempt from disclosure under the Freedom
of Information Act, USC 552.

1.9. Certification
To the best of my knowledge, this GRAS notice is a complete, representative, and balanced
submission that includes unfavorable information, as well as favorable information, known to me
and pertinent to the evaluation of the safety and GRAS status of the intended use of dry whole
milk.

1.10. FSIS Statement

Not applicable.

1.11. Name, Position, and Signature of Notifier

James T. Heimbach, Ph.D., F.A.C.N.

President
JHeimbach LLC
Agent to ByHeart, Inc.
Dry Whole Milk GRAS 5 JHEIMBACH LLC
Part 2: Identity, Methods of Manufacture, Specifications, and Physical and
Technical Effects
2.1. Name of the GRAS Substance
The notified substance is dry whole milk, which is defined in 21 CFR §131.147 as “the
product obtained by removal of water only from pasteurized milk, as defined in §131.110(a), which
may have been homogenized. Alternatively, dry whole milk may be obtained by blending fluid,
condensed, or dried nonfat milk with liquid or dried cream or with fluid, condensed, or dried milk,
as appropriate, provided the resulting dry whole milk is equivalent in composition to that obtained
by the method described in the first sentence of this paragraph. It contains the lactose, milk
proteins, milkfat, and milk minerals in the same relative proportions as the milk from which it was
made. It contains not less than 26 percent but less than 40 percent by weight of milkfat on an as is
basis. It contains not more than 5 percent by weight of moisture on a milk solids not fat basis.” This
section further notes that addition of vitamins A and D is optional, along with carriers for these
vitamins, emulsifiers, stabilizers, anticaking agents, and antioxidants.
The dry whole milk that is the subject of this GRAS notice does not contain added vitamins
A or D or any of the other optional ingredients identified above.

2.2. Source, Description, Manufacture, and Specifications

2.2.1. Source and Description
ByHeart’s dry whole milk is sourced from dairy cows. The composition of dry whole milk,
as described in the U.S. Department of Agriculture’s Nutrient Database for Standard Reference
(USDA 2020) is shown in Table 1. As with any biological substance, there is some natural
variability in the values reported, which is not reflected in the USDA tables.
Table 1. Composition in 100 g Dry Whole Milk Without Added Vitamin D (USDA 2020).

Parameter Level Unit

Proximates
Water 2.47 g
Energy 496 kcal
Energy 2075 kJ
Protein 26.32 g
Total lipid (fat) 26.71 g
Ash 6.08 g
Carbohydrate, by difference 38.42 g
Fiber, total dietary 0 g
Sugars, total including NLEA 38.42 g
Minerals
Calcium, Ca 912 mg
Iron, Fe 0.47 mg
Magnesium, Mg 85 mg
Phosphorus, P 776 mg
Potassium, K 1330 mg
Sodium, Na 371 mg
Zinc, Zn 3.34 mg
Copper, Cu 0.08 mg
Manganese, Mn 0.04 mg
Selenium, Se 16.3 µg

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 Vitamins
Vitamin C, total ascorbic acid 8.6 mg
Thiamin 0.283 mg
Riboflavin 1.205 mg
Niacin 0.646 mg
Pantothenic acid 2.271 mg
Vitamin B-6 0.302 mg
Folate, total 37 µg
Folic acid 0 µg
Folate, food 37 µg
Folate, DFE 37 µg
Choline, total 117.4 mg
Vitamin B-12 3.25 µg
Vitamin B-12, added 0 µg
Vitamin A, RAE 258 µg
Retinol 253 µg
Carotene, beta 55 µg
Carotene, alpha 0 µg
Cryptoxanthin, beta 0 µg
Vitamin A, IU 934 IU
Lycopene 0 µg
Lutein + zeaxanthin 0 µg
Vitamin E (alpha-tocopherol) 0.58 mg
Vitamin E, added 0 mg
Vitamin D (D2 + D3), International Units 20 IU
Vitamin D (D2 + D3) 0.5 µg
Vitamin D3 (cholecalciferol) 0.5 µg
Vitamin K (phylloquinone) 2.2 µg
Fatty Acids & Cholesterol
Fatty acids, total saturated 16.742 g
4:00 0.866 g
6:00 0.24 g
8:00 0.269 g
10:00 0.596 g
12:00 0.614 g
14:00 2.82 g
16:00 7.522 g
18:00 2.853 g
Fatty acids, total monounsaturated 7.924 g
16:01 1.196 g
18:01 6.192 g
20:01 0 g
22:01 0 g
Fatty acids, total polyunsaturated 0.665 g
18:02 0.46 g

Dry Whole Milk GRAS 7 JHEIMBACH LLC

 18:03 0.204 g
18:04 0 g
20:04 0 g
20:5 n-3 (EPA) 0 g
22:5 n-3 (DPA) 0 g
22:6 n-3 (DHA) 0 g
Cholesterol 97 mg
Amino Acids
Tryptophan 0.371 g
Threonine 1.188 g
Isoleucine 1.592 g
Leucine 2.578 g
Lysine 2.087 g
Methionine 0.66 g
Cystine 0.243 g
Phenylalanine 1.271 g
Tyrosine 1.271 g
Valine 1.762 g
Arginine 0.953 g
Histidine 0.714 g
Alanine 0.908 g
Aspartic acid 1.997 g
Glutamic acid 5.512 g
Glycine 0.557 g
Proline 2.549 g
Serine 1.432 g
Other
Alcohol, ethyl 0 g
Caffeine 0 mg
Theobromine 0 mg

2.2.2. Manufacture
ByHeart’s dry whole milk is produced using standard dairy processing techniques involving
purely mechanical procedures as shown in Figure 1. No component of whole milk is concentrated
to greater than naturally occurring levels.

Dry Whole Milk GRAS 8 JHEIMBACH LLC

 Milk

Receiving Ho.ld Tank

Pasteurizer

Evaporata

Storage Tank

High Pressure Ptmip

Spray Drying

Packaging (Bag)

DRY WHOLE MILK

Figure 1. Process Flow Diagram of ByHeart’s Dry Whole Milk.

2.2.3. Specifications
ByHeart has established food-grade specifications for dry whole milk to assure purity.
Table 2 shows the results of analyses of three non-consecutive lots of product to determine
compliance with these specifications. As is shown, all samples were in full compliance, indicating
that the production process is in control and results in product that consistently meets food-grade
specifications.

Dry Whole Milk GRAS 9 JHEIMBACH LLC

 Table 2. Analyses of Three Non-Consecutive Lots of Dry Whole Milk Against Specifications.
Lot Tested
Parameter Specification Method (Eurofins)
MO19-0019 MO20-0014 MO20-0015
Moisture (%) NMT1 5.0 2.30 3.13 3.07 M100_T100 (AOAC 925.09 / 926.08)
Protein (%) NLT2 18.7 25.3 25.0 25.0 DGEN_S (AOAC 968.06 / 992.15)
FAT_BH_S (AOAC
Fat (%) NLT 26 32.9 32.0 31.8
989.05/932.05/986.25/945.48B)
Titratable
NMT 15 <15 <15 <15 QA-PL-10.000 (USDA 918RL)
acidity (%)
Peroxide value
NMT 5 1.0 2.9 2.1 AOAC 965.33
(meq/kg fat)
Cholesterol Typical
107 99.0 99.2 CHOK-S (AOAC 994.10)
(mg/100 g) concentration
Typical
Ash (%) 5.2% 5.2% 5.2% ASHM_S (AOAC 923.03)
concentration
Vitamin A Typical VALC_S (AOAC
804 943 914
(IU/100 g) concentration 992.04/992.06/2001.13)
Vitamin D3 Typical
<4 <4 <4 VDMS_S (AOAC 2011.11)
(IU/100 g) concentration
Typical ICP_S (AOAC 984.27 /
Iron (mg/g) 0.003 0.003 0.003
concentration 985.01/2011.14)
Typical
Iodide (µg/g) 3.32 1.11 1.11 IODICPMS_S (AOAC 2212.15)
concentration
Typical ICP_S (AOAC 984.27 /
Sodium (mg/g) 3.01 2.94 2.92
concentration 985.01/2011.14)
Potassium Typical ICP_S (AOAC 984.27 /
11.06 10.81 10.75
(mg/g) concentration 985.01/2011.14)
Typical CL_SALT_S (AOAC
Chloride (mg/g) 7.97 7.19 7.15
concentration 963.05/971.27/986.26)
Typical
Selenium (µg/g) 0.120 0.703 0.715 SEIF_S (AOAC 2011.19)
concentration
Heavy metals
Arsenic
NMT 500 <10 <10 <10 ICP-MS (AOAC 2011.19 / 993.14)
(µg/kg)
Cadmium
NMT 50 <5 <5 <5 ICP-MS (AOAC 2011.19 / 993.14)
(µg/kg)
Lead (µg/kg) NMT 50 <5 <5 <5 ICP-MS (AOAC 2011.19 / 993.14)
Mercury
NMT 50 <5 <5 <5 ICP-MS (AOAC 2011.19 / 993.14)
(µg/kg)
Microbiological
Aerobic Plate
NMT 10,000 160 60 50 APC (AOAC 966.23)
Count (cfu3/g)
Coliforms
NMT 10 <10 <10 <10 YN_SPRD (AOAC, FDA BAM)
(cfu/g)
Mold (cfu/g) NMT 50 <10 <10 <10 YN_SPRD (AOAC, FDA BAM)
Yeast (cfu/g) NMT 50 <10 <10 <10 YN_SPRD (AOAC, FDA BAM)
B. cereus
NMT 100 <10 <10 <10 YN_SPRD (AOAC, FDA BAM)
(cfu/g)
Enterobacteri-
NMT 10 <10 <10 <10 YN_SPRD (AOAC, FDA BAM)
aceae (cfu/g)
S. aureus NMT 10 <10 <10 <10 YN_SPRD (AOAC, FDA BAM)
Listeria spp. Not Not Not
Negative YN_SPRD (AOAC, FDA BAM)
(in 25 g) detected detected detected
Salmonella
LAMP Not Not Not
Negative SALLAMP (AOAC 091501)
detection (in detected detected detected
25 g)
Cronobacter
Not Not Not
species D (in Negative ICO_EML_LC (AOAC, FDA BAM)
detected detected detected
10 g)
1. NMT = not more than
2. NLT = not less than
3. cfu = colony-forming units

Dry Whole Milk GRAS 10 JHEIMBACH LLC

2.3. Stability
One lot of dry whole milk was stored for ten months at a temperature ranging from 10-30ºC
and relative humidity <70% and two additional lots were stored for four months under the same
conditions. The results of the 10-month study are shown in Table 3 and those of the 4-month
studies in Table 4. The data from all studies indicate that no significant degradation in the quality
of the dry milk occurs over the time periods studied.

