DBGNR Meeting Requests

Information for Logging into FARM/Appian

Requestor: 

Contact Information:

Date of Request:

Subject:

Date Request Received by DBGNR:

Date Prepared by DBGNR:

Prepared by:

If agent, name of company or individual this is on behalf of:

Tania Porsgaard Bayer, Arla tania.porsgaard.bayer@arlafoods.com +4589381562 June 3, 2019 (meeting to be held June 17, 2019) Discussion on intended use of osteopontin in IF June 3, 2019 June 3, 2019 Rachel Morissette
______________________________________________________________________________________________________________________________ 

Memorandum of Meeting

Type Teleconference

Dates & 

Times

November 9, 2017, 11:00 a.m. – 12:00 p.m.

November 20, 2017, 11:00 a.m. – 11:30 a.m.

Location FDA, Center for Food Safety and Applied Nutrition, Office of Food Additive 

Safety, 4300 River Road, College Park, MD 20740

Subject: GRN 000716 (Bovine whey-derived osteopontin (bOPN)) for use as a source of 

protein in milk-based, non-exempt infant formulas for term infants and in powdered beverages 

at levels up to 138 mg/L as consumed.

Summary: This memorandum summarizes the discussion points of OFAS’ teleconference 

meetings with Burdock Group Consultants (agent) on November 9, 2017 and with Burdock 

Group Consultants and Arla Foods Ingredients Group PIS (AFI, notifier) on November 20, 

2017 regarding GRN000716. OFAS has outstanding regarding the evidence for general 

recognition that bOPN is safe for use in infant formulas. The overarching question is whether

the data provided by AFI are adequate to demonstrate general recognition of safety (reasonable 

certainty of no harm) by scientists with the appropriate expertise to evaluate the significance of 

bOPN activity at the intended consumption level by infants. OFAS considers this question to be 

important given the rapid development of the infant immune system, the poorly characterized 

modes of action for bOPN, the potential involvement of human OPN (hOPN) in infant immune 

maturation, lack of clarity regarding substantial equivalence of biological activities between 

bOPN and hOPN, and the large variation of the levels of hOPN in human milk.

On October 3, 2017, OFAS sent questions to AFI (see FDA Questions and Comments). On 

October 20, OFAS received AFI’s responses. The amendment included information on the 

intended use level and resulting exposure to bOPN in infants. The amendment also included 

information on the bioequivalence of hOPN and bOPN. After reviewing AFI’s responses, OFAS 

continues to question the general recognition of the safety of the intended use of bOPN in 

infant formulas. 

On November 9, 2017 OFAS held a teleconference meeting with AFI’s agents, Drs. Burdock and 

Matulka, to discuss the review team’s outstanding questions regarding the GRAS status of the 

intended use of bOPN. 
Participants: November 9, 2017 Meeting

Notifier: Arla Foods Ingredients Group PIS (AFI)’| Agent: Burdock Group Consultants (phone)

George A. Burdock, Ph.D. Owner, Burdock Group Consultants

Ray A. Matulka, Ph.D. Director of Toxicology, Burdock Group Consultants

FDA/CFSAN/ OFAS/DBGNR (HFS-255)

Nadine Bewry, Ph.D., MPH Consumer Safety Officer (CSO)

Jeremiah Fasano, Ph.D. Acting Supervisory CSO

Romina Shah, Ph.D. Chemist

Michael DiNovi, Ph.D. (phone) Supervisory Chemist

Kotaro Kaneko, Ph.D. Toxicologist

Ronald Chanderbhan, Ph.D. Supervisory Toxicologist

FDA/CFSAN/ ONFL/ IFMS (HFS-850) (phone)

Linda Tonucci, Ph.D. CSO

Suzanne Wolcoff, PhD. Senior Dietitian-Nutritionist

Carrie Assar, Ph.D. Lead Nutritionist

OFAS discussed three main lines of evidence contained in the notice and in the notifier’s 

response to one of OFAS’ questions, including the absence of evidence of toxicity in 

toxicological and clinical studies, the similarity of bOPN and hOPN, and existing infant 

exposure to both bOPN and hOPN. 

OFAS noted that:

o OPN has multiple modes of action, including immunomodulatory and pro-inflammatory 

effects. None of the published safety studies discussed in GRN 000716 evaluated 

potential adverse effects of bOPN at the intended use level related to these modes of 

action.

o The available evidence indicates that hOPN and bOPN are not substantially 

bioequivalent in humans from a physiological perspective. 

o The intended use level of bOPN in infant formula is higher than the basal level found in 

milk or milk-based formula. 

 Based on the literature, the levels of bOPN in cow’s milk and cow’s milk-derived 

infant formulas are 18 μg/ml and 5.3-13.0 μg/ml, respectively. However, levels of 

bOPN from intended use is ~138 μg/ml. 

 There is no evidence provided in GRN 000716 or in the October 20, 2017 

amendment to GRN 000716 that infants have been safely exposed to higher 

levels of bOPN from the intended use.

OFAS considers it important that AFI provide evidence that the existing data and information

are adequate to demonstrate general recognition of safety (reasonable certainty of no harm) by 

scientists with the appropriate expertise to evaluate the significance of bOPN activity at the 

intended use level in infants. OFAS further noted that AFI’s GRAS Panel appears to lack
expertise in neonatal immunology, which is relevant to the intended population and the known 

modes of action of bOPN. OFAS explained that the importance of including such expertise 

would be to develop insight into the views of scientists in this area about the significance of the 

intended use of bOPN, including some basis for concluding that these views are broadly 

shared. OFAS informed AFI that simply adding a neonatal immunologist to their current GRAS 

panel would not be sufficient to provide evidence of general recognition. The introduction of an 

additional individual without reanalysis and interpretation of existing data or reference to 

current thinking in their field would not be sufficient to resolve our questions about general 

recognition. Furthermore, OFAS noted that other regulatory authorities, including EFSA, 

JECFA, FSANZ, and Health Canada, have not approved the use of bOPN in infant formula, 

indicating a lack of general recognition of bOPN’s safety in infant formulas. Given these 

outstanding questions regarding general recognition, OFAS advised AFI to request that OFAS 

cease to evaluate GRN 000716.

On November 15, 2017, Dr. Matulka requested a second teleconference meeting with OFAS

because AFI stated that they would like to address OFAS’ questions regarding the notice rather 

than request that OFAS cease to evaluate the notice. The purpose of the meeting was: (1) to

share the steps that AFI will take to address our questions, and (2) to gain clarification on some

of the discussion points from the November 9, 2017 teleconference meeting.

On November 20, 2017, OFAS held a second teleconference meeting with AFI and AFI’s agents.

Participants: November 20, 2017 Meeting

Notifier: Arla Foods Ingredients Group PIS (AFI)’| Agent: Burdock Group Consultants (Phone)

George A. Burdock, Ph.D. Owner, Burdock Group Consultants

Ray A. Matulka, Ph.D. Director of Toxicology, Burdock Group Consultants

Carrie Kennedy, PMP, RAC Project Leader, Burdock Group Consultants

Kal Ramanujam, Ph.D. Senior Scientific Advisor, Arla Foods

Anders Steen Jorgensen Head, Business Unit Pediatrics, Arla Foods

Anne Staudt Kvistgaard Senior Manager, Documentation Pediatrics, Arla Foods

FDA/CFSAN/ OFAS/DBGNR (HFS-255)

Nadine Bewry, Ph.D., MPH Consumer Safety Officer (CSO)

Shayla West-Barnette, Ph.D. Supervisory CSO

Jeremiah Fasano, Ph.D. Acting Supervisory CSO

Rachel Morissette, Ph.D. CSO

Kotaro Kaneko, Ph.D. (phone) Toxicologist

Supratim Choudhuri, Ph.D. Acting Supervisory Toxicologist

FDA/CFSAN/ ONFL/ IFMS (HFS-850) (Phone)

Carrie Assar, Ph.D. Lead Nutritionist

Andrea Lotze, M.D. Medical Officer

OFAS’ discussion points included some of those already covered during the November 9, 2017 

teleconference meeting, as well as the following discussion points:
o OFAS considers that it would not be possible for AFI to address the unresolved 

questions regarding general recognition of the safety of the intended use of bOPN in 

the short term simply by locating or conducting additional studies.

o OFAS emphasized the office’s view that the unresolved questions rest on the issue of 

whether scientists trained to evaluate immune function and development in infants

would accept the existing evidence as adequate to show reasonable certainty of no 

harm.

o OFAS noted that there are several potential strategies to develop evidence for general

recognition of the safety of the intended use of bOPN, which would involve recruiting 

additional expertise and re-engaging with OFAS on the issues we identified.

o OFAS noted that any future consideration of the GRAS status of AFI’s intended use 

of bOPN by the office would include consulting FDA staff with appropriate training 

and expertise relevant to neonatal immune development. 

In conclusion, OFAS still has outstanding questions regarding the evidence for general 

recognition that bOPN is safe for use in infant formulas. OFAS recommends that AFI request 

that we cease to evaluate GRN 000716.

Attachment:

GRN 716 2017-10-03 Email_FDA Questions and Comments

______________________________

Nadine Bewry, Ph.D., MPH

Nadine N. 

Bewry -S

Digitally signed by Nadine N. Bewry -S 

DN: c=US, o=U.S. Government, ou=HHS, 

ou=FDA, ou=People, 

0.9.2342.19200300.100.1.1=0014360008, 

cn=Nadine N. Bewry -S 

Date: 2017.12.20 14:54:05 -05'00'
______________________________________________________________________________________________________________________________ 

Memorandum of Meeting

Type Teleconference

Dates & 

Times

November 9, 2017, 11:00 a.m. – 12:00 p.m.

November 20, 2017, 11:00 a.m. – 11:30 a.m.

Location FDA, Center for Food Safety and Applied Nutrition, Office of Food Additive 

Safety, 4300 River Road, College Park, MD 20740

Subject: GRN 000716 (Bovine whey-derived osteopontin (bOPN)) for use as a source of 

protein in milk-based, non-exempt infant formulas for term infants and in powdered beverages 

at levels up to 138 mg/L as consumed.

Summary: This memorandum summarizes the discussion points of OFAS’ teleconference 

meetings with Burdock Group Consultants (agent) on November 9, 2017 and with Burdock 

Group Consultants and Arla Foods Ingredients Group PIS (AFI, notifier) on November 20, 

2017 regarding GRN000716. OFAS has outstanding regarding the evidence for general 

recognition that bOPN is safe for use in infant formulas. The overarching question is whether

the data provided by AFI are adequate to demonstrate general recognition of safety (reasonable 

certainty of no harm) by scientists with the appropriate expertise to evaluate the significance of 

bOPN activity at the intended consumption level by infants. OFAS considers this question to be 

important given the rapid development of the infant immune system, the poorly characterized 

modes of action for bOPN, the potential involvement of human OPN (hOPN) in infant immune 

maturation, lack of clarity regarding substantial equivalence of biological activities between 

bOPN and hOPN, and the large variation of the levels of hOPN in human milk.

