1

DEPARTMENT OF HEALTH AND HUMAN SERVICES

FOOD AND DRUG ADMINISTRATION

CENTER FOR FOOD SAFETY AND APPLIED NUTRITION

PUBLIC MEETING ON:

GLUTEN-FREE FOOD LABELING

Friday, August 19, 2005

8:30 a.m.

Harvey W. Wiley Auditorium

5100 Paint Branch Parkway

College Park, Maryland 20740

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C O N T E N T S

PAGE

Welcome

Janice Oliver 4

Opening Remarks and Introductions

Barbara Schneeman, Ph.D. 5

Congressional Mandate and Federal Register

Notice Questions

Rhonda Kane, M.S., R.D., ONPLDS 11

Overview of Celiac Disease

Frank Hamilton, M.D., M.P.H. 22

Questions and Answers 44

Industry Perspective on a Gluten-Free Food

Labeling Standard:

North American Millers\' Association

Jane DeMarchi 46

Questions and Answers 60

Bob\'s Red Mill Natural Foods, Inc.

Dennis Gilliam 67

Questions and Answers 77

Miss Roben\'s, Inc.

Jay Berger 84

Questions and Answers 100

Gluten-Free Bakehouse, Whole Foods Market

Lee Tobin 111

Questions and Answers 120

Questions from the FDA Panel 125

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C O N T E N T S (Continued)

PAGE

Gluten Detection Analytical Methods:

Detection of Cereal Proteins and DNA Using MS,

ELISA and PCR

William Hurkman, Ph.D. 135

Questions and Answers 150

Commercial Gluten Test Kits and Methods

Jupiter Yeung, Ph.D. 157

Questions and Answers 169

Consumer Perspective on a Gluten-Free Food Labeling

Standard:

Celiac Sprue Association

Mary Schluckebier, M.A. 183

Questions and Answers 201

Celiac Research Center

Pam Cureton, R.D., L.D.N. 205

Questions and Answers 211

Celiac Disease Center

Anne Lee, M.S., R.D. 215

Questions and Answers 228

Public Statements:

Maryrose Hopke 252

Thomas P. Sullivan 255

Matthew Cox 260

Carol Fenster 263

Anna Ashworth 268

David Browne 271

Ann Whelan 277

Alice Blast 283

Jill Kujo 289

James Blank 291

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1 P R O C E E D I N G S

2 Welcome

3 MS. OLIVER: Good morning. I would like

4 to welcome all of you to College Park this morning

5 for today\'s meeting on gluten-free labeling. I

6 would especially like to welcome the persons who

7 have celiac disease and their caregivers, and we

8 appreciate your interest and your desire to work

9 with us here today, and we appreciate all of your

10 input.

11 Our intention is to develop a rule to

12 define the term gluten-free for voluntary use in

13 food labeling. And, as you are all well aware,

14 persons who have celiac disease must avoid all

15 sources of gluten in their diet and we will hear

16 more about that this morning. A standardized

17 definition of gluten-free is going to enable

18 everybody to have more confidence in selecting

19 foods by having a standardized definition on the

20 label. FDA is here to listen today. We welcome

21 your input; we want your input.

22 We have quite a full program so what I

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1 would like to do, without any further

2 introductions, is to turn the program over to Dr.

3 Barbara Schneeman. Dr. Schneeman is our Director

4 of the Office of Nutritional Products, Labeling and

5 Dietary Supplements, which we affectionately call

6 ONPLDS. Barbara joined us last year and she has a

7 distinguished career in nutrition. She came to us

8 from the University of California at Davis. We are

9 all very glad to have her here. Barbara?

10 \[Applause\]

11 Opening Remarks and Introductions

12 DR. SCHNEEMAN: Thank you, Janice. I am

13 pleased to add my welcome to the Center\'s welcome.

14 We do, indeed, appreciate your participating in

15 this workshop and your interest in helping the

16 agency meet the requirements of FALCPA around a

17 definition for gluten-free.

18 As indicated, the purpose of today\'s

19 meeting is to help FDA better understand how

20 manufacturers make gluten-free foods and the

21 challenges facing them. We are also interested in

22 gaining insight on what consumers, particularly

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1 those who have celiac disease and their caregivers,

2 understand the food labeling term gluten-free to

3 mean. As you know, we are in the process of

4 developing a regulation to establish a uniform

5 definition of the term gluten-free for use by the

6 food industry, both domestic and foreign, to label

7 and market foods as gluten-free in the United

8 States.

9 If you look at our agenda, you see that we

10 divided the agenda into three major topic areas.

11 First will be an industry perspective on

12 gluten-free food labeling standard. The second

13 section is on gluten detection analytical methods,

14 and the third is on the consumer perspective on a

15 gluten-free food labeling standard. These three

16 major themes were in response to the questions that

17 you have in the Federal Register Notice.

18 Certainly, it is our intent to focus on those

19 questions in the Federal Register Notice.

20 Hopefully, you picked up a packet of information

21 when you registered. If not, you can get that

22 information at the registration desk.

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1 Now, after we go through those three major

2 topic areas members of the public who have

3 requested to speak can deliver their statements. I

4 would remind everyone that the maximum amount of

5 time for public comments is five minutes for each

6 speaker. Now, if you did not previously request to

7 make a statement but would like to do so, please

8 let the FDA staff at the registration table know by

9 the end of the second break time. We request that

10 any statement that you make be directly related to

11 the issues and the questions that are outlined in

12 the Federal Register Notice.

13 As Miss Oliver indicated, we do have a

14 very tight schedule. We have a lot of material to

15 cover in our agenda. We have scheduled two

16 15-minute breaks and a one-hour lunch period. For

17 those who are thinking about lunch just a few

18 housekeeping details, certainly, the most

19 convenient place for lunch is Cafe Wiley. Keep in

20 mind that once you leave the building you will have

21 to come back through security when you come back

22 into the building. But there are other places up

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1 on Highway 1. There is the 94th Air Squadron which

2 is located on Paint Branch Parkway but just keep in

3 mind that we only have one hour scheduled.

4 I want the speakers to be aware that as

5 get near the end of your talk you will hear a very

6 gentle beep-beep-beep. That means one minute.

7 And, because we are trying to make sure we cover

8 all the topics, please be cognizant of the need to

9 wrap up your comments when you hear that gentle

10 beep-beep-beep, and Geraldine and I will ensure

11 that you are aware of that. I wore my bright red

12 suit today so when you see me stand up you know.

13 Some other housekeeping details, there are

14 restrooms that are located in the hall leading to

15 this auditorium and also in Cafe Wiley. We do

16 request that you do not bring food and beverages

17 into the auditorium. That is just policy for the

18 Center.

19 This is a public meeting and the meeting

20 will be recorded and a transcript generated. That

21 transcript will be made available on our website

22 approximately one month after this meeting time.

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1 Because of the transcription, we ask that all

2 speakers use the microphone, state their name and

3 affiliation for the record before sharing their

4 comments, and that will be true for all of you who

5 make comments during the public comment period.

6 If you have more information than you have

7 time to present or you have additional data in more

8 detail or references, please be sure to submit that

9 information to the FDA\'s Division of Dockets

10 Management under docket number 2005N-0279. That,

11 again, is described in the Federal Register Notice

12 so it is part of the material you should have

13 received during the registration. All comments on

14 the notice on this meeting are due in dockets by

15 September 19th so you still have time after this

16 meeting to submit additional comments.

17 We have a distinguished panel here in the

18 front. These are members of FDA, members of the

19 Center for Food Safety and Applied Nutrition, and I

20 want to introduce each of them. They will be in

21 charge of questioning each of the speakers and,

22 again, it is with the goal of making sure we

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1 address the issues and the questions that are

2 outlined in the Federal Register Notice.

3 The first member of our panel is Felicia

4 Satchell. She is the Director of the Food Labeling

5 and Standards Staff. That is one of the divisions

6 within my office.

7 Next to her is Rhonda Kane. Rhonda is a

8 consumer safety officer on the Food Labeling and

9 Standards Staff and she has been the lead staff

10 writer working on the gluten-free initiative.

11 Rhonda has spent a lot of time and planning to get

12 this meeting to come off so we appreciate all her

13 effort in that regard.

14 Next is Douglas Park who is the Director

15 of the Division of Natural Food Products within the

16 Office of Plant and Dairy Foods, and is responsible

17 for the gluten detection methods.

18 Next to Doug is Don Zink, who is a senior

19 food scientist in the Office of Plant and Dairy

20 Foods, with an expertise in Good Manufacturing

21 Practices.

22 At the end of the table is Stefano

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1 Luccioli, who is the senior medical officer in the

2 Office of Food Additive Safety, with a specialty in

3 food allergen and intolerances.

4 I will then be serving as the panel

5 moderator and the meeting facilitator.

6 So, our first presentation will be on the

7 FALCPA mandate and the meeting questions, and

8 Rhonda Kane is going to give an overview of the new

9 law that directed FDA to pursue the rule-making to

10 define the term gluten-free and a brief review of

11 the list of questions in the recent Federal

12 Register Notice that announced this public meeting.

13 So, Rhonda?

14 Congressional Mandate

15 and Federal Register Notice Questions

16 DR. KANE: Thank you. Good morning. I

17 wanted to provide you some background information

18 on the reason why FDA will be pursuing a

19 standardized definition for the term gluten-free

20 for use in food labeling. On August 2, 2004 a new

21 law was enacted that is called the Food Allergen

22 Labeling and Consumer Protection Act of 2004. FDA

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1 refers to this new law by the acronym FALCPA. It

2 represents Title II of Public Law 108-282.

3 Now, this new law provided details on the

4 requirements for food labeling if a product is made

5 with ingredients that are or contain a major food

6 allergen as defined by the law. This law also

7 includes a provision that directs the Secretary of

8 Health and Human Services, or FDA by delegation, to

9 consult with appropriate experts and stakeholders

10 to define and permit the use of the term

11 gluten-free in food labeling. We plan to meet this

12 directive by publishing a proposed rule by August

13 2, 2006. So, next August we have to publish a

14 proposed ruling and two years later, August 2,

15 2008, come out with a final rule that defines the

16 term gluten-free and identifies the criteria that

17 would enable the food industry to use that term

18 voluntarily for labeling their products.

19 I want to point out that this law does not

20 mandate that food companies label their products

21 gluten-free. Instead, it mandates that the federal

22 government establish a uniform definition for the

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1 term gluten-free that would apply to both domestic

2 and foreign products that are marketed in the

3 United States that voluntarily include this label

4 claim. Once a federal definition for gluten-free

5 is in effect, then any product that included this

6 claim on its labeling would have to comply with the

7 requirements or it would be deemed misbranded under

8 the Federal Food, Drug and Cosmetic Act.

9 Among the things that FDA has done to meet

10 FALCPA\'s mandate is to publish a Federal Register

11 Notice, which was published on July 19, 2005, a

12 month ago, that announces this meeting and includes

13 a list of specific questions where we have gone out

14 and asked the general public, but we have targeted

15 food industry and those who have celiac disease and

16 their caregivers, to give us feedback on the

17 questions that would be most helpful to us in

18 defining the term gluten-free.

19 In the Notice we have used certain terms

20 and they are gluten, grains of concern and

21 gluten-free foods. I want to point out that these

22 terms are not FDA regulatory definitions. Instead,

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1 they are terminology that we used to explain the

2 questions in our Notice and to solicit comments.

3 In the Notice we use gluten to refer to proteins

4 found in any grains that can cause harm to persons

5 with celiac disease. Grains of concern refers to

6 wheat, rye, barley and oats and their related

7 species such as durum, spelt and kamut or their

8 crossbred hybrids such as triticale, which is a

9 cross between wheat and rye. Gluten-free foods

10 refers to foods marketed in the United States that

11 are either represented to be gluten-free or include

12 statements or symbols in the labeling of those

13 products that indicate that they are free of

14 gluten.

15 Now, our questions in the Notice are

16 organized under five major subheadings, and they

17 are definitions of gluten-free; gluten-free product

18 development; Good Manufacturing Practices and

19 analytical methods; foods as gluten-free; and,

20 lastly, consumer purchasing practices.

21 Now, I want to review the list of

22 questions that are found in the Federal Register

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1 Notice, and copies were available at the

2 registration table. If you didn\'t get a chance to

3 pick one up, you can do so at the break. The

4 wording that I have used on my slides is not

5 identical to that used in the Notice in all cases;

6 I have had to simplify it to put it onto my slides,

7 however, the essence of what I have displayed is

8 the same. I would like to review those questions

9 one by one.

10 Question one asks how do food

11 manufacturers define gluten-free? How does the

12 food industry, or does the food industry, have a

13 generally accepted definition of gluten-free? Does

14 any entity certify finished foods or raw

15 ingredients to be gluten-free? And, if so, how is

16 that term defined and how is a food determined to

17 satisfy that definition?

18 Switching to the subheading of gluten-free

19 product development, question two asks how are

20 gluten-free foods produced and what methods are

21 most commonly used to remove gluten from food?

22 Under the same subheading, question three

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1 asks whether it is technologically and economically

2 feasible to produce two different categories of

3 foods in particular. One is gluten-free flour

4 milled from grains other than those of concern.

5 For example, would it be feasible to mill corn or

6 millet into flour without it containing any gluten

7 from wheat?

8 The other category is oat-based products

9 that do not contain gluten from grains of concern

10 other than oats. For example, would it be feasible

11 for oat-based products to be produced that do not

12 contain any residual amount of wheat gluten?

13 If it is feasible to produce such

14 categories of foods, what additional measures in

15 the milling or the manufacturing process would be

16 needed to produce these products and what would be

17 the incremental cost to do so?

18 Under a different subheading of Good

19 Manufacturing Practices and analytical methods, the

20 first question is four and it asks what measures

21 are in place during the manufacturing, packaging or

22 holding of gluten-free foods to prevent them from

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1 coming in contact with any grains of concern?

2 Continuing, question five asks what

3 analytical methods are used to evaluate gluten-free

4 products? How often are these analyses performed?

5 For example, is every batch of finished product

6 tested or are the bulk containers of each of the

7 ingredients tested? And, what is the cost of such

8 testing?

9 Question six is a whopper. It contains a

10 series of questions that relate to the types and

11 characteristics of different types of analytical

12 methods or test kits that are designed to detect

13 gluten. Among that long list of questions

14 underneath question six are in what grains can the

15 test kit or method detect gluten? What specific

16 mechanism is used to indicate the presence or

17 absence of gluten? In other words, describe in

18 detail how that method or test kit works. What is

19 the sensitivity or lowest level of detection of

20 that test kit or method?

21 Continuing under the same question, is the

22 test kit or method qualitative or quantitative? If

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1 the latter, what is the test kit\'s or method\'s

2 limit of quantification? And, what are the test

3 kit\'s or method\'s false positive and negative

4 rates?

5 Further, question six asks is the

6 effectiveness of the text kit of method itself

7 affected by the nature of the processing of the

8 gluten-free food or by the food matrix, and if so,

9 how? The food matrix refers to the total food

10 environment in which gluten is found in that

11 particular product. So, that includes all of the

12 components that make up that food. If the test kit

13 or method has been validated, by whom and at what

14 level, such as parts per million, of detection was

15 it validated?

16 Further, if the test kit or method has not

17 been validated, have the results of its performance

18 or an evaluation of its performance been published

19 in a peer-reviewed scientific journal? Lastly

20 under question six is the question what is the cost

21 of the test kit or the cost to perform that method

22 of analysis?

19

1 Continuing under this same subheading but

2 under question seven are the following questions:

3 What analytical methods are currently available or

4 under development to detect the presence of oat

5 proteins in food? Which oat proteins are detected

6 and what is the cost to conduct this analysis?

7 Have these methods been validated or published in a

8 peer-reviewed scientific journal?

9 Now switching to a new subheading that

10 relates more to consumer issues is foods marketed

11 as gluten-free. Question eight asks if research

12 data or findings are available on what consumers

13 with celiac disease or their caregivers believe the

14 term gluten-free means. For example, which

15 specific grains or other ingredients should not be

16 in a product that is labeled as gluten-free?

17 Question nine is under a different

18 subheading, and the last of the five, which is

19 consumer purchasing practices. It asks if research

20 data or findings are available on how do consumers

21 with celiac disease or their caregivers identify

22 packaged foods that don\'t contain gluten? How much

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1 time do these consumers devote to identifying such

2 foods?

3 Lastly, question ten asks if there is

4 research data or findings available on the

5 following: Are the packaged foods that consumers

6 with celiac disease or their caregivers currently

7 purchase or consume primarily or exclusively those

8 foods labeled gluten-free?

9 What types of gluten-free packaged foods

10 are purchased or consumed by persons with celiac

11 disease or their caregivers? And, does a

12 gluten-free label influence the purchasing

13 decisions of persons with celiac disease or their

14 caregivers when presented with products having

15 identical ingredient lists? In other words, if two

16 products had identical ingredient lists where one

17 had a gluten-free label claim and the other didn\'t,

18 would the person who had celiac disease or his or

19 her caregiver choose the one that was labeled

20 gluten-free or choose the other one equally if

21 their ingredients are the same?

22 I want to remind everybody that we are

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1 very interested in receiving your written comments

2 on our Notice about this meeting. The deadline to

3 receive your comments is September 19 so it is one

4 month from today. Please note on any

5 correspondence you send FDA about this meeting or

6 the questions in the Notice to the Docket Number

7 2005N-0279. Comments can be submitted by one of

8 three routes. You can submit them by land mail to

9 FDA\'s Division of Docket Management, or to that

10 same division via the internet because they have a

11 website, or via e-mail. The Notice identifies the

12 land mail and website address in it. The one that

13 is not in the Notice that I want to point out to

14 you is the e-mail address I have on my slide, and

15 those addresses are included for your convenience

16 on the slide. I just recently learned that the

17 e-mail address will better accommodate the

18 electronic transmission of comments that have an

19 attachment so you might want to keep that in mind.

20 Well, in closing I want to thank everyone

21 for attending today\'s public meeting and I hope you

22 enjoy the rest of the program.

22

1 DR. SCHNEEMAN: Thank you, Rhonda. As you

2 can see, we do have an ambitious agenda for today.

3 I want to note also for the people attending this

4 session that we are not going to do lengthy

5 introductions of our speakers. You have the

6 background information for our speakers; we

7 provided the bio sketches, but we want to give our

8 speakers as much time as possible so we won\'t be

9 going into length introductions.

10 Our first presentation will be to give us

11 an overview of what celiac disease is, and we have

12 invited Dr. Frank Hamilton who will give this

13 overview, the challenges with treatment of celiac

14 disease and why Congress was prompted to mandate

15 the develop of definitions for gluten-free foods

16 that are marketed in the U.S. Dr. Hamilton is the

17 Chief of the Digestive Diseases Program within the

18 Division of Digestive Diseases and Nutrition at the

19 National Institute of Diabetes and Digestive and

20 Kidney Diseases, which is a part of the NIH. Dr.

21 Hamilton?

22 Overview of Celiac Disease

23

1 DR. HAMILTON: Good morning. I would like

2 to really thank the organizers for inviting me to

3 be a part of this very important public meeting. I

4 have a history, just like most of the patients who

5 have celiac disease. Twelve years ago we were very

6 concerned about celiac disease being an important

7 area of research at the NIH and 12 years ago we had

8 a public meeting, and about the same number of

9 people are here but it has taken almost 12 years

10 for this to really get on the radar screen.

11 What I would like to do is to really give

12 an overview of celiac disease, a very common

13 condition. As most of you know, celiac disease is

14 an immune-mediated disorder caused by sensitivity

15 to gluten primarily in genetically susceptible

16 individuals. It occurs in symptomatic patients

17 with gastrointestinal symptoms as well as non GI

18 symptoms and in some asymptomatic patients

19 affected, such as patients with type 1 diabetes,

20 Down syndrome, Turner syndrome and Williams

21 syndrome, which is a congenital disorder with

22 ataxia and neurologic disorders that are seen in

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1 young children, and selective immunodeficiency

2 syndromes, as well as first degree relatives of

3 individuals with celiac disease.

4 As most of you know, clinical

5 manifestations of celiac disease can be very

6 protean. Usually you can have the classical

7 presentation with the GI symptomatology,

8 non-gastrointestinal or the atypical presentation

9 and the asymptomatic individual.

10 This is a theme that has come out. It is

11 called the celiac iceberg that many of you have

12 already heard about, where there is a small number

13 of people who are identified as having celiac

14 disease but there is a silent number who go around

15 with various manifestations of either GI symptoms

16 or other symptoms. Then there are those patients

17 who have latent celiac disease. These are the

18 patients who may have normal tissue but have

19 positive serology.

20 The clinical manifestations of celiac

21 disease\--this is what we were all taught in medical

22 school\--is that it is the most common thing that

25

1 you see in young children between the ages of 6 and

2 24 months. The patient is usually a child who

3 comes to the pediatrician complaining of chronic or

4 recurrent diarrhea, abdominal distention, loss of

5 appetite, failure to thrive compared to his other

6 siblings, abdominal pain, nausea, vomiting and

7 irritability and sometimes the parents may present

8 with only one of complaint, that is, irritability

9 or a child who is always so fussy and nothing does

10 anything to improve comforting him.

11 This is a typical picture of a child that

12 is seen in the pediatrician\'s office. This is a

13 child with a typical presentation with the

14 abdominal distention. It doesn\'t project very well

15 but around the rectal area you can see some

16 redness, and this represents the chronic irritation

17 of the perirectal area secondary to chronic

18 diarrhea. Also, you notice that the folds around

19 the buttocks are somewhat not prominent, and this

20 is primarily due to weight loss.

21 Now the non-GI manifestations, and these

22 are the ones that physicians really don\'t think

26

1 about but these are the common presentations that

2 we can see in older children or adults: dermatitis

3 herpetiformis, a skin disorder we will see a

4 picture of. The dentist can commonly see patients

5 who have essentially dental hypoplasia or

6 essentially eroding of the enamel of the teeth.

7 Sometimes patients can present with osteopenia or

8 loss of bone mass density, as well as osteoporosis.

9 One of the most common things that we see in

10 adolescents is short stature or delayed puberty in

11 those kids who, in fact, do have celiac disease.

12 Iron-deficient anemia, especially in a young woman

13 who presents to the physician, as most of you know,

14 most physicians will see a woman who is on her

15 menses and says her disorder is due primarily to

16 menstrual cycle. However, this is commonly seen in

17 women who have iron deficiency anemia who have

18 normal periods. Periodically we see patients with

19 inflammation of the liver, arthritis and epilepsy

20 in young children who may have calcifications on

21 their CT scans.

22 Dr. Peter Green, of Columbia University,

27

1 did a very interesting survey of over 1,800

2 patients who had celiac disease and one of the

3 striking things that came out in his survey was

4 that a number of the patients who had celiac

5 disease\--he took a very careful history\--from the

6 time of presentation of the symptoms it was a total

7 of 11 years before the diagnosis was finally made.

8 So, there is a long lag phase before the final

9 diagnosis is made and that is primarily due to the

10 fact that many of us don\'t think, or the clinician

11 or healthcare provider does not think of celiac

12 disease as a potential reason why a patient may be

13 presenting to the office.

14 This is a typical presentation of a

15 patient with dermatitis herpetiformis. This is a

16 very itchy or pruritic lesion seen on extensive

17 surface of the arms of an individual with the

18 disease. For these patients it may be the only

19 manifestation of celiac disease, the unusual rash.

20 Again, as I mentioned, there is the silent

21 phase. There are some patients who may never have

22 any symptoms until their fourth or fifth decade of

28

1 life. However, they may have damaged mucosa and a

2 positive serology. Identified by screening are

3 asymptomatic patients from groups that are at high

4 risk. Again I want to emphasize that first degree

5 relatives of patients with celiac disease have a

6 higher percentage of having the disease. Again,

7 children with Down syndrome, as well as patients

8 with insulin-dependent diabetes will have a high

9 prevalence of celiac disease.

10 In the latent phase are those individuals

11 who have no symptoms and if you do a biopsy on

12 these individuals, with our present requirements

13 for human research, it is not likely that we can

14 get a normal biopsy on an individual who is

15 asymptomatic. The patient usually has a positive

16 serology and usually these are the patients that

17 are sort of the enigma for the primary care

18 physician who comes in with vague symptomatology.

19 Sometimes it is either a viral illness of a

20 bacterial infection that will trigger the

21 manifestation of celiac disease in this patient and

22 they go on frequently to develop celiac disease.

29

1 I will never forget a patient that I had

2 followed at the VA hospital, over in Baltimore.

3 For years this guy had been presenting to the

4 clinic with chronic diarrhea. Our index of

5 suspicion was, you know, that he was just a chronic

6 complainer, and when we finally did a

7 serology\--this was in the early \'80s and at that

8 time antigliadin antibodies were available\--we

9 tested him and he was positive. He was forever

10 grateful because this guy had wasted from about 180

11 lbs. to about 110 lbs. and he was very emaciated.

12 So, for our physicians we really sort of emphasize

13 in our teaching programs the importance of having a

14 high index of suspicion when anybody presents with

15 an unusual presentation with diarrhea.

16 Again, this is just the associated

17 symptomatology. As we mentioned before, the

18 patient\'s first degree relatives, the percentage of

19 them who have celiac disease ranges anywhere from

20 4-18 percent. In first degree relatives with

21 insulin-dependent diabetes the range can be

22 anywhere from 3 percent to as high as 16 percent

30

1 who will have celiac disease. Thyroiditis, another

2 condition which is an autoimmune disease,

3 inflammation of the thyroid gland\--these patients

4 also have a high prevalence of celiac disease.

5 Again, this just goes over some of the

6 data on the healthy population and I will show this

7 in the next slide. Some of the major complications

8 of celiac disease that the clinician, hopefully,

9 will not wait until the end when the patient has

10 developed this is that the pediatricians will

11 always\--you know, parents will come to the

12 pediatrician and say our son is lagging far behind

13 his brother or sister with this short stature.

14 Again, we have seen more commonly than not that

15 dermatitis herpetiformis will present usually in

16 the fourth, fifth and sixth decade of life.

17 But the biggest problem that tends to be

18 underestimated is in dental practice, and part of

19 the NIH consensus conference that was held in June,

20 2004, is emphasizing that the dentist has a primary

21 role. If he has a patient who comes in with

22 recurrent dental hypoplasia or eroding dental

31

1 enamel, he really should start thinking of celiac

2 disease or have the patient referred to a primary

3 care physician for evaluation. Again, recurrent

4 ulcers within the mouth, stomatitis, is very

5 common.

6 One of the conditions that we frequently

7 don\'t think about is women who have recurrent

8 miscarriages. Based on data, there is a great deal

9 of data that show for women who have fertility

10 problems celiac disease is one that we have asked

11 people to really consider, especially in a young

12 woman who may be of European extraction. We will

13 talk about the distribution of the disease later

14 on.

15 Osteoporosis presenting in women of ages

16 30-40\--osteoporosis, as most of you know, is a

17 disease of older women and very commonly you will

18 see young women who are showing signs of bone

19 mineral loss at the age of either 20, 30 or 40.

20 We will talk briefly about refractory

21 celiac disease but the thing that we want to

22 stress\--and some of the European studies have done

32

1 an excellent study. There was a cohort study that

2 was done in Sweden that did a very nice population

3 study of 800 celiac disease patients, from 1974

4 through 1993, and they found that there was an

5 increased mortality of patients who had celiac

6 disease. Whether they were gluten-free or not, or

7 adhering to a gluten-free diet, that was not

8 available in the study that was reviewed.

9 Again, this is the old paradigm that we

10 thought of before 2004, that this was a rare

11 disease of children. We thought the incidence

12 fluctuated. It was always taught that if you were

13 an Irish Catholic you had 1/400 chance of having

14 celiac disease but that whole paradigm has changed.

15 As most of you know, it was thought to be a disease

16 of Europeans.

17 This just shows the sources of finding

18 patients with celiac disease. We talked about

19 first degree relatives, patients with short

20 stature, anemia, fatigue and abnormal liver

21 function tests and, again, the autoimmune disorders

22 are a smaller number that should be followed and,

33

1 again, blood donors, students and general

2 population.

3 This is a study that Dr. Fasano, at the

4 University of Maryland did. He screened over

5 13,000 individuals for celiac disease. This was

6 the thing that really sort of changed our thinking

7 about the prevalence of this disease. As you see,

8 in the healthy individuals there were 4,000 that

9 were healthy and, of that number, 1/133 had a

10 positive serology for celiac disease. If you look

11 at the high risk groups, you see that there is a

12 range of 1/40, 1/22 and 1/39. The upshot of this

13 slide is that usually it has been estimated that

14 there are about 40,000 people in the United States

15 who have celiac disease. But Dr. Fasano and others

16 are supporting this hypothesis that the projected

17 number is really about two million individuals in

18 this country who have celiac disease.

19 I just want to mention the global village

20 of celiac disease. I think this is really how our

21 paradigm has changed in the last few years. It was

22 thought for many years that this was a disease of

34

1 Western Europeans. However, one thing that has

2 really come out in a lot of the epidemiological

3 surveys is that one percent of the patients in

4 countries like Iran and India have a high

5 prevalence of celiac disease. Also in South

6 American we are finding greater numbers of

7 populations who have celiac disease based on the

8 advent of these new serological tests. As I

9 mentioned, most of these cases escape diagnosis and

10 most people think that it is just a product of what

11 the person has eaten over a period of time. Again,

12 we will talk about the role of screening and

13 whether it is indicated. Again, the impact of this

14 is really remarkable.

15 One of the things that we really try to

16 emphasize to our physicians, nurses and healthcare

17 providers is to have a high index of suspicion for

18 celiac disease; think beyond the paradigm of what

19 it was 20 years ago. The important thing is to

20 confirm the diagnosis. This is a life-term

21 commitment to celiac disease. Once a patient is

22 screened for celiac disease, really the important

35

1 thing to do is to do an intestinal biopsy. I

2 underscore that. Although there are a lot of

3 concerns about doing an intestinal biopsy,

4 especially in young children, this is a lifelong

5 term commitment to a gluten-free diet and I think

6 there are some issues of quality of life

7 implications when a patient is placed on this diet,

8 and we will hear from other speakers this morning.

9 The failure to treat potential long-term

10 adverse health events\--I think many people and some

11 of the epidemiologic studies that have been coming

12 out now show that patients who have celiac disease

13 are very prone to develop intestinal lymphoma or

14 specifically non-Hodgkin\'s lymphoma, and it has

15 been found that these patients have a higher

16 prevalence of this disorder in their 40s, 50s and

17 60s. The other thing to remember also is that

18 patients with celiac disease in later years of life

19 have a higher prevalence also of cancer of the

20 small intestine as well.

21 I wanted to mention the role of

22 serological tests. Since the NIH consensus

36

1 conference and prior to 1995 there was a lot of

2 proliferation of kits to test for serology. The

3 NIH consensus conference had essentially an

4 evidence-based approach to evaluating these tests,

5 and the main reason that we emphasize the types of

6 serology is that there are a lot of tests that are

7 being propagated and promoted to be done for

8 suspected celiac disease that are not warranted and

9 are very costly.

10 But the main reason that we strongly urge

11 serological testing is to identify the symptomatic

12 individuals who need a biopsy; secondly, screening

13 of asymptomatic individuals that are at high risk,

14 such as those first degree relatives of celiac

15 disease patients, those patients who have

16 insulin-dependent diabetes, as well as those

17 patients who have family members who may have Down

18 syndrome or Turner syndrome, and really to support

19 the diagnosis. One thing that we really stress is

20 the importance of using this marker to follow

21 patients to determine compliance with the

22 gluten-free diet.

37

1 The NIH consensus conference last year

2 felt very strongly that the antiendomysial antibody

3 test and the TTG or the transglutaminase antibody

4 tests are, in fact, the only tests that you should

5 order for your patients because these have 95

6 percent sensitivity and are 95 percent specific for

7 gluten abnormalities. The HLA typing which can be

8 done on some patients is usually done in patients

9 where there is a question about the positivity of

10 these studies. Again, the NIH really stressed this

11 based on the evidence that was in the literature

12 advocating these two tests to be performed.

13 Most of you know that treatment is a

14 lifelong commitment to a gluten-free diet, and most

15 of you know that there is a strict lifelong

16 commitment of avoiding wheat, rye and barley. Back

17 in the 1960s and \'70s there was a concern about are

18 oats safe, and studies from the 1970s really

19 suggested that oats were toxic in patients with

20 celiac disease.