Table 3. Stability of Dry Whole Milk over 10 Months.

Lot MO19-0019
Time Month Month Month Month Month Month Month Month Month Month
Parameter
0 1 2 3 4 5 6 7 8 9 10
Moisture (%) 2.30 2.51 2.58 2.56 2.18 1.92 3.06 2.61 2.78 3.20 3.48

Free Fat (%) 5.3 3.6 4.6 3.6 6.3 4.9 4.7 3.3 2.4 1.9 3.3
1
Free Fatty Acids (%) 0.03 0.09 --- 0.09 0.08 0.09 0.07 0.06 0.11 0.08 0.14
Hexanal (mg/kg) <1.00 <1.00 1.07 <1.0 <1.0 <1.0 <1.0 <1.0 <1.0 <1.0 <1.0
Peroxide (% mEq/kg) 2.1 1 1.5 1.1 1.8 1.9 2.1 1.8 2.0 1.5 1.4
2
Yeast (cfu /g) --- <10 <10 <10 <10 <10 <10 <10 <10 <10 <10
Mold (cfu/g) --- <10 <10 <10 <10 <10 <10 <10 <10 <10 <10
Aerobic plate count (cfu/g) --- 210 430 390 240 300 200 430 150 150 490
Color (L value)) 92.48 92.32 92.27 92.24 92.45 92.53 92.62 92.27 92.28 --- 92.13
Color (A value) -1.99 -2.03 -2.15 -2.26 -2.07 -2.34 -2.25 -2.38 -2.37 --- -2.40
Color (B value) 21.19 21.67 22.06 22.01 20.63 21.21 20.88 22.06 22.00 --- 22.19

Nitrogen solubility (%) 77 --- --- --- --- --- --- --- --- 73.2 ---
1. Not tested.
2. cfu = colony-forming units

Table 4. Stability of Dry Whole Milk over 4 Months.

MO20-0014 MO20-0015
Parameter Time Month Month Month Month Time Month Month Month Month
0 1 2 3 4 0 1 2 3 4
Moisture (%) 3.13 2.48 2.98 3.40 3.58 3.07 2.39 2.91 3.23 3.41
Free Fat (%) 1.6 1.1 1.5 1.0 1.6 1.7 1.6 1.0 1.3 1.5
Free Fatty Acids (%) 0.10 0.07 0.07 0.06 0.14 0.06 0.07 0.07 0.06 0.13
Hexanal (mg/kg) <1.0 <1.0 <1.0 <1.0 <1.0 <1.0 <1.0 <1.0 <1.0 <1.0
Peroxide (% mEq/kg) 3.5 2.9 1.7 1.5 1.9 1.0 2.1 2.6 1.4 1.5
Yeast (cfu2/g) ---1 <10 <10 <10 <10 --- <10 <10 <10 <10
Mold (cfu/g) --- <10 <10 <10 <10 --- <10 <10 10 <10
Aerobic plate count (cfu/g) --- 80 70 <10 80 --- 60 110 <10 10
Color (L value)) 91.68 91.47 91.76 --- 91.94 91.70 91.70 91.43 --- 91.60
Color (A value) -1.39 -1.33 -1.46 --- -1.71 -1.4 -1.4 -1.45 --- -1.72
Color (B value) 22.94 23.51 22.79 --- 22.54 22.99 23.01 23.56 --- 23.38
Nitrogen solubility (%) 78.9 64.9 --- --- --- 79.7 --- --- --- ---
1. Not tested.
2. cfu = colony-forming units

Dry Whole Milk GRAS 11 JHEIMBACH LLC

2.4. Technical Effect
The intended technical effect of the addition of dry whole milk to nonexempt infant formula
is as a source of protein. It is not intended to serve any function other than nutrition.

Dry Whole Milk GRAS 12 JHEIMBACH LLC

Part 3: Dietary Exposure
3.1. Intended Conditions of Use
21 CFR §107.100 provides nutrient specifications for milk-based infant formula per 100
kcal formula as prepared. These specifications are summarized in Table 5.
Table 5. Nutrient Specifications for Milk-Based Infant Formula (from 21 CFR §107.100).
Minimum Maximum
Unit of
Nutrient Level per Level per
Measurement
100 kcal 100 kcal
Protein g 1.8 4.5
g 3.3 6.0
Fat
% kcal 30 54
mg 300
Linoleic acid
% kcal 2.7
Vitamin A IU 250 750
Vitamin D IU 40 100
Vitamin E IU 0.7
Vitamin K µg 4
Thiamine (Vitamin B1) µg 40
Riboflavin (Vitamin B2) µg 60
Vitamin B6 µg 35
Vitamin B12 µg 0.15
Niacin µg 250
Folic acid (Folacin) µg 4
Pantothenic acid µg 300
Vitamin C (Ascorbic acid) mg 8
Calcium mg 60
Phosphorus mg 30
Magnesium mg 6
Iron mg 0.15 3.0
Zinc mg 0.5
Manganese µg 5
Copper µg 60
Iodine µg 5 75
Selenium µg 2 7
Sodium mg 20 60
Potassium mg 80 200
Chloride mg 55 150

Dry whole milk powder will be added to powdered infant formula at a level not exceeding
16 g/100 g powder. The infant formula to be manufactured by ByHeart will have a hydration rate
of 12.5 g powder/100 ml formula ready to consume; this level is equivalent to 2.0 g dry whole
milk/100 ml formula ready to consume. The function of the addition of dry milk powder is to
provide nutrients more closely resembling those found in breast milk.

3.2. Estimated Daily Exposure

Assuming an average formula intake of 800 ml/day, an infant will consume 16.0 g dry whole
milk powder per day. (This represents the solids content of approximately 120 ml whole milk.)
According to tables of daily energy intake by formula-fed infants provided by Fomon (1993),
the subpopulation of infants with the highest energy intake per kg body weight is boys age 14–27
days. The 90th percentile energy intake by this group is 141.3 kcal/kg bw/day. Among girls, the
highest energy intake is found in the same age group, 14–27 days, and is nearly as high as boys:

Dry Whole Milk GRAS 13 JHEIMBACH LLC

138.9 kcal/kg bw/day1. Most standard formulas contain 67 kcal/100 ml when ready to consume.
Therefore, to obtain 141.3 kcal energy/kg bw, an infant boy must consume 209.0 ml formula/kg bw.
To reach her 90th percentile of energy consumption, 138.9 kcal/kg bw/day, an infant girl must
consume 205.5 ml formula/kg bw. The 90th percentile of formula intake for the two sexes combined
is about 207 ml/kg bw/day.
Since dry milk powder is to be added at a maximum level of 2.0 g dry whole milk/100 ml
formula ready to consume, the 90th percentile daily intake of dry whole milk is estimated to be [2.0 g
dry whole milk/100 ml x 207 ml/kg bw/day] = 4.14 g dry whole milk/kg bw/day.
As the infant grows, formula intake increases, but more slowly than weight gain, so that
consumption assessed as ml formula per kg body weight is lower for infants older than 27 days. As a
result, intake of dry whole milk per kg body weight decreases as the infant grows older and larger.

3.2.1. Phospholipids and Other Lipids

The amounts of phospholipids provided by the intended use of dry whole milk powder,
resulting in 2.0 g dry whole milk/100 ml formula, as compared to levels in human breast milk, are
shown in Table 6. As has been previously noted, the composition of the whole milk has not been
altered in any way; the phospholipids are present at their naturally occurring levels. The amounts
listed in Table 6 are total phospholipid composition that may originate from intact or disrupted
milk fat globules.
As is evident from Table 6, the levels of phospholipids provided by dry whole milk do not
differ remarkably from those provided by the human milk consumed by breastfed infants. When
infant formula is based on nonfat milk, some of the native phospholipids are removed during the
defatting steps and so “Breastfed infants have a higher intake of [these phospholipids] than their
formula-fed counterparts because, traditionally, the [phospholipid] fraction is discarded with the
milk fat when this is replaced by vegetable oils as the fat source in infant formulas” (Timby et al.
2017). Phospholipids are permitted to be added to infant formulas up to a maximum concentration
of 300 mg/100 kcal (equivalent to about 2 g/L) and are regarded as safe (Koletzko et al. 2005).
Phospholipid ingredients such as lecithin used in other commercial formulas today provide partial
replacement of these phospholipids (Scholfield 1981). As is evident in Table 6, the phospholipid
composition of ByHeart’s formula is not remarkably different from currently marketed infant
formulas with and without added MFGM (Fong et al 2013), and the values are within the ranges
observed in human milk (Ma et al 2017).