On October 3, 2017, OFAS sent questions to AFI (see FDA Questions and Comments). On 

October 20, OFAS received AFI’s responses. The amendment included information on the 

intended use level and resulting exposure to bOPN in infants. The amendment also included 

information on the bioequivalence of hOPN and bOPN. After reviewing AFI’s responses, OFAS 

continues to question the general recognition of the safety of the intended use of bOPN in 

infant formulas. 

On November 9, 2017 OFAS held a teleconference meeting with AFI’s agents, Drs. Burdock and 

Matulka, to discuss the review team’s outstanding questions regarding the GRAS status of the 

intended use of bOPN. 
Participants: November 9, 2017 Meeting

Notifier: Arla Foods Ingredients Group PIS (AFI)’| Agent: Burdock Group Consultants (phone)

George A. Burdock, Ph.D. Owner, Burdock Group Consultants

Ray A. Matulka, Ph.D. Director of Toxicology, Burdock Group Consultants

FDA/CFSAN/ OFAS/DBGNR (HFS-255)

Nadine Bewry, Ph.D., MPH Consumer Safety Officer (CSO)

Jeremiah Fasano, Ph.D. Acting Supervisory CSO

Romina Shah, Ph.D. Chemist

Michael DiNovi, Ph.D. (phone) Supervisory Chemist

Kotaro Kaneko, Ph.D. Toxicologist

Ronald Chanderbhan, Ph.D. Supervisory Toxicologist

FDA/CFSAN/ ONFL/ IFMS (HFS-850) (phone)

Linda Tonucci, Ph.D. CSO

Suzanne Wolcoff, PhD. Senior Dietitian-Nutritionist

Carrie Assar, Ph.D. Lead Nutritionist

OFAS discussed three main lines of evidence contained in the notice and in the notifier’s 

response to one of OFAS’ questions, including the absence of evidence of toxicity in 

toxicological and clinical studies, the similarity of bOPN and hOPN, and existing infant 

exposure to both bOPN and hOPN. 

OFAS noted that:

o OPN has multiple modes of action, including immunomodulatory and pro-inflammatory 

effects. None of the published safety studies discussed in GRN 000716 evaluated 

potential adverse effects of bOPN at the intended use level related to these modes of 

action.

o The available evidence indicates that hOPN and bOPN are not substantially 

bioequivalent in humans from a physiological perspective. 

o The intended use level of bOPN in infant formula is higher than the basal level found in 

milk or milk-based formula. 

 Based on the literature, the levels of bOPN in cow’s milk and cow’s milk-derived 

infant formulas are 18 μg/ml and 5.3-13.0 μg/ml, respectively. However, levels of 

bOPN from intended use is ~138 μg/ml. 

 There is no evidence provided in GRN 000716 or in the October 20, 2017 

amendment to GRN 000716 that infants have been safely exposed to higher 

levels of bOPN from the intended use.

OFAS considers it important that AFI provide evidence that the existing data and information

are adequate to demonstrate general recognition of safety (reasonable certainty of no harm) by 

scientists with the appropriate expertise to evaluate the significance of bOPN activity at the 

intended use level in infants. OFAS further noted that AFI’s GRAS Panel appears to lack
expertise in neonatal immunology, which is relevant to the intended population and the known 

modes of action of bOPN. OFAS explained that the importance of including such expertise 

would be to develop insight into the views of scientists in this area about the significance of the 

intended use of bOPN, including some basis for concluding that these views are broadly 

shared. OFAS informed AFI that simply adding a neonatal immunologist to their current GRAS 

panel would not be sufficient to provide evidence of general recognition. The introduction of an 

additional individual without reanalysis and interpretation of existing data or reference to 

current thinking in their field would not be sufficient to resolve our questions about general 

recognition. Furthermore, OFAS noted that other regulatory authorities, including EFSA, 

JECFA, FSANZ, and Health Canada, have not approved the use of bOPN in infant formula, 

indicating a lack of general recognition of bOPN’s safety in infant formulas. Given these 

outstanding questions regarding general recognition, OFAS advised AFI to request that OFAS 

cease to evaluate GRN 000716.

On November 15, 2017, Dr. Matulka requested a second teleconference meeting with OFAS

because AFI stated that they would like to address OFAS’ questions regarding the notice rather 

than request that OFAS cease to evaluate the notice. The purpose of the meeting was: (1) to

share the steps that AFI will take to address our questions, and (2) to gain clarification on some

of the discussion points from the November 9, 2017 teleconference meeting.

On November 20, 2017, OFAS held a second teleconference meeting with AFI and AFI’s agents.

Participants: November 20, 2017 Meeting

Notifier: Arla Foods Ingredients Group PIS (AFI)’| Agent: Burdock Group Consultants (Phone)

George A. Burdock, Ph.D. Owner, Burdock Group Consultants

Ray A. Matulka, Ph.D. Director of Toxicology, Burdock Group Consultants

Carrie Kennedy, PMP, RAC Project Leader, Burdock Group Consultants

Kal Ramanujam, Ph.D. Senior Scientific Advisor, Arla Foods

Anders Steen Jorgensen Head, Business Unit Pediatrics, Arla Foods

Anne Staudt Kvistgaard Senior Manager, Documentation Pediatrics, Arla Foods

FDA/CFSAN/ OFAS/DBGNR (HFS-255)

Nadine Bewry, Ph.D., MPH Consumer Safety Officer (CSO)

Shayla West-Barnette, Ph.D. Supervisory CSO

Jeremiah Fasano, Ph.D. Acting Supervisory CSO

Rachel Morissette, Ph.D. CSO

Kotaro Kaneko, Ph.D. (phone) Toxicologist

Supratim Choudhuri, Ph.D. Acting Supervisory Toxicologist

FDA/CFSAN/ ONFL/ IFMS (HFS-850) (Phone)

Carrie Assar, Ph.D. Lead Nutritionist

Andrea Lotze, M.D. Medical Officer

OFAS’ discussion points included some of those already covered during the November 9, 2017 

teleconference meeting, as well as the following discussion points:
o OFAS considers that it would not be possible for AFI to address the unresolved 

questions regarding general recognition of the safety of the intended use of bOPN in 

the short term simply by locating or conducting additional studies.

o OFAS emphasized the office’s view that the unresolved questions rest on the issue of 

whether scientists trained to evaluate immune function and development in infants

would accept the existing evidence as adequate to show reasonable certainty of no 

harm.

o OFAS noted that there are several potential strategies to develop evidence for general

recognition of the safety of the intended use of bOPN, which would involve recruiting 

additional expertise and re-engaging with OFAS on the issues we identified.

o OFAS noted that any future consideration of the GRAS status of AFI’s intended use 

of bOPN by the office would include consulting FDA staff with appropriate training 

and expertise relevant to neonatal immune development. 

In conclusion, OFAS still has outstanding questions regarding the evidence for general 

recognition that bOPN is safe for use in infant formulas. OFAS recommends that AFI request 

that we cease to evaluate GRN 000716.

Attachment:

GRN 716 2017-10-03 Email_FDA Questions and Comments

______________________________

Nadine Bewry, Ph.D., MPH

Nadine N. 

Bewry -S

Digitally signed by Nadine N. Bewry -S 

DN: c=US, o=U.S. Government, ou=HHS, 

ou=FDA, ou=People, 

0.9.2342.19200300.100.1.1=0014360008, 

cn=Nadine N. Bewry -S 

Date: 2017.12.20 14:51:14 -05'00'
R/D:HFS-255:NNBewry: 11/20/2017

Edit/Comments/Init: HFS-255: RShah:12/5/2017

Edit/Comments/Init: HFS-255: KKaneko:12/4/2017, 12/7/2017

Edit/Comments/Init: HFS-255: JFasano:12/4/2017, 12/7/2017

Edit/Commens:HFS-255: SWestBarnette:12/19/17, 12/20/17

Init:HFS-255: SWestBarnette:12/20/17

F/T: HFS-255:NNBewry: 12/20/2017
______________________________________________________________________________________________________________________________ 

Memorandum of Meeting

Type Teleconference

Dates & 

Times

November 9, 2017, 11:00 a.m. – 12:00 p.m.

November 20, 2017, 11:00 a.m. – 11:30 a.m.

Location FDA, Center for Food Safety and Applied Nutrition, Office of Food Additive 

Safety, 4300 River Road, College Park, MD 20740

Subject: GRN 000716 (Bovine whey-derived osteopontin (bOPN)) for use as a source of 

protein in milk-based, non-exempt infant formulas for term infants and in powdered beverages 

at levels up to 138 mg/L as consumed.

Summary: This memorandum summarizes the discussion points of OFAS’ teleconference 

meetings with Burdock Group Consultants (agent) on November 9, 2017 and with Burdock 

Group Consultants and Arla Foods Ingredients Group PIS (AFI, notifier) on November 20, 

2017 regarding GRN000716. OFAS has outstanding regarding the evidence for general 

recognition that bOPN is safe for use in infant formulas. The overarching question is whether

the data provided by AFI are adequate to demonstrate general recognition of safety (reasonable 

certainty of no harm) by scientists with the appropriate expertise to evaluate the significance of 

bOPN activity at the intended consumption level by infants. OFAS considers this question to be 

important given the rapid development of the infant immune system, the poorly characterized 

modes of action for bOPN, the potential involvement of human OPN (hOPN) in infant immune 

maturation, lack of clarity regarding substantial equivalence of biological activities between 

bOPN and hOPN, and the large variation of the levels of hOPN in human milk.

On October 3, 2017, OFAS sent questions to AFI (see FDA Questions and Comments). On 

October 20, OFAS received AFI’s responses. The amendment included information on the 

intended use level and resulting exposure to bOPN in infants. The amendment also included 

information on the bioequivalence of hOPN and bOPN. After reviewing AFI’s responses, OFAS 

continues to question the general recognition of the safety of the intended use of bOPN in 

infant formulas. 

On November 9, 2017 OFAS held a teleconference meeting with AFI’s agents, Drs. Burdock and 

Matulka, to discuss the review team’s outstanding questions regarding the GRAS status of the 

intended use of bOPN. 
Participants: November 9, 2017 Meeting

Notifier: Arla Foods Ingredients Group PIS (AFI)’| Agent: Burdock Group Consultants (phone)

George A. Burdock, Ph.D. Owner, Burdock Group Consultants

Ray A. Matulka, Ph.D. Director of Toxicology, Burdock Group Consultants

FDA/CFSAN/ OFAS/DBGNR (HFS-255)

Nadine Bewry, Ph.D., MPH Consumer Safety Officer (CSO)

Jeremiah Fasano, Ph.D. Acting Supervisory CSO

Romina Shah, Ph.D. Chemist

Michael DiNovi, Ph.D. (phone) Supervisory Chemist

Kotaro Kaneko, Ph.D. Toxicologist

Ronald Chanderbhan, Ph.D. Supervisory Toxicologist

FDA/CFSAN/ ONFL/ IFMS (HFS-850) (phone)

Linda Tonucci, Ph.D. CSO

Suzanne Wolcoff, PhD. Senior Dietitian-Nutritionist

Carrie Assar, Ph.D. Lead Nutritionist

OFAS discussed three main lines of evidence contained in the notice and in the notifier’s 

response to one of OFAS’ questions, including the absence of evidence of toxicity in 

toxicological and clinical studies, the similarity of bOPN and hOPN, and existing infant 

exposure to both bOPN and hOPN. 