21 The Agency for Healthcare Policy and

22 Research did a very extensive review of the

38

1 literature and one of the things they found very

2 striking is that those studies were very small

3 studies. Those studies had as few as 6, 7, 12

4 patients who were placed on oats. The

5 recommendation from that review that the Agency for

6 Healthcare Policy and Research determined was that

7 those studies were too small to make any

8 statistical statement. Therefore, there was just a

9 better need to really clarify the role of oats in

10 the setting of gluten-free diets.

11 Oats, as most of you know, contain a

12 protein called avenin. This is a protein that is

13 similar to the wheat gliadin. Both are prolamins

14 which are rich in glutamine and proline which are

15 both amino acids that have the same peptide

16 sequence. As we will hear later on from our

17 chemists here, we will hear about the proportion of

18 proline and glutamine compared to gliadin which is

19 very, very low.

20 This was a really landmark decision or a

21 landmark article in 2004, by Dr. Hogberg, which was

22 published last May, which really did the first

39

1 randomized clinical controlled trial looking at

2 gluten-free diets with oats versus gluten-free

3 diets alone. This is a very important study and it

4 was mentioned in the public register also because

5 it was the first to really document large number

6 populations which were fed with oats as well as

7 given a gluten-free diet. They found that patients

8 in this setting had normalization of tissue and the

9 serological markers did not change. Essentially

10 they remained normal when they were placed on oat

11 diets with the gluten-free diet.

12 There was other supporting evidence that

13 was reported in GUT in January, 2003, where there

14 were patients who had dermatitis herpetiformis and

15 they found that the patients\' skin lesions did not

16 worsen with the oats in their diets. Again, this

17 gives other supporting evidence that gluten \[sic\]

18 is not toxic in patients with celiac disease.

19 As most of you know, and there are going

20 to be other discussions, these are the sources that

21 all of us sort of ingest: bread, bagels, cakes, you

22 name it, but the other thing that was not mentioned

40

1 is that periodically cosmetics, lipstick or things

2 in mouth washes as well, have gluten in them as

3 well and some patients are not aware of this. So,

4 I think we have to remember that those things are

5 triggers as well.

6 I am just going to give you essentially

7 what the NIH consensus conference mentioned, that

8 these are the six elements in the treatment of

9 patients with celiac disease. It is a

10 lifelong-term commitment to having a

11 multi-disciplinary approach in how these patients

12 are approached. You have to have a skilled

13 dietitian or nutritionist working with you, the

14 family and the caregivers. And, education is

15 essential not only for the patients but for the

16 healthcare provider. We are beginning to do a

17 public awareness campaign at the NIH targeting

18 physicians, primarily family care providers,

19 through the American Academy of Family Medicine,

20 and also through the American College of

21 Physicians, to really educate the healthcare

22 providers about the importance of this disease and

41

1 consideration when patients come into the office.

2 Again, the identification and treatment of

3 nutritional deficiencies\--as I mentioned before,

4 the many deficiencies that these patients present

5 with, as you well know, are vitamin B deficiency,

6 iron deficiency and thiamine as well as folate.

7 The important thing I want to emphasize about

8 folate, which is so common in our diet, is that a

9 lot of the patients who have celiac disease who

10 present in their 40s and 50s is loss of memory or

11 forgetfulness. It is amazing, when you give them 1

12 milligram of folate a day, it makes a big

13 difference in how they process, in how they reason

14 and think.

15 Again, the importance of advocacy

16 groups\--I cannot underscore that because these are

17 the people who have made this meeting possible

18 because of their strong commitment to bringing the

19 awareness of the public about this very important

20 public health disease, and a continuous long-term

21 follow-up by a multi-disciplinary group.

22 The other thing I just want to mention is

42

1 that people will say why don\'t we screen for celiac

2 disease at an early age. As most of you know, most

3 of the public health screening that is done in this

4 country is based on the fact that you can detect

5 the disease at the time of birth. If you remember

6 when you had your kids, they all got stuck in the

7 ankle for PKU. This disorder is very rare in this

8 country; it is 1/14,000 births. When you see the

9 number of celiacs in this country, that is far more

10 common than PKU is but the reason that this test is

11 not done routinely is that there are a lot of

12 patients who have celiac disease. The TTG, or the

13 transglutaminase, does not appear until age two or

14 three and that is why there hasn\'t been a big push

15 to public screening in kids who may have celiac

16 disease.

17 But, again, we feel this requires

18 knowledge about what gluten-free diet is, and this

19 meeting I think will be very instrumental in really

20 raising our awareness of what gluten-free diets are

21 and understanding the risk and the serious

22 complications of celiac disease.

43

1 The other thing is to reinforce how

2 important it is not only for the caregivers but

3 also the family members to support patients with

4 celiac disease and to be a source of support.

5 Again, the advocacy groups have really been very

6 instrumental in helping a lot of patients who deal

7 with the issues of depression and anxiety really

8 cope with their illness because it is an illness

9 that impacts not only the patient but also their

10 families and their colleagues.

11 Again, I just want to thank the

12 organizers. Really after 12 years of sort of

13 pushing unawareness, it has taken this long for it

14 to hit the radar screen but, hopefully, we will

15 begin to see a difference in how foods are labeled

16 in this country. I was in Canada five years ago or

17 six years ago and I was very struck that most of

18 the Canadian restaurants always label their meals

19 with what is gluten and what is gluten-free.

20 Again, thank you very much for your attention.

21 \[Applause\]

22 DR. SCHNEEMAN: Thank you very much, Dr.

44

1 Hamilton. I think you have given us the scope of

2 the public health significance of what this

3 requirement means to the American public. I will

4 allow our panel from the FDA\--if you have some

5 questions, I think we have a few minutes to address

6 them to Dr. Hamilton. If you would please identify

7 yourself.

8 Question and Answer Period

9 DR. LUCCIOLI: Stefano Luccioli. Dr.

10 Hamilton, thank you for a very informative lecture.

11 I just wanted to clarify with you what your feeling

12 is about the two studies, recent studies on oats

13 showing that there are a few individuals who may

14 react to the avenin portion of oats. What is your

15 feeling about these studies?

16 DR. HAMILTON: Thank you, that is a very

17 good question. I think the evidence is still not

18 in. I think there was some concern raised by some

19 of the reviewers who looked at that article very

20 carefully about the milling and the preparation of

21 those products where there was contamination. I

22 think based on that, the jury is not in. But I

45

1 think the randomized, controlled study by Hogberg

2 is very convincing in a large number of patients,

3 and I think some issues of milling might have

4 affected those studies.

5 DR. LUCCIOLI: Also another question, do

6 you know of any definitive study where the risk of

7 mortality is also shown for individuals who have

8 silent disease or latent disease? I believe most

9 of the epidemiological studies have looked at

10 untreated symptomatic patients and I am wondering

11 if you have any insight on whether there is an

12 equal mortality for all groups of celiac disease.

13 DR. HAMILTON: As I mentioned earlier, the

14 study that was done in Sweden looked at a cohort of

15 patients who had biopsy-proven celiac disease and

16 mortality rates were much higher. That is the only

17 study that I have seen in the literature that looks

18 at that. It didn\'t specify whether these were

19 latent or typical celiacs. So, the information is

20 very limited at this time.

21 DR. LUCCIOLI: Thank you.

22 DR. SCHNEEMAN: Other questions from our

46

1 panel?

2 \[No response\]

3 So, we are now ready for our first panel.

4 As indicated in the agenda, this is where we would

5 like industry representatives to give us their

6 perspective on the gluten-free labeling standard

7 and the questions that we have raised in the

8 Federal Register Notice. Again, because of the

9 nature of this meeting, with each speaker we will

10 ask our panelists to address questions to each

11 speaker and then there will be a more open time for

12 discussion and comment at the end of the panel.

13 So, our first speaker is Miss Jane

14 DeMarchi, who is the coordinator for technical and

15 export programs at the North American Millers\'

16 Association.

17 Industry Perspective on a Gluten-Free Food Labeling

18 Standard North American Millers\' Association

19 MS. DEMARCHI: Good morning. My name is

20 Jane DeMarchi and, as mentioned, I am the

21 coordinator of technical and export programs at the

22 North American Millers\' Association. Thank you for

47

1 giving me an opportunity to speak to your panel

2 today.

3 NAMA, or the North American Millers\'

4 Association, represents the what, corn and oat

5 milling industry. Our members produce 160 million

6 pounds of milled products daily, which is 96

7 percent of the milling capacity in the United

8 States. Our members\' products are put into a

9 plethora of food products that Americans consume

10 every day\--cereal, bread, cakes and cookies, pasta,

11 snack foods and beer.

12 I have been asked to inform the committee

13 on the processes used by the largest segment of the

14 milling industry, and specifically I will attempt

15 to respond to questions two through five from the

16 Federal Register Notice for the meeting.

17 The goal of the milling process is to

18 produce a consistent product through blending. Our

19 customers rely on receiving a product that is

20 uniform in performance attributes and appearance.

21 However, a fact of milling is that the grains

22 received in the mill contain trace quantities of

48

1 other grains in them. The milling process seeks to

2 limit these impurities as much as possible but it

3 cannot extract them 100 percent.

4 Cross contact begins at the farm. The

5 amount of other grains mixed into product depends

6 on a variety of factors, including what part of the

7 country or Canada it is grown in. Oats are grown

8 in agricultural production regions which are also

9 conducive to the production of wheat, barley, rye

10 and other small grains. Most producers in these

11 areas grow a variety of grain in any given year and

12 typically rotate crop species on a piece of land

13 from one year to the next. Kernels that fall into

14 the ground prior to and during harvest one year

15 often grow as volunteer grain in the next year\'s

16 crop. For example, if a producer grows barley one

17 year, followed by oats the next year, the oats

18 harvested from the field often contain a small

19 percentage of barley.

20 In the Illinois corn belt a farmer may

21 just grow corn but in Kansas they may grow corn and

22 wheat. Weather conditions, harvesting practices

49

1 and other variables lead to inconsistent cereal

2 grain admix from concentrations from year to year.

3 This variability makes it difficult to determine an

4 expected level of the presence of other grains in

5 any given product.

6 In the corn and oat business some mills

7 have established purchasing relationships with

8 particular farms to guarantee grain quality. This

9 may or may not have an impact on the presence of

10 other grains. Organic millers do contract

11 purchasing almost exclusively and still have issues

12 with cross contamination of grains.

13 A second source of cereal grain admix is

14 during the handling of cereal grains. Because

15 various crop species are grown in a given region

16 the grain handling systems usually handle multiple

17 grains which can add to the amount of unwanted

18 grain. Since grain handling equipment is expensive

19 and cleaning of equipment is time consuming,

20 different grains are often handled using the same

21 equipment on a farm to minimize capital investment,

22 and the equipment is usually not cleaned out

50

1 between handling the two different grains.

2 The trucks and rail cars used to transport

3 grains are also not thoroughly cleaned out between

4 uses. These problems persist to the elevator that

5 receives the grain from the farm. An elevator may

6 receive a load of wheat from a producer then

7 subsequently receive a load of oats from another

8 producer, without bothering to empty the leg boots

9 or clean the tails of drags. Elevators also do not

10 undertake rigorous cleaning of the silos that store

11 the grains when the grains are changed over in part

12 to minimize dust which causes health and safety

13 concerns. These practices I have described

14 introduce additional cereal grain admix to the

15 grain destined for milling.

16 Grain is inspected and graded prior to

17 delivery and then reinspected when the grain is

18 delivered. The U.S. grain standards, established

19 by USDA and administered by the Grain Inspectors,

20 Packers and Stockyard Administration, allow for

21 other grains to be mixed in. This is considered

22 foreign material and is allowed at up to four

51

1 percent, depending on the grade and the grain.

2 Mills may buy from the higher grades or require

3 their suppliers to sell them grades at a higher

4 standard. Typically, milling quality oats contain

5 0.5 to 1.0 percent cereal grain admix. But

6 specifications can allow up to a maximum of 2-3

7 percent. Standards for grades of corn used in

8 milling generally have 2-3 percent foreign or

9 broken kernels. Similarly, some corn mills may

10 have tighter specifications for 1 percent of other

11 grains, but that is not universal. The U.S. grain

12 standards are based on the realities of production

13 agriculture and the bulk grain handling business,

14 and are not necessarily what the food processing

15 industry would prefer.

16 The milling process\--grain is cleaned

17 prior to milling to remove any foreign material.

18 Part of the objective of the cleaning process is

19 also to remove as much as cereal grain admix as

20 possible. There are three primary technologies

21 that can be used to clean grain: width grading, and

22 this technology is the basis of most screening

52

1 applications and typically relies on the fact that

2 narrower kernels will fall through a slotted or

3 punched sieve while the thicker kernels will remain

4 on the top of the screen or sieve. Length grading,

5 which is the concept of segregating kernels by

6 length, is usually achieved using rotating drums

7 with indented pockets into which the kernels fall.

8 Shorter kernels fall deeper into the rounded

9 pockets, allowing the drug to remove them from the

10 longer kernels that can not fall as deeply into the

11 pockets. Density segregation uses moving air

12 streams or vibration as a basis to separate kernels

13 based on their density.

14 Concentrations of wheat, barley and other

15 cereal grains in oats and corn can be used with the

16 appropriate combination of the above three

17 principles. But these three concepts do not allow

18 for the complete removal of all admixed grain. The

19 success of these mechanical measures is based on

20 the difference in size and shape of the desired

21 grain and the unwanted grain. Wheat and corn are

22 more easily separated because they are quite

53

1 different.

2 However, on this slide you can see

3 pictures that depict how close various grains that

4 are of concern in oats are in appearance to one

5 another. Oats, wheat, barley and rye have some

6 difference in average kernel length, width and

7 density but the natural variation between crop

8 kinds, crop varieties and individual kernels means

9 that significant overlap exists between any two

10 populations.

11 While width grading can be used as the

12 basis of removing many of the larger barley kernels

13 from an oat sample, and length grading can remove

14 many of the shorter wheat kernels, thin barley

15 kernels and long wheat kernels will remain in an

16 oat sample.

17 Density separation similarly can be used

18 to remove some of the wheat due to its high bushel

19 weight, but the best milling oats are close to the

20 same density as barley and diseased or shrunken

21 wheat kernels are often no heavier than oats.

22 Some of the newest color sorting or

54

1 optical sorting technology holds the promise of

2 being able to remove individual kernels of grain

3 admix by evaluating each kernel under various light

4 conditions and comparing to a reference or

5 standard. Kernels failing to match the standard

6 closely enough are removed from the stream

7 typically by a small blast of compressed air.

8 However, the technology is expensive and it is

9 generally of low capacity, and not yet reliable

10 enough to guarantee the level of accuracy needed to

11 be considered an allergen control due to the small

12 difference in the color of the grains that are

13 trying to be sorted. If the mill adheres too

14 tightly to a standard in mechanical cleaning

15 procedures, they run the risk of rejecting too much

16 of the desired grain along with the additional

17 grain that they do not want.

18 Reducing cross contact at the mill is also

19 important. Mills follow Good Manufacturing

20 Practices that require regular cleaning and

21 inspection of equipment. It is critically

22 important to mills that product dust not be allowed

55

1 to gather in the equipment or outside for

2 sanitation purposes. In many cases today mills are

3 dedicated to one grain line. In those instances,

4 which is typically just a portion of the mill,

5 where more than one grain is handled mills

6 undertake a rigorous cleaning protocol when

7 switching between grains. This includes opening

8 the equipment and dry-wiping it down and vacuuming

9 it as necessary after all of the first grain runs

10 through. At the start-up of the next grain a

11 certain amount is run through the line and then

12 discarded. The grains themselves are abrasive and

13 assist with the clean-out procedures. After these

14 procedures the mill is considered saturated with

15 the new product.

16 Corn and wheat mills do not generally

17 conduct tests to determine levels of other grain

18 mixed into the final product. There are several

19 reasons for this. The mills use all of the

20 available technology to separate out the unwanted

21 grain. However, once the grain is milled the

22 presence of other grain is not evenly distributed

56

1 throughout the product. There are no reliable

2 tests that accurately determine the amount of

3 unwanted grain overall in any given lot.

4 ELISA tests are still fairly new and do

5 not have a long history of being used for allergy

6 detection in mills. They test a very minute amount

7 of grain and individual test results are greatly

8 skewed by the presence of one fraction of an

9 unwanted grain. Without thresholds or standards,

10 mills also do not have a target number which they

11 are trying to achieve.

12 Oat mills do have a process they have used

13 for establishing the levels of cereal admix in

14 finished product. This is possible because of the

15 greater size of an oat flake. Representative

16 samples are taken from a lot and then composited.

17 After mixing, a representative 200 gram sample is

18 withdrawn from the larger sample. Each individual

19 flake in the sample is separated by hand and

20 visually inspected in an in-house lab. From there,

21 a concentration of cereal admix in the lot can be

22 derived.

57

1 Economics of grain milling is another

2 consideration. The high volume and low cost of

3 milled products has an impact on the type of

4 screening and testing that mills are able to do.

5 Mills operate as close to 24/7 as possible. Like

6 most food processors, they seek to avoid shut-down

7 time. An average mill may produce a million pounds

8 a day, seven days a week. If they shut down for a

9 day it will have a significant impact. The mills

10 emphasize mechanical means as the best method to

11 address the presence of other grains. Testing

12 every bag of product is not practical. Mills

13 cannot control the fact that product comes to the

14 mill with traces of other grains mixed in.

15 Research has not been conducted on an

16 industry-wide basis to quantify the levels of

17 cereal admix in oats or corn. In some instances a

18 customer may specify what level they are willing to

19 accept and the mill will operate accordingly for

20 those lots, however, this is not common.

21 As previously mentioned, variability of

22 admix from year to year is great. Weather is a

58

1 large factor in this and the effects of the weather

2 are felt far into the future. Herbicide

3 application may also have an impact.

4 It is important to note that generally the

5 levels are in the low parts per million range on

6 all products. However, our members are conscious

7 that without a threshold, gluten-free means zero.

8 For the oat millers zero is, frankly, not

9 achievable both due to the presence of gluten in

10 oats and because of the small presence of other

11 gluten-bearing grains. Currently, corn millers do

12 consider their corn products to be gluten-free.

13 Corn is not gluten-bearing and can more easily be

14 sorted from gluten-bearing grains. The presence

15 of admix in oat products varies depending on

16 product and portion size. Concentrations of wheat

17 protein in oat flour will be higher than those in

18 oat flakes due to the milling process.

19 Although industry-wide research has not

20 been done, I have analyzed an example of what could

21 be considered realistic for the presence of wheat

22 and barley in a sample of oats. In my example a 28

59

1 gram serving of instant oatmeal with a .03 presence

2 of wheat at 15 percent protein and a barley

3 presence of 0.16 percent at 14 percent protein

4 content, this serving would have approximately 7.5

5 milligrams of wheat and barley protein,

6 approximately 40 percent of which, or 3 milligrams,

7 would be gluten.

8 In conclusion, I would like to say it is

9 not a perfect world. The farming system allows for

10 a certain level of mixed grains. The technology is

11 not available currently to separate grains 100

12 percent in the milling process. In an effort to

13 protect the most sensitive members, celiac support

14 groups recognize this situation and do not endorse

15 the consumption of oats.

16 However, there is more work to be done to

17 better understand the relationship between oats and

18 celiac disease. If gluten-free means a zero

19 tolerance level that places the threshold at zero

20 we run the risk of turning products that had been

21 previously been considered safe for celiac

22 sufferers to not be considered gluten-free. Corn

60

1 millers who to date have considered their products

2 to be gluten-free may reevaluate that determination

3 at a zero threshold. As we like to say at NAMA,

4 zero is a very small number.

5 Thank you for allowing me to address this

6 group and I would be happy to answer any questions

7 that I can.

8 \[Applause\]

9 DR. SCHNEEMAN: Great! Thank you very

10 much. I will turn to our panel to see if we have

11 some questions. If you will just use the hand mike

12 that is right here, and be sure and identify

13 yourself.

14 Questions and Answers

15 DR. ZINK: Don Zink, with FDA. Do you in

16 these mills typically use pneumatic systems for

17 moving milled flour, and are these runs of piping

18 fairly long and, if so, how do you go about

19 cleaning them, or can you?

20 MS. DEMARCHI: Yes, they do use pneumatic

21 systems, and the pipes are somewhat long. Mills

22 operate on several levels so they are not

61

1 extensively long pipes; they tend to be broken up

2 but it would be a series of shorter pipes. The

3 cleaning process for the pipes is basically when

4 the grain runs through, it is allowed to completely

5 drain through.

6 DR. SCHNEEMAN: Other questions?

7 DR. PARK: I am Doug Park. I am with FDA.

8 I have actually several questions and they are kind

9 of in sequence a little bit as you go through your

10 processing and product movement. Early on, when

11 you are doing your inspection, I assume this is in

12 conjunction with U.S. federal inspection of the

13 grains. What do you do individually as an industry

14 to supplement and to identify whether there may be

15 cross contamination of the different types of

16 grains?

17 MS. DEMARCHI: Different mills and

18 different companies, depending on the grain, have

19 different systems. There is certain reliance on

20 the grading and the inspection that is done at the

21 elevator level. In most situations it is

22 reinspected on arrival. In some cases the elevator

62

1 will take a sample and send it to the mill for

2 testing, and it is laboratory tested to evaluate

3 the presence of other grains. Usually the process

4 is taking a variety of samples and then compositing

5 them, mixing them and then extracting a smaller

6 sample that is then tested.

7 DR. PARK: Does it take into account the

8 damaged kernels or the percent, because your

9 cleaning is based, obviously as you described, by

10 size, and weight and length, and so forth? Does it

11 take into account the damaged kernels that may be

12 affected?

13 MS. DEMARCHI: In terms of the damaged

14 kernels of the ones you desire or the ones that you

15 don\'t?

16 DR. PARK: Both, exactly, the ones that

17 you desire and the ones you are trying to avoid.

18 MS. DEMARCHI: I know part of the corn

19 specification does take into account damaged

20 kernels. I don\'t know about the oats.

21 DR. PARK: Okay. You talked about the

22 HACCP programs. What do you go through there with

63

1 respect to sampling and then, obviously the

2 analytical testing of that product?

3 MS. DEMARCHI: In terms of the HACCP

4 program, I think for the mills it is identifying

5 the areas that are at the greatest risk for cross

6 contact. If you are in a dedicated mill, and if

7 you are doing a HACCP evaluation for allergen

8 control, there is going to be less risk of cross

9 contact so it would generally be following normal

10 cleaning procedures. Where there are areas where

11 there would be some different grains used in a

12 bagging line, or something like that, they would

13 probably more closely evaluate the cleaning

14 procedures that they are using. But at the moment

15 in mills they don\'t do things like swabbing and

16 testing in that way.

17 DR. PARK: My final question will be

18 dealing with the sampling. Do you have in-line

19 sampling procedures set up, or are you addressing

20 the bulk? Your comment is very correct and it is

21 very difficult to sample bagged product.

22 MS. DEMARCHI: Yes, we do have in-line

64

1 sampling procedures. At the moment though they are

2 not used for allergen characteristics. We use

3 NIRs, the light reference testing generally for

4 performance characteristics but we have not done

5 that type of sampling for allergen, and I don\'t

6 know actually how long it takes to do the allergen

7 analysis but my guess is it is something that would

8 take a while to get your results.

9 DR. PARK: Some of our speakers will

10 address that very appropriately, but they are not

11 an immediate response. There is a time lag. Have

12 you as an industry and as a group addressed that,

13 how then to do the appropriate sampling and testing

14 specifically for the allergen issues? It is kind

15 of a challenge out to you that has to be addressed.

16 MS. DEMARCHI: I think that is something

17 that we are still considering, and I think at the

18 moment it is being done on an individual company

19 basis.

20 DR. PARK: Thank you.

21 MS. SATCHELL: Felicia Satchell, FDA. I

22 guess I just wanted to hear maybe a little more, if

65

1 you could expound, on this new technology, the one

2 that you talked about on differentiation based on

3 color or optical sorting machines. I guess, is

4 there research ongoing to improve this method, to

5 bring the cost down for using it? Is there any

6 manufacturer that is trying to use it or any mill

7 trying to use it in their process?

8 MS. DEMARCHI: My understanding is that it

9 is being used but not\--I think it is being used in

10 corn mills, but I don\'t think it is prevalent in

11 the industry. I think when you talk about the

12 expense, it is largely related to the capacity

13 issues. The mill would have to slow down to a

14 large extent and also the reject level is so high

15 that it is difficult also to put it back into

16 rework stream. There are other issues not just

17 related to the cost of buying a piece of equipment

18 because I would imagine that that is something that

19 could be handled. But it is how to actually work

20 it back into the manufacturing system, and I think

21 that equipment hasn\'t been refined for the milling

22 industry enough.

66

1 DR. SCHNEEMAN: Thank you. A lot of

2 questions. One more.

3 DR. ZINK: Don Zink, with FDA. Just a

4 quick question. Is it common in the milling

5 industry to try to validate cleaning to some

6 particular degree of cleanliness? And if they do

7 validate cleaning methods, say, between grains,

8 what sorts of methodology do they use to measure

9 that degree of cleanliness?

10 MS. DEMARCHI: I am on thin ice a little

11 bit here but, you know, I think that the mills use

12 the FDA\--you know, everything they do is based on

13 FDA guidelines and then they are regularly audited.

14 So, I would say probably it is whatever is

15 generally accepted.

16 DR. ZINK: What I was getting at for

17 example, after they have cleaned up a line, would

18 they go back and test for residue of the previous

19 grain?

20 MS. DEMARCHI: No, they don\'t do that

21 testing currently.

22 DR. SCHNEEMAN: We will have time with the

67

1 panel also later. We don\'t want our first speaker

2 to carry the burden of all the questions. Our next

3 speaker is Mr. Dennis Gilliam. He is the vice

4 president of sales and marketing for Bob\'s Red Mill

5 Natural Foods, Inc. Do you have slides?

6 MR. GILLIAM: No, no slides.

7 DR. SCHNEEMAN: No slides?

8 Bob\'s Red Mill Natural Foods, Inc.

9 MR. GILLIAM: Panel members, you may want

10 to avail yourselves of the packet that I left for

11 you because I will be referring to a piece or two

12 that is in there, and it is up here on the table.

13 It has the assembly of wine in the heart of France,

14 where they are assembling millstones on the cover.

15 Dennis Gilliam, Bob\'s Red Mill Natural

16 Foods, partner, executive vice president, sales and

17 marketing. It is a pleasure to be here and to

18 share. Our company has also brought three other

19 representatives who will speak this afternoon.

20 Just to give you the lay of the land with

21 our company, Jane was mentioning the 96 percent of

22 the millers that come under her umbrella. We do

68

1 not fall under her umbrella. We are a tiny part of

2 the four percent. All right, how we became

3 stakeholders here I believe is relevant so I would

4 like to begin with that.

5 At Bob\'s Red Mill we set up initially,

6 over 30 years ago, with the intention of milling

7 the widest variety of grains available, and we do

8 that. It soon surfaced though that some of these

9 grains were appealing\--not only appealing to but

10 being used by a very unique segment, celiacs and

11 those adverse to gluten. We became a stakeholder

12 in gluten-free more than 10 years ago, and here is

13 how we went about it.

14 After fielding gluten-free questions and

15 comments from our customers, we invited a number of

16 experts into our plant, research scientists, some

17 of whom we have spoken about this morning,

18 gluten-free cookbook authors, lecturers,

19 spokespeople for the celiac community to tour our

20 facility and make recommendations. Based on their

21 assessments and recommendations we then dedicated

22 stand-alone milling and packaging rooms for

69

1 gluten-free production; implemented a testing

2 protocol. And, to assist consumers in their

3 pursuit of the gluten-free products, and this is

4 what you will find in our packet, we drafted a

5 statement. We created a gluten-free logo for our

6 package labels; placed gluten-free product

7 advertisements in diverse publications; implemented

8 a program of gluten-free shelf talkers that pop

9 into the clip strip at the grocery store to

10 identify gluten-free products; created, shared and

11 posted on the internet many gluten-free recipes;

12 published a mail order catalog featuring

13 gluten-free and soon found that to be the shining

14 star of our entire mail order catalog; exhibited at

15 gluten-free and diabetic conferences.

16 I also feel it is significant to share

17 that since we also market in Canada our testing

18 protocol, gluten-free statement and gluten-free

19 logo were carefully designed to meet their

20 specifications and stand the scrutiny of the

21 Canadian food inspection agency. They do not

22 insert a certifying agency into the process but

70

1 their rules are stringent. They are practical and

2 they are fair. They do random testing of products

3 and occasionally issue warning letters, and in

4 rare, rare cases they will remove non-compliant

5 products or products that fail the random testing

6 from store shelves. All of our products withstood

7 the test of that protocol for several years.

8 Based on those experiences, I would like

9 to share with you how we define gluten-free. Now,

10 in the process of defining gluten-free\--well, we

11 from time to time do this but we recently gathered

12 gluten-free foods from 14 manufacturers and

13 examined each package to see how they were handling

14 the claims. This wasn\'t done with a critical eye

15 at all; this was done with an informative eye. We

16 found that five speak of dedicated gluten-free

17 environment; seven speak to being wheat and

18 gluten-free; one says simply ELISA and GF/CF, which

19 I am sure means gluten-free/casein-free; one says

20 100 percent dedicated machinery; and three state

21 they also are free of other allergens.

22 In our business we define gluten-free as a

71

1 product that does not contain in any form or

2 derivation wheat, rye, barley, triticale, spelt,

3 eye corn and kamut grain. To this list, until they

4 can be proven by rigorous cleaning and testing as

5 has been previously mentioned, to be free from

6 other contaminating grains, we have added oats even

7 though we believe oats to be inherently

8 gluten-free. The statement on all of our packages

9 reads, and you will see labels in our packet that

10 will bear this out, quote: Products labeled

11 gluten-free are batch tested in our quality control

12 laboratory. We use an ELISA gluten assay test to

13 determine if a product is gluten-free, end of

14 quote.

15 Along side this statement we place a

16 gluten-free logo of our design, and you will see an

17 8.5 X 11 copy of that in our packet. There is

18 nothing unclear or contradictory in what we do or

19 say. However, I think as you can see as a group,

20 these 14 manufacturers, based on the 14 products we

21 recently reviewed, we manufacturers are all over

22 the board in our approaches to communicating to

72

1 consumers that we are gluten-free.

2 How gluten-free foods are processed in our

3 plant is what I would like to deal with next. The

4 gluten-free foods we manufacture are stone ground

5 on quartz millstones. While these millstones grind

6 a multitude of products, the only products ground

7 on these dedicated mills in a dedicated mill room

8 are inherently gluten-free. In our gluten-free

9 manufacturing process we use only grains, beans and

10 seeds and ingredients that are inherently

11 gluten-free. We manufacture and package over 50

12 gluten-free products.

13 For over 30 years we have used French burr

14 stones to grind all of our products. These have

15 been in production around the world commercially

16 since the 14th century. Our stones easily mill

17 nearly every grain, bean and seed grown. They make

18 flour, meal and cereal that incorporate the bran,

19 germ and endosperm. We currently mill various

20 beans, various types of rice, buckwheat, flax seed,

21 peas, millet, kimwa, sorghum, and teff into

22 gluten-free flours. All are verified gluten-free

73

1 by testing, and more about that in a moment.

2 Future increases in gluten-free production

3 are absolutely assured. We have mills and capacity

4 to satisfy production far into the future. But as

5 your question properly asks, is this technology

6 feasible for others? Well, remember, we are one of

7 the four percent not in Jane\'s umbrella so we are

8 fairly small. But I am not sure, precious few I

9 surmise, have indicated an interest in pouring over

10 old milling journals to learn how to set up and

11 sharpen millstones the way we do. And, there may

12 be a limit to the number of manufacturers willing

13 to implement the necessary control over cross

14 contact and testing protocols. Different milling

15 systems, as we have just heard, are capable of

16 producing flour and cereal from some non-glutinous

17 grains and I am not sure if they can also grind

18 beans and seeds. Others may speak to that later.

19 I would like to share with you measures we

20 employ to prevent cross contamination. We purchase

21 all of our gluten-free grains, beans and seeds,

22 precleaned. Upon receipt of each shipment our

74

1 laboratory does a random sampling ELISA gluten

2 assay test. After incoming products are tested and

3 verified gluten-free, they are moved about in

4 super-sacks or one-ton totes. Each tote is clearly

5 marked gluten-free. These containers, and all

6 containers used for the storage or transportation

7 of gluten-free products are never used to store or

8 transport grains of concern or products containing

9 grains of concern.