1
These estimates are corroborated by data from the 2008 Feeding Infants and Toddlers Study
(FITS; Butte et al. 2010), which reported the 90th percentile energy intake for infants aged birth to 5
months as 779 kcal. Although body weights of the FITS participants on the days diets were
assessed were not available, infant growth charts issued by the Centers for Disease Control and
Prevention indicate that the median body weights for the two sexes combined at birth and at 5
months are about 3.4 and 7.4 kg, respectively. A reasonable estimate of the median body weight of
infants aged birth to 5 months is the average of these two body weights, or 5.4 kg. The 90 th
percentile energy intake of 779 kcal thus represents about 144 kcal/kg, very close to the estimates
in Fomon (1993).

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 Table 6. Phospholipids Provided by Dry Whole Milk vs. Breast Milk and Current US Commercial Formula.
mg/100 ml in mg/100 ml in
mg/100 ml mg/100 ml commercial commercial
% in Whole
Phospholipid in ByHeart in breast product #1 product #2
Milk Powder1
formula2 milk without with added
added MFGM MFGM
Total phospholipid 0.286 13.6 17.0 ± 8.0 53.7 86.2
Phosphatidylcholine 0.067 3.3 2.6 ± 1.7 18.2 26.0
Phosphatidylethanolamine 0.0636 0.3 4.6 ± 2.3 11.7 16.9
Phosphatidylinositol 0.037 1.7 0.7 ± 0.5 7.8 13.0
Phosphatidylserine 0.033 1.7 1.7 ± 1.0 2.6 6.5
Sphingomyelin 0.057 5.0 6.5 ± 3.8 2.6 13.0
1. Analytical data from independent testing laboratory.
2. Calculated from analytical data for 16% addition rate.

Certain other lipids present in human and bovine milk are listed in Table 7. They are largely
removed during defatting of milk but are still present in small amounts in nonfat milk. As shown in
Table 7, their contribution to By Heart’s infant formula from the whole milk is small and their
levels are within the ranges of both human milk (McGuire et al. 1997; Floris et al. 2020) and
commercial infant formula.

Table 7. Other Lipids Provided by Dry Whole Milk vs. Breast Milk and Current US Commercial Formula.
mg/100 ml in mg/100 ml in
% in Whole mg/100 ml mg/100 ml commercial Commercial
Other Lipids Milk in ByHeart in breast product #1 product #2
Powder1 formula2 milk without added with added
MFGM MFGM
Conjugated linoleic acid (mg/g fat) 9.9 - 17.3 2.4* 3.64 ± 0.93 1.7 2.1
Cholesterol (mg/g fat) 3.12 - 3.25 0.90 2.0 – 5.64 0.62 1.6
trans-fatty acids (% total FA) 4.6 - 8.5 1.03 1.28 ± 0.27 0.54 1.14
1. Analytical data from independent testing laboratory.
2. Calculated from analytical data for 16% addition rate.

Although several infant formula feeding studies (e.g., Billeaud et al. 2014) that have been
conducted with MFGM added to infant formula, showed equivalent growth in comparison to infant
formula without MFGM, these conditions do not apply in this situation as the contribution of milk
fat and its lipid components are insignificant in relation to the vegetable fat or those used in
MFGM-supplemented infant formulas. Furthermore, the amounts of phospholipids in ByHeart
formula is similar to the range observed in human milk and that in currently sold commercial infant
formula without added MFGM, and is substantially lower than those in MFGM-supplemented
infant formulas.

3.2.2. Nutrients with Maximum Allowable Levels

The nutrient specifications for milk-based infant formula listed in 21 CFR §107.100 include
ten nutrients for which maximum allowable levels are specified—protein, fat, vitamins A and D,
iron, iodine, selenium, sodium, potassium, and chloride. Table 8 shows the amount of these
nutrients provided by dry whole milk added at the maximum intended level of 16%. These data
show that the intended addition of dry whole milk does not cause the allowable levels of any of
these nutrients to be exceeded.

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 Table 8. Nutrients Provided by Dry Whole Milk and Maximum Allowable Levels.
Level
Provided Maximum
Unit of by Dry Allowable
Nutrient
Measurement Whole Level per
Milk per 100 kcal
I I g
I 100 kcal
0.76
I
4.5
I
Protein
g 0.97 6.0
Fat
% kcal 8.8 54
Vitamin A IU 27 750
Vitamin D IU 0.12 100
Iron mg 0.009 3.0
Iodine µg 5.6 75
Selenium µg 1.5 7
Sodium mg 8.9 60
Potassium mg 33 200
Chloride mg 22 150

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Part 4: Self-limiting Levels of Use
There is no physical limit to the concentration of milk in infant formula; infants have been
fed 100% cow’s milk in the past. However, an excessive amount of milk in the infant formula
would lead to nutrient imbalances, which places a limit on the addition level.

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Part 5: Experience Based on Common Use in Food
The conclusion that the intended use of dry whole milk is GRAS is based on scientific
procedures rather than experience based on common use in food prior to 1958.

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Part 6: Narrative
6.1. Regulatory Status of Whole Milk and Dry Whole Milk
While bovine whole milk is not listed as a GRAS substance in 21 CFR §184, it is
appropriate to note that the long history of use of whole milk (in liquid or dry form) as both a
stand-alone product and an ingredient in a wide variety of products—including infant formula—
suggests that it has been informally recognized as GRAS as an ingredient in conventional foods.
Regarding this point, 21 CFR §182.1 notes that:
“It is impracticable to list all substances that are generally recognized as safe for their
intended use. However, by way of illustration, the Commissioner regards such common
food ingredients as salt, pepper, vinegar, baking powder, and monosodium glutamate as
safe for their intended use. This part includes additional substances that, when used for
the purposes indicated, in accordance with good manufacturing practice, are regarded by
the Commissioner as generally recognized as safe for such uses” (21 CFR §182.1).
The following regulations pertaining to affirmed GRAS substances obtained by physical
separation from bovine milk suggest that the parent product, bovine milk itself, is GRAS as an
ingredient in conventional foods.
21 CFR §184.1979(a)—reduced lactose whey, produced by removal of lactose by physical
separation techniques (e.g., precipitation, filtration, dialysis)
21 CFR §184.1979(b)—reduced minerals whey, produced by removal of a portion of the
minerals by physical separation techniques
21 CFR §184.1979(c)—whey protein concentrate, produced by physical separation of
protein and non-protein constituents
21 CFR §184.1553—peptones, “a variable mixture of polypeptides, oligopeptides, and
amino acids that are produced by partial hydrolysis of casein, … 1, or lactalbumin” using proteolytic
enzymes.
The report listed below from the Select Committee on GRAS Substances and the six GRAS
notices for milk-derived ingredients also suggest that bovine milk is regarded as GRAS.
SCOGS Report No. 37b—enzymatically hydrolyzed casein
GRN000011—mixture of calcium casein peptone and calcium phosphate
GRN000037—whey protein isolate
GRN000037—dairy product solids
GRN000052—whey mineral concentrate
GRN000196—bovine milk basic protein fraction
GRN000504—milk protein concentrate and milk protein isolate
Based on these references, it seems clear that dry whole milk is already GRAS as an
ingredient in conventional foods; consequently, determination that it is GRAS, based on scientific
procedures, as an ingredient in infant formula is properly regarded as an expansion of the allowable
uses of an already GRAS ingredient rather than a novel GRAS determination.

1
The ellipsis omits non-milk sources of peptones, including soy, gelatin, fatty tissue, and egg albumin.

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6.2. Past Use of Whole Milk or Dry Whole Milk in Infant Feeding
While current recommendations dating back more than fifty years recommend against
feeding 100% whole milk to infants from birth to one year of age as the sole source of nutrition
because it does not provide optimal nutrition when consumed alone, there is a long record of safe
consumption of whole milk during this period. Fomon (2001) reviewed infant feeding through the
twentieth century. He noted that, in the early years of the century, “the majority of formula-fed
infants received formulas made in the home from whole milk or ‘top milk’ (i.e., milk with 7-10%
fat).” In the 1920s, “formulas made from whole milk with added Karo® syrup … provided nearly
100 kcal/dl.” Whole milk or evaporated milk remained the usual base for infant formula through
World War II. Fomon (2001): “From the 1930s or early 1940s, most formulas fed to infants in the
United States were prepared by mixing evaporated milk or fresh cow’s milk with water and adding
carbohydrate. … Home-prepared formulas were sometimes made with cow’s milk (usually
pasteurized and homogenized) rather than with evaporated milk.” In the 1950s, according to Fomon
(2001), “it was the opinion of most physicians and the general public that formula feeding was
about as safe and satisfactory as breast-feeding. However, … the low content of iron in the
formulas together with the high intake of inhibitors of iron absorption were responsible for a high
prevalence of iron deficiency.”
Fomon (2001) cited survey data indicating that, in the 1960s, “60% of infants were fed
whole milk by 4 months of age.” In 1971, “>30% of infants from 3 to 4 months of age, >40% of
infants from 4 to 5 months of age and >60% of infants from 5 to 6 months of age were fed cow’s
milk.” Interest in breast feeding in the last thirty years of the twentieth century led to a deferment of
the age of introduction of cow’s milk, but “it was generally recommended (American Academy of
Pediatrics Committee on Nutrition 1976) that for non-breastfed infants >6 months old, formula
feeding was desirable, but cow’s milk plus regular feeding of iron-fortified cereals was a
satisfactory alternative.”