OFAS noted that:

o OPN has multiple modes of action, including immunomodulatory and pro-inflammatory 

effects. None of the published safety studies discussed in GRN 000716 evaluated 

potential adverse effects of bOPN at the intended use level related to these modes of 

action.

o The available evidence indicates that hOPN and bOPN are not substantially 

bioequivalent in humans from a physiological perspective. 

o The intended use level of bOPN in infant formula is higher than the basal level found in 

milk or milk-based formula. 

 Based on the literature, the levels of bOPN in cow’s milk and cow’s milk-derived 

infant formulas are 18 μg/ml and 5.3-13.0 μg/ml, respectively. However, levels of 

bOPN from intended use is ~138 μg/ml. 

 There is no evidence provided in GRN 000716 or in the October 20, 2017 

amendment to GRN 000716 that infants have historically been safely exposed to 

bOPN containing dairy products at levels as high as the intended use level.

OFAS considers it important that AFI provide evidence that the existing data and information

are adequate to demonstrate general recognition of safety (reasonable certainty of no harm) by 

scientists with the appropriate expertise to evaluate the significance of bOPN activity at the 

intended use level in infants. OFAS further noted that AFI’s GRAS Panel appears to lack
expertise in neonatal immunology, which is relevant to the intended population and the known 

modes of action of bOPN. OFAS explained that the importance of including such expertise 

would be to develop insight into the views of scientists in this area about the significance of the 

intended use of bOPN, including some basis for concluding that these views are broadly 

shared. OFAS informed AFI that simply adding a neonatal immunologist to their current GRAS 

panel would not be sufficient to provide evidence of general recognition. The introduction of an 

additional individual without reanalysis and interpretation of existing data or reference to 

current thinking in their field would not be sufficient to resolve our questions about general 

recognition. Furthermore, OFAS noted that other regulatory authorities, including EFSA, 

JECFA, FSANZ, and Health Canada, have not approved the use of bOPN in infant formula, 

indicating a lack of general recognition of bOPN’s safety in infant formulas. Given these 

outstanding questions regarding general recognition, OFAS advised AFI to request that OFAS 

cease to evaluate GRN 000716.

On November 15, 2017, Dr. Matulka requested a second teleconference meeting with OFAS

because AFI stated that they would like to address OFAS’ questions regarding the notice rather 

than request that OFAS cease to evaluate the notice. The purpose of the meeting was: (1) to

share the steps that AFI will take to address our questions, and (2) to gain clarification on some

of the discussion points from the November 9, 2017 teleconference meeting.

On November 20, 2017, OFAS held a second teleconference meeting with AFI and AFI’s agents.

Participants: November 20, 2017 Meeting

Notifier: Arla Foods Ingredients Group PIS (AFI)’| Agent: Burdock Group Consultants (Phone)

George A. Burdock, Ph.D. Owner, Burdock Group Consultants

Ray A. Matulka, Ph.D. Director of Toxicology, Burdock Group Consultants

Carrie Kennedy, PMP, RAC Project Leader, Burdock Group Consultants

Kal Ramanujam, Ph.D. Senior Scientific Advisor, Arla Foods

Anders Steen Jorgensen Head, Business Unit Pediatrics, Arla Foods

Anne Staudt Kvistgaard Senior Manager, Documentation Pediatrics, Arla Foods

FDA/CFSAN/ OFAS/DBGNR (HFS-255)

Nadine Bewry, Ph.D., MPH Consumer Safety Officer (CSO)

Shayla West-Barnette, Ph.D. Supervisory CSO

Jeremiah Fasano, Ph.D. Acting Supervisory CSO

Rachel Morissette, Ph.D. CSO

Kotaro Kaneko, Ph.D. (phone) Toxicologist

Supratim Choudhuri, Ph.D. Acting Supervisory Toxicologist

FDA/CFSAN/ ONFL/ IFMS (HFS-850) (Phone)

Carrie Assar, Ph.D. Lead Nutritionist

Andrea Lotze, M.D. Medical Officer

OFAS’ discussion points included some of those already covered during the November 9, 2017 

teleconference meeting, as well as the following discussion points:
o OFAS considers that it would not be possible for AFI to address the unresolved 

questions regarding general recognition of the safety of the intended use of bOPN in

the short term simply by locating or conducting additional studies.

o OFAS emphasized the office’s view that the unresolved questions rest on the issue of 

whether scientists trained to evaluate immune function and development in infants

would accept the existing evidence as adequate to show reasonable certainty of no 

harm.

o OFAS noted that there are several potential strategies to develop evidence for general

recognition of the safety of the intended use of bOPN, which would involve recruiting 

additional expertise and re-engaging with OFAS on the issues we identified.

o OFAS noted that any future consideration of the GRAS status of AFI’s intended use 

of bOPN by the office would include consulting FDA staff with appropriate training 

and expertise relevant to neonatal immune development. 

In conclusion, OFAS still has outstanding questions regarding the evidence for general 

recognition that bOPN is safe for use in infant formulas. OFAS recommends that AFI request 

that we cease to evaluate GRN 000716.

Attachment:

GRN 716 2017-10-03 Email_FDA Questions and Comments

______________________________

Nadine Bewry, Ph.D., MPH

Nadine N. Bewry -S

Digitally signed by Nadine N. Bewry -S 

DN: c=US, o=U.S. Government, ou=HHS, ou=FDA, 

ou=People, 0.9.2342.19200300.100.1.1=0014360008, 

cn=Nadine N. Bewry -S 

Date: 2018.01.25 13:51:45 -05'00'
www.fda.gov

______________________________________________________________________________________________________________________________ 

Memorandum

Date: April 10, 2018 

From: Jeremiah Fasano, HFS-255 

To: GRN 000716 File 

Subject: Discussion of General Recognition for Use of Osteopontin in Infant Formula 

Attendees 

Jeremiah Fasano CFSAN/OFAS/DBGNR 

Kotaro Kaneko CFSAN/OFAS/DBGNR 

Rachel Morissette (WebEx) CFSAN/OFAS/DBGNR 

Nadine Bewry (WebEx) CFSAN/OFAS/DBGNR 

Ronald Rabin CBER/OVRR/DBPAP 

Joohee Lee CBER/OVRR/DVRPA 

Anubha Tripathi CBER/OVRR/DVRPA 

Jay Slater (WebEx) CBER/OVRR/DBPAP 

Andrea Lotze (WebEx) CFSAN/ONFL/IFMFS 

Carrie Assar (WebEx) CFSAN/ONFL/IFMFS 

Gillian Robert-Baldo (WebEx) CFSAN/ONFL/IFMFS 

Leila Beker (WebEx) CFSAN/ONFL/IFMFS 

Megan Kulas (WebEx) CFSAN/ONFL/IFMFS 

Suzanne Wolcoff (WebEx) CFSAN/ONFL/IFMFS 

Cheryl Issa (WebEx) CFSAN/ONFL/IFMFS 

Members of CFSAN’s Office of Food Additive Safety and Office of Nutrition and Food Labeling met with 

members of CBER’s Office of Vaccines Research and Review to discuss the use of bovine osteopontin (bOPN) as 

an ingredient in infant formula, as well as the broader issue of bioactive milk ingredients used in formula. The 

CBER delegation included members with expertise in immunology. The intent of the discussion was to share the 

evidence for the safety of the intended use of bOPN presented by Arla Foods, as well as other information on 

bOPN available to CFSAN, in order to assess CBER staff’s views on two related questions: 

x Are questions raised by CFSAN reviewers about the potential long-term consequences of bOPN 

exposure in infants at the intended use level reasonable, given what we know about both postnatal 

immunology and the properties of OPN? 

x Is there a broad consensus among clinical immunologists about the kind of data and information that is 

appropriate and adequate to establish reasonable certainty of no harm (the standard for food ingredient 

safety) for this intended use, given the questions raised by CFSAN? 

After a brief discussion about the statutory framework of how food additives and GRAS substances are 

regulated, CFSAN staff described the intended use of bOPN as well as the explicit rationale (to increase 

resemblance to human milk by increasing OPN levels) and the implicit rationale (to enhance or modulate 
Discussion of General Recognition for Use of Osteopontin in Infant Formula – (continued) Page 2 of 3 pages 

immune function and development in infants). CFSAN staff also described their questions about the 

consequences of increased bOPN exposure in this population and the role of general recognition in a GRAS 

conclusion. CFSAN and CBER staff then discussed the current scientific understanding of OPN modes of action, 

the basis for (or the lack thereof) the presumption that incremental changes to infant formula to increase 

resemblance to human milk are unambiguously beneficial and involve no increased risk, and the challenges 

involved in identifying a universally appropriate use level for a bioactive milk protein in infant formula based on 

a sampled arithmetic mean. 

CBER staff expressed concerns about the intended use of bOPN in infant formula. They concurred with CFSAN’s 

view that incremental changes in the direction of human milk could introduce unintended risks, and that 

application of an arithmetic mean value to all individuals consuming formula might not be appropriate. They 

cited insulin, a polypeptide with profound effects on physiological function and extensive pharmaceutical 

applications, as an example of both issues. In response to CFSAN’s overall questions, CBER staff indicated that 

our questions were reasonable, and that, in their view, there was no consensus currently in the immunology 

community about what data would be appropriate and adequate to resolve them. 

CFSAN staff explained that the notifier for the bOPN GRAS notice had been advised to first request that FDA 

cease to evaluate their notice and then to develop a strategy to generate compelling evidence of general 

recognition for their safety data on bOPN, given the questions CFSAN staff had raised to them about the longterm consequences of increased bOPN exposure in the infant population. CBER staff strongly recommended that 

CFSAN consider ways to explore the broad questions associated with the use of bioactive ingredients in infant 

formula in a public setting, such as a workshop or public meeting. 

CFSAN staff concluded the meeting by thanking CBER staff for their time, attention, and advice, and offering to 

circulate a meeting memorandum outlining the discussion. 

 Jeremiah Fasano 

Jeremiah M. 