10 We utilize a dedicated room to house our

11 gluten-free ingredients, and the milling, mixing

12 and packaging equipment used to manufacture them

13 into marketable products. No grains of concern are

14 ever introduced, processed, mixed or packaged in

15 that room. That dedicated room also has its own

16 desk control system. There is no shared desk

17 control.

18 After each batch of products is milled in

19 that dedicated room our laboratory performs another

20 ELISA gluten assay batch test. After being

21 verified to be gluten-free the product proceeds to

22 the mixing, blending and then to packaging. During

75

1 packaging our laboratory does another random

2 sampling gluten assay test. After being verified

3 gluten-free, finished case-packed products are

4 transported about two miles to our distribution

5 warehouse where they are placed in a segregated

6 area for gluten-free products.

7 Analytical methods that we use: Our plant

8 uses an enzyme-linked immunosorbent sandwich assay

9 test method, and it is made by the R-Biopharm

10 Company to determine whether gluten is in our

11 products. This gluten test allows us to measure

12 the gluten quantitatively. The lowest detection

13 level of the test is 10 parts per million gluten.

14 All raw commodities and ingredients destined for

15 products marked as gluten-free are tested before

16 entering our system. Additionally, we test every

17 batch of products prior to their packaging runs.

18 Because batch testing is performed

19 in-house, the costs associated with samples are

20 relatively low. The equipment and the tools that

21 allow us to do the testing were purchased for just

22 under \$10,000. Supplies needed to process and test

76

1 each sample cost less than \$15 per sample. Labor

2 per test is about \$10 per sample. The testing kits

3 and the supplies we use are readily available to

4 the public from the manufacturer. As I am sure you

5 are aware, the technical details and tests are

6 available from that manufacturer.

7 Now I would like to close by sharing what

8 some of our expectations are and hopes are to roll

9 out of all of this. We really do need the total

10 scrutiny and thoroughness for the issues that I am

11 sure are going to roll out of these hearings. We

12 also would like to offer, if it is appropriate, our

13 trademark logo as the gluten-free symbol should one

14 be incorporated into a voluntary protocol. We have

15 a trademark, but under these conditions of uniform

16 nationwide use directed by the FDA, we would waive

17 all of our trademark rights to that logo, and you

18 will find a copy of that in your packet, as you

19 will find many other pieces that we use as we deal

20 with taking gluten-free foods to the consumer.

21 Thank you for the invitation to be here.

22 \[Applause\]

77

1 Questions and Answers

2 DR. SCHNEEMAN: So, we have some time for

3 questions.

4 DR. PARK: Douglas Park, with FDA. I had

5 quite a list of questions that I was going to ask

6 you and you systematically answered those during

7 your presentation.

8 MR. GILLIAM: That is a real compliment.

9 Thank you.

10 DR. PARK: So, I have no further

11 questions.

12 MR. GILLIAM: What?!

13 \[Laughter\]

14 DR. SCHNEEMAN: Dr. Zink?

15 MR. GILLIAM: All right, you will fill in

16 the blanks.

17 DR. ZINK: Don Zink, with FDA. Speaker

18 DeMarchi talked about the problems with inherent

19 contamination of the grain supply with grains of

20 concern for example, and the difficulties with

21 removing those with cleaning. Are you using a

22 different source of supply where you have less

78

1 likelihood of such contamination and how are you

2 doing that? Or, how are you dealing with that

3 problem where others may find that difficult to

4 deal with?

5 MR. GILLIAM: Since no grains of concern

6 ever enter our gluten-free mill room\--most of the

7 other grains, the non-gluten containing grains are

8 of distinctly different shapes. The teff grain,

9 for instance, is a tiny grass seed. It would take

10 about 50 pieces of teff to equal the size of a

11 wheat berry. Now, we buy all of those precleaned

12 from specialty growers who have specialty cleaning

13 equipment so we have a certain comfort level in

14 knowing that they are completely different sizes

15 from the other grains that have been shown on

16 slides. Beyond that comfort level, you just heard

17 of the testing protocol we use also. Did that help

18 or have I been evasive?

19 DR. ZINK: Yes, that helps. Do you

20 encounter a situation where your raw material

21 testing shows it to be acceptable, yet, after it

22 goes through a milling process and you do your

79

1 final test for gluten contamination, have you ever

2 had situations where one turned up positive? In

3 other words, I am trying to get at problems where

4 sampling plans, non-random distribution of

5 contaminants, might result in a negative test one

6 time and a positive test the next. Does that

7 situation occur, and how do you recover from it?

8 MR. GILLIAM: What I would like to do with

9 that question, doctor\--we brought along as part of

10 our team the head of our lab and he deals with

11 those questions daily and would have a better sense

12 of that. You have the sales and marketing guy

13 here, and I don\'t always get every piece of

14 information so I am unable to answer that. Roger,

15 if it is appropriate, would you approach that

16 question in your five minutes this afternoon?

17 Thank you.

18 DR. LUCCIOLI: Stefano Luccioli, FDA. I

19 am wondering what kind of system you have available

20 for consumers to report any adverse events?

21 Obviously, you don\'t use grains of concern but I

22 would be curious to know if individuals have called

80

1 you up to question whether they have had a

2 reaction. Maybe there are some other grains that

3 are concerning to individuals who are reacting. I

4 don\'t know if you have that information or what you

5 do to acquire that information.

6 MR. GILLIAM: Yes, to a certain extent we

7 do. Since we have mail order, and have had for a

8 number of years a very thriving mail order program,

9 we do get a lot of calls and we have four people

10 staffing the lines. And, there is never\--well,

11 never\--never say never\--there is rarely an on hold

12 situation that would cause a consumer to hang up.

13 So, we field all questions. Matt, I am going to

14 ask you, if it is appropriate, to touch on that.

15 Matt is my associate and has his ear, because he is

16 part of the mail order team also, to questions and

17 concerns that come in.

18 One that I am very much aware of that

19 comes in is they look through our catalog and they

20 will not find a gluten-free symbol by corn, and

21 they say, \"well, what\'s the problem? Corn\'s

22 gluten-free.\" And we say to them that because corn

81

1 is a grain of such high usage in our plant at this

2 present time with our present equipment, it would

3 swamp our gluten-free mill room with production.

4 So, it is produced in a gluten-containing mill

5 room. Now, under our scrupulously clean

6 environment and on our scrupulously clean set of

7 stones\--but because in our mind\'s eye we are aware,

8 and in very real terms we are aware that cross

9 contamination means dust particles in the air, and

10 because of that possibility of triticale dust

11 particle connecting with the corn we are

12 voluntarily choosing not to put the gluten-free

13 mark on corn yet.

14 Let me add just one caveat to that. There

15 is one product in our catalog that is corn-based

16 that does carry the gluten-free symbol, and that

17 one is scrupulously isolated and milled only in our

18 gluten-free mill room. So, if you scoured that

19 catalog that would be contradictory unless I

20 clarified.

21 DR. PARK: Douglas Park, with FDA. My

22 focus obviously, as you may surmise, is

82

1 methodology, sampling, reliability of the

2 analytical result, and so forth. Your comments

3 concerning the corn-based brings a whole litany of

4 questions that would come to mind. What is your

5 sampling procedure; your sample preparation; the

6 reliability of the analytical result that deals

7 with those products since they are not in a

8 dedicated environment and run the potential of

9 having cross contamination? What have you set up

10 for those particularly?

11 MR. GILLIAM: I believe it is very, very

12 thin. Remember now, we are one of the four percent

13 and of that four percent we are one of the small

14 ones. I believe it is very thin but, again, I will

15 attempt to lean on Roger Farnnen for a more

16 definitive answer to that in his five minutes.

17 DR. SCHNEEMAN: One more question.

18 MS. SATCHELL: Felicia Satchell, FDA. My

19 question really deals with the Canadian

20 requirement, I think it is anything below 20 parts

21 per million, and the statement that you made

22 regarding the use of the ELISA R-Biopharm kit at a

83

1 detection of 10 parts per million. In your product

2 testing do you allow products to go on the market

3 that are below 20 or are you aiming for the 10

4 parts per million?

5 MR. GILLIAM: We are aiming for the 10,

6 and\--well, we just simply are aiming for the 10.

7 Now, to better clarify the Canadian position, in

8 reality, if you read their position or the

9 government mandate, it is zero. But it is

10 impractical\--impossible at this point because there

11 are no tests that will take it down to zero.

12 Beyond being impractical and impossible, it

13 may\--may, what do I know?\--it may eliminate so many

14 foods from the food chain if it were to take it

15 down to zero that none of us know what would happen

16 under that scenario because we have been limited to

17 experience with tests that only take it to 10.

18 DR. SCHNEEMAN: Great! Thank you very

19 much. Mr. Gilliam made reference to the packet of

20 material that he had provided at the front desk.

21 If any of you want to see some of the material in

22 that packet, I will make my packet available during

84

1 the break if someone would like to take a look at

2 that.

3 I know this is not a major problem with

4 our computer here, but it just guarantees that no

5 one can steal information from an FDA computer and

6 our technical person is here. So, let me go ahead

7 with introducing our next speaker, Miss Jay Berger,

8 who is the vice president and co-owner of Miss

9 Roben\'s, Inc.

10 Miss Roben\'s Inc.

11 MS. BERGER: Well, scaling further down

12 into the food production chain, we are a very small

13 manufacturer and I am here to present a small

14 manufacturer presentation of gluten-free foods. My

15 company is Miss Roben\'s. We are also known as the

16 Allergy Grocer online.

17 If you notice, on most of my slides I

18 reference the questions that were asked of us. So,

19 who is Miss Roben\'s? Basically, we are a dedicated

20 gluten-free manufacturer with over 50-plus mixes of

21 our own. We cater both to celiac and those with

22 multiple food allergies and intolerances. So, we

85

1 are a little different than the mainstream group

2 that caters just to celiacs.

3 We are a dedicated plant. There is no

4 wheat, gluten, dairy, peanuts, tree nuts, eggs, soy

5 except for the lecithin in one of our pre-made

6 chocolate chips, shell fish, fish or sesame found

7 in the plant. We are also a national mail order

8 business for over a thousand other select

9 gluten-free products.

10 As a family owned business, just basically

11 my husband and I, we basically self-educated

12 ourselves to gluten-free and food manufacturing.

13 We didn\'t have the money or means for outside help

14 or consultants. We wear multiple hats so we do

15 research and development; we do overseeing plant

16 production and operations; and also answer the

17 phone when we are short staffed. We have always

18 had less than 15 employees so with one operation

19 site we are able to change on the fly and get rid

20 of a lot of red tape that some corporations have to

21 go through to make changes.

22 We also provide extensive assistance over

86

1 the phone and the internet to the consumer, and

2 sometimes the physician and dietitian who call in.

3 We constantly redirect and network customers to the

4 more appropriate resources that we know of, whether

5 they be medical or dietary or national or local

6 support groups. We will distribute other

7 manufacturer contact information so that they can

8 further follow-up and clarify information. We also

9 provide extensive baking assistance, even if it is

10 not for our own product. I also belong to over 30

11 different celiac and associated e-mail news groups

12 and that allows me somewhat of a bug\'s eye insight

13 to what is being discussed about celiac disease.

14 Just based on this anecdotal experience,

15 it really appears to me that customers rely very

16 heavily on labels for processed foods. They seek

17 out gluten-free on the label and they will often

18 have complaints about multiple extra hours of time

19 spent on both label reading, shopping, and

20 follow-up calls to the manufacturer just to clarify

21 information. Typically, it is sad to say that I

22 think a lot of them have poor knowledge of both the

87

1 manufacturing process and the terms used in the

2 industry, and also the terms defining gluten-free.

3 We will get a call about once a week because they

4 misunderstood or misinterpreted the information

5 that was possibly disseminated to them, possibly

6 not. They often inadvertently purchase unsafe

7 products. They will purchase spelt more commonly

8 in a health food store if somebody unknowingly

9 directs them to such, and calculations are needed

10 for them to be helped for nutritional analysis if

11 it is 100 gram analysis. The European products

12 often come in with labeling and they don\'t

13 understand how to break it down per serving.

14 In defining gluten-free for the general

15 industry, it is no wheat, barley, rye, oats, spelt

16 triticale or kamut; no derivatives, extracts or

17 processing aids from any of the above that would be

18 used in the processing of the foods, with the

19 exception of distilled vinegar, the caveat being

20 malt vinegar. Then, there is anything from 10-200

21 parts per million testing procedures done on

22 ingredients or the finished product ranges that I

88

1 have seen in the industry.

2 Most of the references for gluten-free to

3 the industry that I am aware of come from either

4 Don Kasarda, who is a great scientist who I think

5 is retired by now. The national celiac support

6 groups provide most of the education and the

7 American Dietetic Association and some of the

8 medical journals that have been publishing. The

9 issue with oats has been for the most part, as far

10 as I know, mostly cross contamination.

11 Additionally, at Miss Roben\'s we also

12 define gluten-free to be that whenever possible,

13 over 90 percent come from a dedicated single source

14 ingredient supplier, straight from the farm that

15 makes their own product and does all aspects of the

16 production. So, this helps us provide the least

17 possible risk of cross contamination. The

18 ingredients that come possibly from a distribution,

19 which is less than 10 percent of our products, must

20 come from a supplier that individually farmed the

21 entire product and processed it, and it must come

22 sealed and pre-packaged before they receive it. We

89

1 request that on their own documentation or company

2 letterhead they give us product specifications; 100

3 gram analysis; a processing condition statement

4 which I will refer to in the next slide; if

5 possible, a written certification from a

6 third-party lab of testing, and what I have found

7 is that if testing is done in the lab the testing

8 procedures vary greatly; and further certification

9 for kosher, organic and vegen, again tangential to

10 gluten-free but who we do business with. The

11 product label, the website and the catalog explain

12 in detail to the consumer how we are defining

13 gluten-free and what our processing conditions are.

14 For each product that we supply or

15 ingredients that we utilize we send out this

16 exhaustive, somewhat irritating check list to the

17 company, the actual manufacturer, requesting a

18 quarterly check of both potential allergens, gluten

19 being considered as an allergen and gluten being

20 defined for them. It also allows us to then tell

21 the processing conditions to help define for the

22 customer what we know at the time we made the

90

1 request, and ask for testing procedures and what

2 part per million they test down to.

3 It also allows us a chance to identify any

4 red flags. If a customer states something

5 contradictory in that we may choose not to use them

6 because we feel that they don\'t truly understand

7 gluten-free correctly. They will say spelt is in

8 their products but it is gluten-free. That is kind

9 of a red flag to us. Then, the other is in their

10 cleaning and processing. Sometimes we will find

11 that the final product may not comprise gluten in

12 it but how they came about it may be somewhat

13 intriguing.

14 Some of the challenges to defining

15 gluten-free as a manufacturer, especially a small

16 one like us, since there is no standardized

17 definition the manufacturer then has to decide, by

18 educating themselves and their staff, what the

19 definition is. The current definition can be

20 confusing and vague, especially as a lay person. I

21 mean, my background is more medically oriented and,

22 still, I really struggled to understand the

91

1 definition. Then you have to decide are oats okay,

2 and when is it gluten-free enough. Then you have a

3 customer who calls in who is also possibly

4 misinterpreting, who is basically saying how could

5 you sell this product that has guar and canola in

6 it, which are the two most common questions that

7 come up, and you have to then redirect them without

8 offending them back to appropriate sources.

9 Current gluten-free production, as was

10 suggested by Dennis earlier, is an extremely wide

11 continuum both in the food production and in the

12 plant itself, and it goes anywhere in the entire

13 spectrum from what I would call suspicious to

14 excellent. In Europe, where some of our products

15 come from, wheat starch is considered acceptable

16 although it is not acceptable in the States, so you

17 need to make sure that you are not bringing in

18 products that are not acceptable by our standards.

19 In most companies of my size, a lot of times just

20 no gluten in the actual ingredients but no concern

21 for where the ingredient came from and no issues to

22 prevent cross contamination, all the way up to

92

1 dedicated plants with excellent procedures in place

2 and well-written protocols and testing down to

3 three parts per million.

4 The production also varies. Sometimes it

5 will be done in somebody\'s home. Oftentimes a

6 celiac or a consumer decides I am just going to do

7 this myself and starts their own business.

8 Sometimes it happens that production will be in a

9 shared bakery which is not cleaned between runs and

10 washed down. Sometimes it happens that it is in a

11 dedicated plant so it goes the whole continuum.

12 Some specific challenges to the production

13 of gluten-free foods from my perspective are that,

14 for one, a lot of the flours that we use are

15 lighter and starchier in texture. They have a

16 finer mesh. So, in using a form fill and seal

17 machine, a lot of times they tend to poof. The

18 components of xanthan and guar, which are

19 considered somewhat of a gluten replacer, are a

20 very minute portion of the product but they have to

21 be thoroughly blended in order to get a final mix

22 that is adequate. By the flours poofing, the bags

93

1 have a harder time sealing unless you have the

2 proper mechanisms to throw the flours back down.

3 Also, too, the grains vary from year to

4 year. Even in the rice farming industry, for

5 example, each year the lot may be slightly

6 different. In a wheat environment I know there is

7 a lot more variability also but there is more

8 flexibility in the baking of the product. In a

9 gluten-free environment there are exquisite

10 differences, and I will get into that in a second.

11 Also, too, washing down equipment and floors with

12 these very slippery substances of xanthan and guar

13 can make life a little challenging.

14 For the mix preparation, both for the

15 plant and the consumer, as I am sure Lee Tobin will

16 get into more, most of the flours are more

17 sensitive to environmental conditions. Breads,

18 particularly, are more prone to failure. The exact

19 liquid content you need to add varies from lot to

20 lot, which is different than picking up General

21 Mills Brownie Mix that you just throw in and it

22 always seems to work. The raw dough batter is

94

1 stickier and looser which can change your

2 production. I have helped with some of the

3 productions for finished products and I know one

4 guy was having trouble dropping his donuts because

5 they would fall apart.

6 Also, in order to be successful to the

7 consumer, the label has to be much more exhaustive

8 in terms of explaining how to proceed and make this

9 product, and you have to factor in the costs

10 associated with that replacement.

11 For methods most commonly used to remove

12 the gluten from foods, predominantly in the United

13 States it is the absence of gluten in the

14 ingredient. That is the most common practice.

15 Sometimes the gluten proteins have been processed

16 or denatured out, such as the distilled vinegars

17 and in wheat starch in the European conditions.

18 Is technologically feasible to produce

19 gluten-free products given the potential for grain

20 cross contamination? I think yes. I think if you

21 select ingredients from dedicated grain suppliers,

22 and they are out there, and dedicated gluten-free

95

1 mills that are using good HACCP, Good Manufacturing

2 Practices and allergen protocols in the plant, and

3 also doing that in your situation, providing

4 education to your staff about what gluten-free

5 means and cross contamination, and if you are

6 utilizing shared lines or non-dedicated ingredients

7 performing a universally accepted enzyme-linked

8 immunosorbent assay test, an ELISA test, to confirm

9 potential cross contamination, those would be my

10 suggestions.

11 Is it economically feasible? Again, I

12 think yes. I mean, here I am, a small

13 manufacturer, and we have been viable for 12 years.

14 I think the biggest investment is the time required

15 to source out the ingredients and the appropriate

16 equipment. The ingredient supplier distributors

17 are successful even to small businesses with poor

18 purchasing powers now. We used to buy our

19 ingredients in 50 lb. bags, 100 lb. bags and drag

20 them in. Now we do it by pallet. And, I can

21 sympathize with those who are still doing what we

22 used to do because their buying power is far less,

96

1 and some companies won\'t even break a pallet down

2 to sell to you. So, you have to factor these

3 things into price, and also the customer failures

4 that you are inherently going to have.

5 Manufacturers can also outsource and

6 utilize co-packers. They exist with dedicated

7 gluten-free rooms and equipment. Or, they could

8 utilize dedicated gluten-free manufacturers like

9 ourselves that would benefit from decreasing our

10 operational and ingredient costs. It seems like

11 the customer buying power and interest is already

12 there. There is already 1/133, the last citing for

13 celiac disease. If you consider also the wheat

14 allergic consumer who would have different demands,

15 there is a huge demand for a gluten-free product.

16 Then, there was a recent survey put out by Mantel

17 that basically suggested to the industry that there

18 is excellent potential.

19 As the gluten-free industry grows, the

20 ingredients and production costs would further

21 decline and make the availability increase, which

22 would make it even more affordable to small

97

1 industry. And, if oats were allowed to be

2 considered and we were able to find dedicated

3 suppliers, you know, personally I feel it would

4 enhance both the product taste and texture and the

5 structure, and expand the product line. The

6 question then becomes is it worth it to a large

7 manufacturer to produce.

8 The measures and costs that we use to

9 prevent cross contamination at Miss Roben\'s include

10 using a dedicated plant where no gluten is used

11 in-house; dedicated equipment\--we purchased ours

12 new so we didn\'t have to worry about any risk of

13 potential cross contamination with anything prior;

14 exhaustive research to find the ones that will

15 blend, disperse, seal and clean without any caking

16 or crevices with minimal downtime and waste; and

17 handling the volume runs and wash downs needed to

18 maintain and efficient and economical production.

19 We do use dedicated single ingredient

20 suppliers with a written certificate of analysis,

21 and do quarterly routine checks with the suppliers.

22 If a concern is raised by a consumer, for whatever

98

1 reason, we then source out that ingredient and/or

2 the ingredients within that mix and follow up. We

3 also do written employee allergen training and

4 potential methods of cross contamination regularly

5 and review that. We go over with our staff Good

6 Manufacturing Practices and HACCP. Even the phone

7 staff understands that. And, we have internal

8 policies and procedures for any type of manufacture

9 recalls for products that we do sell that aren\'t

10 ours, as well as customer complaints.

11 In the winter we hope to do more testing

12 and analytical methods, and are hopeful to have the

13 celiac branding which will be discussed later; and

14 in-house ELISA testing each batch for a

15 quantitative sandwich ELISA test of less than 10

16 parts per million, and a quarterly quantitative

17 test done outside by the University of Nebraska

18 which I have been told costs \$80 if you are not a

19 member, \$55 if you are for each mix. They use two

20 sandwich ELISA tests for gliadin, the Neogen

21 Veratox test and the Biopharm test, testing down to

22 three parts per million. My limited knowledge of

99

1 this is that fermented and hydrolyzed samples would

2 require special ELISA testing however.

3 In conclusion, my personal suggestions for

4 manufacturers, should the definition for

5 gluten-free exist, would be to still try to obtain

6 dedicated ingredient suppliers who can provide

7 written certification of analysis and analytical

8 testing with the parts per million or testing

9 procedures based on what the FDA recommendations

10 are; provide ongoing in-house education to the

11 staff using the universally agreed upon gluten-free

12 definition; and easy to follow written education

13 tools for the staff to refer back to; to test for

14 gluten quarterly quantitative analysis outside lab

15 testing and, if shared lines, in-house every batch.

16 The last thing I wanted to mention that is

17 somewhat tangential but related to this, is if more

18 of the educators could be educated to what

19 gluten-free means so that when a patient is

20 diagnosed they are not calling a manufacturer like

21 us to define it for them. Thank you.

22 \[Applause\]

100

1 Questions and Answers

2 DR. SCHNEEMAN: Thank you very much. Do

3 we have some questions? Rhonda?

4 DR. KANE: Thank you, Jay, for that very

5 informative presentation. I had a quick question

6 about your check list that you use for your

7 suppliers and your criteria. You mentioned that

8 you use the Neogen and the R-Biopharm ELISA tests

9 for your own in-house testing. Do you ask the

10 suppliers which methodology they use, or do you

11 require them to use certain methodology? And, do

12 you know what they are using for testing? Because

13 you ask them to report what is it in parts per

14 million, so what is it that they are using to

15 analyze their products, and is there any

16 consistency across your suppliers of using the same

17 test kits you do? Are they using other kits? Are

18 they using other methodology? What are they doing,

19 do you know?

20 MS. BERGER: Well, first to clarify, we

21 hope to test in the fall; we don\'t currently. That

22 is where I feel we are not where we should be, and

101

1 that was economic really more than anything.

2 Secondarily, the testing that we know of

3 that other companies do, they do not share

4 information. The gluten-free is an interesting

5 industry. I think we all know each other but I

6 don\'t think manufacturers like to share what is

7 considered trade secrets, and that is considered

8 possibly a trade secret. I have asked for a parts

9 per million and I don\'t really know that I could

10 evaluate it if I got the information, to be honest,

11 to say one is better than another. So, a lot of

12 what we do is really a compilation of, you know

13 finding out. Sometimes somebody will say they have

14 tested down to one part per million, and that is

15 like a red flag right there, you know, because I

16 know they don\'t test down that far for gluten. So,

17 sometimes it just gives us more information about

18 what the manufacturer may know. You know, even me

19 as a lay person, I can see some red flags.

20 Then, I think to answer your question do

21 they use consistently the same ones, no. Again, we

22 also ask for food allergens as well so, besides

102

1 gluten where we may not look at it in terms of, you

2 know, do you test down to this level and such, for

3 allergens we look at it a lot differently, and part

4 of it is just to see what lengths they are going

5 to; how concerned are they; how scrupulous they

6 are. So, some of it is qualitative in the results

7 and how forthcoming they are about the information.

8 DR. KANE: I just want to make sure I

9 understand. So, you do not ask the manufacturer

10 what methodology they are using. You ask them for

11 the parts per million but you don\'t know how they

12 arrive at that, what test kit or methodology they

13 are using. Is that correct?

14 MS. BERGER: No, if they have tested we

15 have that certificate and that certificate says on

16 there what they have used. But my ignorance would

17 be I would look at it and I would have to call

18 somebody else, like Steve in Nebraska, and say what

19 does this mean to me? You know, I just don\'t have

20 the knowledge to evaluate it critically.

21 DR. KANE: Thank you.

22 DR. PARK: Douglas Park, with FDA. Thank

103

1 you for your presentation. I do have some

2 questions I would like to pose to you. One of them

3 basically is a follow-up a little bit to what Dr.

4 Kane was asking you. On your certification on your

5 products do you do follow-up confirmations of your

6 own when you receive a product, whether it is done

7 on a random basis or whether it is done with each

8 batch of the product that you receive?

9 MS. BERGER: When you say follow-up\--

10 DR. PARK: Do you follow up testing?

11 MS. BERGER: Call the person that did the

12 test?

13 DR. PARK: No, do you do follow-up testing

14 your own? Within your own organization do you have

15 a quality assurance/quality control program that

16 provides you assurance that the product that you

17 are receiving, your raw product, is in compliance

18 and your in-line production is in compliance, as

19 well as your final product?

20 MS. BERGER: We came about how we are

21 doing it now somewhat deductively and not as

22 analytical as I would like, and part of the fall

104

1 testing is not just for gluten but it is going to

2 be for all of the allergenic proteins. Part of how

3 we\--I wouldn\'t say side-stepped, but part of how we

4 tried to stay as scrupulous as we can to our own

5 mixes, which are our products, is to get

6 ingredients from people who only do one thing. So,

7 the sorghum supplier we use, they only grow

8 sorghum; they mill their own sorghum and they

9 package their own sorghum. The rice we have to get

10 all the way from California to get a dedicated farm

11 that does those things. The products that we carry

12 from other companies, which is somewhat separate

13 because we don\'t have a lot of control over that\--I

14 don\'t do in-house testing on those at all but I do

15 pay attention to customer complaints and we have

16 had to follow-up with a voluntary recall and decide

17 not to carry a product that the company still lists

18 as gluten-free on their website today.

19 The plan is to do this fall in-house

20 testing on our own ingredients. Even though we

21 know inherently that they are gluten-free because

22 they have been farmed as such, I still want that

105

1 level of assurance for myself\--you never know\--and

2 test each thing to all the eight major allergens

3 plus gluten in particular so that I can feel the

4 best level of comfort that what we say we do, we

5 do. But the problem really has been mostly cost

6 and actually too my educational process to

7 understanding because, again, I put my research hat

8 on and actually had\--I mean, I bugged University of

9 Nebraska and called people that are dietitians that

10 are friends of mine and just plugged them for

11 questions.

12 So, we are not where I want to be and

13 where I would like to be and comfortable to be to

14 give a true sense of self. So, we are very clear

15 with the consumer, particularly the food allergic

16 consumer. Here is what we do; here is how we do

17 it. We challenge you at any time, please call the

18 manufacturer; please let us know if something has

19 changed; please let us know if you ever have an

20 issue with us. And, we do testing; we take

21 ingredient lot numbers and then we take a mix and

22 we make a lot number out of that, and we will go

106

1 back to every single ingredient and check, even

2 though we do a quarterly, and just second-guess the

3 supplier. So, yes and no.

4 DR. PARK: Do you anticipate setting up in

5 your process a HACCP program which would be then

6 also tied in with an in-house quality

7 assurance/quality control program?

8 MS. BERGER: Definitely. That is, again,

9 the goal with the ELISA testing, not only to have

10 fail-safe mechanisms to prevent but, if they should

11 occur, how would we handle it and, actually most

12 importantly to me is how do we let the customer

13 know? Because we are a national mail order, we go

14 overseas and how do I let this person know? So, we

15 have a database that can tell us a customer has

16 purchased a product but we don\'t know what lot

17 number it has come from to re-reference it, and how

18 do you communicate to people who don\'t necessarily

19 have e-mail; you don\'t have a phone number

20 sometimes, and how to do it adequately? So, we

21 have discussed with food allergy and anaphylactic

22 networks to help us. Then, being part of these

107

1 e-mail news groups you can kind of get the word

2 out. I mean, part of how we did the pasta was to

3 politely let everybody know that our comfort level

4 exists such that we would like to retract the

5 product without trying to inflame the company.

6 DR. PARK: In the meantime, do you

7 envision using an outside organization to do your

8 testing for you on a regular basis\--

9 MS. BERGER: Yes, in the fall.

10 DR. PARK: \--and not necessarily

11 quarterly\--

12 MS. BERGER: No, I want to do quarterly\--

13 DR. PARK: \--I am talking about daily?

14 MS. BERGER: I want to do quarterly. I

15 would feel more comfortable with quarterly because

16 we do change suppliers regularly. You know, we

17 will have to change a rice supplier because they

18 are now doing something besides rice, or whatever.

19 Maybe this is overkill but I would like to test

20 every batch in-house that we do. Then I would like

21 to use an outside independent lab by University of

22 Nebraska, which is what I have chosen so far, to

108

1 double check my procedures and have it more honest.

2 And, part of the celiac branding that I am looking

3 forward to is, again, an outside body like the

4 kosher certification that comes in and says you are

5 doing what you are supposed to be doing. They have

6 more knowledge than you, and they see things that

7 you may not see.

8 DR. PARK: Along that line, have you

9 looked at the economic impact of doing that?

10 MS. BERGER: Yes. I have 53 mixes and if

11 my husband stops me now we will stay at 53, but I

12 figure 53 mixes times 80 per quarter. But I don\'t

13 think that is unreasonable to provide the level of

14 safety I want to provide considering what I want to

15 do. And, I want customers to feel that, to the

16 best we possibly can do it, it is as clean as they

17 possibly can get.

18 DR. PARK: Thank you.

19 DR. LUCCIOLI: Stefano Luccioli, FDA. In

20 your talk you referenced that you often look for

21 grains in Europe, which I think is a very good idea

22 since Europe has a much longer history of dealing

109

1 with celiac disease and I am sure that they have

2 tackled a lot of these problems. What are things

3 that you have learned that maybe the American

4 market could improve on in milling their grains?

5 For instance, I understand that countries such as

6 Scandinavia produce oats without wheat so that is

7 never a problem. Is it economically feasible to do

8 that in this country?

9 MS. BERGER: I don\'t know if I am your

10 bird of choice. I know more about the actual

11 finished product than the raw ingredients. We do

12 get raw ingredients from overseas. The corn starch

13 that we get that only does corn can comes from

14 overseas sometimes because it is not as prevalent

15 in this country, that you can find corn where they

16 are only growing corn and they are only milling

17 corn.