6.3. Studies in Animals

Because cow’s milk contains estrogens, progesterone, and insulin-like growth factor 1,
which are associated with breast cancer, Nielsen et al. (2011) studied prepubertal exposure to
whole milk in pregnant Sprague-Dawley rats. Pups were given either water or whole milk from
post-natal day 14 to day 35 and mammary tumorigenesis was induced with 7,12-dimethylbenz[a]-
anthracene on day 50. Rats exposed to milk before puberty exhibited reduced carcinogen-induced
mammary carcinogenesis. The authors concluded that “drinking milk before puberty reduces later
risk of developing mammary cancer in rats.” Importantly, there was no suggestion that prepubertal
consumption of whole milk increases the risk of cancer; further, test and control rats did not differ
in weight gain and no adverse effects associated with milk feeding were reported.
Li et al. (2014) assigned 34 preterm Large White X Danish Landrace X Duroc piglets
delivered by caesarean section at 105 days gestation to one of 3 feeding regiments in which they
were fed via orogastric feeding tubes for 4 days. The feeding consisted of reconstituted whole milk
powder (n = 15), infant formula (n = 10), or raw bovine milk (n = 9). Pigs were monitored every 3
hours for symptoms of necrotizing enterocolitis (NEC) such as abdominal distension lethargy,
cyanosis, or bloody diarrhea. Pigs were euthanized on day 5 and intestinal tissue samples were
taken. Pigs fed whole milk powder had significantly healthier intestinal structure (mucosal weight,
villus height) and function (nutrient absorption, gut permeability, and reduced NEC severity) than
those fed raw bovine milk, and both milk diets were superior to infant formula. No adverse effects
associated with the interventions were reported.

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6.4. Studies in Infants and Toddlers
Twenty-three studies were found in the literature in which whole milk was given to infants
or toddlers. This includes 12 prospective, randomized, controlled clinical trials and a number of
longitudinal or retrospective cohort studies. While safety was rarely the primary endpoint, the
publications most often addressed reporting of adverse events. In none of these studies were any
adverse events attributable to feeding of whole milk reported other than iron deficiency among
children not receiving iron fortification or supplementation. These studies are summarized in
Table 9.

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 Table 9. Published Research on Bovine Whole Milk.

Study Design
Reference Subjects Intervention and Duration Safety-Related Results
and Objective
Alarcon et Prospective, 85 Peruvian 110 kcal/kg bw/day from: Children in all groups gained weight with no differences in
al. 1991 randomized, multi- infants and 1) Dried whole milk, potato anthropometric status, energy intakes, energy absorption, nitrogen
arm trial of the children aged 5- flour, carrot flour, sucrose & retention, or fecal output and no differences in treatment failure. The
treatment of acute 24 months veg oil authors concluded that “these locally available, low-cost staple food
childhood diarrhea hospitalized for 2) Wheat flour, pea flour, carrot mixtures [i.e., interventions 1 and 2] offer a safe and nutritionally
acute diarrhea flour, sucrose, & veg oil adequate alternative to a commercially produced lactose-free formula
3) Soy-protein isolate lactose- for the dietary management of young children with acute diarrhea in
free formula this setting.”

Bonuck et Observational 286 low-income Measurements of dietary Normal weight and overweight toddlers did not differ in consumption of
al. 2014 cohort study of infants and intake, anthropometrics, meal- whole milk, mean daily energy intake, intake of fat, saturated fat, or
dietary intake and toddlers aged time behavior protein. The total sample consumed a mean of 2.0±1.8 cups of whole
overweight at 12 12.6±0.5 months milk per day. Whole milk consumption was lower in overweight vs.
months of age (186 normal, 100 normal weight toddlers (1.7±1.8 vs. 2.1±1.8 cups/day). Thus,
overweight) consumption of whole milk was not associated with overweight.
Brown et al. Prospective, 116 Peruvian 55 to 110 kcal/kg bw/day from: The combination of milk and noodles resulted in reduced stool outputs,
1991 randomized, male infants and 1) Whole milk & wheat noodles shorter durations of diarrhea, and lower rates of treatment failure than
double-blind, toddlers aged 3- 2) Lactose-hydrolyzed whole did milk alone. The authors concluded that “the noodle-milk diets
placebo-controlled 24 months with milk & wheat noodles employed during this study were safer than the milk diets for the
trial of the acute diarrhea 3) Modified whole milk dietary management of children with acute diarrhea.”
management of 4) Lactose-hydrolyzed milk
acute childhood formula
diarrhea
Fomon et Prospective, 81 normal Given pasteurized whole milk Incidence of blood in stool was greater among infants fed whole milk
al. 1981 randomized, healthy infants (n = 39) or Enfamil (n = 42) for from age 112 to 140 days; no difference thereafter. [N.B. No iron
placebo-controlled aged 112 days 12 weeks supplementation was provided.] No difference in mean hemoglobin,
trial of whole-milk hematocrit, serum iron, total iron-binding capacity, or transferrin
feeding in infancy saturation.

Hertramph Prospective, 190 healthy 84 infants received whole milk All iron nutritional parameters were higher in the supplemented group.
et al 1990 randomized, infants supplemented with 15 mg Iron-deficiency anemia was reported in 34% of the control but 0% of
placebo-controlled ferrous sulfate & 100 mg the treatment group. The authors concluded that, “The product
trial of fortification ascorbic acid/100 g powder; exhibited excellent tolerance and could therefore be used to eradicate
to prevent iron- 104 infants received the same iron-deficiency anemia of the infant.”
deficiency milk with no supplement for 9
months

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 Table 9. Published Research on Bovine Whole Milk.

Study Design
Reference Subjects Intervention and Duration Safety-Related Results
and Objective
Hjelt et al Prospective, 52 infants and Subjected to either rapid The two regimens produced similar results with regard to duration and
1989 randomized, children aged 6- refeeding (lactose-treated severity of diarrhea and vomiting. The rapid-refeeding group derived
placebo-controlled 46 months whole milk as only fluid intake; more energy from fat and protein and less from carbohydrate than did
trial of refeeding in hospitalized with n = 27) or gradual refeeding the gradual-refeeding group. Milk provided 47-59% of the daily energy
acute pediatric acute gastro- (fluids other than whole milk; n intake of the rapid-refeeding group. The authors reported that the
gastroenteritis enteritis after oral = 25) for 7 days whole milk was well accepted and no signs of cow’s milk protein
rehydration intolerance were observed. They suggested that the milk-based rapid-
refeeding regimen can be employed “without the fear of negative
effects on the outcome.”
Houghton Prospective, 181 healthy Toddlers received red meat or After 20 weeks, serum 25(OH)D concentrations but not parathyroid
et al. 2011 randomized, toddlers aged 12- vitamin D-fortified whole milk hormone were significantly raised in the milk group. The prevalence of
single-blind, 20 months (mean for 20 weeks. having a serum 25(OH)D <50 nmol/L remained unchanged at 43% in
placebo-controlled age 17 months) the meat group, whereas it decreased to between 11 and 15% in
trial of vitamin D- those consuming fortified whole milk. The authors concluded that
fortified whole milk “habitual consumption of vitamin D-fortified milk providing a mean
& 25-hydroxy- intake of nearly 4 μg/d was effective in achieving adequate year-round
vitamin D level serum 25(OH)D for most children.”

Isolauri et Prospective, 65 infants and Refeeding included whole milk The authors reported that, “There was no difference between the
al. 1986 randomized, toddlers (aged (n = 38) or no milk (n = 27) groups in the clinical recovery from diarrhea. No child had prolonged
placebo-controlled 14.7±7.2 months) diarrhea. No new cases of clinical atopy were observed at 1-month
trial of refeeding in hospitalized for follow-up, and there were no significant increases in the total or milk-
acute pediatric acute gastro- specific IgE levels. Serum IgG and IgA antibodies to β-lactoglobulin
gastroenteritis enteritis and α-casein were initially present in the majority of the children, but
there were no appreciable changes in these cow’s milk antibodies
after gastroenteritis regardless of the type of diet. It is concluded that
cow milk and milk products can be safety given in acute gastroenteritis
as parts of the mixed diet for children over 6 months of age.”
Lamkjaer et Prospective, 83 healthy In a 2x2 design, infants Intake of whole milk significantly increased protein energy percentage
al. 2009 randomized, infants received whole milk or infant and serum urea nitrogen; there was no effect on anthropometric
placebo-controlled formula, with or without fish oil measures of growth. The whole-milk intervention increased IGF-I in
trial of whole milk boys but not in girls. Intake of fish oil had no effect on the outcomes.
v. infant formula The authors concluded that, “Randomization to whole milk had no
on growth and overall effect on growth. However, the positive effect of whole milk on
IgF-I IGF-I in boys and the positive association between protein energy
percentage and IGF-I at 9 and 12 months is consistent with the
hypothesis that a high milk intake stimulates growth.”

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 Table 9. Published Research on Bovine Whole Milk.