Fasano -S

Digitally signed by 

Jeremiah M. Fasano -S 

Date: 2019.03.22 

00:20:30 -04'00'
Discussion of General Recognition for Use of Osteopontin in Infant Formula – (continued) Page 3 of 3 pages 

Drafted:HFS-255:JMFasano:04/18/2018 

Comments:HFS-255:RMorissette:04/18/2018 

Comments:HFS-255:KKaneko:04/18/2018 

Edit:HFS-255:JMFasano:05/03/2018 

Init:HFM-422:RRabin:05/03/2018 

Init:HFM-422:JSlater:05/07/2018 

Init:HFS-850:CAssar:05/09/2018 

Edit/Comments:HFS-255:NNBewry:05/07/2018 

F/T:HFS-255:JMFasano:03/09/2018 
DBGNR Meeting Requests

Information for Logging into FARM/Appian

Requestor: 

Contact Information:

Date of Request:

Subject:

Date Request Received by DBGNR:

Date Prepared by DBGNR:

Prepared by:

If agent, name of company or individual this is on behalf of:

Cathryn Sacra, EAS Consulting Group, LLC 571-447-5500 (main); 571-447-5505 (direct) csacra@easconsultinggroup.com November 5, 2018 Intended use of bovine lactoferrin November 5, 2018 November 30, 2018 Shayla West-Barnette Glanbia Nutritionals
DEPARTMENT OF HEALTH AND HUMAN SERVICES 

Food and Drug Administration 

Memorandum of Meeting

Subject: Internal meeting with a CFSAN immunologist 

Date: March 22, 2019 – 2:00 PM 

Location: University Station Building, Room 2031 

Center for Food Safety and Applied Nutrition (CFSAN) 

 College Park, Maryland 

Participants: 

Office of Food Additive Safety (OFAS)/Division of Biotechnology and GRAS Notice Review (HFS-255) 

Kotaro Kaneko, Ph.D. Toxicologist 

Supratim Choudhuri, Ph.D. Toxicologist 

Office of Compliance 

Stefano Luccioli, MD Senior Medical Officer/Food Allergen Program Coordinator 

Dr. Kaneko asked Dr. Luccioli to meet with DBGNR representatives to discuss questions and concerns 

raised during GRAS review of bioactive/immunomodulatory ingredients for use in infant formula. Dr. 

Jeremiah Fasano from DBGNR could not attend due to scheduling conflicts. 

Dr. Kaneko briefly introduced the background information on osteopontin for use in infant formula, the 

subject of GRN000716, as well as on a presubmission request for bovine lactoferrin for infant formula at 

use levels higher than previous GRN notices for bovine lactoferrin. Drs. Kaneko and Choudhuri then 

briefly described the concerns by DBGNR raised during the review, which included information pertinent 

to establishing not only the safety standard of “reasonable certainty of no harm” but also the “general 

recognition” of that safety. Dr. Kaneko also briefly described the meeting highlights with CBER 

colleagues in the Office of Vaccines Research and Review, who agreed with our concerns on the use of 

osteopontin in infant formula. 

Dr. Luccioli stated that he was in agreement with the concerns raised by the DBGNR reviewers. He 

acknowledged that GRAS evaluation for these types of immunomodulatory ingredients for use in infant 

formula may require reevaluation of the current safety paradigm for risk assessment. He also stated 

that determining safe use levels for these types of ingredients in infant formula from data on breast milk 

is problematic because, due to many competing immune factors in the milk. Levels of osteopontin in 

breast milk may not predict its immunomodulatory status. When asked whether he is aware of any 

clinically accepted methodologies to evaluate safety of immunomodulatory ingredients in infants, he 

responded that he was not aware of such methodologies. 

The meeting ended with Drs. Kaneko and Choudhuri thanking Dr. Luccioli for taking the time to discuss 

this topic, as Dr. Luccioli is not only an expert as a clinical immunologist but also has the appropriate 

background to assess food safety having worked in OFAS for many years. 

Kotaro J. Kaneko, Ph.D. 

Toxicologist 
Page 2 – immunomodulatory ingredients in infant formula 

R/D:HFS-255:KJKaneko:04/30/2019 

Comments/edits: HFS-255:SChoudhuri:05/21/2019 

Comments/edits: HFS-605:SLuccioli:05/21/2019 

Comments/edits: HFS-255:RChanderbhan: 06/25/2019 

F/T:HFS-255:KJKaneko: 06/25/2019 
MEMORANDUM OF MEETING (GPS00010)

Date: June 17, 2019 

Time: 9:00 a.m. – 10:30 a.m. EST

Location: FDA, Center for Food Safety and Applied Nutrition, Office of Food 

Additive Safety, 5001 Campus Drive, College Park, MD 20740

Participants:

Visitors (via WebEx):

Tania Porsgaard Bayer Arla Foods

Kal Ramaujam Arla Foods

Anders Steen Joergensen Arla Foods

Anne Staudt Kvistgaard Arla Foods

Lotte Neergaard Jacobsen Arla Foods

Ashley Roberts Intertek

James W. McGrath Building Block Nutritionals

Gene Scavola Building Block Nutritionals

CFSAN/OFAS/DFI:

Rachel Morissette, Ph.D. HFS-255

Susan Carlson, Ph.D. HFS-255

Supratim Choudhuri, Ph.D. HFS-255

Kotaro Kaneko, Ph.D. HFS-255

Jeremy Mihalov, M.S. HFS-255

Jannavi Srinivasan, Ph.D. HFS-255

Paulette Gaynor, Ph.D. (via WebEx) HFS-255

Molly Harry, Ph.D. HFS-265

Diana Doell, Ph.D. HFS-265

Susan Carberry, Ph.D. HFS-265

Scott Thurmond, Ph.D. HFS-265

CFSAN/OFAS/DST:

Jeremiah Fasano, Ph.D. HFS-255

CFSAN/ONFL/IFMFS:

Carrie Assar, Pharm.D. HFS-850

Andrea Lotze, M.D. HFS-850

Suzanne Wolcoff, M.S., R.D. (via WebEx) HFS-850

CFSAN/OC:

Stefano Luccioli, M.D. (via WebEx) HFS-200
Subject: Pre-submission meeting for the intended use of bovine whey-derived 

osteopontin (bOPN) in infant formula

Background:

In an email dated May 13, 2019, Ms. Tania Porsgaard Bayer of Arla Foods (Arla) 

requested a meeting with FDA/CFSAN to discuss their approach for addressing safety 

and general recognition concerns that FDA raised during the review of GRN 000716.1

The issues raised during our review were primarily captured in a scientific 

memorandum, a policy memorandum, and a memorandum of meeting between DFI 

and the Center for Biologics Evaluation and Research (CBER) for the intended use of

bOPN as an ingredient in infant formula. Arla had requested these memoranda under 

the Freedom of Information Act on April 5, 2019. In an email dated May 1, 2019, we 

reiterated our position regarding the unsettled nature of the science surrounding the 

biological effects of bOPN and the lack of general recognition in the scientific 

community regarding the safety of bOPN intended for use as an added ingredient in 

foods and infant formula. Additionally, we stated that we would welcome a continuing

dialogue with Arla on long-term strategies to address the above-mentioned concerns, 

which led to today’s meeting. 

June 17, 2019:

During the meeting, Arla gave a presentation covering four main points: general 

recognition, toxicology and safety, human OPN (hOPN) in human milk, and history of 

consumption. In support of general recognition, Arla stated that their safety data were

presented to and discussed with 19 experts in pediatrics and immunology.2 However, 

the specific context of the questions, the data and information discussed, and the

responses received from these experts were not provided to FDA. Thus, it was not clear 

whether the questions and concerns raised during FDA’s review of GRN000716 were 

fully described, appropriately framed in the context of the Federal Food, Drug, &

Cosmetic Act food ingredient safety standard, and adequately addressed in these 

discussions. Arla also stated that they intend to submit a Novel Food application to the 

European Food Safety Authority for the use of bOPN in infant formula at 138 mg/L. 

In support of toxicology and safety, Arla discussed pre-clinical in vitro and animal safety 

studies, as well as clinical studies, with a new focus on immune markers to address 

concerns raised during our review of GRN 000716. Arla noted a recently published

study by Lönnderdal et. al. showing that formula fed infants have high circulating levels 

of endogenous hOPN that they believe may be of immunological benefit in infants.3 Arla 

requested guidance regarding the types of studies they should pursue to address our 

safety questions and what we consider to be a “long-term” study. 

To compare hOPN and bOPN, Arla discussed the structural homology and posttranslational modifications found between the species and stated that functional and 

 

1 Bovine whey-derived osteopontin was the subject of GRN 000716. At Arla’s request we ceased our 

evaluation of this notice and responded in a letter dated February 1, 2018.

2 A list of conferences and publications was provided in an email to FDA dated June 3, 2019.

3 Jiang and Lönnerdal (2019) Pediatric Research 85(4), 502-505.
structural differences between the two proteins are found more in extracellular 

secretions and in organs, rather than in milk. Arla referenced an FDA guidance 

document relevant to drug biosimilarity to support that molecules are considered 

similar if minor structural differences do not result in adverse functional differences.4

We noted that the potential relevance of guidance on drug efficacy assessment for 

protein-based biosimilars emphasized the novelty and challenging nature of the issues 

under discussion in a food safety context. 

Finally, Arla discussed the history of consumption of hOPN. Arla showed data from 

human milk samples from a total of 629 women in four countries that showed a mean 

concentration of 167.4 mg/L hOPN; however, the concentrations varied widely across 

samples and throughout the lactation period. Arla stated that there have been no 

adverse events reported so far in China, Korea, and the European Union where bOPN 

has been marketed as an ingredient in infant formula. Additionally, Arla stated that a 

U.S. clinical trial using bOPN-enriched infant formula reported no safety concerns.

Arla ended the presentation by asking for guidance on strategies to achieve general 

recognition of safety for bOPN, further studies they may undertake to support a safety 

conclusion, and clarification on what we consider “long-term” studies.

FDA provided comments emphasizing the following points:

x While general recognition is an important component of GRAS, the bigger issue 

is the unsettled nature of the science surrounding the safe use of bOPN in infant 

formula. Issues surrounding general recognition cannot be addressed until the 

safety of bOPN is demonstrated. A more basic scientific understanding of bOPN’s 

biological effects in the body is needed.

x Arla has acknowledged that the science surrounding bioactive ingredients is 

evolving and their safety cannot be determined by traditional toxicological 

endpoints. Arla demonstrated this by exploring other means of studying 

immunomodulatory effects and their impact on the developing infant immune 

system.

x Arla stressed the perceived beneficial effects of bOPN. However, the expectation 

is that either this ingredient has no biological effect on the infant gut and 

immune system, or it has such effects that must be evaluated for potential 

adversity without mitigation by anticipated benefits. The food safety paradigm, 

unlike drugs and biologics, does not involve the kind of risk/benefit analysis 

presented in Arla’s slides. We cautioned Arla about the challenges involved in 

pursuing intended food uses driven by anticipated benefits, especially in infant 

formula. 

x To address the safety concerns surrounding bOPN, a long-term, on-going, and 

robust debate is needed among different scientific and medical disciplines. Likely 

more basic research will be required to answer these questions. Depending on the 

outcome of that debate and research, there is no guarantee that a consensus of 

 

4 Guidance to Industry: Scientific Considerations in Demonstrating Biosimilarity to a Reference Product, 

from the Center for Drug Evaluation and Research and CBER, April 2015.
opinion on the safety of bOPN will be reached. We agreed to provide guidance on 

the types of disciplines and suggest potential experts in the relevant disciplines as 

a starting point for that debate. We would also identify the types of scientific 

forums most suited to discuss the safety of the use of bOPN in infant formula and 

food. Assembling of this broader platform of expertise could help serve Arla’s and 

FDA’s considerations for what constitutes an appropriate long-term study.