18 As far as economics and their knowledge, I

19 think they are ahead of us in a lot of ways. I am

20 not really sure if it is just that\--like Dr. Shar

21 for an example that has been around for years. In

22 the pharmacies for years you have been able to

110

1 purchase gluten-free products and it has been

2 identified for you so the consumer would walk

3 somewhere and they would go get their prescribed

4 diet. It may be more limited. It may be not as

5 appealing but they felt safe that somebody had

6 given them what they needed to work around instead

7 of setting them loose in the Giant to try to figure

8 out for themselves this pile of paperwork that they

9 have compiled.

10 I can\'t really speak intelligently. I

11 mean, I can tell you off the top of my head but I

12 can\'t really tell you intelligently. I know that

13 there are a lot of manufacturers out there overseas

14 that are trying to bring products in, and there is

15 a huge industry. I get letters almost monthly

16 asking me if I want to be an importer or the

17 retailer in this industry for it.

18 DR. SCHNEEMAN: For some of those

19 questions we might be able to come back to the

20 general panel too if there we have time. Was there

21 anything else from the panel?

22 \[No response\]

111

1 Great! Thank you very much. Our last

2 presentation for this panel is Mr. Lee Tobin, who

3 is the team leader for the Gluten-Free Bakehouse at

4 Whole Foods Market.

5 Gluten-Free Bakehouse, Whole Foods Market

6 MR. TOBIN: Thank you. The last audience

7 I spoke to I think was a little more challenging

8 than the FDA. I did a cooking demonstration for

9 some group of children at the GIG celiac camp in

10 North Carolina, and the six year-olds sat in the

11 front row.

12 \[Laughter\]

13 I can assure you that celiac children are

14 very well behaved, especially when you feed them.

15 I wanted to start out by thanking the FDA for

16 inviting me and Whole Foods Market to participate

17 in these meetings. I would like to thank Jill Kuzo

18 who is our research and consumer relations

19 coordinator at the Bakehouse and Joe Dixon from

20 Whole Foods quality standards offices, both of whom

21 helped to prepare this presentation.

22 The Whole Foods Market Gluten-Free

112

1 Bakehouse is a dedicated facility that grew from a

2 dedicated production run which I developed in one

3 of our in-store bakeries after my diagnosis with

4 celiac disease in \'96.

5 We opened our new bakehouse\--it is a

6 fairly new facility, we opened less than a year ago

7 in Morrisville, North Carolina last October. We

8 produce 27 different baked goods from scratch. We

9 are packaging everything in pallet size quantities

10 and distributing them to approximately 170 of our

11 stores throughout the U.S.

12 In this presentation I will be covering

13 sections A, B and C of the Federal Register Notice;

14 discuss our framework for defining gluten-free; and

15 the Good Manufacturing Practices and the analytical

16 methods we use to ensure that our products meet

17 these standards.

18 Our stake in decisions involving

19 gluten-free labeling is three-fold. Our primary

20 concern is the confidence of our customers. They

21 trust that an item labeled gluten-free meets their

22 expectations. Secondly, it is consistency. We

113

1 need to assure that other products labeled

2 gluten-free are set to the same or similar

3 standards as those we have set for ourselves.

4 Last, any standards set by the FDA of labeling of

5 gluten-free products will necessarily impact our

6 production and the measures we take to exclude

7 gluten.

8 There are three methods we use to support

9 our claim of gluten-free status. We gather

10 testaments from ingredient suppliers. We perform

11 ELISA testing on our ingredients and finished

12 products, and we dedicate our entire facility to

13 production of gluten-free with the exclusion of

14 gluten from the premises. In the future we would

15 consider participating in a third-party

16 certification program, one that follows FDA

17 guidelines, perhaps modeled after kosher or organic

18 certification which Whole Foods has considerable

19 experience with.

20 In addition to screening our ingredients

21 for gluten, we also exclude artificial colors,

22 flavors and preservatives. In most cases Whole

114

1 Foods Market support of minimally processed

2 ingredients has made searching for gluten-free

3 ingredients easier. Virtually all of our

4 ingredients, with the exception of extracts and

5 emulsions, are inherently gluten-free and not

6 rendered gluten-free through processing.

7 We made a concerted effort to educate our

8 suppliers and manufacturers about hidden gluten and

9 sources of gluten cross contamination issues with

10 shared lines or concurrent production. Once we

11 have determined that each ingredient is gluten-free

12 we gather statements from suppliers that express

13 understanding of the term gluten-free and give

14 assurance that their ingredients are free of

15 gluten.

16 In addition, our facility employs a lot

17 tracking system. We record lot numbers of each

18 ingredient used in each batch and each recipe

19 produced. This system traces all ingredients used

20 from their origin to each batch of our finished

21 product and allows us to initiate recall procedures

22 as a safeguard should gluten, or any other form of

115

1 contamination, be discovered in our ingredients.

2 This screen illustrates points in the

3 processing of ingredients that farmers,

4 manufacturers and suppliers should be aware of to

5 prevent gluten contamination. It refers mainly to

6 grain and flour production which are higher risk

7 ingredients but could be applied to other

8 ingredients as well.

9 Crops should not be rotated with any form

10 of wheat, rye or barley and should be harvested,

11 stored, transported, milled and packaged with

12 gluten-free equipment or in a gluten-free

13 environment. We have always excluded oats from our

14 production due to concerns about cross

15 contamination, and we will continue to do so until

16 the safety of oats can be consistently confirmed

17 through the process.

18 Gluten testing\--testing protocols are

19 challenging to establish because there is no one

20 method we can use to test 100 percent of our

21 products. Samples must be taken at key points in

22 the process and the number of samples needed

116

1 depends on the level of risk of contamination. We

2 use the BioKits rapid gluten test from Tepnel

3 Biosystems. It costs about \$16 per test. This is

4 a qualitative stick test that detects the presence

5 of gliadin as low as 50 parts per million and

6 yields results in about five minutes. We chose

7 this test because it is fairly simple to use.

8 All testing is done at the bakehouse by

9 our quality control person. We looked into sending

10 out samples to a lab for testing but, as Jane

11 mentioned, the costs are prohibitive. We currently

12 test all new ingredients and a new source of an

13 existing ingredient if we are to change suppliers

14 since this is the best point in the process to

15 exclude gluten from our bakehouse.

16 We also test random samples of finished

17 products for additional verification. Finished

18 products need to be sampled carefully so that

19 particulates in the sample do not obscure test

20 results, which has required us to do additional

21 tests when we have had inconclusive results. Our

22 sampling plan continues to evolve as we grow and

117

1 increase our production volumes.

2 We are in the process of developing a

3 HACCP program which will include screening for

4 gluten as a critical control point. With this

5 program we intend to test samples from each lot of

6 all high risk ingredients coming into the bakehouse

7 and one finished product sample from each of our

8 production runs. This testing program could be

9 part of a possible third-party certification

10 program, as I mentioned earlier.

11 Our decision to dedicate our entire

12 bakehouse and work staff exclusively to gluten-free

13 production was made primarily on the basis of

14 minimizing the risk of contamination. Facilities

15 that process wheat or gluten ingredients will

16 always run a higher risk if they also choose to

17 process gluten-free products.

18 This screen illustrates levels of

19 dedication that food processors can use to reduce

20 risks. Some dedicate production run and clean

21 equipment thoroughly between runs. Some dedicate

22 certain pieces of equipment or an entire line of

118

1 equipment, and some dedicate their whole facility

2 to gluten-free production. Each higher level

3 eliminates more points of potential contamination.

4 Cross contamination within our

5 facility\--there are some steps that we take to

6 reduce contamination risks at the bakehouse and at

7 our stores as well. We provide full uniforms for

8 all of our employees and replace them daily. We

9 also provide them with shoes and aprons. The

10 aprons are worn over the uniforms but remain in the

11 work area during work breaks as a protective

12 barrier for any gluten that might be on their

13 clothing. Visitors to the bakehouse are supplied

14 with lab coats if they enter our production areas.

15 We share our building with a warehouse that the

16 company runs and there are several employees;

17 people are coming in an out so we require those lab

18 coats. We also signage throughout the facility to

19 alert anyone who is coming in and our employees as

20 well that it is a gluten-free production area and

21 we need to exclude wheat, rye, oats and barley.

22 We employ strict cleaning procedures

119

1 between production runs to prevent any allergen

2 cross contamination. I should mention that we are

3 not an allergen-free bakehouse. We use dairy, soy,

4 nuts and some of the other allergens but we do not

5 promote our products as being allergen-free, just

6 gluten-free.

7 At the store level we have initiated

8 training programs that stress cross contamination

9 issues with gluten and other allergens when

10 employees in our store are either serving or

11 sampling our products. We feel that education of

12 all our employees is key to reducing potentials for

13 cross contamination.

14 Any standards that are set for gluten-free

15 labeling must meet the expectations of our

16 customers. Customers must have the confidence that

17 food labeled gluten-free is safe for them to

18 consume and will not make them ill. In addition,

19 standards must be feasible for producers to meet.

20 Feasibility is determined by relative difficulty to

21 implement, reliability of results and, of course,

22 the cost. There also needs to be consistency in

120

1 definitions so that fair comparisons between brands

2 of products can be made, and these definitions must

3 be easy for the general public to understand.

4 Education of consumers, manufacturers and lawmakers

5 is essential to create a label that easily

6 distinguishes gluten-free foods for celiacs who are

7 medically required to be on a gluten-free diet.

8 Thank you.

9 \[Applause\]

10 Questions and Answers

11 DR. SCHNEEMAN: First, why don\'t we take

12 some time to see if there are some specific

13 questions for Mr. Tobin, and then we will have time

14 I think for more questions to be addressed to the

15 panel speakers. So, do we have some specific

16 questions?

17 DR. PARK: Thank you. This is Douglas

18 Park, with FDA. You indicated, and correct me if I

19 am wrong, that for many of your raw products you

20 obtain certification that they are gluten-free. Is

21 that correct?

22 MR. TOBIN: We obtain letters from our

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1 suppliers and manufacturers claiming gluten-free

2 status, yes.

3 DR. PARK: And I will ask you the same

4 question that I asked the previous speaker, do you

5 confirm in your own testing in your own laboratory

6 that they are, in fact, gluten-free?

7 MR. TOBIN: Yes, we have done a limited

8 amount of testing to confirm that. Our intention

9 is to ramp up our testing once we have our HACCP

10 program developed.

11 DR. SCHNEEMAN: Excuse me, let me

12 interject. Do you have a certain expectation of

13 what kind of test they would use in order to

14 certify to you that they are gluten-free?

15 MR. TOBIN: No, we have not questioned our

16 suppliers whether they have used testing

17 procedures.

18 DR. PARK: That is a good follow-up

19 question. You indicated that you are developing a

20 HACCP program. Would you share with us a little

21 bit your initial ideas as to what you would

22 consider an appropriate HACCP program for a

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1 gluten-free plant?

2 MR. TOBIN: I can\'t give you specifics

3 because it is still under development and I am not

4 the person who is working on it. We actually run

5 two bakehouses. Our gluten-free facility is

6 umbrella\'d under an existing bakehouse that has

7 been in operation for a number of years. It is

8 located a quarter mile away and we have a quality

9 control person who does work for both of our

10 bakehouses and is working on developing that

11 program. But the gluten testing will be a

12 significant part of that program.

13 DR. PARK: In your dedicated facility you

14 prepare only products that fall under your

15 gluten-free assurance and label? Is that correct?

16 MR. TOBIN: That is correct. All of the

17 wheat-based products are made at our other

18 bakehouse.

19 DR. PARK: What about other cereals, other

20 than just wheat-based?

21 MR. TOBIN: I am not sure I understand.

22 DR. PARK: Well, we are concerned not only

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1 just with wheat; we are concerned with oats and

2 some of the hybrids and specialty grains. Are

3 those brought into that gluten-free area?

4 MR. TOBIN: No, not at all. Our warehouse

5 that shares the facility primarily stores

6 equipment, coffee and drinking water, firewood,

7 pallets, that sort of thing. There is nothing

8 stored on the premises, or processed.

9 DR. PARK: Those are all my questions.

10 DR. LUCCIOLI: Stefano Luccioli, FDA. I

11 just wanted to follow-up. Did you define what you

12 consider gluten-free? Do you consider oats in that

13 definition?

14 MR. TOBIN: Not at this time, to deal with

15 the cross contamination issues.

16 DR. LUCCIOLI: So, basically what all the

17 other presenters have said, that is what your

18 definition of gluten-free is?

19 MR. TOBIN: For the most part, yes.

20 DR. SCHNEEMAN: I was going to suggest why

21 don\'t we have the panel come up? Don, go ahead and

22 ask your question and then we can raise other

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1 questions for other speakers. Go ahead, Don.

2 DR. ZINK: Don Zink, with FDA. Have you

3 had situations where a supplier has certified that

4 they are gluten-free and you have tested it and

5 found it to contain gluten? And, have you had a

6 situation where your raw materials passed muster

7 but then, when you produced the finished product

8 and ran the test, you had a positive gluten? I

9 asked this question earlier. I am just trying to

10 get a feel for the synchrony of claims of

11 gluten-free with the actual test, as well as

12 possible lot sampling and non-random distribution

13 of contamination issues.

14 MR. TOBIN: To the first part of your

15 question, we have not had any of our own in-house

16 testing that conflicted a supplier\'s claim of an

17 ingredient being gluten-free. With the finished

18 product, we had a couple of tests that were

19 inconclusive due to our inexperience with the

20 testing method. The samples were shaken a little

21 too much and rendered the inconclusive results, and

22 we retested the samples of the same product and

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1 that was confirmed gluten-free to greater than 50

2 parts per million.

3 Questions the FDA Panel

4 DR. SCHNEEMAN: Can the panel come up?

5 Thank you very much. Stefano, you had a question

6 of the last speaker about import, and I am

7 wondering if Miss DeMarchi might be able to address

8 the nature of the question that you had. So, I was

9 thinking you might want to restate the nature of

10 the question you were getting at. We will give you

11 a microphone to respond.

12 DR. LUCCIOLI: Yes, Stefano Luccioli. I

13 guess as a follow-up I have a question about oats.

14 Why do we have a problem with oats contaminated

15 with wheat? Is there just not demand for

16 gluten-free oats, and why maybe in other countries

17 are they able to supply these grains? Obviously,

18 maybe it is an economic issue.

19 MS. DEMARCHI: This is Jane DeMarchi from

20 the North American Millers\' Association. I think I

21 would caution you about cross contamination.

22 Although wheat contamination may be our greatest

126

1 problem in the U.S. and Canada with oats, rye and

2 barley are the grains of concern in Europe. I

3 think in Ireland there are problems with rye

4 contamination. I don\'t know as much about

5 Scandinavian countries. I think that they may have

6 a greater level of purity but I am not totally sure

7 about that.

8 In reference to an earlier question you

9 had asked about products coming from Europe, and I

10 don\'t know if this is true but if they have a

11 different type of identity preservation system that

12 is used on grains in Europe, in part because of

13 concerns about biotechnology, that may impact the

14 level of grain mixture not just in oats but in

15 other grains in the grain system in Europe.

16 MS. BERGER: Just in addition, as a

17 manufacturer, if we were to find for an example a

18 source that we felt to be clean, like I have heard

19 McKane\'s oats hypothetically has been touted as

20 clean and, yet, there was another one that disputed

21 it\--I think right now, if we were to take oats in,

22 because there is so much in the understanding of

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1 what is gluten-free to the community, we would

2 basically be discrediting ourselves as a

3 gluten-free supplier because there controversy is

4 so great about it that even if we were to obtain

5 it, until the definition is laid out that everybody

6 is in consensus, I think everybody is very cautious

7 to want to even introduce it anyway.

8 DR. LUCCIOLI: That is a good point. That

9 is my feeling, that the demand, since you are going

10 to have to include it in gluten-free anyway, then

11 maybe there is not the demand to find a more

12 purified form.

13 MR. GILLIAM: I totally concur with that

14 statement. There is a real hesitancy within our

15 company to put something in a package and put it in

16 the marketplace and be labeled and in whatever

17 percent, 50 percent of the celiacs\' minds it is now

18 being possibly tainted. We are just staying away

19 from that.

20 DR. SCHNEEMAN: Please identify yourself.

21 MR. TOBIN: Lee Tobin, from Whole Foods

22 Market. I just wanted to add that I agree with

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1 what these folks are saying. We were approached

2 about eight months ago by a woman representing a

3 group of farmers, I believe in Montana, who were

4 interested in growing dedicated gluten-free oats.

5 I don\'t know how far along they are in the process

6 of bringing a product to market, but we would

7 certainly be interested if they could confirm

8 gluten-free status of the products.

9 DR. SCHNEEMAN: Great! Thank you.

10 Felicia?

11 MS. SATCHELL: Felicia Satchell, FDA. My

12 question is for Mr. Tobin. I just want to make

13 sure I am clear on your testing, and you are

14 testing at 50 parts per million?

15 MR. TOBIN: That is correct.

16 MS. SATCHELL: So, for products that are

17 below 50 parts per million, they proceed through

18 production and distribution channels. Do you have

19 any type of system set up where you get adverse

20 event reports? Have you gotten any? Do you have a

21 system that allows you to trace back to any

22 particular product that might have been the subject

129

1 of an adverse event?

2 MR. TOBIN: Good question. Yes, we do get

3 a tremendous amount of feedback from our customers,

4 mostly through e-mail. We have someone working

5 full time answering e-mail for us. We get phone

6 calls as well. We have been growing out our

7 product region by region and most of the issues we

8 get, phone calls or e-mails we get from customers,

9 are from customers who are new to our products as

10 we have just rolled out to their local store. I

11 would say all cases of customers claiming to have a

12 reaction, we have not found that to be the case.

13 They were either not diagnosed with celiac\--we sell

14 to customers who are celiac and customers who are

15 on a gluten-free diet for whatever reasons, and

16 some of them have various reactions, maybe caused

17 by consuming gluten or consuming something else.

18 We have never been able to confirm any

19 contamination with our products. As I mentioned,

20 we do have lot numbers. We track lot numbers with

21 ingredients and we date code all of our products so

22 when they are at the store and a customer has a

130

1 complaint or an issue with a specific product, we

2 can track the date of production. We have actually

3 had samples sent back to us and we have sent them

4 out for testing, and we have not had any issues, no

5 confirmed issues.

6 MS. SATCHELL: Thank you.

7 DR. KANE: Rhonda Kane, FDA. Lee, just to

8 follow-up about your definition of gluten-free

9 specifically, could you list the different grains

10 that you exclude, and do they include spelt and

11 kamut and triticale? Could you just state what the

12 grains are that you do not use?

13 MR. TOBIN: Sure. For the most part, what

14 everyone else had mentioned. We exclude all

15 varieties of wheat. We are using sorghum flour,

16 soy flour, rice flour of course, tapioca starch,

17 potato starch, bean flours, kimwa flour and

18 buckwheat and millet in their whole grain form. I

19 think that is everything, and there are other

20 grains that we would consider to be gluten-free

21 that we are not using currently.

22 DR. KANE: You didn\'t mention rice.

131

1 MR. TOBIN: Yes, we use rice, quite a bit

2 of it.

3 DR. LUCCIOLI: Stefano Luccioli. How about

4 corn?

5 MR. TOBIN: Oh, yes, corn. Absolutely.

6 We use corn meal in our cornbread and corn starch

7 as well.

8 DR. KANE: Rhonda Kane, FDA. In the

9 different grains that you use, do you ask the

10 suppliers if they are dedicated, or do you only

11 deal with dedicated suppliers? Or, is it up to

12 them but you ask them to provide some sort of

13 certification that their product is gluten-free?

14 What type of suppliers do you deal with, with these

15 other grains?

16 MR. TOBIN: We deal with a variety of

17 suppliers. Bob\'s Red Mill is actually one of our

18 suppliers. Most of our flours are brought in

19 pallet size quantities, but we do ask for letters

20 of certification, and we don\'t specifically ask for

21 their testing methods, no.

22 DR. KANE: And they are not all dedicated

132

1 facilities? Correct? Is that true?

2 MR. TOBIN: The millers are, yes.

3 DR. KANE: The millers?

4 MR. TOBIN: They claim to be.

5 DR. SCHNEEMAN: I am going to ask the

6 panel if there are just some last questions that

7 you might have.

8 DR. PARK: Douglas Park, FDA. The

9 question which just came across my mind is, is

10 there such a thing as a gluten-free alcoholic

11 beverage, such as beer and that type of thing? If

12 so, what grains are used in those?

13 MS. BERGER: Jay Berger. Yes, there are

14 two. One is using sorghum and I have forgotten

15 what the other is\--honey. One is a honey lager.

16 So, yes. There has been a big interest. I don\'t

17 know how it fares, to be honest, but there has been

18 a big interest.

19 DR. SCHNEEMAN: Felicia, did you have a

20 last question?

21 MS. DEMARCHI: Just as a follow-up to the

22 oats discussion also, I think the demand of

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1 interest to purchase is tremendous. I think the

2 hesitation is, okay, when is it going to be

3 considered safe enough that we all can bring it in

4 comfortably and feel confident that we are

5 providing something that isn\'t contradictory to

6 what they are hearing otherwise.

7 MR. GILLIAM: Dennis Gilliam, Bob\'s Red

8 Mill. Tangential to that, I would say if oats are

9 determined to be safe or found to be

10 uncontaminated, being in marketing, I have a sense

11 that taking out full page ads in \"Living Without\"

12 and other publications similar to that, it would

13 take a six-month campaign of full-page ads to

14 educate the celiac community to the fact that they

15 are, in fact, acceptable.

16 DR. SCHNEEMAN: I think I am going to

17 close this morning\'s session. I want to start by

18 thanking our panel. These have been excellent

19 presentations. I appreciate, number one, your

20 sticking to the time but, number two, really

21 focusing in on those questions and issues that FDA

22 had put in the Federal Register. I think you have

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1 provided us a wealth of information and your

2 responsiveness to the questions has been very

3 helpful as well. We are going to take our first

4 break. I know many of you are probably anxiously

5 waiting for that. It is 11:15.

6 There are restrooms. As you leave the

7 auditorium, if you head back toward where you came

8 in, there are restrooms along that corridor.

9 Again, I would remind you that if you do leave the

10 facility to go out to Cafe Wiley you will have to

11 come back in through security. So, just keep that

12 in mind if you are coming back in. Also, I would

13 remind some of you who would like to add to the

14 public comment period this afternoon, it you would

15 like to do that please be sure and pre-register for

16 that with the registration desk that is out in the

17 foyer. So, with that, we will take a 15-minute

18 break and we will reconvene promptly at 11:30.

19 Thank you.

20 \[Brief recess\]

21 DR. SCHNEEMAN: I think it is going to be

22 time to reconvene. Knowing that we have a lot to

135

1 cover in a short amount of time, I want to keep us

2 on time as much as possible. The next panel, of

3 course, has the challenge that they are the panel

4 between you and lunch so I know they will want to

5 make sure we keep to the schedule here. We are

6 going to do a little bit of a switch. The panel

7 members can sit in the front row for the

8 presentations but then we will want our speakers to

9 actually be in the front for the question period.

10 Our next section of the agenda is to

11 address questions around the gluten detection

12 analytical methods. We have two speakers for this

13 particular section. Our first speaker is going to

14 be Dr. William Hurkman, who is a plant physiologist

15 with the Pacific Western Regional Office of the

16 Agriculture Research Service of the U.S. Department

17 of Agriculture.

18 Gluten Detection Analytical Methods

19 Detection of Cereal Proteins and DNA Using MS,

20 ELISA and PCR

21 DR. HURKMAN: Well, thanks for inviting me

22 here. It has been a pleasure listening to the

136

1 presentations this morning, and my presentation

2 will be a little bit different. I am Bill Hurkman,

3 from Western Regional Research Center in Albany,

4 California, and my topic will be detection of

5 cereal proteins and DNA using mass spectrometry,

6 ELISA and PCR.

7 DR. SCHNEEMAN: Excuse me, Bill, could you

8 move the microphone?

9 DR. HURKMAN: Is this better? I always

10 have a problem standing close. So, I will take a

11 different approach. I am a plant physiologist and

12 I like to see how things work and take them apart.

13 I like to look at assays and understand what is

14 going on.

15 So first of all I thought, not to insult

16 the audience but I thought I would start out

17 defining some of these terms because they can be

18 confusing. Wheat flour, when you combine it with

19 water, forms a dough, as you all know, and it makes

20 many nice things, some of which you may have eaten

21 for breakfast this morning. If you knead it with

22 excess of water you can get rid of the starch

137

1 granules and you are left only with the protein

2 portion, and that is called gluten. Now, gluten

3 consists of two protein groups, the gliadins and

4 the glutenins, and these can be separated from each

5 other by mixtures of water and alcohol.

6 So, that is all well and good but then you

7 come across this term prolamins, and gliadins, and

8 glutenins are also called prolamins, and together

9 they make up gluten. So, it can be slightly

10 confusing. Then to add to this, there are

11 prolamins in other cereals besides wheat. I am

12 going to focus today on the gliadins, so the wheat

13 prolamins are called gliadins. In barley they are

14 called hordeins; in rye, secalins; and in oat,

15 avenins. So, I thought with that introduction,

16 maybe as I mix these terms I won\'t lose you; I will

17 try not to do that.

18 The topic of today\'s talk is detection

19 methods, and there are several analytical tools

20 available for detecting the presence of cereal

21 prolamins in food products. Today I will just

22 cover three of them. They are the ones that are

138

1 used principally. They are mass spectrometry,

2 monoclonal antibodies and polymerase chain

3 reaction, abbreviated as PCR almost by everyone.

4 Now, the first topic I am going to cover

5 is the use of mass spectrometry for protein

6 identification. The schema you see here is the one

7 I use in my laboratory for identifying the many

8 proteins present in wheat endosperm. Essentially,

9 what you are doing is isolating proteins from the

10 seed, and we focus on endosperm so we isolate

11 endosperm, extract the proteins and run them in a

12 two-dimensional gel so the net result is a 2D gel.

13 Now, what that is, it is a separation of

14 proteins in a first dimension gel by charge, and

15 then that gel is laid on top of a second gel\--the

16 rectangle you see on the screen there\--which

17 separates them by size. Once we have done this, we

18 visualize the proteins with a blue stain. That is

19 why the protein spots are blue. Then we scan the

20 gels to get a digital image.

21 This digital image is used to match spots

22 between different gels, for example, for comparing

139

1 different samples grown under different conditions.

2 Once this gel is scanned, we then cut out the spots

3 and we add trypsin to the spots to break them into

4 fragments so that the mass spectrometer can handle

5 them. The fragments are created by an XY robot.

6 In this case we have one made by Digest Pro. Then

7 these fragments are analyzed by the mass

8 spectrometer which is a rather large instrument,

9 about 8 ft. by 3 ft. and about as high as the

10 podium.

11 What you end up with is data like this.

12 To the uninitiated that doesn\'t look like much, but

13 what that represents is the size of these fragments

14 in their amino acid sequence. With that

15 information, you plug it into a computer and check

16 databases and you can come out with the identity of

17 the proteins. This has really been a marvelous

18 piece of equipment in my research. I always like

19 to tell the story that when I identified my first

20 protein it took two years. Now we can do 50 a day

21 using this technology.

22 Here is an example of two fractions of

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1 proteins from wheat endosperm, the gluten proteins

2 and the albumins and globulins. What you see is

3 that there is a whole bunch of proteins in these

4 fractions. There are several hundred here and over

5 a thousand proteins in this fraction. What we have

6 attempted to do using mass spectrometry is to

7 identify all these proteins.

8 On the slide I haven\'t done that but since

9 this meeting is basically to talk about wheat

10 allergen proteins, I thought I would show a few on

11 the slides. The gluten proteins contain the omega,

12 alpha, gamma gliadins and the high and low

13 molecular weight glutenins. So, that is quite a

14 few proteins that celiac patients can be allergic

15 to or react to.

16 In the albumin and globulin fraction I

17 have just labeled areas in the gel where these

18 other known allergens, IgE allergen proteins are

19 located. They include the serpins, glyceryl

20 aldehyde 3-phosphate dehydrogenase, the GAPDH on

21 the slide, peroxidase and also alpha trypsin

22 inhibitors of which there is a large number in the

141

1 low molecular weight region of the gel. So, this

2 technology is wonderful in that, if you can

3 separate the proteins either on a gel or using

4 HPLC, you can identify and separate specific

5 proteins out of all the proteins present in wheat

6 endosperm.

7 Advantages of the mass spectrometer

8 identifying proteins are that, as you saw in the

9 previous slides, it can separate and visualize many

10 proteins at once. Protein identification is

11 relatively rapid. Proteins can be quantified.

12 Another useful thing about this technology is that

13 proteins that you separate can be used to make

14 antibodies against specific proteins of interest.

15 One thing I didn\'t point out on this slide is that

16 you can use this technology also in combination

17 with antibodies and Western Blots to identify, for

18 example, wheat allergy proteins.

19 The limitation to this method is that you

20 can only visualize the most abundant proteins, but

21 this can be overcome to some extent by

22 fractionation, which I showed on the previous slide

142

1 where I used KCl to separate the two protein

2 fractions. Also, the method is technically

3 demanding. You need skilled people in your

4 laboratory to do the protein separations and the

5 mass spectrometry. Also, the equipment and the

6 associated software is quite expensive.

7 Another one you have heard a lot about

8 today is the ELISA, and that is short for

9 enzyme-linked immunosorbant assay. This assay

10 takes advantage of the ability of antibodies to

11 recognize and bind to specific proteins which are

12 termed antigens. It is more rapid and less

13 expensive than mass spectrometry and is highly

14 specific through the use of monoclonal antibodies.

15 On this slide is an outline of how

16 monoclonal antibodies are made. First, the antigen

17 is injected into a mouse to stimulate the

18 production of antibodies. The antibodies are made

19 in specific cells in the spleen called lymphocytes.

20 These then are isolated and fused with myeloma

21 cells to produce antibody-producing hybrid cells.

22 If you look at the slide you can see that

143

1 the little lines on each of the cells are

2 different. What that is showing is that each of

3 these cells make different antibodies. So, you can

4 screen for the antibody of interest, and once you

5 find that cell line you can clone it to produce

6 unlimited amount of antibody for future studies.

7 What do we do with this antibody? We use

8 it in what is called a sandwich ELISA. This is

9 done in 96 well plates. The blue cylinder there is

10 representative of one well and a plate. The first

11 thing that needs to be done is to bind the

12 monoclonal antibody to the wells of the plate.

13 Then you add the sample and you also compare the

14 sample with the standard so you can quantify the

15 results. You incubate for a time and wash the

16 sample to remove excess antigens. Then you add a

17 conjugate. Now, what a conjugate is, it is another

18 antibody that recognizes the antigen that is

19 connected to an enzyme. Later I will tell you what

20 that is about. Then you again wash it so that you

21 have just your antigen in a sandwich. That is

22 where the name comes from. It is a sandwich

144

1 between an antibody and a plate and an antibody

2 connected to an enzyme. Then you add the

3 substrate, and what happens is that the conjugate

4 has the enzyme which utilizes the substrate and

5 alters its color. After a certain time you stop

6 the reaction with a stopping reagent and the color

7 that is in the well is correlated with how much of

8 the antigen is present. So, I thought it is an

9 interesting assay and it is nice to know how these

10 things work.

11 With respect to gluten proteins, what has

12 become available in recent years is the R5

13 monoclonal antibody. This was produced by Mendez

14 and his collaborators in Spain, and the reference

15 is at the bottom of the slide. This antibody

16 detects gliadins, hordeins and secalins but not the

17 avenins. You might wonder how is this possible.

18 Well, the way this works is that the

19 antibody recognizes the five amino acid sequence,

20 QQPFP, and for those who aren\'t familiar with the

21 shorthand, it is at the bottom of the slide and it

22 stands for

145

1 glutamine-glutamine-proline-phenylalanine-proline.

2 If you look at this sequence, this is a sequence of

3 a wheat gliadin and I said that it is a prolamin

4 because it has a lot of glutamines and prolines.

5 If you look in there you see a whole lot of Ps and

6 Qs so that is where that name comes from.

7 What you will see in this wheat gliadin is

8 that that five amino acid peptide is in there 14

9 times. So, that is why this assay works because

10 processing it this peptide gets fragmented and

11 there are 14 chances that you can detect this

12 particular protein using the antibody. It is a

13 pretty cool method. Now, this sequence is found

14 also in the hordeins and secalins but not avanins.