Study Design
Reference Subjects Intervention and Duration Safety-Related Results
and Objective
Maulen- Prospective 227 generally Toddlers and children “The milk was well tolerated and widely accepted.” Anthropometric
Radovan et longitudinal study healthy infants consumed 500 ml fortified measures, hemoglobin, serum iron, vitamin B12, and folic acid all
al. 1999 of the impact of and children whole milk/day for 90 days increased. The authors concluded, “The consumption of a fortified
fortified whole milk aged 8-60 whole milk during 90 days improved significantly the nutritional status
in children months; included of the children, the weight for height Z score, the plasma level of
45 malnourished vitamin B12 and Hb, and decreased the number of anemic and
& 36 anemic malnourished children.”
children

Penrod et Retrospective 100 infants and 55 infants had been receiving The infants receiving the fortified infant formula had significantly better
al. 1990 cohort study of toddlers aged infant formula for at least 3 iron status than those receiving whole milk and lower weight. [N.B. No
infant formula vs. 45.6±1.0 weeks months prior to enrollment; 45 iron supplementation was provided.] The two groups did not differ in
cow’s milk in infants had been receiving other measures of nutritional status. The authors noted that some
infancy whole cow’s milk differences may result from differences in beikost rather than primary
beverage.

Stekel et al. Mono-and double- 364 infants and Following an overnight fast, There was no significant difference in absorption of iron from the milk
1986 isotopic analysis toddlers aged 5- formulas containing 59FeSO4 or from ferrous sulfate supplementation due to the level of milk fat. Iron
of iron absorption 18 months were fed by bottle; infants absorption ranged from 2.9 to 5.1%, with no correlation with the milkfat
by infants con- consumed 100-250 ml in a content. These findings indicate that use of whole milk rather than
suming different single bolus dose of one of 7 lowfat milk in infant formula does not interfere with the absorption of
types of cows’ types of lowfat milk or one of 4 iron from the formula.
milk formulas types of whole milk and iron
absorption was measured

Stekel et al. Prospective, 554 infants with 276 infants received whole The authors reported that, “the acceptability of this milk was excellent.”
1988. randomized, birthweight milk supplemented with ferrous 2.5% of infants in the group receiving whole milk + supplements had
placebo-controlled >2500 g sulfate & ascorbic acid for 12 iron deficiency anemia compared with 25.7% of the control group.
trial of months
supplemented vs.
unsupplemented
whole milk

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 Table 9. Published Research on Bovine Whole Milk.

Study Design
Reference Subjects Intervention and Duration Safety-Related Results
and Objective
Svahn et al. Prospective, 38 healthy Fed one of 4 milks for 6 There was a lower percentage of saturated fatty acids in plasma
2000 randomized, infants and months: triacylglycerol in toddlers fed low-fat milk or milk with 50% or 100%
placebo-controlled toddlers aged 12 1) lowfat cow’s milk vegetable fat than in children fed whole milk. Plasma polyunsaturated
trial of the effect of months 2) whole cow’s milk fatty acid levels were significantly higher in children fed milk with
quantity and 3) partially veg. fat milk vegetable fat than in children fed whole milk. Blood lipid concentra-
quality of fat 4) wholly veg. fat milk tions were lower in children fed milk with 50% vegetable fat. No
adverse events were reported.

Thomas et Longitudinal 820 healthy Infants were receiving: Levels of fecal hemoglobin and FA1AT were low in all groups and
al. 1986 cohort study of infants aged 2 1) whole milk (n = 146) showed little difference by type of feeding. The authors reported that,
infant feeding and weeks to 12 2) breast milk (n = 354) “unrecognized intestinal abnormalities, as based on hemoglobin and
excretion of months 3) infant formula (n = 320) FA1AT excretion, appear to be uncommon in healthy infants fed a
hemoglobin and balanced diet and fresh cow’s milk. Human milk-fed infants had higher
α1-antitrypsin FA1AT concentrations than infants receiving formula or cow’s milk.
(FA1AT) However, total daily FA1AT excretion was similar in all three milk-
feeding groups. The differences in FA1AT concentration were a
function of differences in daily stool output in response to diet.” They
concluded, “our data support the recent recommendation of the
Committee on Nutrition of the American Academy of Pediatrics to
allow introduction of pasteurized, fresh whole cow’s milk into the diets
of infants older than 6 months of age.”
Torres et al. Longitudinal open- 335 toddlers <2 Toddlers consumed dry whole Average hemoglobin increased from 10.4 to 11.6 g/dl. No intervention-
1995 label study of iron- years of age milk fortified with 9 mg iron & associated adverse events were reported and the authors concluded
fortified whole milk 65 mg vitamin C/100 g for 6 that, “the utilization of enriched foods is an excellent alternative in the
and toddler’s months treatment of iron deficiency in populations of children under 2 years of
nutritional status age.”

van der Case-controlled 105 children 49 children were encouraged The intervention group demonstrated a greater decrease in IgE (9.2
Gaag and retrospective aged 1-18 years to consume at least 200 ml vs. 0.1 kU/L) and were more likely to report improvement in symptoms
Forbes study of a high-fat (median age = whole milk/day, beef, butter, (53.2% vs. 28.6%). The authors concluded that, “Overall, the effects of
2014 diet in children 4.65 years) with and green vegetables, while nutrients and vitamins on the decrease in IgE are promising.” They did
with non-specific non-specific 56 were not. Children were not report any intervention-associated adverse events.
elevated IgE elevated IgE followed for 1 year.

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 Table 9. Published Research on Bovine Whole Milk.

Study Design
Reference Subjects Intervention and Duration Safety-Related Results
and Objective
van der Retrospective 121 children All children received dietary In the group following the advice to consume a diet high in saturated
Gaag et al. cohort study of a aged 1-16 years advice to consume whole milk, fat, including whole milk, there was a significant reduction in the
2017 high-saturated-fat (median age = beef, butter, and green cholesterol/HDL ratio and non-HDL-cholesterol and an increase in
diet in children 3.6 years) vegetables. 55 of them HDL-cholesterol, while there was no difference in the BMI and BMI z-
adhered to the advice, while scores. The authors reported that, “The dietary advice has no adverse
66 did not. Measures were effect on the lipid profile, BMI, and BMI z-scores in children, but has a
taken over 3 months significant beneficial effect on the cholesterol/HDL ratio, non-HDL-
cholesterol, and the HDL-cholesterol,” and concluded, “The dietary
advice can, therefore, be safely recommended and might be beneficial
for children with recurrent respiratory tract infections.”
van der Prospective, 118 toddlers 58 children were encouraged Children in the dietary advice group had a mean of 4.8 days per month
Gaag et al. randomized, aged 1-4 years to consume at least 300 ml with symptoms of an upper respiratory tract infection in the last three
2020 controlled trial of a (mean age = whole milk/day, beef, butter, months of the study, compared to 7.7 in the control group. The use of
high-saturated-fat 2.4±1.1 years) and green vegetables, while antibiotics was significantly reduced in the dietary advice group. No
diet in pediatric with recurrent 60 were not. Children were adverse events were reported. The authors suggested that “this diet
upper respiratory upper respiratory followed for 6 months. provides parents with a tool to improve the health of their children.”
tract infections tract infections
Vanderhout Cross-sectional 2745 healthy Adjusted bivariate linear Children who drank whole milk had a 5.4-nmol/L higher median
et al. analysis of milk-fat urban toddlers regression of milk-fat 25(OH)D concentration and a 0.72 lower BMI z-score than children
(2016a) percentage and and children percentage and BMI z-score who drank 1% milk. The authors concluded that, “Whole milk
BMI in early aged 12-72 and 25-hydroxyvitamin D consumption among healthy young children was associated with
childhood months status higher vitamin D stores and lower BMI.”

Vanderhout Cross-sectional 2857 healthy Adjusted multivariate linear Children who drank 1% milk needed 2.46 cups of milk to have the
et al. analysis of milk-fat urban toddlers regression of milk-fat 25(OH)D status of children who drank 1 cup of whole milk. Children
(2016b) percentage and and children percentage and milk volume who consumed 1% milk had 2x higher odds of having a 25(OH)D
25-hydroxyvitamin aged 12-72 and 25-hydroxyvitamin D concentration <50 nmol/L than children who consumed whole milk.
D in childhood months status The authors concluded that “recommendations for children to drink
lower-fat milk (1% or 2%) may compromise serum 25(OH)D levels and
may require study to ensure optimal childhood health.”

Wong et al. Longitudinal study 2890 children Statistical analyses of the There was a small positive correlation between milkfat intake and non-
2019 of milk fat intake aged 2-8 years relationship between cow’s HDL cholesterol, but not with the odds of having high non-HDL
and non-HDL in milkfat intake and serum non- cholesterol. The authors concluded that the correlation exists, but with
young children HDL cholesterol concentration no indication of leading to high non-HDL cholesterol.

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 Table 9. Published Research on Bovine Whole Milk.