We concluded the meeting by agreeing to provide Arla a list of needed expertise in 

relevant scientific and medical disciplines as a starting point for the needed broader 

discussion on the safety of bOPN in infant formula within 3-4 weeks of this meeting. 

Additionally, we agreed to share a copy of this memorandum of meeting with Arla.

________________________________

Rachel Morissette, Ph.D.

ATTACHED:

1. Updated attendee list (email dated June 17, 2019)

2. List of questions for FDA (email dated June 17, 2019)

3. Agenda and list of conferences (email dated June 3, 2019)

4. Meeting Request (email dated May 13, 2019)

5. Email from FDA to Arla (dated May 1, 2019)

6. Powerpoint presentation

Rachel 

Morissette -S

Digitally signed by 

Rachel Morissette -S 

Date: 2019.07.11 

13:57:42 -04'00'
R/D:HFS-255:RMorissette:7/1/19, 7/2/19, 7/3/19, 7/5/19

Edit/Comment/Init:HFS-255:KKaneko:7/2/19

Edit/Comment/Init:HFS-255:SChoudhuri:7/1/19

Edit/Comment/Init:HFS-255:JFasano:7/2/19

Edit/Comment/Init:HFS-255:JMihalov:7/3/19

Edit/Comment/Init:HFS-255:JSrinivasan:7/3/19

Edit/Comment/Init:HFS-265:SCarberry:7/3/19

Edit/Comment/Init:HFS-265:MHarry:7/3/19

Edit/Comment/Init:HFS-265:MHonigfort:7/5/19

Edit/Comment/Init:HFS-255:SCarlson:7/5/19

F/T:HFS-255:RMorissette:7/11/19
From: Tania Porsgaard Bayer

To: Morissette, Rachel

Subject: SV: Arla"s request for a meeting to discuss osteopontin

Date: Monday, June 17, 2019 8:37:03 AM

Attachments: image007.png

image015.png

image021.png

Hi Rachel

Besides the attendance listed below there will be 2 additional attendances:

Lotte Neergaard Jacobsen, Arla Foods Ingredients, Scientist

Gene Scavola, Building Block Nutrition

I hope this is okay

Med venlig hilsen / Best regards

Tania Porsgaard Bayer

+4589381562

Fra: Morissette, Rachel <Rachel.Morissette@fda.hhs.gov> 

Sendt: 17. juni 2019 14:05

Til: Tania Porsgaard Bayer <tania.porsgaard.bayer@arlafoods.com>

Emne: RE: Arla's request for a meeting to discuss osteopontin

Hi Tania,

Can you please confirm the attendance list below? Sometimes it’s difficult to catch everyone’s names

over the phone.

Tania Porsgaard Bayer, Arla Foods Ingredients, Director of Global Regulatory

Kal Ramaujam, Arla Foods Ingredients, Senior Scientific Advisor

Anders Steen Joergensen, Arla Foods Ingredients, Director BU pediatric

Anne Staudt Kvistgaard, Arla Foods Ingredients, Senior Manager Science and sales

development

Ashley Roberts from Intertek, Senior Vice President – Food & Nutrition

James W McGrath, Building Block Nutrition

Thanks,

Rachel

-------------------------------------------------------------

Rachel Morissette, Ph.D.

Regulatory Review Scientist

Center for Food Safety and Applied Nutrition
Office of Food Additive Safety

U.S. Food and Drug Administration

rachel.morissette@fda.hhs.gov

From: Tania Porsgaard Bayer <tania.porsgaard.bayer@arlafoods.com> 

Sent: Monday, June 17, 2019 2:07 AM

To: Morissette, Rachel <Rachel.Morissette@fda.hhs.gov>

Subject: SV: Arla's request for a meeting to discuss osteopontin

Dear Rachel

Just for the overview I’ve gathered all our questions in one document that I have attached in this

email. All the questions are in the previously send presentation, and are all questions we would like

to discuss with FDA or get some guidance from FDA.

I look forward to speaking to you and your team tomorrow.

Best regards, Tania

Med venlig hilsen / Best regards

Tania Porsgaard Bayer

Director / Head of Global Regulatory Affairs

Arla Foods Ingredients Group P/S

Phone: +4589381562

VAT no.: 33372116

tania.porsgaard.bayer@arlafoods.com

http://www.arlafoodsingredients.com

This e-mail is proprietary and confidential and may contain legally privileged information.

This e-mail is intended for the addressee(s) stated above only. If you receive this e-mail by mistake,
please inform us by returning this e-mail without producing, distributing or retaining copies hereof.

Fra: Morissette, Rachel <Rachel.Morissette@fda.hhs.gov> 

Sendt: 3. juni 2019 20:26

Til: Tania Porsgaard Bayer <tania.porsgaard.bayer@arlafoods.com>

Emne: RE: Arla's request for a meeting to discuss osteopontin

Ok, thank you!

Rachel

-------------------------------------------------------------

Rachel Morissette, Ph.D.

Regulatory Review Scientist

Center for Food Safety and Applied Nutrition

Office of Food Additive Safety

U.S. Food and Drug Administration

rachel.morissette@fda.hhs.gov

From: Tania Porsgaard Bayer <tania.porsgaard.bayer@arlafoods.com> 

Sent: Monday, June 03, 2019 2:18 PM

To: Morissette, Rachel <Rachel.Morissette@fda.hhs.gov>

Subject: SV: Arla's request for a meeting to discuss osteopontin

Dear Rachel

Thank you very much for your fast reply for arranging a meeting.

I’ll send you a presentation next week that I would like to go through at the meeting

Med venlig hilsen / Best regards

Tania Porsgaard Bayer

+4589381562

Fra: Morissette, Rachel <Rachel.Morissette@fda.hhs.gov> 

Sendt: 3. juni 2019 19:08

Til: Tania Porsgaard Bayer <tania.porsgaard.bayer@arlafoods.com>

Emne: RE: Arla's request for a meeting to discuss osteopontin

Hi Tania,
I have scheduled your teleconference for Monday June 17, 2019 from 9:00-10:30 am EST. If you have

other materials that you would like me to circulate to the review team, or if you have presentation slides

you’d like to show, please let me know prior to the meeting. I will forward a calendar invite with WebEx

information to you shortly. Please let me know if you do not receive it by the end of the day. If you have

any further questions at this time, please let me know.

Best regards,

Rachel

-------------------------------------------------------------

Rachel Morissette, Ph.D.

Regulatory Review Scientist

Center for Food Safety and Applied Nutrition

Office of Food Additive Safety

U.S. Food and Drug Administration

rachel.morissette@fda.hhs.gov

From: Tania Porsgaard Bayer <tania.porsgaard.bayer@arlafoods.com> 

Sent: Monday, June 03, 2019 11:13 AM

To: Morissette, Rachel <Rachel.Morissette@fda.hhs.gov>

Subject: VS: Arla's request for a meeting to discuss osteopontin

Hi Rachel

Any meeting before 11th July will be okay for us, we will prioritize the meeting and are just happy

that you can set aside time for meeting with us over phone. If possible, we would like a meeting

before lunch (your time), since we are based in Europe and are 7 hours in front of you timewise.

Based on the different documents from the FOIA request, I’ve extracted 4 main points that FDA

have addressed as concerns before the agency can confirm that GRN 000716 "reasonable certainty

of no harm", all 4 points is what we would like to have on the agenda, below is my suggestion for an

agenda for our meeting.

Agenda:

Arla wishes to discuss with the FDA how best to address the concerns raised by FDA, the points

raised by FDA that we would like to address is:

1. General recognition

The safety data we have on hOPN have been presented for a total on 19.000 experts

within pediatric and immunology on 12 different conferences, we believe this show a

broad consensus among clinical immunologists about the data and information presented

establish reasonable certainty of no harm for the use of bOPN in infants. (list of

conferences attached)

2. Toxicological and safety
We would like to present our strategy for showing ‘absence for adverse effects’, and

inform about the similar concerns addressed in Europe by EFSA, and how we are working

with EFSA to address the concern

3. hOPN in human milk

Since the 29 milk samples, FDA are referring to in the scientific memo, we have plenty of

new human milk OPN-level information that we would like to present to FDA

Bruun et al. 2018 - +800 milk samples from Korea, China, Japan and DK

Jiang & Lönnerdal 2019 – milk samples from USA

4. History of consumption

We would like to show data that hOPN has been consumed by infants for many years.

Furthermore, we can show that the homology between hOPN and bOPN is very high and

the functional domains are conserved. In order to show history of consumption.

Arla looks forward to having dialogue with the agency on these matters in the hope of obtaining

guidance on the strategy as develop.

List of participants from our side would be (might vary depending on the date of the meeting):

Tania Porsgaard Bayer, Arla Foods Ingredients, Director of Global Regulatory

Kal Ramaujam, Arla Foods Ingredients, Senior Scientific Advisor

Anders Steen Joergensen, Arla Foods Ingredients, Director BU pediatric

Anne Staudt Kvistgaard, Arla Foods Ingredients, Senior Manager Science and sales

development

Ashley Roberts from Intertek, Senior Vice President – Food & Nutrition

James W McGrath, Building Block Nutrition

Please let me know if you have any questions. I look forward to hearing from you

Med venlig hilsen / Best regards

Tania Porsgaard Bayer

Director / Head of Global Regulatory Affairs

Arla Foods Ingredients Group P/S

Phone: +4589381562

VAT no.: 33372116

tania.porsgaard.bayer@arlafoods.com

http://www.arlafoodsingredients.com
C:\Users\Rachel Morissette\AppData\Local\Microsoft\Windows\Temporary Internet Files\Content.Outlook\JWHP4AQ6\Questions to FDA 20190617.docx

Questions to FDA- Pre-submission meeting- Bovine Osteopontin 17th June 2019

General Recognition:

x Bovine OPN safety and efficacy has been presented in many conferences and 

the list of publication that is directly relevant is also listed.

Question 1:

1) Furthermore, we plan to assemble a round table panel with leading pediatric, immunology and OPN structural experts to discuss short and long-term safety of 

OPN. Would FDA scientists be available to participate?

Safety and Toxicology:

x Published studies and available information at the time of our Lacprodan OPN-10 

dossier compiled led to the safety of the dosage (138 mg/L) requested. As 

pointed out by FDA, immune end points were not studied in the pre-clinical safety 

protocol. The clinical study looked at immune markers, vaccine response and infection rates and did not see any safety concerns when compared to the breast 

fed infants. New information on the analysis of plasma samples from clinical study 

(not presented in the dossier or discussed with FDA previously) shows high levels 

of endogenous hOPN even in formula fed infants that might play a role in immune 

programming and contributing to long term health outcomes in all infants. Compared to hOPN, the bOPN measured even in supplemented infants was 20 fold 

less and is lower than any of the plasma levels observed and presented in the 

dossier (Table 17, Page 69).Also, high levels of endogenous OPN in plasma will 

create complexity in designing exogenous bovine OPN feeding studies to look at 

long term outcomes as the specific immune role of bOPN will be difficult to prove. 