15 So, that is why you have the specificity.

16 The advantage of the ELISA assay is that,

17 as you saw, it detects wheat, barley and rye but

18 not oat prolamins. It works well for a variety of

19 processed and unprocessed foods. It is relatively

20 rapid. The R-Biopharm assay literature says that

21 it can accomplish this in an hour and 30

22 minutes\--not too bad but not fast enough for

146

1 assembly line production. In a laboratory setting

2 it is sensitive down to 1.5 parts per million, and

3 it is available in several commercial kits.

4 Two of these kits were tested by 20

5 laboratories in a study that came out in a

6 symposium proceedings by the Prolamin Working Group

7 last year, and the conclusion was that it was rapid

8 and reliable, and that statistically reproducibly

9 it was quite good. This assay has been temporarily

10 endorsed by the Committee on Methods of Analysis

11 and Sampling, which is part of the Codex

12 Alimentarius Commission. The reason it is

13 temporary is that they would like to see more data;

14 they would like to see more samples tested, and so

15 forth. Anyway, it is a good start for that.

16 The disadvantage is that it does not

17 distinguish between wheat, barley and rye so if you

18 have all three contaminants in one sample all you

19 know is that it is contaminated, but not with what

20 and in what proportion.

21 Another issue is that it detects only

22 gliadins in wheat. Some celiac patients also react

147

1 to high and low molecular weight glutenins. So,

2 this may not be a major issue in ingredients that

3 contain gliadins and glutenins but some, most

4 notably starch, preparations don\'t always have

5 gliadins associated with them and they have

6 glutenins. So, it is something to be aware of.

7 The last assay I want to talk about is PCR

8 amplification. Essentially, this is a method to

9 amplify a specific segment of DNA to levels high

10 enough to detect by assay. The reaction consists

11 of three parts. The first is to denature or unwind

12 the DNA template so you go from this helix to

13 double strands. What this does, it allows the

14 primers to anneal or bind to the DNA segment for

15 which they are directed. Once the primer is

16 annealed onto the DNA, then you can have the

17 synthesis of the peptide of interest.

18 Now, what you need are forward and reverse

19 primers, which is indicated here, to carry out this

20 reaction, and when you want to extend these

21 polymers you need DNA polymerase and nucleotide

22 bases. You have probably heard of a thermal

148

1 cycler. It is how this assay is done. What it

2 does, it cycles through this a number of times to

3 increase the DNA to high enough levels to work

4 with.

5 Now, what I did, I took from this

6 publication by Sandbert et al. some data to show

7 you how PCR works and why it is so specific. The

8 red boxes indicate the forward primers; the blue

9 boxes the reverse primers. This sequence, here, is

10 specific to wheat gliadin. In other words, it is

11 not found in rye, barley or oat. Similarly, this

12 sequence is specific only to rye and is not found

13 in wheat.

14 Again, just to show this for hordein, the

15 same thing. Here is the specific sequence and this

16 is the specific sequence for avenin. What this

17 means is that, unlike the ELISA assay, you can tell

18 which of the cereals are within your sample by

19 doing this DNA detection.

20 Here is sort of a summary table showing

21 how specific these primers are. The wheat primers

22 detect only wheat, not rye, barley or oat and all

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1 of these types of wheat make that selected DNA

2 sequence. In other words, whether the sample

3 contains winter wheat, spring wheat, durum wheat,

4 spelt, kamut or triticale wheat, it detects that.

5 The rye primer only detects rye; barley, only

6 barley; and oat only detects oat.

7 So the advantage of PCR is that it is

8 species specific. In any given sample you can tell

9 whether or not it has any wheat, rye or barley

10 within it. It is sensitive and rapid. It

11 complements ELISA results. In other words, the

12 disadvantage is that it detects DNA rather than

13 protein. ELISA detects protein but if there is

14 contamination, say, from rye the ELISA shows that

15 this test is contaminated. The PCR probe with tell

16 you that the contamination is due to rye. So, that

17 is kind of a nice thing.

18 In summary, mass spectrometry is an

19 excellent tool for protein identification. It is

20 sensitive but not really rapid when you compare it

21 to ELISA and PCR. It is expensive and technically

22 demanding. The ELISA works well for a variety of

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1 unprocessed and processed food. It is sensitive

2 and rapid. The main advantage of PCR is that it is

3 species specific, complements ELISA and it also is

4 sensitive and rapid.

5 What I have to say is that, as a user of

6 mass spectrometry, I think that if you want to

7 confirm absolutely results of ELISA it is the way

8 to go. So, that is all I have to say today.

9 \[Applause\]

10 Questions and Answers

11 DR. SCHNEEMAN: We will take some

12 questions right now from the panel. Also, if some

13 of the other speakers are trying to get some

14 questions, please alert one of the panel members

15 that you have a question. I think it is the

16 easiest way to get recognized. We know Doug will

17 have questions.

18 DR. PARK: Douglas Park, with FDA.

19 Considering the viewpoint of the individual that is

20 susceptible to gluten, is it crucial that you know

21 exactly which allergenic protein is present?

22 DR. HURKMAN: I would say the answer to

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1 that is no as long as they know that it is

2 contaminated with wheat\--

3 DR. PARK: Or one of the others.

4 DR. HURKMAN: \--or one of the others, yes.

5 DR. PARK: So, then going the next step

6 and saying if we try to set up a two-tier testing

7 system, first with ELISA as you have presented here

8 and then a confirmation with either PCR or mass

9 spec., throwing away your bias for mass spec.,

10 which would you recommend would be a confirmation?

11 DR. HURKMAN: I think you answered that it

12 is PCR because of its specificity and it is a lot

13 less work than mass spec., for sure. But if you

14 run into a question that you can\'t answer maybe

15 mass spec. might be\--

16 DR. PARK: Three-tier testing. Relative

17 cost\--I know you indicated that this is very

18 expensive, and also relative time for both the mass

19 spec. and the PCR. Could you elaborate on that a

20 little bit?

21 DR. HURKMAN: I will try. Mass

22 spectrometry, if you want to use a company that

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1 provides that service, runs about \$150 to \$200 per

2 sample. That means that you are preparing this

3 sample and giving it to them, which can take some

4 time. The samples that we prepare take roughly a

5 day and then with the mass spectrometer you can do

6 50 samples in a 24-hour period. So, that is where

7 I got that it is relatively slow and expensive.

8 On the ELISA, I can only tell you that a

9 kit is roughly \$300 for 42 assays and it takes

10 about an hour and a half. I was asking Jupiter

11 about that timing. That includes the pipetting of

12 the sample into the wells through reading the final

13 results.

14 For PCR I don\'t quite know. In our

15 laboratory we often start PCR the night before and

16 get the samples the next morning. We can do a

17 96-well plate and machines can do, of course, more

18 than one plate. Its cost is mainly for kits.

19 Again, they are roughly \$200 or \$300 for a kit that

20 can keep you happy for about a week or two.

21 DR. KANE: Rhonda Kane, FDA. Thank you,

22 Bill, for your presentation. On one of your slides

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1 you mentioned that some ingredients have glutenins

2 and not gliadins. Can you give me any examples

3 where you would have a food ingredient that would

4 not come with both proteins together?

5 DR. HURKMAN: We are doing a project

6 looking at various manufactured starches, and those

7 are what I am referring to. The starches are

8 relatively free of protein, low protein content,

9 and of the proteins that are there, they are

10 glutenins and not gliadins. Along with other

11 cellular proteins, they seem to be a magnet for

12 cell proteins. They are like a non-specific column

13 for endosperm proteins.

14 DR. KANE: Is this wheat protein that you

15 are talking about?

16 DR. HURKMAN: Yes.

17 DR. KANE: That only has the glutenins and

18 not the gliadins? Is that correct?

19 DR. HURKMAN: No, it has the glutenins\--

20 DR. KANE: I am sorry, glutenins and not

21 the gliadins?

22 DR. HURKMAN: And this is wheat starch.

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1 DR. KANE: And it is wheat starch. I had

2 another question about the ELISA method that was

3 mentioned by Jay Berger, where she said that the

4 University of Nebraska mentioned that hydrolyzed

5 protein and fermented proteins require a special

6 ELISA\--

7 DR. HURKMAN: Right.

8 DR. KANE: \--could you elaborate on that?

9 What is so problematic about detecting those types

10 of proteins?

11 DR. HURKMAN: What happens is that on

12 processing with heat, whether wet or dry, the

13 proteins denature and once they are denatured you

14 can\'t solubilize and assay them. So, it is

15 interesting. One objection I have to R5 monoclonal

16 antibody is that it is patented and not anybody can

17 do this so you have to run around and either create

18 antibody yourself because they won\'t sell it to you

19 and it only comes in a kit, or you figure out how

20 to do it. In this case, it is very funny\--I always

21 try to find out how to do things and there is a

22 patented solubilization buffer exactly for those

155

1 types of proteins that they either include in the

2 kit or you buy separately. That kit contains

3 agents that denature the proteins so that when they

4 go into solution you can assay them. Of course,

5 the ingredients are secret. But in one publication

6 I read it includes beta mercapito ethanol and, of

7 course, it would. I mean, that is a standard

8 component for doing that sort of thing.

9 DR. KANE: I have one last question and

10 that goes back to the starch. Do you know anything

11 about modified food starch and how it may differ

12 from just regular wheat starch\--

13 DR, HURKMAN: No.

14 DR. KANE: \--and if the proteins in that

15 are\--

16 DR. HURKMAN: No. Unfortunately, I

17 haven\'t read up on that yet.

18 DR. KANE: Thank you.

19 DR. ZINK: Don Zink, with FDA. Is this R5

20 monoclonal antibody the one that is used in all of

21 the commercial test kits now? What I am getting at

22 is do these commercial test kits suffer from an

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1 inability to detect glutenins?

2 DR. HURKMAN: You could ask Jupiter. He

3 can shake his head. But my feeling to your answer

4 is yes. Is that correct? I am not sure about that

5 because the Mendez kit is from Spain and I have no

6 idea how many kits\--at least two or three use them

7 and I don\'t know how many kits are out there. DR.

8 YEUNG: This is Jupiter Yeung. Actually, I am

9 going to talk about three different kinds of

10 antibodies that are used in the commercial market.

11 The Mendez kit uses a different polyclonal antibody

12 made by themselves.

13 DR. SCHNEEMAN: It would probably make

14 sense to go ahead and have Dr. Yeung give his

15 presentation.

16 DR. ZINK: Actually, I have one more quick

17 question. On the refined starch do you

18 consistently have enough DNA there to make the PCR

19 reliable?

20 DR. HURKMAN: That is a good question and

21 I think the only way it could be answered is by

22 someone that has done it. We have not done that in

157

1 our lab so I can\'t answer that. But it is a good

2 question because it is not clear always that there

3 will be enough DNA in your particular samples.

4 DR. SCHNEEMAN: Great! Thank you very

5 much. Our next speaker in this section is going to

6 be Dr. Jupiter Yeung, who is going to talk about

7 some of the commercial test kits and methods.

8 Commercial Gluten Test Kits and Methods

9 DR. YEUNG: My name is Jupiter Yeung. I

10 am the principal scientist with the Food Products

11 Association.

12 There are three different test methods, as

13 has been alluded to previously, and I am

14 concentrating on just the commercial test kits

15 based on the immunochemical methods, the ELISA and

16 the lateral flow device that is the dipstick. The

17 mechanism has been alluded to so I am going to skip

18 it.

19 In the commercial world for the gluten

20 test there are three different antibodies that are

21 being used. The first one is the skerritt

22 monoclonal antibody which recognizes the omega

158

1 gliadin. Although it is a monoclonal antibody, it

2 has also been identified that this antibody, also

3 recognizes the R5 gliadin. So, the reactivity

4 towards three different varieties of grains are

5 different, with the wheat being 100, rye 120

6 sensitivity and barley only 5. The monoclonal

7 antibody has been available for a long time, since

8 1991, and is the AOAC approved official method, in

9 \'95.

10 The other kind of monoclonal antibody

11 commonly being used is the Mendez R5 which

12 recognizes the five amino acid sequence and that

13 recognizes R5 beta, gamma and omega gliadins and

14 they are supposedly equally sensitive to wheat, rye

15 and barley. Both antibodies recognize raw and

16 cooked prolamins.

17 Here are the commercial test kits

18 available in the U.S. market. There are six

19 companies. Neogen is a U.S. company. R-Biopharm

20 is from Germany. Tepnel and Hallmark are from the

21 U.K. Diffchamb is from Sweden and Morinaga, a new

22 company currently just getting into the market, is

159

1 a Japanese company. Only the first one, the Neogen

2 Alert is a qualitative test. The rest of the test

3 kits are all quantitative.

4 The limit of detection and limit of

5 quantitation and the range are all in ppm gliadin.

6 So, if you want to convert it to gluten you have to

7 X 2. Within this box you insert how many mcg/ml or

8 ng/ml so I converted it to ppm to make it a little

9 bit easier for everybody to compare. But recognize

10 that for the Japanese one\--actually, I should have

11 two stars there because the reporting unit is

12 different from anybody else. It is not just

13 gliadin but, rather, a wheat protein. So, when you

14 do the interpretation, they are not the same. If

15 it is a quantitative analysis, once you look at the

16 error kill, the error kill is from 1 ppm to 50 ppm

17 detection limit.

18 The Tepnel and the Hallmark, although they

19 are two different companies from the U.K., are

20 essentially the same product because the owner,

21 originally from Tepnel, developed all the test kits

22 for Tepnel and now has his own company so they are

160

1 essentially the same. So, all the companies

2 Neogen, R-Biopharm\--they use the R5 monoclonal

3 antibody. Tepnel and Hallmark and Diffchamb use

4 the skerritt antibody. With the skerritt antibody,

5 they always have two different analyses, the

6 regular one and the sensitivity is 50 ppm of

7 gliadin but they all have a high sensitivity

8 protocol that includes Tepnel, Hallmark and

9 Diffchamb.

10 The high sensitivity assay will give you 5

11 ppm of gliadin so, depending on which method you

12 use, you have different sensitivity and this is how

13 many replicates you have to do per sample. The

14 cost is here. But recognize that for the cost you

15 can not just divide it by how much money and how

16 many samples you have to run. Every time you run

17 an assay you have to run the standard curve; you

18 have to run your quality control samples so one

19 cannot just say because they charge you \$15, it is

20 \$15 a sample. It is not that cheap actually. But

21 then one has to also recognize that they spent

22 hundreds and thousands of dollars to develop the

161

1 test kit so those are factored into your final

2 product. Like the mass spec. you have an expensive

3 instrument that you have to outlay.

4 Here, is the validation of the test kits.

5 The RidaScreen was validated by the Ring trials of

6 the Prolamin Working Group. For the BioKits and

7 the HAVen one they used the AOAC method but

8 original protocol was verified by the AOAC but not

9 the test kit itself. All the test kits would have

10 the validation data either internally or neutral

11 site testing. If you ask the company, I think they

12 will share with you\--I don\'t know if they will

13 share with everybody but I have all the validation

14 data.

15 They have two different kinds. One uses

16 the skerritt antibody, the other uses the R5

17 antibodies. So, the first one was validated

18 actually by Sweden, the national food authority

19 administration, the government agency. Morinaga

20 was verified by the National Institutes of Health

21 Sciences in Japan. I haven\'t seen the data yet but

22 they are going to present in the AOAC meeting this

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1 month. From what I heard, it satisfied the

2 government.

3 Here is one of the ELISA tests we use.

4 This is the standard curve we use, and in all the

5 samples you compare the color intensity with the

6 standard curve. But this is not exactly that all

7 commercial kits use this color scheme so it is

8 different and another company product will give you

9 a different color scheme, but it is all based on

10 comparison with your controls.

11 If you look at the lateral flow device,

12 the dipstick, there are primarily two different

13 companies providing it. The R-Biopharm gives you

14 10 ppm of gluten. This time it is gluten because

15 that is what the company insert declared. The

16 Tepnel uses 100 ppm of gluten. Although it is two

17 different kinds, essentially they are the same

18 sample; everything is the same except they don\'t

19 have the controls for the home test kit.

20 The mechanism is exactly the same as the

21 ELISA test. It is a sandwich mechanism. So, if

22 you have the antibody labeled and the antibody

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1 trapping in your sample in here and the control

2 antibodies here when you dip into the sample, the

3 sample containing gliadin, for example, will pull

4 up and will bind with the antibody and will be

5 trapped by another antibody for the test, and will

6 give you a sandwich and will give you a color, and

7 the control will be trapped here and give you a

8 different color. So, it is essentially the same

9 use. It will give you a few minutes for the

10 reaction and for the whole thing to occur, but you

11 have to wait until it dries up. So, in a total of

12 about five minutes you will have your result.

13 So, if you have two lines it is positive

14 according to this company\'s product, the control

15 and the test line\--so positive two lines, negative

16 one line, and if there is no line it means

17 something is wrong. Either your sample is not

18 meant for this method. In fact, it happened. Then

19 you have to do it again. Sometimes it is your

20 problem; sometimes it is your sample\'s problem.

21 But most of the dipsticks are two lines.

22 So, if you use a different company product\--this

164

1 one actually is the Tepnel one\--two lines is

2 negative; three lines is positive. If it is only

3 one line your sample is overloaded. So, one has to

4 recognize which commercial dipstick you are using

5 so your interpretation will be different.

6 But also recognize here when they say 10

7 ppm or 50 ppm, when you see the line it does not

8 mean it is 10 ppm or 50 ppm. It can mean much less

9 than that. And we also have data to show that even

10 if the detection is 10 ppm, you can see it; 5 ppm,

11 can see it, depending on how strong the line is.

12 If you are color blind you may not see it, but if

13 you are not you can see it.

14 So, there are different issues with the

15 gluten test kits. Depending on which test kit you

16 are using and depending on whether it is the

17 skerritt antibody or the R5 antibody the reactivity

18 is different and the extraction media is also

19 different depending on methods. Some use 40

20 percent, some use 60 percent alcohol and some use

21 cocktails and some don\'t; whether it is cooked or

22 not; or if you don\'t know whether it is processed

165

1 or not processed. And there are also different

2 standards being used in different kits. Most of

3 the European test kits use the Prolamin Working

4 Group standard now with the IRMM-480, but then the

5 480 is not commercially available yet to the

6 market. Some use the AOAC standard. All the

7 standards are not identical.

8 If you have a false positive and false

9 negative in the ELISA, it is very, very difficult

10 to confirm it because most of the alternative

11 confirmatory methods, like mass spec. or PCR, are

12 not available to most food companies, although one

13 can use the antibody based Western Blot to confirm

14 it but it is still the same mechanism.

15 Obviously, same as any other allergens or

16 other contaminants, there are no official or no

17 recognized sampling plans so random testing\--what

18 is random testing mean? I can get a positive

19 sample and I can get a negative sample very easily

20 if you know what you are doing.

21 Extraction media\--there are different

22 extraction media and cocktails, and also either

166

1 alcohol or the cocktail and in the cocktail some

2 ingredients are not known, and some we know

3 interact with the antigens and antibodies and the

4 mechanism is the antigen/antibody reaction.

5 The cocktail is also known to interfere

6 with some of the complex matrices and it is

7 reported in the Prolamin Working Group proceedings.

8 Another thing is that when samples have a high

9 polyphenol, tannins or syrups, that kind of thing,

10 your recovery tends to be very, very low if you

11 don\'t take care of it. Some have additives in.

12 Some people add fish gelatin to improve their

13 recovery.

14 Here is some of the information that we

15 know. Here is R-Biopharm data. Here is 40 percent

16 and 60 percent ethanol, 40 percent ethanol here,

17 and the cocktail here. One can see from the same

18 sample, the same homogeneous sample, that it will

19 give you all different numbers. Usually the

20 cocktail will give you quite a bit higher number.

21 But are these high numbers the true numbers or not?

22 One has to ask the question. The previous speaker,

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1 Bill, mentioned these 14 repeating units in the DNA

2 sequence. So, is the antibody recognizing one unit

3 or recognizing multiple units?

4 This is the PCR and it can differentiate

5 or speciate in a different one but not for the

6 antibody-based methods. For the partial hydrolysis

7 from the syrup if you use the sandwich-based ELISA

8 your recovery will be low so the Mendez group

9 actually has an alternative method. Instead of a

10 sandwich ELISA, they have a competitive ELISA to,

11 so-called, better quantify the hydrolyzed product,

12 and it has been published. But it still depends on

13 whether you have access to the antibodies or not so

14 it really doesn\'t help too much.

15 Reference material\--IRMM and TLC in Europe

16 have the 480 for wheat gliadin but, unfortunately,

17 it is still not available. The nice thing about is

18 it is fully characterized and also it is soluble.

19 If you use the reference material, there are

20 different kinds and they are not identical so what

21 do you choose? Alternatively, you can buy from

22 Sigma, you can buy from any other companies but

168

1 they are not the reference material and they are

2 not identical either as far as a confirmation

3 method goes, and I think the previous speaker,

4 Bill, has already mentioned this and discussed it

5 with you.

6 Here is the information for the three

7 different methods. These numbers are the ELISA

8 quantitation numbers. If you mass spec. you can

9 see all the alfa, beta and gamma gliadins using the

10 mass spec. method. You can use the immunoblot of

11 the antibody here, at the R5 antibody gel, and it

12 will tell you which proteins will be recognized.

13 This is the PCR for two different samples. So,

14 mass spec. and the PCR methods would be a good

15 marker to identify the allergens.

16 For detection and speciation, the

17 antibody-based method can give you a summation of

18 all the different kinds of grains\--wheat, rye and

19 barley. But the PCR and the mass spec. will give

20 you alternatives or speciate which grain may be

21 involved. If Health Canada is going to require

22 speciation of source labeling of the wheat for

169

1 celiacs, then we need an alternative method to tell

2 whether it is wheat, rye, barley or oat. That is

3 all for me now.

4 \[Applause\]

5 DR. SCHNEEMAN: Thank you very much. We

6 will take some specific questions. Dr. Hurkman, do

7 you want to come up to the front and we can have

8 some specific questions for you right now and we

9 can address the panel as a whole? Rhonda?

10 Questions and Answers

11 DR. KANE: Thank you, Jupiter. I had a

12 question so I understand one of your slides. It is

13 the fourth one in your series where you have

14 gliadin antibody specificity, and you have wheat

15 100 percent. Is rye 120 or is it 20?

16 DR. YEUNG: It is 120 because the antibody

17 was originally starting from rye so it is more

18 reactive to rye than wheat.

19 DR. KANE: Can you explain what those

20 percentages actually mean?

21 DR. YEUNG: It is the cross reactivity of

22 the antibody. So, if you plot an inhibitory curve,

170

1 the IC50, then you know that rye is more reactive

2 so it is more to the left than wheat and than

3 barley.

4 DR. KANE: Thank you. I have just one

5 more question. You mentioned, I thought, that

6 there were three types of antibodies.

7 DR. YEUNG: Yes.

8 DR. KANE: What is the third?

9 DR. YEUNG: The third one is Morinaga\'s

10 polyclonal antibody. They make it themselves.

11 They did not get a license from any of the

12 producers.

13 DR. KANE: So, that is not on that slide?

14 Is that correct?

15 DR. YEUNG: It is not on the slide because

16 Morinaga just came to the U.S. market and at this

17 point in time they are trying to evaluate the test

18 kits.

19 DR. KANE: Thank you, Jupiter.

20 DR. YEUNG: You are welcome.

21 DR. PARK: Doug Park, FDA. Thank you very

22 much for a very comprehensive summary of the

171

1 methodology. I do have some questions and to some

2 of the questions we already know the answer but I

3 think we need to have that brought out. You

4 pointed out and discussed briefly standards, the

5 availability of standards and so forth. Would you

6 address the composition of the standards that you

7 listed and the potential availability to any

8 organization that would want to have the standard

9 for confirmation of their testing program?

10 DR. YEUNG: The reference material from

11 NIST and IRMM, for that matter, too, they are the

12 official reference material organization, and it is

13 available to the whole world. It doesn\'t matter

14 who buys it or where you buy it, it would be the

15 same material, unlike if you buy it from Sigma; it

16 would not be the same. All the NIST materials are

17 available. The IRMM-480 are not officially

18 available yet but 480 is an alcohol soluble protein

19 and is meant for this kind of work. The NIST

20 reference material, the different varieties of

21 wheat, was not originally meant for allergens. So,

22 for characterization it is different. You look at

172

1 how much percent protein, carbohydrate,

2 minerals\--all the basic quantitative data that you

3 can get from NIST.

4 DR. PARK: Thank you.

5 DR. YEUNG: The reason why we always push

6 on reference material, the same as FDA\--we worked

7 together for a long time, pushing for the reference

8 material because if you use different reference

9 materials you would get different numbers that you

10 would generate, different numbers from your test

11 kit, and if you used it for your quality control

12 samples they would also give you a very, very

13 different number than what you are going to see,

14 and your recovery would be different because you

15 use a different standard so you are comparing a

16 little bit different\--it is not the difference

17 between oranges and apples but it is definitely a

18 different species so you will get a different

19 result.

20 DR. PARK: Thank you. Also, on your slide

21 where you showed the various levels of

22 quantitation, and so forth, the Tepnel method has

173

1 50 parts per million. Does that mean that is the

2 lowest you can go with that or are there other

3 options?

4 DR. YEUNG: The Tepnel one originally was

5 based on the skerritt procedure, the AOAC official

6 method, \'95. Because it is the official method it

7 has been used for a long time but for the last

8 couple of years, with everybody looking at the

9 Codex number pushing down to 20, they are pushing

10 it down to 20 ppm, so-called, the high sensitivity

11 procedure. Then they put in a factor of 2 and made

12 it 10 ppm.

13 DR. PARK: You also mentioned the matrix

14 effect of some of the extraction procedures, in

15 particular the cocktail. Are there issues where

16 that can be addressed as well?

17 DR. YEUNG: Issues have been reported but

18 because we do not know exactly what is in the

19 cocktail\--we know it is there\--and some companies

20 use it so you can imagine what would be there but

21 we do not know exactly what kind of issues there

22 are. But in our hands, when we use the regular

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1 procedure for testing and also when you add the

2 cocktail in the numbers are different,

3 substantially different. So, as a scientific

4 organization, we probably want to take a closer

5 look at these issues.

6 DR. PARK: You identified in your slide

7 for instance milk but do you have that same effect

8 with the cereal grains?

9 DR. YEUNG: I do not have experience in it

10 but that has been reported by the European group in

11 the 2004 proceedings.

12 DR. PARK: Was that the cocktail that was

13 used for the validation study in Europe?

14 DR. YEUNG: That is right.

15 DR. PARK: And the data there suggests

16 that it is fairly consistent and acceptable for

17 those commodities that were tested.

18 DR. YEUNG: Are you talking about the Ring

19 trial?

20 DR. PARK: The Ring trial.

21 DR. YEUNG: All the data reported from the

22 Ring trial is consistent with all the other

175

1 multi-lab validation procedures.

2 DR. PARK: This is my last question, and

3 you will never be able to answer it because it is

4 one of the biggest challenges. You did point out

5 the difficultly with sampling, sample preparation,

6 and so forth. I would like you to just take a

7 minute longer and point out some of the

8 difficulties associated with sampling as it deals

9 with potentially allergenic products, dealing with

10 the raw product as well as the finished product.

11 DR. YEUNG: I think everybody is trying to

12 look at FDA and trying to get a guidance document

13 to see what FDA\'s guidance is as far as sampling is

14 concerned. I know you guys had an extensive look

15 at this and we were told before that the guidance

16 document will come out soon. I don\'t know if it

17 will be soon or not. But I think most people still

18 want to have guidance from the regulatory agencies

19 so what we do can reflect that the inspector who

20 comes to the plant and takes a sample will be

21 consistent with what a company would want to do.

22 Of course, the problem of allergens is that the

176

1 contamination is heterogeneous and it is very

2 sporadic, and also the sample would be very\--you

3 can have contamination at one portion of the

4 process in-line or during the production cycle.

5 So, sampling would be the biggest challenge. At

6 the same time, because of the expense of the

7 testing and the time involved with the testing, one

8 cannot over-test during production.

9 DR. PARK: In your opinion, when you look

10 at the analytical result which is a sum of errors

11 associated with sampling, sample preparation and

12 analytical, where is the largest error associated

13 with those three categories?

14 DR. YEUNG: I think Whitaker presented and

15 published in the journal of OAOC recently, in 2004,

16 and if my memory serves me right, which doesn\'t

17 happen very often, it is the sampling that gives

18 you the highest variability, not the analytical

19 method. Actually, the analytical procedures gives

20 you the least uncertainty.

21 DR. HURKMAN: I think you asked a good

22 question, and that is what about different

177

1 samples\--flour versus process? To me, and the work

2 that I do, that is the critical point.

3 Unfortunately, what we find is that for every

4 sample we do we optimize the extraction methods and

5 I think it is going to take quite a lot of work to

6 categorize samples and how to extract them for best

7 results or reproducible results.

8 DR. LUCCIOLI: Stefano Luccioli, FDA. I

9 guess with the availability of some confirmatory

10 tests like PCR or mass spec., do we have

11 preliminary data on false-negative rates for the

12 ELISA kits or is that something that we just don\'t

13 have data on? I mean, how many times can one of

14 these tests be falsely negative and it has been

15 confirmed with a PCR?

16 DR. HURKMAN: I don\'t have a full answer.

17 The Ring study is the only study I know with that

18 sort of data. Right? If it even has it, and this

19 was published in the symposium proceedings. That

20 is hard to get. I have a copy back at the lab.

21 So, that hasn\'t been directly addressed and I think

22 that is why the assay is temporarily recommended

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1 rather than fully endorsed.

2 DR. LUCCIOLI: Thank you.

3 DR. PARK: I would like to comment on

4 that, and I am going to put on my FDA hat. This is

5 Doug Park. That is the reason why it is crucial

6 that methods are validated because that is the type

7 of data that you get from a validation study. The

8 Ring trial is an example of that. The AOAC

9 harmonized protocol is an example of that, where

10 you have 95 percent confidence in the analytical

11 result, and that addresses your false positives,

12 false negatives.

13 DR. YEUNG: This is Jupiter Yeung. I

14 think for the false positives and false negatives,

15 from the Ring trial there is information\--I don\'t

16 have the exact data with me, but the challenge is

17 on the actual sample. It would be very, very

18 difficult to prove if it is a false positive or

19 false negative from a real sample because all the

20 test kits are meant for all food matrices.

21 Obviously, everyone is going to spend a little bit

22 of time in the lab. You know, it is not possible;

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1 it is all matrix dependent.

2 DR. SCHNEEMAN: Do you have one last

3 question?

4 DR. LUCCIOLI: Yes, a follow-up to that.

5 I guess we could be able to get information on

6 which matrices may be more difficult to detect, and

7 so forth. So, I mean, some information. I don\'t

8 know if it is available but I was just curious, I

9 think Miss Berger talked about how she sent samples

10 to labs, to Steve Taylor\'s lab and the University

11 of Nebraska, and I am just curious to know what has

12 been the lowest level of detection, parts per

13 million, of a consumer complaint, if that data is

14 available.

15 DR. YEUNG: If you are looking at the

16 company claim for the limit of detection, the

17 lowest one is the R-Biopharm RidaScreen, which is

18 1.5 ppm of gliadin. That is 3 ppm of gluten. That

19 is the lowest one. The rest are all 10 ppm and

20 gluten.

21 DR. SCHNEEMAN: Did you want to comment on

22 that question? Identify yourself.

180

1 MS. BERGER: Jay Berger, Miss Roben\'s. I

2 was just wondering, you know, as a manufacturer of

3 the products trying to come up with the appropriate

4 testing for celiac disease and allergens, will the

5 summation of this discussion evolve into specific

6 procedures, specific tests and how to go about

7 doing them so that we can provide the best accuracy

8 to the product for the consumer?

9 DR. SCHNEEMAN: FDA is certainly in the

10 process of gathering as much information as we can.

11 So, we can make decisions within what we are

12 charged to do under the law. So, you know, at this

13 point we are trying to learn where we can go with

14 the information, and that is really the purpose of

15 this particular session, to learn as much as

16 possible so that we can then make some regulatory

17 decisions.

18 I think at this point we will need to

19 break for lunch. I do want to again thank our two

20 speakers for excellent presentations.

21 \[Applause\]

22 We really do appreciate your looking at

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1 the questions and issues we have and helping us get

2 the information out that we need.