Study Design
Reference Subjects Intervention and Duration Safety-Related Results
and Objective
Ziegler et Prospective, 52 healthy term 26 infants each were assigned There were no differences between groups in parental reports of
al. 1990 randomized, infants aged 24 to receive whole cow’s milk or regurgitation, vomiting, constipation, or other feeding-related behavior.
placebo-controlled weeks infant formula for 12 weeks. Stool hemoglobin concentration increased with the introduction of
trial of infant whole cow milk from 622±527 µg/g dry stool at baseline to 3598±
feeding and GI 10,479 µg/g dry stool during the first 28 days of Ingestion of whole cow
blood loss milk. Among infants fed formula, stool hemoglobin did not Increase
and was significantly less than in the whole milk group. Stools with
occult blood increased from 3.0% at baseline to 30.3% in the whole-
milk group during the first 28 days of the trial, whereas the proportion
of positive stools remained low (5.0%) with the feeding of formula. The
proportion of occult-blood-positive stools among whole-milk-fed infants
declined later, but for the entire trial it remained significantly elevated.
The authors concluded that, “a large proportion of normal nonanemic
infants respond to the feeding of pasteurized cow milk [i.e., whole milk
as the sole source of nutrition and no added iron] with increased fecal
loss of blood.”

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6.5. Safety Assessment and GRAS Determination
This section presents an assessment that demonstrates that the intended use of dry whole
milk in nonexempt infant formula is safe and is GRAS based on scientific procedures.
This safety assessment and GRAS determination entail two steps. In the first step, the safety
of the intended use of dry whole milk is demonstrated. Safety is established by demonstrating a
reasonable certainty that the exposure of infants and toddlers to dry whole milk under its intended
conditions of use is not harmful. In the second step, the intended use of dry whole milk is
determined to be GRAS by demonstrating that the safety of this substance under its intended
conditions of use is generally recognized among qualified scientific experts and is based on
generally available and accepted information.
The regulatory framework for establishing whether the intended use of a substance is
GRAS, in accordance with Section 201(s) of the Federal Food Drug and Cosmetic Act, is set forth
under 21 CFR §170.30. This regulation states that general recognition of safety may be based on
the view of experts qualified by scientific training and experience to evaluate the safety of
substances directly or indirectly added to food. A GRAS determination may be made either: 1)
through scientific procedures under §170.30(b); or 2) through experience based on common use in
food, in the case of a substance used in food prior to January 1, 1958, under §170.30(c). This
GRAS determination employs scientific procedures established under §170.30(b).
A scientific procedures GRAS determination requires the same quantity and quality of
scientific evidence as is needed to obtain approval of the substance as a food additive. In addition
to requiring scientific evidence of safety, a GRAS determination also requires that this scientific
evidence of safety be generally known and accepted among qualified scientific experts. This
“common knowledge” element of a GRAS determination consists of two components:
1. Data and information relied upon to establish the scientific element of safety must
be generally available; and
2. There must be a basis to conclude that there is a consensus among qualified experts
about the safety of the substance for its intended use.
The criteria outlined above for a scientific-procedures GRAS determination are applied
below in an analysis of whether the intended use of dry whole milk in nonexempt infant formula is
safe and is GRAS.
6.5.1. Evidence of Safety
Whole milk and dry whole milk are widely consumed by infants, toddlers, children, and
adults with no adverse effects specifically attributable to whole milk other than allergic reactions in
susceptible individuals. Over many years prior to the 1970s during which whole milk was widely
used as a sole source of nutrition for infants, there was no reported pattern of adverse effects and no
evidence of malnutrition other than iron deficiency.
The many controlled studies of feeding of whole milk to infants and toddlers elicited no
reports of adverse effects. In a number of studies in which nutrition with unfortified whole milk
was compared with iron-fortified infant formula, the latter usually resulted in superior iron status.
This deficiency, it was shown, is remedied by fortifying or supplementing the milk with iron. Thus,
this finding that unfortified milk alone may not provide adequate iron has no relevance to the
intended use of dry whole milk by ByHeart, which is as a component of infant formula with iron
rather than as a stand-alone source of infant nutrition.

Dry Whole Milk GRAS 28 JHEIMBACH LLC

 In summary, the body of generally available evidence from history of use and controlled
scientific studies supports the safety of By Heart’s intended use of dry whole milk.

6.5.2. Conclusion of the GRAS Panel

The intended addition of dry whole milk to nonexempt infant formula has been determined
to be safe through scientific procedures set forth under 21 CFR §170.30(b). This safety was shown
by animal studies in rats and pigs; uncomplicated human digestion via well-established metabolic
pathways without adverse effects; current safe consumption of whole milk and dry whole milk
including consumption by infants, toddlers, and children; and controlled clinical trials showing no
adverse effects associated with consumption of whole milk or dry whole milk by infants or
toddlers. Finally, because this safety assessment satisfies the common knowledge requirement of a
GRAS determination, this intended use is GRAS.
Determination of the safety and GRAS status of the intended use of dry whole milk has
been made through the deliberations of a GRAS Panel consisting of Ronald Kleinman, M.D.,
Berthold V. Koletzko, M.D., Ph.D., and Robert J. Nicolosi, Ph.D. These individuals, qualified by
scientific training and experience to evaluate the safety of food ingredients intended for addition to
infant formula, independently and collectively critically evaluated the publicly available
information on the safety of whole milk and dry whole milk and the potential exposure to infants
and toddlers anticipated to result from its intended use. They individually and collectively
determined that no evidence exists in the available information on whole milk and dry whole milk
that demonstrates, or suggests reasonable grounds to suspect, a hazard to infant or toddlers under
the intended conditions of use of dry whole milk.
It is the GRAS Panel’s opinion that other qualified scientists reviewing the same publicly
available data would reach a similar conclusion regarding the safety of dry whole milk under its
intended conditions of use. Therefore, the intended use of dry whole milk in nonexempt infant
formula intended for consumption by healthy term infants from the first day of life is GRAS by
scientific procedures.

6.6. Statement Regarding Information Inconsistent with GRAS

I have reviewed the available data and information and am not aware of any data or
information that are, or may appear to be, inconsistent with our conclusion of the GRAS status of
__ _r . _
the intended J__
use of dry whole milk.,1,_
_

Dry Whole Milk GRAS 29 JHEIMBACH LLC

6.7. Statement of the GRAS Panel
We, the undersigned members of the GRAS Panel, are qualified by scientific education
and experience to evaluate the safety of substances intended for addition to infant formula. We
have critically evaluated the publicly available information on dry whole milk and have
individually and collectively determined that no evidence exists in the available information on
dry whole milk that demonstrates, or suggests reasonable grounds to suspect, a hazard to infants
or toddlers under the intended conditions of use of dry whole milk.
We unanimously conclude that the intended addition of dry whole milk, produced
consistent with current good manufacturing practice (cGMP) and meeting the food-grade
specifications presented in this monograph, to nonexempt infant formula intended for
consumption by healthy term infants from the first day of life, at the level specified in the
monograph, is safe and is GRAS by scientific procedures.
It is our opinion that other qualified and competent scientists reviewing the same publicly
available information would reach a similar conclusion.

Ronald Kleinman, M.D.

Professor of Pediatrics
Harvard Medical School
Boston, Massachu~e_tt_s__/7_ ...,_ _ _-

Signature: _ _ Date: 11/16/2020- - - - -

V

Berthold V. Koletzko, Dr med, Dr med habil (M.D., Ph.D.)

Professor of Pediatrics
University of Munich
Munich, Germany

Signature: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ Date: _ _ _ _ __

Robert J. Nicolosi, Ph.D.

Professor Emeritus
University of Massachusetts-Lowell
Lowell, Massachusetts
Signature: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ Date: _ _ _ _ __
6.7. Statement of the GRAS Panel
We, the undersigned members of the GRAS Panel, are qualified by ~cientific education and
experience to evaluate the safety of substances intended for addition to infant formula. We have
critically evaluated the publicly available infmmation on dry whole milk and have individually and
collectively determined that no evidence exists in the available information on dry whole milk that
demonstrates, or suggests reasonable grounds to suspect, a hazard to infants or toddlers under the
intended conditions of use of dry whole milk.
We unanimously conclude that the intended addition of dry whole milk, produced
consistent with current good manufacturing practice (cGMP) and meeting tbe food-grade
specifications presented in this monograph, to nonexempt infant formula intended for consumption
by healthy term infants from the first day of life, at the level specified in the monograph, is safe and
is GRAS by scientific procedures.
It is our opinion that other qualified and competent scientists reviewjing the same publicly
available information would reach a similar conclusion.

Ronald Kleinman, M.D.

Professor of Pediatrics
Harvard Medical School
Boston, Massachusetts

Signature: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ Date: _ _ _ _ __

Berthold V. Koletzko, Dr med, Dr med habil (M.D., Ph.D.)

Professor of Pediatrics
University of Munich
Munich, Germany

Signature: _ _ _ __ _ _.11..._ _ _ _ _ ____,1:---- --

Date: I 1/ jJ fV . ino

Robert J. Nicolosi, Ph.D.

Professor Emeritus
University of Massachusetts-Lowell
Lowell, Massachusetts
Signature: _ _ __ __ _ _ _ _ __ _ __ __ _ Date: _ _ __ _ _

Dry Whole Milk GRAS 30 JHEIMBACH LLC

6.7. Statement of the GRAS Panel
We, the undersigned members of the GRAS Panel, are qualified by scientific education and
experience to evaluate the safety of substances intended for addition to infant formula. We have
critically evaluated the publicly available information on dry whole milk and have individually and
collectively determined that no evidence exists in the available information on dry whole milk that
demonstrates, or suggests reasonable grounds to suspect, a hazard to infants or toddlers under the
intended conditions of use of dry whole milk.
We unanimously conclude that the intended addition of dry whole milk, produced
consistent with current good manufacturing practice (cGMP) and meeting the food-grade
specifications presented in this monograph, to nonexempt infant formula intended for consumption
by healthy term infants from the first day oflife, at the level specified in the monograph, is safe and
is GRAS by scientific procedures.
It is our opinion that other qualified and competent scientists reviewing the same publicly
available information would reach a similar conclusion.