Given this we need following guidance from FDA.

Questions 2-7:

2) The FDA has raised the concern of the “...long-term consequences of perturbing 

the developing infant immune system...”. In the design of studies to answer this 

concern, what is the agencies definition of “long Term”? 

3) Given information presented on high levels of endogenous hOPN early in infancy, 

is there a reason to consider additional animal safety studies ?

4) Does the agency agree that the proposed mini pig model with dosing and immune 

assessment study will provide toxicological answers to the potential long term effects of Osteopontin (OPN)? (follow up to the question above)

5) Does additional measurement of hOPN in USA infants add value to existing knowledge and evaluation of our application?

6) Given the current safety information, publications and general recognition presented, is there any level beyond the 13 mg/ L (innate) that FDA is comfortable 

approving?

7) Given substantially higher levels of hOPN compared to bOPN, does the agency 

agree that any long term effects would be attributed to hOPN
C:\Users\Rachel Morissette\AppData\Local\Microsoft\Windows\Temporary Internet Files\Content.Outlook\JWHP4AQ6\Questions to FDA 20190617.docx

hOPN and bOPN structural similarity:

Experts acknowledged that differences in post translational modifications are noted 

within lactation period and between breast milk and other secretions. Since there is substantial similarity in amino acid sequence and active binding domains, post translational 

modifications may have minimal functional consequences (if any). Based on available 

literature information, bOPN plays a beneficial role in model systems studied. 

Questions 8-9:

8) Does the FDA agree that the minor differences noted in homology may not be 

functionally consequential?

9) Given this complexity, is there any binding studies the FDA would recommend to 

alleviate its concerns?

Miscellaneous Questions 10-11:

10) How helpful is the BBN OPN clinical safety study to safety of OPN?

11) Would the agency like to see the full results of the BBN safety clinical in support 

of the OPN GRAS approval?
C:\Users\Rachel.Morissette\Desktop\Files (new)\Pre-Submission Meetings\Osteopontin (Arla)\OPN-overview.docx 

Year Conference/event Presenter Format Title 

2009 Milk Genomics, Sharon Donovan Oral presentation OPN gene expression 

2011 ESPGHAN, Sorrento Esben Skipper 

Sørensen 

Oral presentation Osteopontin – a bioactive 

milk protein with implications 

in infant nutrition? 

2011 ESPGHAN, Sorrento Sharon Donovan Oral presentation Transcriptional responses of 

the neonatal Rhesus intestine 

to Osteopontin 

2011 ESPGHAN, Sorrento Bing Wang Oral presentation Osteopontin – a bioactive 

milk protein with implications 

in infant nutrition? 

2014 Early Nutrition, Power of Programming, Munich Bo Lönnerdal Oral presentation Growth, nutrition and early 

programming of 

immune function in breastfed infants and infants 

fed formula with added osteopontin (OPN)

2014 Experimental Biology, San Diego Sharon Donovan Oral presentation Osteopontin supplementation of formula shifts the peripheral blood mononuclear 

cell transcriptome to be more 

similar to breastfed infants 

2014 Experimental Biology, San Diego Bo Lönnerdal Poster Growth, nutrition and immune function of breast-fed 

infants and infants fed formula with added osteopontin 

2014 Experimental Biology, San Diego Sharon Donovan Poster Dietary bovine osteopontin 

increases vaccine response, 

T-cell phenotype and cytokine secretion in piglets 

2017 Nestlé 90th Symposium Sharon Donovan Webcast Proteins in human milk – 

composition and biological 

effects 

2018 Ordesa Symposium, Madrid Lotte Neergaard 

Jacobsen 

Oral presentation Osteopontin – cornerstone in 

immunology 

2018 ESPGHAN, Geneve Signe Bruun Oral presentation Osteopontin levels in human 

milk vary across 

countries and within lactation period: Data 

from a multicenter study 

2019 Event Catedra Ordesa, VI 

International Scientific Symposium, 

Palma de Mallorca 

Lotte Neergaard 

Jacobsen 

Oral presentation Osteopontin in human milk 

and infant nutrition 
C:\Users\Rachel.Morissette\Desktop\Files (new)\Pre-Submission Meetings\Osteopontin (Arla)\OPN-overview.docx 

Publication list OPN: 

Ren et al. 2019. Gut and immune effects of bioactive milk factors in preterm pigs exposed to prenatal 

inflammation. Am J Physiol Gastrointest Liver Physiol. 15 . [Epub ahead of print] 

(https://www.ncbi.nlm.nih.gov/pubmed/31091150)

Donovan 2019. Human milk proteins: Composition and physiological significance. Nestle Nutr Inst Workshop Ser. 90: 93-101 (https://www.ncbi.nlm.nih.gov/pubmed/30865978) 

Jiang & Lönnerdal 2019. Osteopontin in human milk and infant formula affects infant plasma osteopontin concentrations. Pediatr Res. 85(4): 502-505 (https://www.ncbi.nlm.nih.gov/pubmed/30636771) 

Chen et al. 2018. Osteopontin-enriched formula feeding improves the T-cell-dependent humoral immune 

response in infant rats. Int J Food Sci Nutr. 69(8): 969-975 (https://www.ncbi.nlm.nih.gov/pubmed/30001650)

Bruun et al. 2018. Osteopontin levels in human milk vary across countries and within lactation period: 

Data from a multicenter study. JPGN. 67(2): 250-256 (https://www.ncbi.nlm.nih.gov/pubmed/29668569)

Demmelmair et al. 2017. Benefits of lactoferrin, osteopontin and milk fat globule membranes for infants. 

Nutrients. 9(8) (https://www.ncbi.nlm.nih.gov/pubmed/28788066)

Lönnerdal 2017. Bioactive protein in human milk – potential benefits for preterm infants. Clin Perinatol. 

44(1): 179-191 (https://www.ncbi.nlm.nih.gov/pubmed/28159205)

Jiang & Lönnerdal 2017. Biological roles of milk osteopontin. Curr Opin Clin Nutr Metab Care. 19(3): 

214-219 (https://www.ncbi.nlm.nih.gov/pubmed/27504516)

Lönnerdal 2016. Human milk: Bioactive proteins/peptides and functional properties. Nestlé Nutr Inst 

Workshop Ser. 86: 97-107 (https://www.ncbi.nlm.nih.gov/pubmed/27337145)

Christensen & Sørensen 2016. Structure, function and nutritional potential of milk osteopontin. Int Dairy 

J. 57: 1-6 (https://www.sciencedirect.com/science/article/pii/S0958694616300437)

Lönnerdal 2016. Bioactive proteins in human milk: Health, nutrition, and implications for infant formulas. J

Pediatr. 173: S4-S9 (https://www.ncbi.nlm.nih.gov/pubmed/27234410)

Lönnerdal et al. 2016. Growth, nutrition, and cytokine response of breast-fed infants and infants fed formula with added bovine osteopontin. JPGN. 62(4): 650-657

(https://www.ncbi.nlm.nih.gov/pubmed/26465791)

Donovan et al. 2014. Bovine osteopontin modifies the intestinal transcriptome of formula-fed infant rhesus monkeys to be more similar to those that were breastfed. J Nutr. 144(12): 1910-1919 

(https://www.ncbi.nlm.nih.gov/pubmed/25320184)
C:\Users\Rachel.Morissette\Desktop\Files (new)\Pre-Submission Meetings\Osteopontin (Arla)\OPN-overview.docx 

Kvistgaard et al. 2014. Pre-clinical in vitro and in vivo safety evaluation of bovine whey derived osteopontin, Lacprodan® OPN-10. Food Chem Toxicol. 73: 59-70 (https://www.ncbi.nlm.nih.gov/pubmed/25072164)

Lönnerdal 2014. Infant formula and infant nutrition: bioactove proteins of human milk and implications for 

composition of infant formulas. Am J Clin Nutr. 99(3): 12S-17S (https://www.ncbi.nlm.nih.gov/pubmed/24452231)

Chatterton et al. 2013. Anti-inflammatory mechanisms of bioactive milk proteins in the intestine of the 

newborns. Int J Biochem Cell Biol. 45(8): 1730-1747 (https://www.ncbi.nlm.nih.gov/pubmed/23660296)

Lönnerdal 2011. Biological effects of novel bovine milk fractions. Nestlé Nutr Workshop Ser Pediatr Program. 67: 41-54 (https://www.ncbi.nlm.nih.gov/pubmed/21335989)

Schack et al. 2009. Considerable variation in the concentration of osteopontin in human milk, bovine milk, 

and infant formulas. J Dairy Sci. 92(11): 5378-5385 (https://www.ncbi.nlm.nih.gov/pubmed/19841198)
List of participants from our side would be (might vary depending on the date of the meeting):

Tania Porsgaard Bayer, Arla Foods Ingredients, Director of Global Regulatory

Kal Ramaujam, Arla Foods Ingredients, Senior Scientific Advisor

Anders Steen Joergensen, Arla Foods Ingredients, Director BU pediatric

Anne Staudt Kvistgaard, Arla Foods Ingredients, Senior Manager Science and sales

development

Ashley Roberts from Intertek, Senior Vice President – Food & Nutrition

James W McGrath, Building Block Nutrition

Please let me know if you have any questions. I look forward to hearing from you

Med venlig hilsen / Best regards

Tania Porsgaard Bayer

Director / Head of Global Regulatory Affairs

Arla Foods Ingredients Group P/S

Phone: +4589381562

VAT no.: 33372116

tania.porsgaard.bayer@arlafoods.com

http://www.arlafoodsingredients.com

This e-mail is proprietary and confidential and may contain legally privileged information.

This e-mail is intended for the addressee(s) stated above only. If you receive this e-mail by mistake,

please inform us by returning this e-mail without producing, distributing or retaining copies hereof.

Fra: Morissette, Rachel <Rachel.Morissette@fda.hhs.gov> 

Sendt: 21. maj 2019 16:09

Til: Tania Porsgaard Bayer <tania.porsgaard.bayer@arlafoods.com>

Emne: RE: Arla's request for a meeting to discuss osteopontin

Hi Tania,

Thank you for your response. I would be happy to set up a teleconference to discuss your strategy. As I
mentioned before, we will not be able to accommodate an in-person meeting at this time. Please suggest

several possible dates and times over the next two months that could work for you and I’ll try to

accommodate your schedule as best as possible. Keep in mind that it may be more difficult to

accommodate a summer meeting with staff travel schedules. Also, please provide a list of attendees and

an agenda, along with any materials you’d like our review team to look at ahead of time. Please note that

any materials you send may be releasable under the FOIA. Please let me know if you have any

questions.

Best regards,

Rachel

-------------------------------------------------------------

Rachel Morissette, Ph.D.