3 Again, we have an hour scheduled for the

4 lunch break so I would like to see everyone back

5 here at 1:35 for our next panel. The most

6 convenient place is the Wiley Cafe but you will be

7 exiting security. For those that are more

8 adventuresome, certainly there are some areas in

9 College Park that are possible too but just keep an

10 eye to the time. Thank you.

11 \[Whereupon at 12:35 p.m., the proceedings

12 were adjourned for lunch, to reconvene at 1:35

13 p.m.\]

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1 A F T E R N O O N P R O C E E D I N G S

2 DR. SCHNEEMAN: Well, I think we had

3 better get started. We are ready for our third

4 panel and I do want to comment. I know we kept

5 telling you that Cafe Wiley may be your best and

6 simplest option, and I understand that there were

7 some problems with the delivery and food service.

8 We thought that we had sufficiently prepped them

9 for having the public meeting and having the types

10 of food that would be appropriate. So, I apologize

11 if any of you were inconvenienced. We are going to

12 follow-up to see where the gap was. It is

13 embarrassing to us to have you here as our guests

14 and not be able to offer the service that we

15 thought we had prepared for. I hope that wasn\'t a

16 hardship for anyone in particular and, please,

17 accept our apology.

18 As I said, our next panel will be to focus

19 on the consumer perspective on a gluten-free food

20 labeling standard. We will follow exactly the same

21 format that we have been following so far where we

22 will have the three presentations and some

183

1 questioning of each of the presentations and then,

2 hopefully, we will have enough time at the end to

3 have questions to the panel as a whole.

4 So, our first speaker is Miss Mary

5 Schluckebier, who is the executive director of the

6 Celiac Sprue Association, and I hope I pronounced

7 that close to the way you like it pronounced.

8 Consumer Perspective on a Gluten-Free Food

9 Labeling Standard

10 MS. SCHLUCKEBIER: Good afternoon. I want

11 to thank you again for the opportunity to be here.

12 I am Mary Schluckebier from the Celiac Sprue

13 Association, and I think it is really kind of an

14 interesting opportunity to get to share with you

15 some of the things that are happening with our

16 members, or what our members share with us 24 hours

17 a day sometimes. It is very nice to have answering

18 machines, and e-mail and calls. There are just a

19 lot of people being diagnosed now that have more

20 questions, and those are the ones really asking the

21 questions of the manufacturers so that they are now

22 looking to help us by ways of communicating with

184

1 each other.

2 At time of diagnosis\--Dr. Hamilton did a

3 very good job talking about the diagnosis and all

4 that stuff as kind of a clinical thing. You have

5 to think about it as this is a person. You have

6 been eating a normal diet for years and they tell

7 you these couple of things, first of all, about the

8 disease itself; that there is no known threshold at

9 this point that will create an immune response in

10 people with celiac disease. There is no way to

11 measure the presence of the offending amino acid

12 sequences, and it shows in research that if you

13 don\'t adhere to a strict diet you are going to get

14 sicker\--you know, that whole list of all the

15 complications that can happen.

16 So, then you are told eliminate all foods

17 and medications that are derived from wheat,

18 barley, rye and oats at this time\--I am going to

19 abbreviate these as WBRO from now on\--any of these

20 foods that have the amino acids that evoke an

21 immune response in people with celiac disease,

22 which is what we mean. We mean that whole basket

185

1 but we are going to call it WBRO. For the

2 remainder of your life do this and then you will be

3 healthy.

4 That is exactly what happens for most

5 people. After a few weeks on a gluten-free diet

6 people are feeling really great and then they get

7 into something that has wheat in it, and they want

8 to avoid this if at all possible. Now that people

9 are taking less than 11 years to be diagnosed, we

10 are finding people who have basically no symptoms

11 at all when they consume some wheat, rye, barley or

12 oats.

13 That makes it even a little more confusing

14 and they begin to rely more on information from

15 food manufacturers. So, again, from this time on

16 what you put in your mouth is your responsibility

17 and the consequences are really up to you, and how

18 successful you are in reading labels, gathering

19 information and making your decisions.

20 I would like to say that all of us process

21 this information. We don\'t All of us who have

22 celiac disease set up some type of way we make a

186

1 decision multiple times a day on whether we are

2 going to consume a product or not consume a

3 product. Most people will seek information of one

4 kind. Now, knowing that all information is not

5 equal and that we all can\'t absorb everything the

6 first week you are diagnosed and that it is a

7 life-long disease, your decision-making process

8 changes over the years.

9 But you seek out information and you have

10 coping techniques. So, people with celiac disease

11 often have a very broad-based knowledge about the

12 disease and food. As a support group, we do have

13 some help in helping people learn to do a

14 self-management guide which has three stages. The

15 initial stage is really looking at what you are

16 eating right now and how can that be adapted to

17 meet a gluten-free lifestyle so you don\'t have to

18 make major changes immediately, and then slowly

19 adding and evaluating foods that you want to change

20 and adapt your diet and expand it to greater and

21 greater food choices.

22 One of the things that we have

187

1 published\--we are now getting ready for the tenth

2 edition\--is a 375-page resource for people with

3 celiac disease where manufacturers have given us

4 permission to put in print their products that they

5 consider to be gluten-free or they consider

6 appropriate for people with celiac disease and

7 dermatitis herpetiformis.

8 We do spot-check some of these and have an

9 ELISA test done on them, usually at 10 parts per

10 million. Most companies\' products always test

11 below the level of detection of these. There are a

12 few that do not, and a few that have surprised us,

13 like beer. We tested three kinds of lite beer with

14 an ELISA at 10 parts per million and they all came

15 out below level of detection. We tested another

16 product that had barley as a second ingredient, and

17 the company gave us the test and it had been tested

18 with one of the older ELISAs that was only

19 sensitive for the gluten. So, we tested it at 3

20 parts per million in one that was cross-reactive; 3

21 parts per million barley, the second ingredient,

22 below level of detection.

188

1 We are not sure why for some of these

2 things, but what we do is we take the information

3 back confidentially to the manufacturer and see if

4 they can help us understand it. Often then they

5 make changes that make it more appropriate for

6 people with celiac disease if it is over, or they

7 feel great because they are doing what they think

8 they are doing.

9 To make an informed decision you need to

10 know what is present in a product and where it

11 really came from. Natural flavorings has been a

12 problem for people with allergies and celiac

13 disease, and it is one of the really good examples

14 though it is really hard to know, especially since

15 barley is a very common flavor enhancer.

16 So, in a person with celiac disease the

17 ingredient list gives you a good idea of what is in

18 the product. Calling the manufacturer on

19 processing and packaging is sometimes necessary if,

20 in your decision-making process, when you have

21 tried the product something isn\'t working and you

22 are trying to eliminate which product of all the

189

1 20-something you ate during the last little bit.

2 Then you often call the manufacturer and find out a

3 little bit more about the product\'s processing and

4 packaging and see if there is any other way that

5 this could be cross contaminated, or if you can

6 eliminate that this is not the problem food.

7 But when you eat 20 or 30 things a

8 day\--just think of how many things you eat\--trying

9 to figure out which one created a problem\--now, we

10 are doing this on symptoms, and all of you know

11 that symptoms are not a good indicator of what is

12 going on and they are very misleading. The symptom

13 really may be that I am catching a cold so I am

14 reacting to something that may be totally

15 unrelated\--maybe catching a cold isn\'t a good idea.

16 So, people use their decision-making

17 process and try and ferret out what is good for

18 their diet. That is why this meaning, full

19 verifiable and consistent, is really what we are

20 trying to pull together, and this meaningful thing

21 is when I say gluten-free it can mean so many

22 things to all of us. I am glad we use the

190

1 definition\--you know, we kind of came up with

2 definitions of how we are going to talk today but

3 when I am newly diagnosed and somebody says you are

4 giving up gluten and you have never even heard of

5 gluten, it is really hard and there is a learning

6 curve. Again, as consumers, often our manufacturer

7 consumer service groups have been the educators of

8 our members.

9 Verifiable\--we were talking again about

10 the ELISA or being consistent. So, when I see

11 gluten-free on one label it should mean the same as

12 everything else. And, generally on gluten-free our

13 members said they want it to mean the absence of

14 wheat, barley, rye and oats and that whole basket

15 of other things. But generally if you have any of

16 those other items on a food label they are going to

17 be in the label because they are a selling point

18 and a marketing point for the manufacturers.

19 These are some of the things that people

20 develop in their decision-making process. The

21 cross contact\--now, again, that can go from the

22 field to the fork and often, as a home economist, I

191

1 watch people prepare something and it often happens

2 right there in the kitchen. It happens when

3 somebody dips into the peanut butter jar and puts

4 it on the bread and goes in again and then gives it

5 to the person who is trying to avoid a wheat

6 product. It is very difficult to explain to people

7 that a person with celiac disease may have to watch

8 and be cognizant of all these potentials for their

9 entire consuming life. And, I am thinking why I

10 gained weight. Sometimes I wonder if we just

11 shouldn\'t eat just a few things and then there

12 would be a lot less to figure out and we wouldn\'t

13 gain weight, and it would be a weight loss program

14 and it would be easier to sell.

15 The cross contact begins at the farm, and

16 I am a farmer. This was near our farm. Harvesting

17 of summer wheat, spring wheat, winter wheat and

18 oats often in the Midwest is within two or three

19 weeks of each other. They are always going out to

20 harvest just before a rain because it is coming,

21 and you have to get it out and you know if you let

22 it go\--so it is always under pressure. I have been

192

1 married 30-some years and it is always under

2 pressure. We don\'t do this anymore. We don\'t do

3 the wheat anymore. But this one is near our farm.

4 There is no fence. There is no buffer zone. And

5 there is not, at this time, any regulation that

6 would call for that. But here the wheat has

7 already been cut. If you notice, there is a green

8 tinge to the oats. It is not quite ready but there

9 is wheat growing in the oats and oats growing in

10 the wheat. But we don\'t have to worry about cross

11 pollination because these are not cross pollinating

12 crops but they are harvested and handled in much

13 the same manner and through the same harvesting

14 equipment, and they are a consideration.

15 Now, I said my husband used to be a wheat

16 grower. We don\'t do wheat anymore. But there is a

17 quality control that I think about

18 applying\--olives, the olives for the olive oil,

19 they go through and they separate them by grades.

20 Maybe we just need a few more grades so that a

21 pharmaceutical grade would be adequate for people

22 with allergies and gluten-free. As a farmer, I

193

1 think this kind of sounds good because we maybe

2 could get more money for our crops. But right now

3 it is not even a near possibility.

4 So, when we ask our members across the

5 country about oats, right now eliminating oats from

6 their diet, 151 said they ate it and 22 had no

7 answer to the question. When we asked how would

8 you like to have gluten-free defined, the first

9 time we asked that a few years ago we said so many

10 parts per million and gave them checks. They

11 basically said, \"don\'t tell me the parts per

12 million, I want it absent of wheat, barley, rye and

13 oats. I don\'t know what these numbers mean.\"

14 I think there is a potential for oats

15 here. It shows that there are people who really

16 don\'t know what it is and are eating. It is

17 totally inconclusive on oats from everything I have

18 read. When I became a celiac in 1986 they were

19 questioning oats, whether or not to have oats. We

20 had 1,101 define gluten-free as the absence of WBRO

21 and 77 others who said they would like to see it

22 that way but they don\'t know whether oats should be

194

1 included or not be included in the definition.

2 At the threshold meeting, Dr. Colin

3 presented the fact that in the study that they did

4 10 percent of the participants with CD did get

5 immune symptoms and 19 percent of DH, and I just

6 think that maybe we need to look into this subset

7 and see if it is a real subset of people with

8 celiac disease who can or cannot ingest oats

9 without any immune response.

10 On packaging, if it could be that

11 gluten-free means the absence of all wheat products

12 in the product itself and then be verified with

13 testing, we would avoid things like this. Both of

14 these gravy mixes are marked gluten-free. One has

15 hydrolyzed wheat protein, and then it says ELISA

16 tested and gluten is removed, There is no

17 standardization for any of this and it is confusing

18 for a consumer.

19 The other package has rye malt extract as

20 a seventh ingredient, again, you saw gluten-free on

21 the other side. We had this one tested at the

22 University of Nebraska with the RidaScreen and it

195

1 tested 3,630 parts per million and we were talking

2 10 and 3 earlier. When we have tested things there

3 isn\'t a real consistency, and I wish there were.

4 One of the things is we have to have all

5 the ingredients on the product label. This is

6 candied walnuts. This one has wheat starch in with

7 the walnuts. Some of the food processing people

8 can help me a little bit with this, but I think

9 wheat starch is one of the wonderful coatings you

10 can use to help keep things fresh. That also then

11 creates a problem for a person with celiac disease.

12 They learn to read labels even when you think you

13 don\'t need to read labels. One manufacturer said

14 since I started working with people with celiac

15 disease I have learned about a new technique.

16 Celiacs pick up a package and give it the celiac

17 twist, they turn it and look at the ingredients.

18 If you want to know anything about any ingredient

19 you would probably ask the person with celiac

20 disease. They probably know that food and

21 nutrition label better than anyone else because

22 they have practiced a lot.

196

1 Also things that are a little confusing on

2 labels are wheat fiber that is certified

3 gluten-free and we don\'t know what the

4 certification program for it is. Wheat grass,

5 again, wheat grass has not been really tested

6 because the people who test wheat test it as it is

7 emerging and then as it is a mature crop, and as a

8 grass there is no research. Hydrolyzed wheat

9 protein, again, is one of those where the ELISA

10 test is not the most effective way of recognizing

11 it. So, this is an area that requires a little

12 more research before we really know how to even

13 deal with these. So, again, a definition that just

14 says the absence of anything from wheat, barley,

15 rye and oats is probably the most conservative at

16 this point.

17 When we ask manufacturers whether they

18 have these ingredients in their products, \"well

19 gluten is not present in oats and barley because we

20 use only the outer portion of the grain kernel and

21 that is gluten-free.\" \"Wheat fiber is certified to

22 be gluten-free.\" \"We adhere to the Codex

197

1 definition of gluten-free.\" \"And it tested below

2 the level of detection for gliadin so it is

3 gluten-free.\" When they were talking about the

4 testing, there are some that are just specific for

5 gliadin and some that do a crossover for the other

6 prolamins.

7 If you want to know what our group looks

8 like that were in the last two surveys, we are

9 mostly women. We are over 45 that stay members of

10 CSA. One of the things that happens with

11 membership in an organization like a support group

12 is that as soon as people become very comfortable

13 in their decision-making process they are like

14 butterflies and they fly off and go do their own,

15 and feel like they can manage their own disease,

16 which is good but it means that often we don\'t have

17 everybody who is a celiac as part of our

18 organizations. In Europe, if you are diagnosed you

19 automatically become a member of organizations,

20 such as in England.

21 This is the one that always surprises me.

22 When you ask the educational level, the education

198

1 level of our members\--those last three columns\--is

2 some college, college and postgraduate. I don\'t

3 know if it takes somebody really smart to get

4 diagnosed or, like one of my medical advisers said,

5 you can\'t make any kind of claim on those. But it

6 does mean that we do have people who are readily

7 reading labels. But we also have people who are

8 celiacs that are blind, they can\'t hear, and we

9 have those who have below 100 in mental capacity,

10 and we have had social workers call and say, \"how

11 am I going to protect the child that has a mother

12 who is not functional in the grocery store and at

13 reading labels?\" The one to the right is to show

14 you that most people who have celiac disease are

15 just normal people with all the other problems that

16 we can have, including other food concerns and you

17 will notice that milk is the most common. When we

18 ask how many food concerns do you have, or

19 allergies, or whatever, it was real interesting

20 that almost half of us have something else we are

21 looking at that label for. So, just marking

22 gluten-free, if this is indicative and you can use

199

1 this small group to predict the larger group, there

2 will be at least half the people who have to read

3 the label for something else.

4 But when we ask them what do you consider

5 your greatest challenge as a person with celiac

6 disease, the top one, overwhelmingly the top one is

7 lack of good food labeling. Now, I don\'t know how

8 you evaluate this part but they put avoiding cross

9 contamination along with concerns with traveling

10 and making decisions when you are eating out. They

11 weigh both about the same.

12 Where do you go to purchase your products?

13 People overwhelmingly say health food stores,

14 followed by grocery stores, mail order, internet

15 and super stores. When we ask them also where do

16 you think other people with celiac disease go to

17 buy their foods\--grocery stores.

18 We ask people to rate themselves with how

19 sensitive they thought they were to food,

20 medications, the skin, contact of medications, hair

21 products, detergents and lotions and soaps, you

22 will see that it is kind of all over the place.

200

1 People all say that their food concerns are the

2 highest. They are most sensitive to food. But

3 notice that there are people from very highly

4 sensitive to those that are hardly sensitive at

5 all.

6 Then we ask them how will you rate your

7 risk of choosing a product if you have incomplete

8 information. Will you take a risk? What is your

9 risk management technique? No matter where they

10 were on that sensitivity curve, we don\'t repeat the

11 same one here. It is almost overwhelmingly that

12 they are adverse to risk. They will take as little

13 risk as they need to, to continue on their diet.

14 So, what else do you look at when you are

15 looking at a label to purchase something? First of

16 all, most people are going to look at the

17 ingredients even if there is a marking that says

18 gluten-free. Then, after that, will they buy a

19 product with a seal or something that says it is

20 gluten-free? Most people will buy it at least

21 once.

22 This is what we are doing as part of our

201

1 program to recognize those companies that are

2 utilizing the WBRO and have given us good

3 documentation that there are procedures in place

4 that will assure a person with celiac disease that

5 they are making a choice by purchasing this

6 product, that it is free of wheat, barley, rye and

7 oats and everything else.

8 These are the general terms of the

9 license. We say that it is generally free in

10 product, processing and packaging. Everything is

11 kept confidential. Confidentiality I think is very

12 important in this type of communication between

13 consumer and the company. And, this is the seal of

14 agreement.

15 Questions and Answers

16 DR. SCHNEEMAN: Maybe we will take just

17 one or two quick questions, if there are some, and

18 then we will save the others for discussion.

19 DR. KANE: Thank you very much. Rhonda

20 Kane, FDA. Mary, with your certification program

21 do you ask them what parts per million their

22 products have to stay below for any sort of test

202

1 for gluten, or do you require them to have a test

2 with the results shared with you? What is the

3 scoop there?

4 MS. SCHLUCKEBIER: We require them to

5 submit some product and we will go pick things up

6 from the grocery store periodically. Depending,

7 again, on the processing, they are assured that it

8 is in place. If it is a dedicated plant and they

9 have only two products our testing requirements are

10 a lot less than if they have 20 products. They

11 have dedicated lines but in a somewhat segregated

12 area. So, it really depends on the company itself

13 and what procedures they already have in place and

14 they may already be testing. If they are, then we

15 do ask for copies of those and we do also do our

16 own independent testing. We will also do on-site

17 if the situation is one where that looks like a

18 prudent choice for helping people with celiac

19 disease that it is a product that is staying

20 consistent with no WBRO.

21 DR. KANE: Do you have a cut-off point

22 though? In other words, do you use 10 parts per

203

1 million or below as receiving permission to use

2 your seal? Or, can it go higher?

3 MS. SCHLUCKEBIER: I really don\'t see any

4 time when it would go higher than 10 parts per

5 million. It often might be lower. Many of the

6 products that we are testing where we have tried at

7 3 parts per million, they are doing beautifully.

8 It is not detectable at all at 3 parts per million.

9 DR. KANE: Thank you.

10 MS. SATCHELL: Felicia Satchell, FDA. I

11 wanted to ask about your CSA gluten-free product

12 testing and if there are any criteria that

13 manufacturers have to meet in order to get their

14 manufacturing information or products listed in the

15 manual.

16 MS. SCHLUCKEBIER: Right now, because

17 there is no FDA definition, we send the

18 manufacturer our list of what we consider necessary

19 to assure people that it is a product that is free

20 of wheat, barley, rye and oats. Most companies are

21 very, very good at voluntarily saying which of

22 their products are the best choices. We can\'t test

204

1 all of them and we don\'t; we take their word for

2 it. Often when we get communications from a

3 manufacturer who wants to be in it, you can kind of

4 tell\--again, those red flags. There are some

5 things that just don\'t seem right here. So, we

6 will do some extra checking and we will ask for

7 more documentation.

8 MS. SATCHELL: A follow-up question, do

9 you know if these products that are included in

10 your manual labeled as gluten-free are actually on

11 the product package?

12 MS. SCHLUCKEBIER: Probably very, very few

13 of those are marked gluten-free. Those companies

14 that do provide it are basically a niche market to

15 those who are trying to stay free of wheat, barley,

16 rye and oats for any reason. We do have an area in

17 the back that is a vendors\' section where we give

18 the company an opportunity to share a few

19 paragraphs about their company that helps provide

20 the people with celiac disease additional

21 information to make their decisions.

22 DR. SCHNEEMAN: Can you hold your question

205

1 for later discussion, please? Our next speaker

2 will be Miss Pamela Cureton, who is a dietitian who

3 works at Celiac Research Center which is affiliated

4 with the University of Maryland, located in

5 Baltimore, Maryland.

6 Celiac Research Center

7 MS. CURETON: Good afternoon. I happen to

8 be one who had a great lunch this afternoon so I

9 thank you. It was delicious. My name is Pam

10 Cureton. I am a dietitian at the Center for Celiac

11 Research at the University of Maryland.

12 Recently, in July, we presented a

13 conference. We did a conference for both

14 professionals and patients. It was about a day

15 before the conference was scheduled and we were

16 running around, extremely busy, trying to get ready

17 to put on the conference, when we got an e-mail

18 from Rhonda saying, by the way, do you have any

19 questionnaires, surveys, any information that we

20 might be able to use in helping us answer our

21 questions? So, I got an e-mail from Dr. Fasano

22 saying, hey, this is a great opportunity. I said,

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1 well, I had a couple of hours slated for a little

2 sleep; I can forego those. So, quickly we put

3 together a survey trying to look at some or the

4 questions that the FDA is looking at in the Federal

5 Register.

6 So, this is just a quick summation of what

7 that survey was. Taking a look at who completed

8 our survey in demographics, you can see that these

9 are all members of CSA because they meet the same

10 profile. The sample size was about 57, mainly

11 female. People completing the survey were aged in

12 a range from 11-78 years old. Actually, a person

13 on a gluten-free diet ranged from 3-78. They are

14 of a higher income level and had at least some

15 college. They are predominantly European American.

16 And, about a half of them had at least two years on

17 a gluten-free diet but some were just newly

18 diagnosed, less than a month, and some for more

19 than five years.

20 I wanted to know how carefully they

21 thought they were following their diet, how

22 strictly did they follow that diet and how

207

1 compliant were they. About 53 percent said that

2 they never ingest gluten. As part of the question

3 we asked are you concerned about questionable

4 ingredients or cross contamination? And, these

5 people felt that they did not ingest any gluten and

6 there was no concern for ingredients or cross

7 contamination. Thirty-seven percent, however, were

8 trying hard to follow their diet but weren\'t sure

9 about these questionable ingredients or if they

10 were getting cross contamination in their diet.

11 Five percent actually knowingly ingest gluten.

12 In trying to answer question number eight

13 talking about ingredients that should not be

14 present in gluten-free foods, I also found this one

15 interesting when we just listed ingredients that

16 somebody with celiac disease might question. So,

17 there are a lot of things on this list that are

18 perfectly safe and really don\'t need to be

19 questioned. But you can see that a lot of our

20 respondents were concerned. Overall, it shows that

21 people are very confused about ingredients, what

22 goes into ingredients, and whether it contains

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1 gluten or not. For example, starch, as this

2 committee is well aware\--if the word starch appears

3 on a food label, it is from corn, therefore, it is

4 completely safe to eat.

5 Also, some known gluten-free or

6 non-gluten-containing grains like millet and

7 buckwheat, again, are of concern to some of our

8 respondents. Things like distilled alcohol and

9 vinegar are still concerns. So, people have a lot

10 of questions about what is on that food label and

11 what is in those food ingredients.

12 So, we asked what does gluten-free mean.

13 Are we talking about no detectable levels? Are we

14 talking about trace amounts that are probably safe

15 to eat? Or thought to contain gluten and

16 definitely contain gluten.

17 There is no surprise here. Seventy-one

18 percent of the respondents felt that a food item

19 labeled gluten-free should have no detectable

20 gluten. There should be no detectable gluten in

21 the product. A few responded that there could be

22 trace amount and they would consider that safe to

209

1 include. Only two percent said it may contain

2 gluten.

3 Again, the same question was asked, what

4 should it mean? You have your perception of what

5 you think it means; what should it mean? Again,

6 very much similar response and 83 percent reported

7 it should mean no detectable gluten; 17 again

8 reported that they would consume it if it had trace

9 amount and feel that it would be safe to consume.

10 So the perceptions of what people think gluten-free

11 means and what it should mean are virtually the

12 same. An overwhelming amount say that there should

13 be no detectable gluten.

14 At looking again at trying to identify

15 foods with gluten, and I think it was question

16 number nine, we asked how consumers identify

17 packaged foods that do not contain gluten. When

18 you are reading labels how do you identify those

19 foods? Of course, reading labels was number one.

20 Our respondents could check more than one answer so

21 they could check from a list of questions which

22 ones they would use. Thirty-two would rely on the

210

1 food labeling gluten-free; 25 would call the

2 manufacturer. Other choices which were not

3 selected would include asking healthcare

4 professionals, like dietitians and physicians\--that

5 made me feel good! We also asked about risks and

6 product guides. Those were other selections that

7 people used to find out if their food had gluten.

8 Question number ten refers to packaged

9 foods like consumers with celiac disease purchase

10 or consume are primarily or exclusively those foods

11 labeled gluten-free, so kind of what influences the

12 purchase. Only 24 respondents reported that they

13 would rely on those gluten-free foods, while others

14 would rely on the manufacturer or, again, rely on

15 the safe food lists that are published or on the

16 internet. They would use those as reference.

17 We did ask how likely they were to

18 purchase the food if the food was gluten-free, if

19 there was nothing on the label that indicated that

20 it contained gluten but it was manufactured in a

21 plant that also manufactures other foods that do

22 contain gluten. So, how likely were they to

211

1 purchase that food? They were evenly divided on

2 either extreme. Only nine percent said they

3 absolutely would and only nine percent said they

4 absolutely would not. So, the majority of the

5 people were in the middle and would probably

6 purchase the food if the food was gluten-free but

7 still was manufactured in a non-dedicated plant or

8 where other gluten-containing grains are.

9 Obviously, there are limitations to this

10 study. It may not generalize well to all of our

11 celiac patients. It was a sample of convenience

12 and, again, these were predominantly high income,

13 well educated Caucasian Americans participants with

14 an average age of 47. So, it was a small sample

15 size and based on self-report. Thank you.

16 \[Applause\]

17 Questions and Answers

18 DR. SCHNEEMAN: Do we have some questions?

19 Yes?

20 DR. LUCCIOLI: I have a question on a

21 slide where you say what does GF mean. You have a

22 trace amount of gluten and in parentheses you have

212

1 less than 10 mg.

2 MS. CURETON: It should be 10 parts per

3 million

4 DR. LUCCIOLI: Okay, that answers that.

5 What does the consumer understand? Do they

6 understand the significance of the level 10 mg/kg

7 or that it also is a factor of how much they eat?

8 MS. CURETON: Based on clinical experience

9 in a clinic when I instructed patients, they

10 basically have no clue as to what a part per

11 million is, what a milligram is, how much you can

12 eat, that there is anything in the foods that they

13 eat that is listed gluten-free. They are assuming

14 there is nothing there; that they are getting any

15 source of contamination when they are reading their

16 labels and following the recommendations, and how

17 much they can eat. This doesn\'t enter into their

18 thought process.

19 We have patients who are more sensitive to

20 gluten and we have a hard time getting the antibody

21 levels down to normal. So, some patients can do

22 the basic diet, follow it carefully, read the

213

1 labels and do quite well. But there are those that

2 are more sensitive and we have a hard time getting

3 their levels down. Those are the patients that I

4 spend more time with talking about those types of

5 issues\--how much of the gluten-free products they

6 are getting. I try to explain to them there could

7 be some contamination or low levels of gluten that

8 they are very sensitive to, and they are very

9 surprised when they hear me say that.

10 DR. LUCCIOLI: Thank you.

11 DR. KANE: Rhonda Kane, FDA. Thank you

12 very much, Pam. I had a question about

13 gluten-free. You talked about no gluten, but as

14 far as the grains that they consider being sources

15 of gluten, are they the typical ones we have heard

16 about from others, and what about oats? Could you

17 elaborate, please?

18 MS. CURETON: They would be the typical

19 grains. Again, the patients that we see are well

20 aware of wheat, rye, barley. I am questioned

21 frequently on oats. But wheat, rye and barley are

22 the standard grains that they are well aware of.

214

1 DR. KANE: And does that include the

2 crossbred hybrids like triticale and also other

3 varieties or other species within the triticum

4 genus with kamut, spelt durum wheat, etc.? Are

5 they including those too?

6 MS. CURETON: I think a lot of them, like

7 me, didn\'t even know what triticale is\--I can\'t

8 even say it\--before I started looking into celiac

9 disease, and kamut and all of these things. I

10 don\'t think most people knew what they were. Those

11 things they are less aware of, and spelt is still a

12 big one, as we commented on earlier. Health food

13 stores are promoting gluten-free diet being okay to

14 have spelt and a lot of people are very confused

15 about that.

16 DR. KANE: What about the oats issue? Are

17 they including oats or not?

18 MS. CURETON: They are not including it;

19 they are asking. They are asking for permission.

20 When they come to see us they are asking for

21 permission. At this point we do not allow oats at

22 our center. There are other centers that do. I

215

1 basically give them that information. I tell them

2 that we are not recommending at this time and I

3 tell them other centers are, and they are okaying

4 it, and what I ask them to, if they do decide to

5 make a decision to try oats, to please let me know

6 so we can then follow their antibody levels to make

7 sure that they are doing it safely. So, we would

8 just follow those patients if they choose to do

9 that. We, again, present them with the latest and

10 what our opinions are and just ask them to tell us

11 if they are going to try oats and then we will

12 follow them for their antibody levels.

13 DR. SCHNEEMAN: Thank you very much. Our

14 third speaker for the panel is Miss Anne Lee, who

15 is a nutritionist who works with the Celiac Disease

16 Center which is affiliated with Columbia University

17 located in New York City.

18 Celiac Disease Center

19 MS. LEE: I want to thank you for inviting

20 me. I am very honored and, indeed, pleased to be

21 part of this momentous occasion in helping the FDA

22 determine what should be included in gluten-free

216

1 labeling and to help direct that.

2 Today we are going to be talking about

3 different topics that need to be addressed.

4 Actually, Tricia Thompson\'s name is on the program

5 also. She is the lead author on a diet survey that

6 we will be looking at. What we have done is

7 combine Tricia Thompson\'s article on the survey of

8 gluten-free food consumption, in addition to

9 surveys that we are doing ongoing at Columbia which

10 look at consumption patterns, the price of

11 gluten-free food, in order to pool the latest

12 research information that we have together to

13 better address the various questions the FDA has

14 asked us to look at.

15 In the gluten-free diet survey we reviewed

16 the food records for 47 adults, 39 females, 8

17 males. Again, this seems to be representative of

18 the population of people with celiac disease. It

19 was interesting in this population that as we

20 looked at their consumption patterns and the types

21 of foods that they ate that across gender they

22 tended to eat the same types of foods.

217

1 What was also very interesting is that the

2 largest group of foods that they tended to eat were

3 the prepackaged, pre-prepared foods that were

4 labeled gluten-free. The patterns also noted that

5 there was a large influence of corn-based products,

6 particularly snack type corn-based products, like

7 the chips, the savory snacks, and only two

8 participants out of the 47 actually consume the

9 other gluten-free safe grains. There were two that

10 use bean flour or millet on a routine basis.

11 So, when we look at these consumption

12 patterns, we are finding that many people relying

13 on the labeling of gluten-free and relying on

14 things that are safe. And, I think that is an

15 important thing to note.

16 The other thing we found is that the type

17 of food groups, whether it be sandwich bread and

18 pastas or corn tortillas, also had a determining

19 factor on whether or not the product they consumed

20 had a gluten-free label, and it was depending on

21 the particular groupings of food whether or not

22 those foods were labeled.