Ronald Kleinman, M.D.

Professor of Pediatrics
Harvard Medical School
Boston, Massachusetts

Signature: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ Date: _ _ _ _ __

Berthold V. Koletzko, Dr med, Dr med habil (M.D., Ph.D.)

Professor of Pediatrics
University of Munich
Munich, Germany

Signature: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ Date: - - - - --

Robert J. Nicolosi, Ph.D.

Professor Emeritus
University of Massachusetts-Low~ll
Lowell, Massachusetts
..-----=------------.
Signature: - -i..,__ _ _ _ _ _ _ _ _. - - - - - - - - - - - : -
Part 7: List of Supporting Data and Information
Alarcon P, R Montoya, F Perez, JW Dongo, JM Peerson, KH Brown. 1991. Clinical trial of home
available, mixed diets versus a lactose-free, soy-protein formula for the dietary management
of acute childhood diarrhea. J Pediatr Gastroenterol Nutr 12:224-232.
American Academy of Pediatrics Committee on Nutrition. 1976. Iron supplementation for infants.
Pediatrics 58:765-768.
Billeaud C, G Puccio, E Saliba, B Guillois, C Vaysse, S Pecquet, P Steenhout. 2014. Safety and
tolerance evaluation of milk fat globule membrane-enriched infant formulas: a randomized
controlled multicenter non-inferiority trial in healthy term infants. Clin Med Insights
Pediatr 8:51-60.
Bonuck K, SB Avraham, M Hearst, R Kahn, C Hyden. 2014. Is overweight at 12 months associated
with differences in eating behaviour or dietary intake among children selected for
inappropriate bottle use? Matern Child Nutr 10:234-244.
Brown KH, F Perez, AS Gastanaduy. 1991. Clinical trial of modified whole milk, lactose-
hydrolyzed whole milk, or cereal-milk mixtures for the dietary management of acute
childhood diarrhea. J Pediatr Gastroenterol Nutr 12:340-350.
Butte NF, MK Fox, RR Briefel, AM Siega-Riz, JT Dwyer, DM Deming, KC Reidy. 2010. Nutrient
intakes of US infants, toddlers, and preschoolers meet or exceed dietary reference intakes. J
Am Diet Assoc 110(Suppl):S27-37.
Floris LM, B Stahl, M Abrahamse-Berkeveld, IC Teller. 2020. Human milk fatty acid profile
across lactationa stages after term and preterm delivery: a pooled data analysis.
Prostaglandins Leukot Essent Fatty Acids 156:102023.
Fomon SJ. 1993. Energy intake by normal infants. In Nutrition of Normal Infants, p. 104–111.
Baltimore, MD: Mosby.
Fomon SJ. 2001. Infant feeding in the 20th century: formula and beikost. J Nutr 131:409S-420S.
Fomon SJ, EE Ziegler, SE Nelson, BB Edwards. 1981. Cow milk feeding in infancy: gastrointes-
tinal blood loss and iron nutritional status. J Pediatr 98:540-545.
Fong B, M Lin, C Norris. 2013. Analysis of phospholipids in infant formulas using high
performance liquid chromatography–tandem mass spectrometry. J Agric Food Chem
61:858-865.
Haug A, AT Hostmark, OM Harstad. 2007. Bovine milk in human nutrition—a review. Lipids
Health Dis 6:25.
Hertrampf E, M Olivares, T Walter, F Pizarro, G Heresi, S Llaguno, V Vega, M Cayazzo, P
Chadud. 1990. [Iron-deficiency anemia in the nursing infant: its elimination with iron-
fortified milk]. Rev Med Chil 118:1330-1337. [Article in Spanish]
Hjelt K, A Paerregaard, W Petersen, L Christiansen, PA Krasilnikoff. 1989. Rapid versus gradual
refeeding in acute gastroenteritis in childhood: energy intake and weight gain. J Pediatr
Gastroenterol Nutr 8:75-80.
Houghton LA, AR Gray, EA Szymlek-Gay, A-LM Heath, EL Ferguson. 2011. Vitamin D-fortified
milk achieves the targeted serum 25-hydroxyvitamin D concentration without affecting that
of parathyroid hormone in New Zealand toddlers. J Nutr 141:1840-1846.
Isolauri E, T Vesikari, P Saha, M Viander. 1986. Milk versus no milk in rapid refeeding after acute
gastroenteritis. J Pediatr Gastroenterol Nutr 5:254-261.

Dry Whole Milk GRAS 31 JHEIMBACH LLC

Koletzko B, S Baker, G Cleghorn, UF Neto, S Gopalan, O Hernell, QS Hock, P Jirapinyo, B
Lonnerdal, P Pencharz, H Pzyrembel, J Ramirez-Mayans, R Shamir, D Turck, Y
Yamashiro, D Zong-Yi. 2005. Global standard for the composition of infant formula:
recommendations of an ESPGHAN coordinated international expert group. J Pediatr
Gastroenterol Nutr 41:584-599.
Lamkjaer A, C Hoppe, C Molgaard, KF Michaelsen. 2009. The effects of whole milk and infant
formula on growth and IGF-I in late infancy. Eur J Clin Nutr 63:956-963.
Li Y, ML Jensen, DEW Chatterton, BB Jensen, T Thymann, AS Kvistgaard, PT Sangild. 2014.
Raw bovine milk improves gut responses to feeding relative to infant formula in preterm
piglets. Am J Physiol Gastrointest Liver Physiol 306:G81-G90.
Ma L, AKH MacGibbon, HJBJ Mohamed, SL Loy, A Rowan, P McJarrow, BY Fong. 2017.
Determination of phospholipid concentrations in breast milk and serum using a high-
performance liquid chromatography–mass spectrometry–multiple reaction monitoring
method. Int Dairy J 71:50-59.
Maulen-Radovan I, S Villagomez, E Soler, R Villicana, L Hernández-Ronquillo, JL Rosado. 1999.
[Nutritional impact of whole milk supplemented with vitamins and minerals in children].
Salud Publica Mex 41:389-396. [Article in Spanish]
McGuire MK, Y Park, RA Behre, LY Harrison, TD Shultz, MA McGuire. 1997. Conjugated
linoleic acid concentrations of human milk and infant formula. Nutr Res 17:1277-1283.
Nielsen TS, G Khan, J Davis, KR Michels, L Hilakivi-Clarke. 2011. Prepubertal exposure to cow’s
milk reduces susceptibility to carcinogen-induced mammary tumorigenesis in rats. Int J
Cancer 128:12-20.
Penrod JC, K Anderson, PB Acosta. 1990. Impact on iron status of introducing clow’s milk in the
second six months of life. J Pediatr Gastroenterol Nutr 10:462-467.
Scholfield CR. 1981. Composition of soybean lecithin. J Am Oil Chem Soc 58:889-892.
Stekel A, M Olivares, F Pizarro, P Chadud, I Lopez, M Amar. 1986. Absorption of fortification
iron from milk formulas in infants. Am J Clin Nutr 43:917-922.
Stekel A, F Pizarro, M Olivares, P Chadud, S Llaguno, M Cayazzo, E Hertrampf, T Walter. 1988.
Prevention of iron deficiency by milk fortification. III. Effectiveness under the usual
operational conditions of a nation-wide food program. Nutr Rep Int 38:1119-1128.
Svahn JCE, F Feldl, NCR. Raiha, B Koletzko, IEM Axelsson. 2000. Fatty acid content of plasma
lipid fractions, blood lipids, and apolipoproteins in children fed milk products containing
different quantity and quality of fat. J Pediatr Gastroenterol Nutr 31:152-161.
Thomas DW, KM McGilligan, M Carolson, SP Azen, LD Eisenberg, HM Lieberman, EM
Rissman. 1986. Fecal α1-antitrypsin and hemoglobin excretion in healthy human milk-,
formula-, or cow’s milk-fed infants. Pediatrics 78:305-312.
Timby N, M Domellof, B Lonnerdal, O Hernell. 2017. Supplementation of infant formula with
bovine milk fat globule membranes. Adv Nutr 15:351-355.
Torres MA, K Sato, NF Lobo, S de Souza Queiroz. 1995. [The effect of the use of milk fortified
with iron andvitamin C on hemoglobin levels and nutritionalstatus of children under 2]. Rev
Saude Publica 29:301-307. [Article in Portuguese]
U.S. Department of Agriculture. 2020. Nutrient database for standard reference. Available online
at https://fdc.nal.usda.gov/download-datasets.html

Dry Whole Milk GRAS 32 JHEIMBACH LLC

van der Gaag EJ and K Forbes. 2014. The immunomodulating effect of a diet consisting of green
vegetables, beef, whole milk and full-fat butter for children with non-specific elevated IgE.
Int J Vitam Nutr Res 84:310-319.
van der Gaag EJ, R Wieffer, J van der Kraats. 2017. Advising consumption of green vegetables,
beef, and full-fat dairy products has no adverse effects on the lipid profiles in children.
Nutrients 9:nu9050518.
van der Gaag EJ, R Brandsema, R Nobbenhuis, J van der Palen, T Hummel. 2020. Influence of
dietary advice including green vegetables, beef, and whole dairy products on recurrent
upper respiratory tract infections in children: a randomized controlled trial. Nutrients
12:nu12010272.
Vanderhout SM, CS Birken, PC Parkin, G Lebovic, Y Chen, DL O’Connor, JL Maguire. 2016a.
Relation between milk-fat percentage, vitamin D, and BMI z score in early childhood. Am J
Clin Nutr 104:1657-1664.
Vanderhout SM, CS Birken, PC Parkin, G Lebovic, Y Chen, DL O’Connor, JL Maguire. 2016b.
Higher milk fat content is associated with higher 25-hydroxyvitamin D concentration in
early childhood. Appl Physiol Nutr Metab 41:516-521.
Wong VCH, JL Maguire, JA Omand, DWH Dai, G Lebovic, PC Parkin, DL O’Connor, CS Birken.
2019. A positive association between dietary intake of higher cow's milk-fat percentage and
non-high- density lipoprotein cholesterol in young children. J Pediatr 211:105-111.
Ziegler EE, SJ Fomon, SE Nelson, CJ Rebouche, B Edwards, RR Rogers, LJ Lehman. 1990. Cow
milk feeding in infancy: Further observations on blood loss from the gastrointestinal tract. J
Pediatr 116:11-18.