Regulatory Review Scientist

Center for Food Safety and Applied Nutrition

Office of Food Additive Safety

U.S. Food and Drug Administration

rachel.morissette@fda.hhs.gov

From: Tania Porsgaard Bayer <tania.porsgaard.bayer@arlafoods.com> 

Sent: Monday, May 13, 2019 11:20 AM

To: Morissette, Rachel <Rachel.Morissette@fda.hhs.gov>

Subject: SV: Arla's request for a meeting to discuss osteopontin

Dear Rachel

Sorry for the late reply, we needed an internal evaluation of your comments below.

We would however, like to proceed with a meeting with FDA, we would prefer a physical meeting

since it is often beneficial to sit face-to-face, but understand the shortage of staff and resources.

We will like to talk about a general topic on how to generate compelling evidence of general

recognition, we have several ideas and proposals and would like FDA to give some advice to our

suggestions. Further we are well aware of the lack in long term effects of our ingredient and would

like to work with FDA and experts to create a guideline on this. We are already involved in this at EU

level, where EFSA have addressed similar questions.

We hope that this meeting could lead to a more in-depth discussion of GRN 000716 where we can

present our strategy the questions addressed by FDA in the scientific memo.

I look forward to hearing from you, hopefully with a date for our meeting.

Best regards, Tania
Med venlig hilsen / Best regards

Tania Porsgaard Bayer

Director / Head of Global Regulatory Affairs

Arla Foods Ingredients Group P/S

Phone: +4589381562

VAT no.: 33372116

tania.porsgaard.bayer@arlafoods.com

http://www.arlafoodsingredients.com

This e-mail is proprietary and confidential and may contain legally privileged information.

This e-mail is intended for the addressee(s) stated above only. If you receive this e-mail by mistake,

please inform us by returning this e-mail without producing, distributing or retaining copies hereof.

Fra: Morissette, Rachel <Rachel.Morissette@fda.hhs.gov> 

Sendt: 1. maj 2019 17:17

Til: Tania Porsgaard Bayer <tania.porsgaard.bayer@arlafoods.com>

Emne: Arla's request for a meeting to discuss osteopontin

Dear Tania,

Thank you for your request to meet with FDA to discuss Arla’s scientific and regulatory strategies for

concluding that osteopontin is safe for use in infant formula. Before we move ahead with a meeting, I

want to clarify a few points and make sure that Arla is in agreement with FDA’s approach.

By now you’ve likely had a chance to read the documents that were requested under FOIA, specifically

the policy memo, CBER memo, and scientific memo regarding ostepontin and its use in infant formula.

FDA’s position on this ingredient is clear in these documents: the science surrounding osteopontin, and

bioactive ingredients in general, is unsettled and there does not appear to be a general consensus of

safety in the greater scientific community. FDA has not seen evidence that questions regarding the longterm consequences of perturbing the developing infant immune system have been asked, let alone there

being any sort of consensus on the issue by the greater scientific community. Therefore, FDA is of the

position that until this paradigm shift occurs in terms of considering non-traditional toxicological endpoints

and possible long-term effects from using bioactive ingredients in infants, and is vetted by the broader

scientific community, including experts with appropriate infant immunological expertise, or new data and

information become available, FDA would still have questions regarding the basis for a GRAS conclusion

for the intended use of osteopontin (and potentially other bioactive ingredients, in general) in infant

formula.
With that caveat, FDA is committed to assisting industry in finding a way to generate the general

recognition and expert consensus that’s currently missing in the field. Therefore, FDA is willing to meet

with Arla to discuss its long-term strategies for achieving this goal should Arla still want to move ahead

with what will likely be a long-term and resource-intensive endeavor. I want to emphasize that our

discussion will focus on Arla’s ideas to facilitate a broader discussion to achieve consensus in the greater

scientific community surrounding the questions FDA has put forth in its various communications to Arla,

and that our discussion should not involve how to “fix” GRN 000716 or spin the existing scientific data to

support a current GRAS conclusion.

I should also note that due to a severe shortage in staff and resources, we are currently not accepting inperson meeting requests; however, we can accommodate a teleconference. If Arla is amenable to this

approach, then I am happy to work on setting up a meeting.

Please let me know what you think and whether we should move ahead with a teleconference.

Best regards,

Rachel

-------------------------------------------------------------

Rachel Morissette, Ph.D.

Regulatory Review Scientist

Center for Food Safety and Applied Nutrition

Office of Food Additive Safety

U.S. Food and Drug Administration

rachel.morissette@fda.hhs.gov

From: Tania Porsgaard Bayer <tania.porsgaard.bayer@arlafoods.com> 

Sent: Tuesday, April 30, 2019 4:57 AM

To: Morissette, Rachel <Rachel.Morissette@fda.hhs.gov>

Cc: Dodson, Sharon R <Sharon.Dodson@fda.hhs.gov>

Subject: SV: FOI2019-2922 RE: requestor requires assistance with submitting a FOIA

Hi Rachel

Thank you for you fast reply.

No problem, the important thing is that we have the right records for preparation of our meeting.

Do you know when we can expect to have the pre-submission meeting that we have requested? Just

for me to prepare flight tickets and arrange hotel.

Thanks.

Tania
Med venlig hilsen / Best regards

Tania Porsgaard Bayer

+4589381562

Fra: Morissette, Rachel <Rachel.Morissette@fda.hhs.gov> 

Sendt: 29. april 2019 17:23

Til: Tania Porsgaard Bayer <tania.porsgaard.bayer@arlafoods.com>

Cc: Dodson, Sharon R <Sharon.Dodson@fda.hhs.gov>

Emne: FOI2019-2922 RE: requestor requires assistance with submitting a FOIA

Hi Tania,

Yes, these are the same documents. I apologize that you haven’t received your responsive records for

FOI2019-2922. I fulfilled your FOIA request weeks ago.

Sharon, can you please check on the status of this FOI and whether the records were sent or not?

Best regards,

Rachel

-------------------------------------------------------------

Rachel Morissette, Ph.D.

Regulatory Review Scientist

Center for Food Safety and Applied Nutrition

Office of Food Additive Safety

U.S. Food and Drug Administration

rachel.morissette@fda.hhs.gov

From: Tania Porsgaard Bayer <tania.porsgaard.bayer@arlafoods.com> 

Sent: Monday, April 29, 2019 11:03 AM

To: Morissette, Rachel <Rachel.Morissette@fda.hhs.gov>

Cc: Dodson, Sharon R <Sharon.Dodson@fda.hhs.gov>

Subject: SV: requestor requires assistance with submitting a FOIA

Dear Rachel

I hope you are doing well.

A customer of ours send me the attached documents last week, that are related to GRN 716 and the
minutes of meetings that you previously referred to. I just wanted to ask you, if you know whether

this is the documents we are waiting requested in the FOIA I submitted.

If this is the documents, there is no need for you to spend your time on this 

I hope to hear from you soon and look forward to meeting you when we get the pre-submission

meeting.

Thanks,

Tania

Med venlig hilsen / Best regards

Tania Porsgaard Bayer

Director / Head of Global Regulatory Affairs

Arla Foods Ingredients Group P/S

Phone: +4589381562

VAT no.: 33372116

tania.porsgaard.bayer@arlafoods.com

http://www.arlafoodsingredients.com

This e-mail is proprietary and confidential and may contain legally privileged information.

This e-mail is intended for the addressee(s) stated above only. If you receive this e-mail by mistake,

please inform us by returning this e-mail without producing, distributing or retaining copies hereof.

Fra: Morissette, Rachel <Rachel.Morissette@fda.hhs.gov> 

Sendt: 2. april 2019 22:41

Til: Tania Porsgaard Bayer <tania.porsgaard.bayer@arlafoods.com>; Dodson, Sharon R

<Sharon.Dodson@fda.hhs.gov>

Cc: Dodson, Sharon R <Sharon.Dodson@fda.hhs.gov>

Emne: requestor requires assistance with submitting a FOIA

Hi Tania,
I’m sorry you’re still having problems getting this FOIA submitted. I’m ccing our office’s FOIA contact,

Sharon Dodson. Sharon will be able to help you find someone else to help if you’re not getting anywhere

with Yessenia. The policy memo is referenced in the scientific memo and various emails in the GRN

000716 record. The memo of meeting held by the Office of Food Additive Safety with participants from

CBER is the second document that you should request. This memo originated from CFSAN and therefore

does not require a record search by CBER.

Sharon, can you please assist Ms. Bayer with her FOIA request? If you recall, she was having technical

difficulties when trying to submit the request online and kept getting error messages. I referred her to

Yessenia Garcia as you suggested, but she has not been able to get a hold of her.

Thanks,

Rachel

-------------------------------------------------------------

Rachel Morissette, Ph.D.

Consumer Safety Officer

Center for Food Safety and Applied Nutrition

Office of Food Additive Safety

U.S. Food and Drug Administration

rachel.morissette@fda.hhs.gov

From: Tania Porsgaard Bayer <tania.porsgaard.bayer@arlafoods.com> 

Sent: Tuesday, April 02, 2019 10:18 AM

To: Morissette, Rachel <Rachel.Morissette@fda.hhs.gov>

Subject: SV: Request for a Pre submission meeting GRN 000716

Dear Rachel

I didn’t manage to get a hold on Yessenia Garcia, but I’ll try again.

We do have the memo from the meeting we had on March 1st and also the scientific memo. What

we do not have is the meeting memo you refer to, the interaction with CBER. Also, I am not sure

what is the OFAS policy memo.

I am not sure whether we are missing additional documents, hence I’ll try to get a hold on Yessenia

Garcia and submit a FOIA.

Thank you for your support on this.

Best regards, Tania

Med venlig hilsen / Best regards
Tania Porsgaard Bayer

Director / Head of Global Regulatory Affairs

Arla Foods Ingredients Group P/S

Phone: +4589381562

VAT no.: 33372116

tania.porsgaard.bayer@arlafoods.com

http://www.arlafoodsingredients.com

This e-mail is proprietary and confidential and may contain legally privileged information.

This e-mail is intended for the addressee(s) stated above only. If you receive this e-mail by mistake,

please inform us by returning this e-mail without producing, distributing or retaining copies hereof.

Fra: Morissette, Rachel <Rachel.Morissette@fda.hhs.gov> 

Sendt: 28. marts 2019 18:01

Til: Tania Porsgaard Bayer <tania.porsgaard.bayer@arlafoods.com>

Emne: RE: Request for a Pre submission meeting GRN 000716

Dear Tania,

I just wanted to follow-up with a point of clarification on this FOIA request. This is a CFSAN-only

document search. The mention of “CBER” in the request may trigger the FOIA office to forward this to

both CFSAN and CBER. If the FOIA office reaches out to you for clarification, you can inform them that

this is a memo for a meeting that was held by CFSAN with a few CBER attendees. Therefore, it is a

CFSAN meeting memo and does not require a search by CBER. Please ask them to reach out to me

directly if there are any issues.

Best regards,

Rachel

-------------------------------------------------------------

Rachel Morissette, Ph.D.

Consumer Safety Officer

Center for Food Safety and Applied Nutrition

Office of Food Additive Safety

U.S. Food and Drug Administration

rachel.morissette@fda.hhs.gov
From: Tania Porsgaard Bayer <tania.porsgaard.bayer@arlafoods.com> 

Sent: Tuesday, March 26, 2019 11:05 PM

To: Morissette, Rachel <Rachel.Morissette@fda.hhs.gov>

Subject: SV: Request for a Pre submission meeting GRN 000716

Dear Rachel

Thank you for your feedback.