218

1 The foods that are in the sandwich bread

2 group, which included muffins, pizza crust,

3 pretzels and those things predominantly, these

4 foods were all well labeled gluten-free and

5 participants overwhelmingly chose the ones that

6 were labeled gluten-free over those that were not

7 labeled gluten-free, and the labeling was prominent

8 on the packages, as you can see. It was front and

9 center and highlighted, which we feel was an added

10 bonus of security to the patients buying these

11 products.

12 In the pasta group, again, we find the

13 same sort of purchasing patterns. Again, these

14 foods tend to be specialty food items. They were

15 done in designated facilities. They were

16 prominently labeled as gluten-free, and most were

17 labeled gluten-free, not all, but the list of

18 ingredients was the second determining factor in

19 this group. Again, the labeling tended to

20 be prominent rather than being small or on the back

21 of the package, which was an influencing factor,

22 and it was everything from saying gluten-free in

219

1 the middle of the bag to just the universal symbol

2 that is often used on the European products.

3 In the pasta and ready-to-eat cereal, the

4 group of products in this main category that were

5 not as prominently labeled were those that we call

6 more ethnic type foods, like the Asian rice

7 noodles, and these foods tend to be naturally

8 gluten-free. They are only made with rice or

9 buckwheat so, therefore, are gluten-free. These

10 were the products in this main heading that were

11 not labeled and these were the ones that the

12 participants used the list of ingredients to

13 determine their safety.

14 The next group of foods is snacks and

15 crackers, and this was a product area that actually

16 presented some problems. This was a group that was

17 one of the largest food consumption groups overall.

18 When we look at all the different products that our

19 patients and clients were, consuming, the snacks

20 and crackers and these prepared foods actually

21 comprised over 50 percent of their daily intake.

22 Now, as a dietitian, you know, red flags

220

1 start going up, and when we see that someone\'s

2 grain and carbohydrate intake is over 50 percent of

3 snack foods, it makes me be very concerned about

4 the nutritional content of the diet overall.

5 Indeed, Tricia had done other work that notes that

6 the nutritional intake and nutritional value of

7 someone on a gluten-free diet is not meeting the

8 standards we need.

9 One of the things too in this area of

10 products is that we find much mislabeling. As you

11 can see, one brand of the rice crackers was labeled

12 \"no gluten added\" on the front and on the back it

13 says it contains trace amounts of wheat. What is a

14 consumer to do? Which side of the package do you

15 believe? So, standardized labeling would help

16 alleviate a lot of that.

17 As we said, the corn products were one of

18 the areas that were heavily relied on. Again, it

19 was a lot of the pre-prepared snack types of foods

20 that, again, raise some concern. As many of these

21 products are considered naturally gluten-free\--a

22 corn tortilla for the most part is corn and a

221

1 little bit of salt so it is generally safe.

2 However, the heavy reliance on corn-based products

3 also has a negative impact on the nutritional

4 quality of the person\'s diet. We are missing

5 fiber; we are missing the iron; we are missing

6 other B complex vitamins.

7 The other area besides the corn and snack

8 food, as we said before, is the large selection of

9 frozen prepared foods that many of the participants

10 use. The good piece of information on this is they

11 chose foods that were clearly labeled gluten-free

12 but, again, there are so many questions about

13 nutritional density of those choices.

14 Based on these findings. we were concerned

15 that with this type of an intake and with knowing

16 that gluten-free labeling was an important factor

17 in these consumption patterns, we wanted to look at

18 the next step. What is it that makes a consumer or

19 a client determine whether or not to buy a product?

20 So, again as Pam had done, we did a survey of about

21 57 people who came to see us at the office and the

22 Celiac Disease Center and asked them\--we gave them

222

1 a short, little survey\--what was it that made them

2 decide to buy one product over another.

3 One of the outstanding pieces of

4 information we got from this is that 100 percent of

5 the participants, 57/57, said that if there were

6 two products side by side with identical

7 ingredients and one was labeled gluten-free and one

8 was not, they would purchase the one that is

9 gluten-free, which is a wonderful endorsement for

10 the labeling. However, it also brings to mind the

11 concern of does that make one had of broccoli safer

12 than the next? So, I think we need to keep in mind

13 that there is an overwhelming need for labeling,

14 but labeling of the appropriate product.

15 I had one woman tell me, well, I know that

16 this can of tomatoes is okay and it is better than

17 the other one because it says it is gluten-free.

18 There is really no foundation for that. A can of

19 tomatoes is a can of tomatoes. So, we know that

20 there is a drive by the consumer, by our patients,

21 to look for that safety in the labeling but we, as

22 the industry and we as the professionals in the

223

1 health field, need to also direct them and teach

2 them which way to go.

3 We did find that the presence of the

4 gluten-free label did, indeed, have a very huge

5 impact. When a label was not available on those

6 products\--again, the savory snacks, the crackers,

7 the naturally gluten-free products\--the second

8 thing that the clients look for, in a 2:1 ratio,

9 was the list of ingredients. They will look down

10 the list of ingredients and try to determine from

11 that whether or not the product is gluten-free.

12 What we found, however, is that there are

13 many questions. Is spelt, indeed, what or not?

14 What is triticale? And, where does kimwa fall into

15 place? So, they try to decide from the label but

16 more information is needed there.

17 Now that we are going to be better

18 understanding what is influencing our patients\' and

19 clients\' practices, we also need to know how to

20 teach them well. For this part of the presentation

21 I wanted to highlight the ADA, the American

22 Dietetic Association, manual and the client

224

1 education material that is available for all

2 dietitians because I think not only do we need to

3 educate the consumer, but we need to educate

4 ourselves so that we also know the grains and

5 things that we are going to be teaching them about.

6 However, at the time of this presentation

7 the 2004 ADA manual is the one that we are showing

8 you here. The 2005 edition, which will reflect the

9 2004 food allergen labeling law is in the last

10 stage and may be ready for the September 19 docket

11 deadline, but at this time it is not. That one

12 would give a better picture of what we really need

13 to teach our clients and how we really need to

14 direct them and steer them through the food

15 labeling and the ingredient list.

16 We would be able to say that malt is still

17 something to worry about because it is barley

18 based, whereas the modified food starch is going to

19 be corn based and it will say it so that we will be

20 able to better teach them things to look for there.

21 As we said, barley and rye will continue

22 to be an issue in the 2005 edition, but that is

225

1 something that we will make sure that our client is

2 educated on. The ADA manual does tend to be

3 client-centered so that we give them the tools that

4 will be able to give them that shopping list, that

5 hand-held kind of piece of paper to take to the

6 store so they can make those informed decisions and

7 can maneuver through the various products, with it

8 be a rice cake, the kind of thing that might not be

9 currently labeled and the ingredients may be

10 difficult to get through.

11 In all of this, we realize that we are

12 purchasing many products, that we have increased

13 availability of food, increased availability of

14 labeling and increased availability of foods in the

15 various vendors, whether it be a supermarket, a

16 health food store.

17 But we found, as we are looking at

18 different patients and they are reporting back to

19 us, that in what was influencing their purchasing

20 practices there was an underlying tone of \"but I

21 can\'t find it\" and \"I can\'t find that.\" If you

22 started asking them where they shopped and how they

226

1 purchased their food, we found overwhelmingly that

2 they tended to do it in the grocery store, the

3 health food store, online or through specialty

4 vendors. But this raised the question to me\--and

5 we actually did a survey of the difference in cost

6 of the products in these four different spaces.

7 The regular grocery story availability depended

8 upon where they were. We surveyed stored in

9 Portland, Oregon, Rapid City, South Dakota,

10 Chicago, Illinois, New York and Atlanta, Georgia.

11 What we found is that depending upon your

12 location\--and I can guarantee you know exactly

13 which store had products and which one didn\'t\--that

14 determined what that client was able to obtain.

15 The patients who were looking for things in the

16 Midwest, in the Rapid City are, they had to go

17 online. That was the only choice they had. That

18 brought up the question to me, because the online

19 products tend to be more expensive than those

20 products, if you can find them, in the local health

21 food store or grocery store.

22 So, in addition to the labeling that our

227

1 clients have to decipher, we also have the

2 additional burden of finding the food and the

3 economic cost of it. So, maybe if the foods were

4 labeled in the regular grocery store, those rice

5 crackers and things, it may increase the

6 availability of food to these people in these other

7 locations. We are fortunate on the East Coast to

8 have a great availability of food but that is not

9 true for many people across the country. And, we

10 get calls frequently at the Center from people in

11 Iowa, in South Dakota asking is it safe to eat X,

12 Y, and Z product? And, we have to try and direct

13 them as best we can through those ingredients

14 because that may be all that is available to them.

15 We looked at two different groups because

16 those tend to be the largest consumed products, the

17 gluten-free pastas, as we have seen, and the

18 gluten-free bread, and in both cases there was an

19 increased price for buying the product online.

20 What we did is we took two products and looked at

21 them both in the health food store and online, and

22 this was the difference in cost even before we

228

1 added in shipping and handling. So, the concern is

2 that for those consumers where the market may not

3 have quite caught up to them yet there is not only

4 the burden of reading those labels but the economic

5 one, as we said.

6 The final thoughts are that for our

7 clients with celiac disease we do want to encourage

8 them to consume a wide variety of foods. They do

9 include many various products, both labeled

10 gluten-free and not. Those that are not labeled

11 gluten-free, they try to obtain those that are

12 manufactured in dedicated facilities. That is not

13 always possible. There is a strong preference to

14 purchase the foods that are labeled gluten-free

15 when available and when possible. Many have

16 reported that it is difficult to determine the

17 gluten-free status of a product that is not clearly

18 labeled. Thank you very much.

19 \[Applause\]

20 Questions and Answers

21 DR. SCHNEEMAN: We will have some specific

22 questions for Anne. Then, if the other panel

229

1 members could come up we will have the general

2 panel immediately following. So, if we have some

3 specific questions right now? I will let Don go

4 first.

5 DR. ZINK: Don Zink, FDA. You talked

6 about looking for products made in dedicated

7 facilities. How frequently do manufacturers label

8 or indicate if a product is made in a dedicated

9 facility, and how do they do that?

10 MS. LEE: Often through advertising.

11 There are certain manufacturers that do state it is

12 a dedicated facility. It may be on the label. It

13 may be in the advertising in various magazines and

14 journals. But, again, the consumer is left to try

15 and find that out before they can even purchase the

16 product.

17 DR. ZINK: I guess a follow-up, is it

18 desirable? If you have gluten-free labeling, is it

19 desirable to also have some sort of labeling if it

20 is in a dedicated facility or not? Does that

21 improve comfort level?

22 MS. LEE: It would improve comfort level

230

1 but, indeed, if we had uniform gluten-free

2 labeling, my understanding would be that it would

3 meet those standards and the additional labeling

4 that it is a dedicated facility would not need to

5 be on it because it is already going to meet the

6 standards of being gluten-free.

7 DR. PARK: Doug Park, with FDA. I noticed

8 oats is missing in your presentation. Would you

9 like to explain that?

10 MS. LEE: We say that oats are okay, with

11 this caveat, because oats are a wonderful grain and

12 scientifically it is gluten-free. It is the

13 milling, the handling, that cross contamination

14 that is an issue. From work that was done by Colin

15 and Thompson who have looked at the issue of gluten

16 contamination in oats, there are a couple of oats

17 that are available that we feel do meet those

18 standards. We have looked at the research out of

19 Europe and we really feel that including clean oats

20 in the diet enhances the diet. It helps add those

21 nutrients back that right now are sorely missing.

22 However, we beat our patients up a little bit.

231

1 They can\'t start oats until they are symptom free.

2 We are not going to add a new twist into the diet

3 unless we know that their antibody levels have come

4 down; they are symptom free. Then if we add oats

5 we know the variable we are adding. We add oats in

6 from the two different providers that we say are

7 safe and then we follow up with them both with

8 antibody testing as well as symptoms. If there are

9 any changes there are no more oats. We instruct

10 them very, very carefully. It doesn\'t mean oats on

11 any label; it is specifically the can of oats that

12 are clean, designated oats.

13 DR. PARK: Thank you.

14 MS. LEE: You are welcome.

15 DR. KANE: Anne, I have a question. You

16 said several times in your slides that the presence

17 of a gluten-free claim or symbol strongly

18 influences purchasing choices of people who have

19 celiac disease. Is that correct?

20 MS. LEE: Absolutely correct.

21 Specifically on the two products side by side that

22 were identical based on the ingredients, if one is

232

1 labeled gluten-free and one is not, in our survey

2 100 percent of the respondents picked the one

3 labeled gluten-free.

4 DR. KANE: Okay, I am going to take you to

5 the next step because you gave a very good example

6 about canned tomatoes\--

7 MS. LEE: Yes.

8 DR. KANE: \--say, all canned tomatoes, if

9 they are strictly canned tomatoes with tomatoes and

10 salt and possibly another second ingredient but it

11 is tomatoes, period\--

12 MS. LEE: Right.

13 DR. KANE: \--if they are all inherently

14 gluten-free and one has a gluten-free claim and the

15 other doesn\'t, just because they don\'t choose to

16 put it on there, not that it isn\'t; it is

17 identical\--

18 MS. LEE: Right.

19 DR. KANE: \--in your opinion, what would

20 be a way to make it less confusing for consumers

21 who are looking to make the right choices and not

22 being concerned that one brand is okay but the

233

1 other brand isn\'t, and get the message across that

2 all of the same type or category of food is

3 gluten-free whether they have a claim or not? So,

4 what would be your suggestion if somebody used a

5 claim of gluten-free to kind of rectify that?

6 MS. LEE: What we do, and I am sure Pam

7 does something similar with her patients too, we

8 try to educate the patient, because we start there,

9 that there are certain foods you need to be careful

10 of. Things like your fruits and tomatoes, if they

11 are just inherently that product\--the can of

12 tomatoes, the head of broccoli, the frozen

13 carrots\--that naturally is gluten-free. It does

14 not need a label. What we would recommend is that

15 the manufacturing community follow the same thing.

16 There is no need to say a tomato is gluten-free.

17 It is gluten-free.

18 Where the labeling would help is on those

19 grain products that do present a question as to

20 whether or not they are gluten-free. If we could

21 recommend that the law would include those products

22 that would raise a question\--the pastas, the

234

1 breads, the cereals, the crackers\--because those

2 are the things that we need to help identify for

3 our patients. A broccoli is a broccoli, is a

4 broccoli. It doesn\'t matter whether it says it is

5 gluten-free or not.

6 DR. SCHNEEMAN: If I could maybe just

7 clarify what I think Rhonda is getting at, so, if a

8 person still chose to do label their broccoli or

9 tomatoes because they feel it is a truthful

10 statement, is there other information that should

11 go on that product to help consumers or the clients

12 that you are concerned about, or is it okay for

13 them just to do it that way?

14 MS. LEE: It is not false labeling. It is

15 okay for them to label it. It may be misleading in

16 that it may make the product appear enhanced even

17 though it is still the same product. I don\'t know

18 how you would, you know, differentiate on that.

19 DR. KANE: Are there any different ways

20 that a product could include a gluten-free claim

21 but the way it is worded, would that help? And, do

22 you have any ideas of how additional wording should

235

1 be added or, in other words, word it one way if

2 there is a potential that it could contain gluten

3 and this is special because the processing is

4 there, versus all of the same foods in the same

5 category is gluten-free\--all milk? So, what would

6 you get across to let people know that all milk is

7 gluten-free and not just certain brands?

8 MS. LEE: Naturally gluten-free. I think

9 the terminology that this food is naturally

10 gluten-free, just by the nature of its composition,

11 may be the way to go. Whereas, a rice cracker or a

12 pasta is not naturally gluten-free and that is a

13 special manufactured product. So, if it is labeled

14 that this is a gluten-free grain or this is a

15 gluten-free product versus a naturally gluten-free

16 product may be the way to differentiate that the

17 tomato is the tomato but the pasta is a rice-based

18 pasta and, therefore, a different type of product.

19 DR. SCHNEEMAN: Would that help?

20 DR. KANE: Yes, that is very helpful.

21 Thank you.

22 DR. SCHNEEMAN: We can have your question

236

1 but if we can get the other two panel members to

2 come up? Felicia, do you want to go ahead?

3 MS. SATCHELL: Felicia Satchell, FDA.

4 Actually, this question is directed at both Tricia

5 \[sic\] and Pam. It goes back to the statements that

6 you made about patients who are eating oats. I

7 think in your case, Pam, you advised that if they

8 do that to let you know and that you would continue

9 to monitor their levels. I guess I just wanted to

10 know in cases where you have patients that have

11 eaten oats, have they had any problems as you have

12 monitored their levels? Have they been able to

13 maintain the oat diet? And, in your case, Pam, the

14 oat products that they ate, were they shelf

15 products or were they specially marketed products,

16 similar to the ones that Tricia\'s patients have

17 consumed?

18 MS. CURETON: Generally our patients

19 don\'t. I don\'t see a lot of patients who do eat

20 oats. Our patients are asking permission before

21 they would do that. I have seen so few that I

22 don\'t think it is really significant. I have had I

237

1 think one patient in the last six months that came

2 to us already on oats. It so happened that their

3 antibody levels were normal and there were no

4 symptoms. It was a child and they were growing

5 well. I did not pull them off the oats. They were

6 using I think McKane\'s oats, but not another

7 product.

8 MS. LEE: Anne, from Columbia University.

9 When a patient comes and requests oats there are a

10 couple of types of patients in whom we actually

11 encourage the inclusion of oats. Our patient

12 population is predominantly adults. We have

13 several males. As a normal male, we have

14 cholesterol issues and we find that including the

15 higher fiber grains\--oats, kimwa, buckwheat,

16 millet\--that is a way to help enhance the nutrient

17 density and fiber content of the gluten-free diet.

18 But, again, we only recommend two types of oats.

19 It is not the commercially prepared oat bars or oat

20 cookies. And, we do closely monitor them.

21 DR. LUCCIOLI: Stefano Luccioli. What

22 percentage, would you say, of your patients

238

1 eventually have to drop oats from their diet, or

2 haven\'t you had really anybody?

3 MS. LEE: We have had one or two people

4 that have not tolerated them well but it is really

5 few. Interestingly, it was two adults. The kids

6 that we have that are doing oats, as Pam\'s patient

7 also\--they are thriving; they are thriving, which

8 is one gentleman and one female. So, it didn\'t

9 seem to be a gender issue, just an individual

10 tolerance. Again, when we introduce oats we do

11 things, as we do with any trial type of a diet, we

12 don\'t let them go gang-busters. I feel that many

13 patients do react to oats initially if they go from

14 a very low fiber diet, which the traditional

15 gluten-free diet can be, very devoid of fiber, and

16 if they add a lot of the alternate grains that are

17 very high fiber, you can get a reaction. Anyone

18 would get a reaction to that dramatic increase in

19 fiber. So, we instruct them to add the oats slowly

20 and monitor. They even do it as an alternate day

21 until we establish the tolerance for the oats and

22 the other grains also.

239

1 DR. LUCCIOLI: And does your clinic have a

2 policy on the wheat starch since that was also

3 another issue that in Scandinavia they tend to

4 recommend as well?

5 MS. LEE: They do. We don\'t recommend

6 wheat starch at this time.

7 DR. LUCCIOLI: Is there a particular

8 reason for that?

9 MS. LEE: We feel that for oats there has

10 been enough documentation for that to be considered

11 safe. The wheat, starch we don\'t feel we have

12 enough information on that as yet.

13 DR. LUCCIOLI: Just one more question

14 probably for the panel. I think we had a recent

15 meeting on thresholds, about a month or so ago.

16 And, it was proposed that maybe a two-tier labeling

17 method could be used, kind of what Rhonda was

18 saying before, where maybe, you know, where you

19 could have gluten-free and really gluten-free\--I

20 mean that kind of jokingly, but do you think that

21 your patients or members would appreciate something

22 where a strong statement would say that this will

240

1 not have gluten, whereas another statement would

2 say, well, we can\'t guarantee that this doesn\'t

3 have traces of gluten. Do you think that that is

4 something that consumers with celiac would want?

5 MS. LEE: Anne Lee. I think generally our

6 patients are looking for any definition on the

7 packaging of the foods that they purchase. If it

8 is a two-tiered effect, with the understanding\--and

9 we can instruct them as to what is really

10 gluten-free and what is gluten-free but in a

11 non-dedicated facility, I think that gives them the

12 information so they can make an educated choice. I

13 think they are clamoring for that type of

14 information and for that security even if it is on

15 a two-tier or three-tier basis that this is

16 absolutely gluten-free; this is gluten-free but not

17 in a dedicated facility; and these tomatoes are

18 perfectly fine because they just are perfectly

19 fine, they would love it. And, I think that it

20 would enhance their comfort level and their ability

21 to expand their diet from where they are at this

22 point in time.

241

1 MS. SCHLUCKEBIER: This is Mary

2 Schluckebier, from CSA. I think that an area where

3 you could absolutely be sure that this product is

4 totally, unequivocally absent of any barley, rye,

5 oats, or anything, would be in a hospital when you

6 aren\'t choosing your own food and you are already

7 under a stress condition. I think many of our

8 patients express that their experiences in

9 hospitals, working with a dietitian and someone

10 else as a caregiver, either hospital staff,

11 training table person, a child care facility, for

12 those people to be able to make choices that they

13 know are unequivocally very precisely meeting the

14 prescription of the diet, I think is a place for

15 that.

16 DR. SCHNEEMAN: Actually, I would like you

17 to also comment\--I was curious about your

18 certification system, do you also get reporting

19 from consumers about adverse events, about things

20 where it was certified but they had some sort of

21 reaction? Do you get that information from them?

22 MS. SCHLUCKEBIER: Right now there is very

242

1 little certification program out there anywhere

2 except companies doing some ELISA on their own.

3 Yes, we do get information from members who tell us

4 that they have had a bad experience with something.

5 What we do, we have them send the product. We will

6 have it examined. What we try and do, if they have

7 used some of the product, we do also ask them if

8 they could go and purchase a product with the same

9 oat in it or we try and purchase one locally that

10 is the same company to see what kind of results we

11 are getting, and we do pay for that. Generally,

12 the products have come out with a low level of

13 detection. There are a few cases. There was a

14 loaf of bread and it came out over 5,000 parts per

15 million, which means basically a wheat bread.

16 DR. PARK: Douglas Park, with FDA. This

17 is for Mary. I am glad you had your previous

18 question because that is a segue back to what I

19 wanted to go into, your certification presentation,

20 part of your presentation. In your certification

21 do you actually visit the facilities and conduct an

22 inspection to confirm that it is either dedicated

243

1 or addressing the issues of trying to avoid

2 contamination?

3 MS. SCHLUCKEBIER: It depends on the

4 product. We can have a representative of CSA,

5 because we have chapters and members all over the

6 United States, so generally we can have a team with

7 a check list go in and to an on-site observation.

8 There are times when we have had the company make

9 photographs for us to have on file. We do have a

10 relationship with a company that does certification

11 for some other areas that has agreed to go in and

12 follow our protocol to do on-site visits.

13 DR. PARK: Along that same line, do you

14 audit the companies on a regular basis, annually,

15 semi-annually, whatever, to confirm that they are

16 still preparing a product and then follow-up with

17 actually testing of the product?

18 MS. SCHLUCKEBIER: Absolutely. Again, the

19 calendar of those events does depend on how much

20 flexibility they have; if they have changed

21 suppliers. Yes, some of those things would create

22 a testing earlier than would be normally scheduled.

244

1 DR. PARK: Thank you.

2 DR. LUCCIOLI: As a follow-up, I guess I

3 want to get a little bit more insight on quality of

4 life of celiac patients. I have read some studies

5 where there supposedly is no change in their

6 quality of life, where it seems like once a celiac

7 patient knows what they need to do they are

8 content. Do you get a sense that this is not the

9 case? That they are screaming to you to have more

10 products available, or is there a subset of people

11 who would be willing to take some risks just to

12 have more products to consume?

13 MS. SCHLUCKEBIER: This is Mary, at CSA.

14 I will tell you, it depends on age. It depends on

15 how long they have been diagnosed. We have an 86

16 year-old member. I think she was number 16 at NIH

17 when she was in her 30s and just had a child, and

18 was in Japan and was diagnosed with celiac disease,

19 as was the child later. She is 86. She gets very

20 unhappy when the 40 year-olds no longer ask her to

21 play tennis with them. She would love to have oats

22 back in her diet. She would love to be able to

245

1 take some risks, and she probably takes more risks

2 than I do. She has had over 50 years on the diet.

3 She is very comfortable with what she can eat and

4 she probably has a more varied diet than most

5 non-celiacs in the U.S.

6 DR. SCHNEEMAN: Do you want to comment?

7 MS. CURETON: I would say, based on the

8 time that I have been working in this area for the

9 last 12 years, when I first started so few were

10 diagnosed 10, 12 years ago I think your diet would

11 be very limited and there wasn\'t a lot to chose

12 from. The products today are far beyond what was

13 available 10 years ago. So, somebody diagnosed

14 today I think has wonderful choices, and we supply

15 them with a list of manufacturers and vendors so

16 the quality of their products is equal to what we

17 would use for wheat products. So, I have been very

18 pleased with the products. You have wonderful

19 tasting products. Probably the area that is a

20 problem is the cost and convenience. They are

21 usually mail order and there are not a lot of times

22 you can get them right off the grocery store shelf.

246

1 You have to make a separate trip to the grocery

2 store or you have to order them by mail. But the

3 quality of the products is just phenomenal. So, I

4 think those who are diagnosed today I think are

5 having a better quality of life of life and it is

6 easier to follow the diet because of what is

7 available.

8 MS. LEE: If I may\--it is Anne Lee from

9 Columbia University. We are actually finishing up

10 a huge quality of life study based on the impact of

11 symptoms as well as the gluten-free diet. What we

12 have found does concur with that, that in that

13 first year from the onset of diagnosis and the

14 first year on a gluten-free diet there is a

15 wonderful increase in quality of life, and people

16 feel better; they are symptom free; they feel that

17 they are going to live. So, there is a very huge

18 upturn in their perception of general health and

19 quality of life.

20 In two to five years since diagnosis it

21 tends to drop back down both in males and females.

22 The feeling is that at that point they now have

247

1 gotten to the point where they know they are going

2 to live. They know they feel better, but the

3 routines of daily life become more of a burden. It

4 is that extra trip to purchase the loaf of bread.

5 Travel and business meetings are one of

6 the major complaints and issues for the males in

7 the population group. Females have found that

8 traveling and dining out was just a burden where

9 30-40 percent, depending on age category, of

10 females with celiac disease would choose not to

11 dine out because it is too much of a burden.

12 So, there is an issue with quality of

13 life. Labeling will, indeed, help some but,

14 hopefully, down the road not only will we get

15 labeling under control but maybe even get menus and

16 things done because these are the areas of their

17 life that people without celiac disease don\'t think

18 twice about, for stopping for the coffee and

19 something but for someone with celiac disease it

20 requires thought, preplanning and purchasing that

21 product and, hopefully, that product is

22 appropriately labeled.

248

1 So, there are studies on quality of life.

2 The ones out of Europe tend to have a better rate

3 overall of quality of life on a gluten-free diet,

4 but the question that comes up with that is, is it

5 because they allow the oats, the wheat starch and

6 the labeling is better? We don\'t know. So, we are

7 hoping to do some studies with Colin to compare the

8 two populations.

9 MS. CURETON: This is Pam. The other

10 thing too, we talked about patients earlier that

11 took 11 years to diagnose, those patients are very

12 sick and felt very bad. Once they started the

13 gluten-free diet it was a huge change in their

14 life. Those patients would not take a risk. They

15 would not add anything back to their diet because

16 they know how sick they were. But with better

17 diagnosis or screening and a person who is

18 asymptomatic, that is the type of person who would

19 have a much harder time with the quality of life

20 and issues that they are faced with, but those that

21 were very sick would not touch gluten in any shape,

22 form or for any reason.

249

1 DR. SCHNEEMAN: We need to start finishing

2 up this panel so I am going to have one more

3 question. Felicia?

4 MS. SATCHELL: Felicia Satchell, FDA.

5 This question is really not meant to put you on the

6 spot but, just in your professional opinion and

7 experience, a definition for gluten-free should or

8 should not include oats?

9 MS. LEE: Anne, from Celiac Disease,

10 Columbia. I will start. I think it should, but it

11 should define what the level is and it should

12 define that the oats need to be clean. So, I think

13 if we can define gluten-free with the appropriate

14 level of parts per million, and we can have oats

15 labeled as clean I think it would enhance the

16 gluten-free diet and alleviate some of that burden

17 of illness for those patients. I know that is out

18 on a limb but I honestly believe it makes a

19 difference to our patients.

20 MS. CURETON: This is Pam. I think at

21 this stage there is a lot of confusion still, and I

22 do agree they are technically gluten-free from the

250

1 standpoint of the oats themselves. But with the

2 contamination issues and some of the other

3 tolerance issues, at this point I would not include

4 them.

5 MS. SCHLUCKEBIER: Mary, at CSA. At this

6 time I wouldn\'t include them. If oats are in a

7 product at some later date, again, they are

8 probably going to be clearly labeled as oats, and

9 at some point when there is a standard, to add oats

10 if it has passed all the rigors of study, I don\'t

11 think it would be difficult to add that. For the

12 first few years it may need to have some additional

13 notes on labels with oats that would also include a

14 gluten-free label so that people would not be

15 confused. But at this time I just think it is

16 premature to add oats in with gluten-free.

17 DR. SCHNEEMAN: Of course, some of our

18 panels may not understand the difference between

19 difficulty from a scientific point of view and

20 difficulty from a rule-making regulatory point of

21 view. There is a difference. I have only been

22 here a little bit over a year and I have learned

251

1 that lesson.

2 Again, thank you very much. This has been

3 a wonderful panel and really helped address many of

4 the questions that we have.

5 \[Applause\]

6 Now it is time for our afternoon break,

7 which is scheduled for 15 minutes. We are going to

8 ask you to be back as close as possible to 3:15. I

9 will give you two extra minutes. I do want to make

10 sure that anyone who has signed up to speak, you

11 need to do something during the break. So, if you

12 pre-registered to speak before the meeting today,

13 please see Jean Latham. Jean is right back here

14 with her hand up. For those who registered on-site

15 today, please see Lauretta Carey. Lauretta is

16 right back there, waving her hand. So, we can get

17 it set up to start right after the break. Thank

18 you.

19 \[Brief recess\]

20 DR. SCHNEEMAN: I think we really need to

21 get started. We have several individuals who have

22 asked to provide comments so we want to make sure

252

1 that we allow time for that. I am asking our FDA

2 panel to take a seat at the front so that we can

3 hear the comments. As indicated before, each of

4 you will have five minutes to make the

5 presentation. It is very important that you

6 identify who you are and if you are representing a

7 group or speak on behalf of a group. Please

8 identify that affiliation. We will keep track of

9 the time here and, hopefully, we can keep it well

10 within the time. I think we are going to start

11 with the group here.

12 Public Statements

13 MS. HOPKE: My name is Maryrose Hopke,

14 and I am representing the Celiac Disease

15 Foundation. CDF is a national organization that

16 strives to promote awareness and build a supportive

17 community for celiac patients, families and

18 healthcare professionals. The information we

19 provide is evidence-based, not anecdotal. On

20 behalf of CDF, we thank members of this FDA

21 committee for the opportunity to express our

22 opinion on this important subject, gluten-free

253

1 labeling.

2 We all understand that celiac disease is a

3 life-long disease that has no cure. Yet, as we are

4 also aware, it can be effectively controlled

5 through a gluten-free diet. Confirmation by the

6 NIH that 1/133 individuals in the United States are

7 affected means that, consequently, two to three

8 million consumers will have to watch everything

9 they eat and drink and every medication they take.

10 The celiac community is at a distinct

11 disadvantage at this time to properly answer the

12 questions posed by this committee: What should

13 gluten-free mean on a food label? How does the

14 celiac identify foods that do not contain gluten?

15 How much time do we spend identifying foods? What

16 percentage of the foods purchased and what type of

17 foods are marked gluten-free? How are the buying

18 practices of the celiac community influenced by the

19 word gluten-free on a label as opposed with a

20 product with the same ingredients without the words

21 gluten-free?

22 These questions are just beginning to be

254

1 asked in our community. The major grassroots

2 efforts of the celiac community to get the word

3 wheat included in FALCPA and the subsequent

4 conditions of that bill have brought about these

5 meetings. In the past sufficient data has not been

6 available to intelligently answer the questions

7 posed. This information has to be accurate, not

8 anecdotal, and it is just now being collected.