Dry Whole Milk GRAS 33 JHEIMBACH LLC

 Form Approved: OMB No. 0910-0342; Expiration Date: 07/31/2022
(See last page for OMB Statement)
FDA USE ONLY
GRN NUMBER DATE OF RECEIPT
000980 Nov 20, 2020
DEPARTMENT OF HEALTH AND HUMAN SERVICES
ESTIMATED DAILY INTAKE INTENDED USE FOR INTERNET
Food and Drug Administration

GENERALLY RECOGNIZED AS SAFE NAME FOR INTERNET

(GRAS) NOTICE (Subpart E of Part 170)
KEYWORDS

Transmit completed form and attachments electronically via the Electronic Submission Gateway (see Instructions); OR Transmit
completed form and attachments in paper format or on physical media to: Office of Food Additive Safety (HFS-200), Center for
Food Safety and Applied Nutrition, Food and Drug Administration,5001 Campus Drive, College Park, MD 20740-3835.

SECTION A – INTRODUCTORY INFORMATION ABOUT THE SUBMISSION

1. Type of Submission (Check one)
New
 Amendment to GRN No.
 Supplement to GRN No.

2. All electronic files included in this submission have been checked and found to be virus free. (Check box to verify)
3 Most recent presubmission meeting (if any) with
FDA on the subject substance (yyyy/mm/dd): 2020-11-04
4 For Amendments or Supplements: Is your (Check one)
amendment or supplement submitted in

Yes If yes, enter the date of
response to a communication from FDA?

No communication (yyyy/mm/dd):

SECTION B – INFORMATION ABOUT THE NOTIFIER

Name of Contact Person Position or Title

Gyan Rai Director, Regulatory

Organization (if applicable)

1a. Notifier ByHeart, Inc.

Mailing Address (number and street)

689 5th Avenue 14th Floor

City State or Province Zip Code/Postal Code Country

New York New York 10022 United States of America
Telephone Number Fax Number E-Mail Address
978-400-9668 [email protected]

Name of Contact Person Position or Title

James T. Heimbach President
1b. Agent
Organization (if applicable)
or Attorney
(if applicable) JHeimbach LLC

Mailing Address (number and street)

923 Water Street #66
City State or Province Zip Code/Postal Code Country
Port Royal Virginia 22535 United States of America

Telephone Number Fax Number E-Mail Address

8047425543 [email protected]

FORM FDA 3667 (10/19) Page 1 of 3

 SECTION C – GENERAL ADMINISTRATIVE INFORMATION

1. Name of notified substance, using an appropriately descriptive term

Dry whole milk
2. Submission Format: (Check appropriate box(es)) 3. For paper submissions only:
~ Electronic Submission Gateway
• Paper • Electronic files on physical media Number of volumes

If applicable give number and type of physical media

Total number of pages

4. Does this submission incorporate any information in CFSAN’s files? (Check one)

• Yes (Proceed to Item 5) No (Proceed to Item 6)

5. The submission incorporates information from a previous submission to FDA as indicated below (Check all that apply)

• a) GRAS Notice No. GRN

• b) GRAS Affirmation Petition No. GRP

• c) Food Additive Petition No. FAP

• d) Food Master File No. FMF

• e) Other or Additional (describe or enter information as above)

6. Statutory basis for conclusions of GRAS status (Check one)
Scientific procedures (21 CFR 170.30(a) and (b))
• Experience based on common use in food (21 CFR 170.30(a) and (c))
7. Does the submission (including information that you are incorporating) contain information that you view as trade secret
or as confidential commercial or financial information? (see 21 CFR 170.225(c)(8))

• Yes (Proceed to Item 8

~ No (Proceed to Section D)
8. Have you designated information in your submission that you view as trade secret or as confidential commercial or financial information
(Check all that apply)

• Yes, information is designated at the place where it occurs in the submission

• No

9. Have you attached a redacted copy of some or all of the submission? (Check one)

• Yes, a redacted copy of the complete submission

• Yes, a redacted copy of part(s) of the submission

• No

SECTION D – INTENDED USE

1. Describe the intended conditions of use of the notified substance, including the foods in which the substance will be used, the levels of use
in such foods, and the purposes for which the substance will be used, including, when appropriate, a description of a subpopulation expected
to consume the notified substance.
As a nutritive ingredient in non-exempt infant formula intended for consumption by healthy term infants from the first day of life.

2. Does the intended use of the notified substance include any use in product(s) subject to regulation by the Food Safety and Inspection
Service (FSIS) of the U.S. Department of Agriculture?
(Check one)

• Yes No

3. If your submission contains trade secrets, do you authorize FDA to provide this information to the Food Safety and Inspection Service of the
U.S. Department of Agriculture?
(Check one)

• Yes
• No , you ask us to exclude trade secrets from the information FDA will send to FSIS.

FORM FDA 3667 (10/19) Page 2 of 3

 SECTION E – PARTS 2 -7 OF YOUR GRAS NOTICE
(check list to help ensure your submission is complete – PART 1 is addressed in other sections of this form)

PART 2 of a GRAS notice: Identity, method of manufacture, specifications, and physical or technical effect (170.230).

PART 3 of a GRAS notice: Dietary exposure (170.235).

PART 4 of a GRAS notice: Self-limiting levels of use (170.240).

PART 5 of a GRAS notice: Experience based on common use in foods before 1958 (170.245).

PART 6 of a GRAS notice: Narrative (170.250).

PART 7 of a GRAS notice: List of supporting data and information in your GRAS notice (170.255)

Other Information
Did you include any other information that you want FDA to consider in evaluating your GRAS notice?

 Yes
~ No
Did you include this other information in the list of attachments?

 Yes
 No

SECTION F – SIGNATURE AND CERTIFICATION STATEMENTS

1. The undersigned is informing FDA that James T. Heimbach

(name of notifier)

has concluded that the intended use(s) of dry whole milk

(name of notified substance)

described on this form, as discussed in the attached notice, is (are) not subject to the premarket approval requirements of the Federal Food,
Drug, and Cosmetic Act based on your conclusion that the substance is generally recognized as safe recognized as safe under the conditions
of its intended use in accordance with § 170.30.

2. ByHeart, Inc. agrees to make the data and information that are the basis for the
(name of notifier) conclusion of GRAS status available to FDA if FDA asks to see them;
agrees to allow FDA to review and copy these data and information during customary business hours at the following location if FDA
asks to do so; agrees to send these data and information to FDA if FDA asks to do so.

Office of JHeimbach LLC, 923 Water Street, Port Royal VA 22535

(address of notifier or other location)

The notifying party certifies that this GRAS notice is a complete, representative, and balanced submission that includes unfavorable,
as well as favorable information, pertinent to the evaluation of the safety and GRAS status of the use of the substance.The notifying
party certifies that the information provided herein is accurate and complete to the best or his/her knowledge. Any knowing and willful
misinterpretation is subject to criminal penalty pursuant to 18 U.S.C. 1001.

3. Signature of Responsible Official, Printed Name and Title Date (mm/dd/yyyy)

Agent, or Attorney
James T. Heimbach, President, JHeimbach LLC 11/16/2020

FORM FDA 3667 (10/19) Page 3 of 3

 SECTION G – LIST OF ATTACHMENTS
List your attached files or documents containing your submission, forms, amendments or supplements, and other pertinent information.
Clearly identify the attachment with appropriate descriptive file names (or titles for paper documents), preferably as suggested in the
guidance associated with this form. Number your attachments consecutively. When submitting paper documents, enter the inclusive page
numbers of each portion of the document below.

Attachment Folder Location (select from menu)

Attachment Name
Number (Page Number(s) for paper Copy Only)

Form3667.pdf Administrative

ByHeartGRASNotice.pdf Administrative

SignatureKleinman.pdf Administrative

SignatureKoletzko.pdf Administrative

SignatureNicolosi.pdf Administrative

OMB Statement: Public reporting burden for this collection of information is estimated to average 170 hours per response, including
the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and
reviewing the collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information,
including suggestions for reducing this burden to: Department of Health and Human Services,Food and Drug Administration, Office of Chief
Information Officer, [email protected]. (Please do NOT return the form to this address.). An agency may
not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB
control number.

FORM FDA 3667 (10/19) Page 4 of 3