Unfortunately, I’m not able to submit the FOIA, attached it the request, but when I press ‘submit’ I

keep getting a message that I’ve entered invalid data and have to start over again, but I’ve only filled

in the required data.

In the FOIA I’ve asked for:

I would like to get a copy of the policy memo (OFAS policy) referenced in the GRN 000716

documents.

and I would request CBER meeting memos related to osteopontin and GRN 000716.

Any additional materials and documents related to osteopontin and GRN 000716 would also be of

interest. Thanks

Can you send me this based on the attached request?

Med venlig hilsen / Best regards

Tania Porsgaard Bayer

+4589381562

Fra: Morissette, Rachel <Rachel.Morissette@fda.hhs.gov> 

Sendt: 26. marts 2019 12:59

Til: Tania Porsgaard Bayer <tania.porsgaard.bayer@arlafoods.com>

Emne: RE: Request for a Pre submission meeting GRN 000716

Hi Tania,
Sorry for the delay. Before we move ahead with scheduling this meeting, I want to let you know that we

have finalized the policy memo that was referenced in the GRN 000716 documents. We strongly

encourage Arla to FOIA this document. There is also a meeting that occurred between our staff and our

colleagues at the Center for Biologics Evaluation and Research (CBER). We also suggest that Arla FOIA

this meeting memo. In your FOIA request you can reference the OFAS policy and CBER meeting memos

related to osteopontin and GRN 000716. I will receive that FOIA request and will fill it promptly, as the

documents are ready to go. Once you’ve had a chance to review those documents, then we can schedule

a meeting. We wanted Arla to have all the information necessary in preparation for a meeting with FDA

on the intended use of its bovine osteopontin product. Please let me know if you have any questions at

this time.

Best regards,

Rachel

-------------------------------------------------------------

Rachel Morissette, Ph.D.

Consumer Safety Officer

Center for Food Safety and Applied Nutrition

Office of Food Additive Safety

U.S. Food and Drug Administration

rachel.morissette@fda.hhs.gov

From: Tania Porsgaard Bayer <tania.porsgaard.bayer@arlafoods.com> 

Sent: Thursday, March 14, 2019 8:02 AM

To: Morissette, Rachel <Rachel.Morissette@fda.hhs.gov>

Cc: Ashley Roberts Intertek (ashley.roberts@intertek.com) <ashley.roberts@intertek.com>; Kal

Ramanujam <Kal.Ramanujam@arlafoods.com>; Anders Steen Jørgensen

<anders.steen.jorgensen@arlafoods.com>; Ida Aabrandt Ottosen

<ida.aabrandt.ottosen@arlafoods.com>; Anne Staudt Kvistgaard

<anne.staudt.kvistgaard@arlafoods.com>

Subject: SV: Request for a Pre submission meeting GRN 000716

Dear Rachel

Our suggestion for an agenda is:

RE: To discuss the development of a future scientific and regulatory strategy to support the future

general recognition of the safety of the intended use of bOPN in infant formula.

In the last face to face meeting held on March 1st 2018, and subsequent correspondence with FDA,

we have been advised to consult FDA after going through information outlined in scientific memo

dated June 29th 2018. We have reviewed the scientific memo and previous discussions with FDA and

also consulted scientific experts and have outlined several possible avenues. We would like to

discuss with FDA how best to address the safety and general recognition concerns raised by the
agency. We would like to discuss the following topics in the pre-submission meeting and seek

guidance on the relevant approaches that would help us navigate the safety concerns expressed.

As part of this process Arla wishes to outline the following within the meeting;

1. How to develop evidence to support the general recognition of the intended use of bOPN.

 the use of an Expert Panel, a publication program within a supplementary scientific journal,

or a third approach

2. A review of current evidence to address the potential adverse consequences of exogenously

provided bOPN on the developing immune system as expressed by FDA.

3. A review of the recent published studies on hOPN levels within breast milk within various

regions/locations to provide support for the recommended levels of bOPN to be added to

infant formula

4. Any additional topics or avenues to be pursued

Arla looks forward to having dialogue with the agency on these matters in the hope of obtaining

guidance on the strategy as develop.

List of participants from our side would be (might vary depending on the date of the meeting):

Tania Porsgaard Bayer, Arla Foods Ingredients, Director of Global Regulatory

Kal Ramaujam, Arla Foods Ingredients, Senior Scientific Advisor

Anders Steen Joergensen, Arla Foods Ingredients, Director BU pediatric

Anne Staudt Kvistgaard, Arla Foods Ingredients, Senior Manager Science and sales

development

Ida Ottosen, Arla Foods Ingredients, Regulatory Specialist

Ashley Roberts from Intertek, Senior Vice President – Food & Nutrition

James W McGrath, Building Block Nutrition

Med venlig hilsen / Best regards

Tania Porsgaard Bayer

Director / Head of Global Regulatory Affairs

Arla Foods Ingredients Group P/S

Phone: +4589381562

VAT no.: 33372116

tania.porsgaard.bayer@arlafoods.com

http://www.arlafoodsingredients.com
This e-mail is proprietary and confidential and may contain legally privileged information.

This e-mail is intended for the addressee(s) stated above only. If you receive this e-mail by mistake,

please inform us by returning this e-mail without producing, distributing or retaining copies hereof.

_____________________________________________

Fra: Morissette, Rachel <Rachel.Morissette@fda.hhs.gov> 

Sendt: 26. februar 2019 15:44

Til: Tania Porsgaard Bayer <tania.porsgaard.bayer@arlafoods.com>

Emne: RE: Request for a Pre submission meeting GRN 000716

Hi Tania,

Can you please provide an agenda with list of participants for this pre-submission meeting?

Thank you.

Rachel

-------------------------------------------------------------

Rachel Morissette, Ph.D.

Consumer Safety Officer

Center for Food Safety and Applied Nutrition

Office of Food Additive Safety

U.S. Food and Drug Administration

rachel.morissette@fda.hhs.gov

From: Morissette, Rachel 

Sent: Monday, February 25, 2019 12:50 PM

To: 'Tania Porsgaard Bayer' <tania.porsgaard.bayer@arlafoods.com>

Subject: RE: Request for a Pre submission meeting GRN 000716

Hi Tania,

I just wanted to reach out and let you know that I’ll be handling your pre-submission meeting request. I’ll

be in touch shortly to start the scheduling process.

Best regards,
Rachel

-------------------------------------------------------------

Rachel Morissette, Ph.D.

Consumer Safety Officer

Center for Food Safety and Applied Nutrition

Office of Food Additive Safety

U.S. Food and Drug Administration

rachel.morissette@fda.hhs.gov

From: Tania Porsgaard Bayer <tania.porsgaard.bayer@arlafoods.com> 

Sent: Thursday, February 21, 2019 3:14 PM

To: West-Barnette, Shayla <Shayla.WestBarnette@fda.hhs.gov>

Cc: Morissette, Rachel <Rachel.Morissette@fda.hhs.gov>

Subject: SV: Request for a Pre submission meeting GRN 000716

Dear Shayla

I hope you are well, and I was sorry for the lock down of your department in January that I know

have resulted in a heavy workload for you after returning. Nevertheless I wanted to ask you if you

have appointed a Consumer Safety Officer that will work with us on a pre submission meeting for

GRN 000716?

Med venlig hilsen / Best regards

Tania Porsgaard Bayer

Director / Head of Global Regulatory Affairs

Arla Foods Ingredients Group P/S

Phone: +4589381562

VAT no.: 33372116

tania.porsgaard.bayer@arlafoods.com

http://www.arlafoodsingredients.com
This e-mail is proprietary and confidential and may contain legally privileged information.

This e-mail is intended for the addressee(s) stated above only. If you receive this e-mail by mistake,

please inform us by returning this e-mail without producing, distributing or retaining copies hereof.

Fra: West-Barnette, Shayla <Shayla.WestBarnette@fda.hhs.gov> 

Sendt: 18. december 2018 15:26

Til: Morissette, Rachel <Rachel.Morissette@fda.hhs.gov>; Tania Porsgaard Bayer

<tania.porsgaard.bayer@arlafoods.com>

Emne: RE: Request for a Pre submission meeting GRN 000716

Thank you, Rachel.

Ms. Bayer, I will work on routing your request to a Consumer Safety Officer who can help you.

Regards,

Shayla

From: Morissette, Rachel 

Sent: Tuesday, December 18, 2018 8:51 AM

To: Tania Porsgaard Bayer <tania.porsgaard.bayer@arlafoods.com>

Cc: West-Barnette, Shayla <Shayla.WestBarnette@fda.hhs.gov>

Subject: RE: Request for a Pre submission meeting GRN 000716

Dear Ms. Bayer,

Thank you for reaching out to me regarding your request for a pre-submission meeting. I apologize that

you haven’t been able to reach our staff. Nadine Bewry is no longer with the agency. However, I am ccing

her former supervisor, Dr. Shayla West-Barnette (who was also the supervisor involved in GRN 000716),

on this email. Dr. West-Barnette or a member of her team will reach out to you shortly. Merry Christmas

to you as well.

Best regards,

Rachel

-------------------------------------------------------------

Rachel Morissette, Ph.D.

Acting Supervisory Consumer Safety Officer

Center for Food Safety and Applied Nutrition

Office of Food Additive Safety

U.S. Food and Drug Administration

rachel.morissette@fda.hhs.gov
From: Tania Porsgaard Bayer <tania.porsgaard.bayer@arlafoods.com> 

Sent: Tuesday, December 18, 2018 7:43 AM

To: Nadine.Bewry@fda.hhs.gov

Cc: Better-Nolan, Robin * <Robin.Better-Nolan@fda.hhs.gov>

Subject: Request for a Pre submission meeting GRN 000716

Dear Rachel Morissette

I’m reaching out to you because I keep getting a ‘non-delivery’ message when I write to Nadine

Bewry, she has been the contact person when we had any contact with FDA on our previous GRAS

submission of GRN000716. I hope you can help me with my request or pass the email on the to

relevant person.

Back in June 2018 we (Arla Foods Ingredients) received a scientific memorandum based for our

ingredient bovine osteopontin (GRN 000716). Internally we have discussed how to best

accommodate the safety concerns raised, and I hope we can get a pre-submission meeting with

CFSAN and/or other relevant staff members, to discuss our approach for addressing the safety

concerns raised by FDA.

Attached is my request for a meeting, I hope it will be possible to meet in the beginning of the new

year.

Please let me know if you need further from be before such a meeting can be arranged.

Merry Christmas.

Med venlig hilsen / Best regards

Tania Porsgaard Bayer

Director / Head of Global Regulatory Affairs

Arla Foods Ingredients Group P/S

Phone: +4589381562

VAT no.: 33372116

tania.porsgaard.bayer@arlafoods.com

http://www.arlafoodsingredients.com