9 On July 27, in a newspaper article,

10 \"Gluten-Free Market Goes Mainstream,\" it stated

11 that gluten-free products will now be available at

12 Walmart. That is good news. But who made the

13 determination that these products are, in fact,

14 gluten-free? This false sense of food safety is

15 misleading and unfortunate for people who rely on

16 the truthfulness and scientific accuracy of a

17 label.

18 When a celiac eats a product that is

19 assumed to be gluten-free because the manufacturer

20 says so, without any regulation from the FDA, the

21 results can be great physical distress, as well as

22 emotional upset because what the consumer believed

255

1 to be safe has now harmed them.

2 Those in the celiac community are devoted

3 label readers. Labels that carry the statement

4 that the product was produced in a facility that

5 also makes products containing other allergens as

6 well as wheat is most helpful, calling the consumer

7 to make an informed decision before purchasing the

8 product. Products that are naturally gluten-free

9 do not require the GF label. But all foods that

10 have been processed, blended, combined and

11 determined to be gluten-free must meet the criteria

12 to be set by the FDA.

13 The FDA has always been a champion in its

14 responsibility for the safety of food products to

15 the public. This is why the FDA unequivocally must

16 be the regulatory agency determining what is

17 gluten-free. It will be the FDA seal that celiacs

18 will trust and depend on when selecting appropriate

19 gluten-free foods. Thank you.

20 DR. SCHNEEMAN: Thank you, and exactly on

21 time! Good model, folks! The next person?

22 MR. SULLIVAN: Good afternoon. My name is

256

1 Thomas Sullivan. I have the honor of being the

2 president of the Celiac Sprue Association for this

3 year.

4 I am not myself a celiac. I have a wife

5 who is, a son who is and a great-niece who is.

6 However, if you were to come into our house you

7 would effectively find a gluten-free house. Now,

8 there are four items in the house that are not

9 gluten-free. One is the toaster. There are two

10 toasters on the counter because there is no way in

11 the world that you can avoid cross contact by

12 putting two different types of bagel, bread or

13 anything else in a toaster. So, there is a GF

14 toaster and another. That other one is mine. The

15 two never coexist. There are three other food

16 products in the house that are non-gluten-free.

17 They are bread, cookies and cereal. They don\'t

18 exist out front. They are underneath the stove.

19 There is a very simple reason. It isn\'t

20 that I don\'t enjoy eating gluten-free; I do, very

21 much so. But products now, compared to ten years

22 ago, are phenomenal. If you were to take the arena

257

1 of foods non-gluten-free ten years ago and

2 gluten-free, they didn\'t meet. If you take those

3 two universes now and overlap them, the center

4 where products are available to both sides are

5 much, much larger than ever existed. So, the

6 gluten-free diet itself is improving.

7 One quick example, the no-bun button for

8 low calorie products and fast food markets was done

9 by celiacs years before because we came in to say I

10 want that hamburger with lettuce and tomato, no

11 bun. How do we do it? You put it in a box. You

12 give it to me with a knife and a fork and I can

13 eat! That is how it happened. Now you just go in

14 and say low calorie\--no problems. So, we had to do

15 what is coming along automatically and this is how

16 the two universes of foods are overlapping.

17 The thousands of celiac patients that have

18 been involved with CSA over the last 20 years have,

19 in fact, defined gluten-free. When they started

20 out they started to ask the manufacture do you have

21 gluten in your product? Yeah. Okay, I can\'t have

22 your product. No problems. Then they started to

258

1 ask the question do you have gluten in this product

2 specifically? Yeah. Now, wait a minute, you don\'t

3 make it with corn, you make it with rice. Why are

4 you saying yes? Because that is corn gluten or

5 rice gluten. Okay, let\'s ask the question the

6 other way. So, they did. What is the source

7 ingredient for your modified food starch? What is

8 the source ingredient for your enzymes? Those

9 questions started to come through and the answers

10 started to become easier for the patients very

11 quickly.

12 So, the concept of gluten-free is now

13 wheat, barley, rye and oats in a product or in any

14 of their derivatives. By definition and by

15 actuality that has evolved to what is the current

16 definition. No wheat, barley, rye or oats or any

17 other derivatives means gluten-free. I can use it.

18 I have no problems. And, the quickest way and why

19 you have the celiac patient pick up a product and

20 flip it to the ingredients, go down the list\--do I

21 see something I don\'t recognize the ingredient

22 source on, I put it down and I get another product.

259

1 If I see the term wheat, barley, rye or oats, I put

2 it down. That is the quickest way.

3 There are examples of where that occurs

4 with a newly diagnosed patient. We see them all

5 the time, hear them all the time, and I get calls

6 from all over the world. When you start with a

7 newly diagnosed celiac patient, they are in

8 absolute terror. That is this overwhelming wall of

9 don\'t each anything with wheat, barley, rye and

10 oats. Okay, what do I do? So, you give them three

11 words and one direction. Your direction is read

12 the label. The words, starch, vinegar, malted

13 extract. Well, what do you mean? Malted extract

14 has malt in it. By definition of the federal

15 government malted extract is from potatoes, rice or

16 corn. It is good for you. Starch, corn. Vinegar,

17 single word vinegar, apples. Life is great. You

18 have three defined words, three source ingredients.

19 If I see them on a label, no problem.

20 DR. SCHNEEMAN: Tom, your time is up.

21 MR. SULLIVAN: I do thank you. It has

22 been a great day.

260

1 DR. SCHNEEMAN: Thank you so much.

2 MR. COX: Hello! My name is Matthew Cox

3 and I am a representative of Bob\'s Red Mill Natural

4 Foods. I want to thank you all for your endeavors,

5 and thanks for the opportunity of letting us come

6 here and give our point of view.

7 I wanted to clear up one of the questions

8 that was posed to Dennis Gilliam by the panel

9 regarding how we deal with the consumer that has

10 reported to us that a product that we have marketed

11 as gluten-free, they suspect, is contaminated with

12 gluten, and how we deal with that. It is really a

13 pretty simple process. We take it very seriously

14 though and what we do is we communicate with the

15 consumer directly and try to get as much

16 information from them as we can. We want to find

17 out where did they buy the product, what product is

18 it. We definitely want to get the lot numbers

19 because all the products are identified with a lot

20 number that we can track and, you know, look back

21 at the sourcing, and all those sort of relevant

22 details. We get other information from the

261

1 consumer, like what other ingredients did you use?

2 You know, we primarily manufacture baking

3 ingredients. So, what did you combine with this

4 flour to make your baked goods? You know, we have

5 no idea how to gauge how well informed they are.

6 Maybe they are using ingredients that they are not

7 aware contain gluten, like an extract, malted

8 barley, or something like that.

9 After getting as much information as we

10 can, we provide a report to our quality assurance

11 department and that report is then evaluated and,

12 if necessary, we try to acquire a sample from the

13 consumer, maybe a sample of their product so we can

14 compare that with the product that we have

15 in-house. If it is warranted, we also audit the

16 manufacturing process. Again, it is visual

17 inspections and, you know, just a basic run-through

18 to see if there is anything that we are missing,

19 any gaps that have been left open leading to some

20 potential for contamination.

21 We have only had reports like this\--in

22 four years I can only recall maybe a dozen people

262

1 reporting that products that we market as

2 gluten-free have caused a reaction in them, and

3 none of them have ever resulted in a recall, or

4 anything like that, which we could implement if we

5 needed to. We would just simply track the entire

6 lot and get all that product back, and that is what

7 we would do if there was such a case. So, I hope

8 that that answers the question for you.

9 I also wanted to mention that I have

10 talked to a lot of our consumers. We have lots of

11 calls to action, inviting our consumers to give us

12 feedback if they have any questions or concerns at

13 all, and all our literature, all our products are

14 widely open for them to contact us. As a result,

15 we have had many, many conversations with our

16 celiac consumers. I know personally that labeling

17 products gluten-free does make a difference for

18 them. It does make it easier for them to shop for

19 products they need to eat and enjoy life.

20 We also use a symbol on our products.

21 Yes, it is a marketing device but it also helps

22 consumers. We have many products and many of them

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1 are not gluten-free and we want to make it easy for

2 them to tell which products are gluten-free. So,

3 this symbol that they can notice on the packaging

4 is very useful to them and I have had reports on

5 that from consumers.

6 I would like the FDA, if possible in the

7 final ruling, to allow for the use of symbols that

8 imply that a product is gluten-free. Also, I might

9 ask that the FDA ban or bar companies from using a

10 symbol that imply gluten-free when that product

11 contains gluten in it. One example might be a

12 manufacturer that makes a spelt bread and might use

13 a symbol that has a grain shaft that is crossed

14 out, which we use and I know other organizations

15 use similar symbols. So, just to limit the level

16 of confusion, and there is plenty of that already

17 for celiac consumers, I might ask the FDA to

18 address those issues. That is it. Thank you.

19 DR. SCHNEEMAN: Great! Thank you. That

20 was another star performance, within five minutes!

21 MS. FENSTER: Hello! My name is Carol

22 Fenster, and I am president and founder of Savory

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1 Palate, Inc. For the past ten years I have been

2 providing a cookbook and publishing and consulting

3 information on the gluten-free diet. As the author

4 of six of those cookbooks on gluten-free cooking

5 and developer of gluten-free products for

6 manufacturers, including Bob\'s Red Mill who is

7 present here today, the importance of correct,

8 consistent labels is critically.

9 When I formulate a recipe for one of my

10 cookbooks I rely on the ingredient label. When I

11 search the grocery stores or health food stores or

12 go online for hard to find items, I look to see if

13 the ingredient is labeled gluten-free somewhere on

14 the package. I have learned that this label can be

15 very large on some products, even incorporated into

16 the overall design of the package. On other

17 products I have to search very hard for the words

18 gluten-free and sometimes I find them on the back

19 of the package in tiny, little letters. Even then

20 I look at the list of ingredients just to be sure

21 because I know that not all companies use the same

22 criteria, and I have learned to take nothing for

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1 granted.

2 As I read through the list of ingredients,

3 sometimes I don\'t even recognize the words and for

4 help I consult a book that has kind of become my

5 bible, \"The Consumer\'s Dictionary of Food

6 Additives: Descriptions in Plain English of More

7 than 8,000 Ingredients, Both Harmful and Desirable,

8 Found in Food.\" It is kind of a long title to

9 begin with. It is by Ruth Winters. This book does

10 not address gluten-free in any way, shape or form

11 but at least it gives me a working knowledge of

12 what this rather strange ingredient is. Then, for

13 help with other ingredients that I wonder if they

14 are gluten-free or not, I turn to publications like

15 \"Gluten-Free Living\" which carefully researches

16 many suspect foods, or the \"Quick-Start Diet

17 Guide,\" or all the other manuals that things that

18 were mentioned today. I reference all of those. I

19 also consult lists and where there are constant

20 changes.

21 Once I have all the information I decide

22 with that ingredient is appropriate to use in my

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1 recipes in my cookbooks. If I decide that it just

2 doesn\'t meet my criteria, then I simply don\'t use

3 it. When in doubt, don\'t use it.

4 Now, the same process I use for my own

5 recipes and my own cookbooks becomes even more

6 complex when you develop products for corporations

7 because of what we call the sourcing issue.

8 Sometimes the ingredients I must use are not

9 available to me as a general consumer, and I don\'t

10 have access to the label to read it, or the

11 manufacturer of a consumer ingredient that I buy on

12 the store shelf is not quite the same as the one

13 manufactured by the commercial provider which only

14 other corporations can buy. In other words,

15 certain products out there only other corporations

16 can buy wholesale and have the whole issue of

17 labeling all over again. Whereas, I am a consumer,

18 and I am gluten-free, by the way also, I have

19 learned to rely on very specific lists.

20 This means that my client needs to source

21 out or to research on my behalf the right sources

22 for ingredients, and not always having access to

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1 all the relevant information, the sources may not

2 be required or may downright refuse to disclose

3 exact ingredients because of proprietary issues.

4 Since many of these sources provide a myriad of

5 products, some gluten-free and some not, there is

6 always the risk of whether there is a cross

7 contamination. So, this all has to be considered.

8 My concern with these ingredients is only

9 amplified when we talk about more complex processed

10 foods such as certain dairy products, whether

11 yoghurt, sour cream or Worcesteshire sauce. By the

12 way, I had an interesting thing happen to me. I

13 was very confident that a certain brand of

14 Worcesteshire sauce, here in the U.S., was

15 gluten-free. I specified that brand in my

16 cookbook, only to learn that in Canada that brand

17 is not gluten-free. So, there we are with issues

18 of labeling for us internationally.

19 At any rate, in summary, I think a

20 standardized set of guidelines about what is

21 gluten-free will help me make recipes that I know

22 are safe for my customers. It will help my

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1 customers locate the same safe ingredients that I

2 specify in my recipes. And, it will give

3 manufacturers guidance in selecting gluten-free

4 ingredients for their products whether they are

5 developed in-house or by consultants such as me.

6 It is time that we all agree on what

7 gluten-free means and what is not, and implement

8 guidelines that assure a correct, consistent label.

9 Thank you very much.

10 DR. SCHNEEMAN: Thank you.

11 MS. ASHWORTH: Hello! My name is Anna

12 Ashworth and I am the vice president of business

13 and administration for the Gluten-Intolerance

14 Group, and I am also a representative for the

15 Gluten-Free Certification Organization. I also

16 have celiac disease.

17 Cynthia Cooper, the executive director for

18 the Gluten-Intolerance Group, conducted an online

19 consumer survey to get the gluten-free consumers\'

20 perspective on issues of labeling, purchasing

21 decisions and determination of what gluten-free

22 means to them. This survey, which was sent to the

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1 FDA on August 15, had nearly 2,100 responses

2 worldwide and confirmed what we already knew, that

3 gluten-free consumers want products that are

4 clearly labeled to be gluten-free and that they

5 know to be free of cross contamination.

6 Gluten-free consumers would benefit from a

7 gluten-free certification program and manufacturers

8 would benefit from their consumers\' increased

9 confidence in their products. To meet these needs,

10 over the past two years the Gluten-Intolerance

11 Group, in conjunction with a committee of

12 scientific advisers, has worked to develop an

13 independent certification program for gluten-free

14 food processing. This program, the Gluten-Free

15 Certification Organization, or GFCO, is the first

16 program of its kind in the world. GFCO was

17 developed in cooperation with Food Services, Inc.,

18 a subsidiary of the Orthodox Union, the world\'s

19 largest and oldest kosher certification agency,

20 with food inspection agents all over the world.

21 Key elements of the GFCO process will

22 include the following: Individual ingredients will

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1 be reviewed down to the original supplier. There

2 will be on-site inspections by independent,

3 experienced, specially trained field inspection

4 agents provided by the global resources of Food

5 Services, Inc., a subsidiary of the Orthodox Union.

6 Products and ingredients will be tested using

7 scientifically proven AOAC approved test methods.

8 There will be regular spot plant visits

9 and product testing by field inspection agents.

10 The GFCO certification mark will appear on product

11 packages for easy identification. The manufacturer

12 and the Gluten-Free Certification Organization have

13 a written agreement that states what can go into

14 the product and how it is produced. The GFCO must

15 be consulted in advance of any ingredient or

16 processing changes to ensure that the product\'s

17 gluten-free status is not affected. As a global

18 program, the GFCO uses the highest standards for

19 gluten-free ingredients and a safe processing

20 environment based on a continual review of the

21 current scientific and testing methodologies,

22 existing global standards such as Codex in Canada,

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1 and balanced by reasonable application by the

2 manufacturer.

3 A new Gluten-Free Certification mark on

4 food labels will allow gluten-free consumers to eat

5 easily and confidently, identify safe food that has

6 been independently verified to meet the highest

7 standards for gluten-free. We already have food

8 manufacturers who have signed on with the GFCO

9 program and we have received enthusiastic interest

10 from many more. We are providing this program on

11 behalf of the community who have voiced their

12 strong interest in having gluten-free

13 certification. Our standards are always available

14 for public inspection on our website, www.gfco.org.

15 Thank you.

16 DR. SCHNEEMAN: Thank you.

17 MR. BROWNE: Hello there! Thank you for

18 allowing me to speak. My name is David Browne. I

19 work for a company called SPINS. We are a San

20 Francisco-based organization. I am the director of

21 content services there.

22 SPINS is a leading provider of information

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1 to the natural products industry. Specifically

2 what we do, we track the sale of bar coded products

3 moving through natural supermarkets, including

4 Whole Foods and Wild Oats and many independent

5 stores. We also track the sale of natural and

6 organic products moving through conventional

7 supermarkets such as the Safeway and other drug

8 stores.

9 Through this, in the last several months

10 we started tracking gluten-free products

11 specifically and flagging them in our database of

12 over 400,000 products. I wanted to use my time

13 today to provide some top-line information,

14 statistical information on what we found with

15 gluten-free products.

16 First of all, my team calls manufacturers

17 and checks product websites to identify products

18 that are marketed and claim on their labels that

19 they are gluten-free. In instances where it is not

20 labeled, we are still talking to the manufacturer

21 to ask some other information. Generally, we found

22 that there are about three buckets that companies

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1 that are making gluten-free products fall into.

2 One is that their product is gluten-free and it is

3 labeled as such. Two, the product is gluten-free

4 but it is not labeled as such and in general the

5 reply is that with the new labeling that they are

6 going to be generating, new labels will have that

7 but they have to go through their existing labels

8 before they move forward. Thirdly, the product is

9 gluten-free but they will not guarantee it, for all

10 the reasons that we talked about earlier today as

11 far as cross contamination and manufacturer

12 warehousing where they are storing these goods. In

13 the case of that, we are only coding items that are

14 actually labeled as gluten-free at this point.

15 First off, I just want to summarize what

16 we have found. We have researched over 10,000

17 products that fall into food categories where

18 gluten-free products are known to exist, categories

19 like bread and baked goods, cookies, cereals,

20 frozen entrees, and other categories such as soup

21 and candy where product labeling for gluten-free is

22 common. At this point we have identified over

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1 2,000 products moving in the U.S., with sales over

2 600 million dollars. This is a growth of 1.6

3 percent year over year, and that is both channels,

4 both natural supermarkets and conventional

5 supermarkets combined.

6 As far as UPC codes go, the vast majority

7 of the are still moving in natural supermarkets.

8 There are over 2,000 that are moving in natural

9 supermarkets at this point. That is an increase of

10 9 percent over last year when there were over 1,965

11 items that were labeled as gluten-free. In the

12 conventional channel there are about half, there

13 are only about 1,200 items at this point that are

14 labeled as gluten-free but, because of the volume

15 of sales that occur in conventional, that 600

16 million dollar figure is broken down into being 400

17 million approximately moving in conventional

18 supermarkets and 200 million moving in natural

19 supermarkets.

20 For today\'s session I tried to encapsulate

21 just about 9 categories where there is a lot of

22 activity both in volume and quantity of UPCs. The

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1 9 categories include, as I say, chips and snacks,

2 puddings and desserts, entrees and mixes, cookies,

3 soup, baking mixes and supplies, bread and baked

4 goods, frozen entrees and candy. In the natural

5 channel sales are growing for these gluten-free

6 products at 12 percent. In the conventional

7 channel they are growing at 17.8 percent. That may

8 seem ironic but, in fact, as a lot of us know,

9 gluten-free products have long been available in

10 natural product supermarkets and what is happening

11 over the last several years is that they are

12 migrating into the conventional channel. Because

13 of that, their growth rates are much larger and

14 their volume.

15 One of the other interesting points that I

16 want to mention today is that when you take some of

17 these categories as a whole and look at their

18 growth rates, and then look at the gluten-free

19 products that are labeled within that and look at

20 their growth rates, the gluten-free products far

21 exceed the growth of the category as a whole.

22 Essentially, they are driving the growth of the

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1 category.

2 Take a category like candy for example,

3 which had a lot of up and down last several years

4 due to low carb diets and products like Atkins bar

5 on the market which were essentially candies but

6 they were sugar-free version, the category is still

7 showing positive growth in the natural channel at

8 about 22 percent, but gluten-free candy is growing

9 at 47 percent. Take a category like baking mixes

10 and supplies, the category is relatively flat in

11 the natural channel about 5 percent growth;

12 gluten-free products are growing at 18.6 percent

13 growth.

14 DR. SCHNEEMAN: We do need you to wrap up,

15 but this sounds like the kind of data that would be

16 great to submit to us.

17 MR. BROWNE: I have already submitted it,

18 yes. I just want to say one last thing. Another

19 important element of the growth of gluten-free

20 products is that the share of the total sales for

21 gluten-free products within a category is

22 increasing year over year. If you take a category

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1 like baking mixes and the share of total sales

2 within that category for gluten-free products went

3 from 36 percent last year to 39 percent this year.

4 So, more consumers are buying baking mixes and

5 supplies that contain gluten-free products in

6 volume than they were a year ago. Thank you very

7 much.

8 DR. SCHNEEMAN: Thank you.

9 MS. WHELAN: My name is Ann Whelan, and

10 together with Amy Rettner I have published

11 \"Gluten-Free Living,\" a national magazine for

12 people who have celiac disease, for the last ten

13 years. Over those years we have concentrated our

14 research efforts on ingredients and their relation

15 to celiac disease.

16 I was asked to respond to questions eight,

17 nine and ten. Question eight, are there available

18 research data or findings on what consumers with

19 celiac disease or their caregivers believe the term

20 gluten-free means? For example, do the research

21 data or findings show consumers\' belief as to what

22 specific grains or other ingredients are not

278

1 present in foods labeled gluten-free?

2 I believe there are at least two ongoing

3 research studies as we speak, and from what I have

4 heard today there are probably more. We did a

5 survey nine years ago and some of the results of

6 that survey are relevant to question nine. But we

7 are planning on another survey which will probably

8 be presented in our next issue, and in the new

9 climate of celiac disease which is much different

10 than it was nine years ago, I am very curious to

11 see what we will find out.

12 You ask what people think the term

13 gluten-free means. In the current climate it would

14 be difficult for people to explain what they think

15 gluten-free means. The reason it would be

16 difficult is found in the second part of your

17 question, meaning disagreement within the celiac

18 community over specific grains and specific

19 ingredients that are gluten-free. The specific

20 grains part of the question is more easily

21 addressed, and you have heard it today. Everyone

22 agrees on wheat, rye and barley as grains not being

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1 found in foods marketed as gluten-free and, as

2 everybody else said, at this point I think people

3 expect oats to be in that category too. We have

4 spelt, kamut and triticale that aren\'t found that

5 much. Spelt is a problem. In the past, and you

6 have heard this, some spelt companies have said

7 spelt is safe for people who are sensitive to

8 gluten, and it is still not clear, at least on one

9 spelt site, that spelt is not safe for anybody who

10 has celiac disease. So, any definition of

11 gluten-free would have to emphasize that the

12 product does not contain spelt. Most celiacs

13 recognize corn, rice, potatoes and tapioca as being

14 gluten-free. Uneasiness about some of the

15 alternative grains like buckwheat and kimwa seems

16 to have been addressed now and everybody is cool I

17 think on that issue.

18 The ingredients portion is much less

19 easily resolved. First, many celiacs do not know

20 who to believe. There is a lot of information out

21 there that seems to have been put forward on the

22 basis of no evidence whatsoever. Some of our

280

1 readers ask us you say this, but I read that

2 elsewhere. At this point I explain to them how we

3 do our research and recommend that they go back to

4 the other source and find out how they do their

5 research. For the record, we do our research by

6 querying the people who should know the answers to

7 the questions. We include the FDA, the USDA grain

8 scientists, ingredient makers, food processors,

9 food companies and other relevant sources of that

10 ilk. Over nearly ten years we have developed a

11 relationship with these groups and, therefore, have

12 a place to start when we begin researching

13 something new.

14 Second, people do not understand what

15 certain ingredients are, and for good reason. For

16 example, malt comes from barley and, therefore,

17 would not be included in a product labeled

18 gluten-free. Dextran can be derived from several

19 grains, one of which is wheat. So, a product

20 labeled gluten-free wouldn\'t contain dextran

21 derived from wheat. Malt dextran, on the other

22 hand, as you heard, is gluten-free. However, it if

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1 comes from outside the United States, and even

2 sometimes from inside the United States, it may

3 contain wheat but it will be wheat malt dextran or

4 malt dextran wheat.

5 Now, I can explain that quickly because I

6 have done in-depth research on many ingredients.

7 But when you are used to picking up a product off a

8 shelf and throwing it into your shopping cart, and

9 on top of that you know that some of these products

10 and ingredients are going to make you sick, the

11 learning curve required to be comfortable and

12 efficient and effective with the diet is daunting.

13 We are currently working on a booklet of

14 ingredients and I hope that will help people make

15 safe decisions.

16 We work very hard to explain ingredients

17 as clearly as possible but ingredients are what

18 they are and some explanations are complex. In

19 fact, I suspect the complexity of the diet is the

20 main reason why most people we ask say just tell me

21 if the product is gluten-free. Just tell me what

22 can I eat. We asked over the last two weeks what

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1 people would like to see and everybody told us some

2 version of the same thing. Make it easy to read.

3 I hate to have to read a label forever. I want the

4 label to specifically say gluten-free. I don\'t

5 want to have to assume it is gluten-free just

6 because it doesn\'t contain wheat. Just tell me

7 plain and simple gluten-free.

8 Third, people are afraid of what they

9 don\'t know, especially if they have been very sick.

10 That is understandable. The fear is amplified by

11 misinformation that suggests molecules of gluten

12 are dangerous or tries to define the diet by brands

13 versus ingredients, and that is kind of a complex

14 issue that I won\'t go into. But an acceptable

15 agreement on what gluten-free means when it appears

16 on the label would solve that problem.

17 Fourth, people perceive some ingredients

18 as being gluten-free some of the time and not

19 gluten-free other parts of the time, and that is

20 truly confusing. Starch is a good example. Starch

21 and food starch on a food label mean corn starch.

22 Modified food starch may, and usually does mean

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1 modified corn starch. The FDA regulation on this

2 ingredient is currently understood as saying

3 modified food starch could be modified anything

4 starch.

5 DR. SCHNEEMAN: Ann, we need to finish up.

6 MS. WHELAN: Okay. I think that it is

7 doable right now for us to define the gluten-free

8 diet and to solve all of these ingredient problems.

9 It is my humble opinion that we need a better

10 agreement on the specific grains and ingredients

11 that would be excluded from a product label of

12 gluten-free before you can regulate the use of the

13 term gluten-free on a food label. I offer our ten

14 years of research to anybody that would like it in

15 order to determine this.

16 DR. SCHNEEMAN: That would be great, and I

17 hope you do submit that to the docket.

18 MS. WHELAN: Fine. Thank you.

19 DR. SCHNEEMAN: Thank you.

20 MS. BAST: My name is Alice Bast and I am

21 the founder and the executive director of the

22 National Foundation for Celiac Awareness. I want

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1 to say that Ann Whelan has incredible information.

2 The information I am presenting today is customer

3 surveys. Her information is scientifically vetted.

4 On behalf of the of the Americans who

5 suffer from celiac disease, I appreciate the

6 opportunity to provide information on consumer

7 understanding of the term gluten-free and the

8 purchasing practices of celiac patients and their

9 caregivers in the public meeting on gluten-free

10 labeling.

11 The National Foundation prepared a short

12 survey which was posted on our website and was

13 e-mailed to support group members around the

14 country. We received informative and heartfelt

15 responses to the seven questions that were

16 developed based on questions eight, nine and ten in

17 the Notice for today\'s public hearing. We will

18 submit the full responses in part of our written

19 comments and I will summarize the results today.

20 The respondents are educated consumers

21 that spend considerable time and effort in

22 educating themselves and researching the contents

285

1 of the food they buy in stores and eat in

2 restaurants. They rely on the gluten-free label

3 and express to us and the food manufacturers who

4 have policies not to hide allergens and gluten.

5 When given a choice, they buy products that are

6 labeled gluten-free over those that are not. They

7 are thrilled that the food labeling will soon be

8 improved because it will save time, reduce

9 frustration and provide a measure of confidence

10 that they and their families are eating foods that

11 are safe.

12 The following are the questions we asked

13 and a summary of the responses we received. What

14 does the term gluten-free mean to you? The

15 overwhelming response was that gluten-free means

16 gluten-free, that is, the product contains no

17 wheat, barley, rye and related grains and

18 derivatives. A few mention above a safe threshold

19 but the general respondents expressed an

20 understanding that no gluten is present in the food

21 product either directly or as a result of cross

22 contamination and, again, there was confusion over

286

1 spelt and oats.

2 How do you identify foods that do not

3 contain gluten? The primary response was read the

4 label, followed by calling or e-mailing

5 manufacturers, food lists from select support

6 groups, reference provided by medical providers,

7 newsletters and the internet. Often people read

8 labels and call manufacturers to confirm, having

9 learned about cross contamination potential and

10 changing manufacturing practices as the hidden

11 source of gluten. Many mentioned calling the

12 manufacturer in the grocery store in order to be

13 able to make a safe purchase. Respondents

14 expressed the need to look for ingredients which

15 are derivatives of wheat, barley and rye and other

16 ingredients which contain these in reality but not

17 in their names. Also, many said fear played a

18 role. They are worried about buying products when

19 they didn\'t recognize the name so they would

20 automatically not buy those products because they

21 weren\'t sure whether they contain gluten or not.

22 Many mentioned the difficulty in eating out safely

287

1 because restaurants don\'t always know whether

2 gluten is contained in the bulk ingredients that

3 they buy.

4 How much time to you spend identifying

5 gluten-free foods? The response to this question

6 varied. Some folks indicated that they are

7 educated and they carry lists with them and just

8 buy the same foods again and again. Others spend

9 30 minutes extra each week reading labels and

10 researching ingredients. Others said that grocery

11 shopping takes twice as long as normal.

12 Many have come to rely on the current

13 gluten-free label as a time saver and seek out

14 brands from companies who have voluntarily made

15 allergen and gluten information available in their

16 packaging. Most expressed the need for a uniform

17 label so it would be faster and easier for them to

18 obtain the information.

19 Four, when you purchase packaged foods, do

20 you purchase foods that are primarily or

21 exclusively labeled gluten-free? Many respondents

22 indicated that they do prefer to purchase products

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1 that are labeled gluten-free if available. They

2 also indicated that they must purchase products

3 that are not labeled and, in order to do so, must

4 read the ingredient lists. Many mentioned the

5 added expense of products that are labeled

6 gluten-free.

7 Five, if so, what types of packaged foods

8 that are labeled gluten-free do you purchase? For

9 example, breads, dairies, canned vegetables, and

10 there is a whole list of a variety of products that

11 they do purchase.

12 Does a gluten-free label influence your

13 purchasing decision when you have a choice among

14 products having identical ingredient lists? The

15 overwhelming response was yes. People indicated

16 they felt confident that the food was safe for them

17 to eat if it had a gluten-free label.

18 Seven, would you like to share any other

19 thoughts about a need for accurate understanding of

20 food labeling in your experience with food

21 labeling? The overwhelming response was that

22 people are looking forward to having clear,

289

1 unambiguous food labeling so they could be sure the

2 food they were planning to eat was, in fact,

3 gluten-free and, therefore, safe. Many expressed

4 the challenge of complying with the gluten-free

5 diet when labels do not clearly indicate whether

6 gluten is present.

7 In conclusion, as the NFCA analyzed the

8 responses to our survey, we reinforced our own

9 belief that clear, unambiguous labeling of food is

10 a win-win for everyone\-- celiac disease patients

11 and food providers throughout the food chain.

12 People with celiac disease will save time and will

13 greatly improve their ability to select foods that

14 are safe to eat. Food providers, by clearly

15 indicating whether gluten is present in the foods

16 they produce or serve, will engender the trust of

17 celiac sufferers and, therefore, create loyal

18 consumers for their brands. Thank you for the

19 opportunity to speak with you today.

20 DR. SCHNEEMAN: Great! Thank you.

21 MS. KUJO: Hi! My name is Jill Kujo. I

22 am here representing Whole Foods Market. My

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1 official title is research and customer relations

2 coordinator. That means I answer the phones,

3 answer all the e-mail and I also talk to our

4 ingredient suppliers. I collect the letters of

5 certification.

6 I really wanted to bring out that while we

7 focus a lot on the breads and cakes and desserts

8 that celiacs can\'t eat, there are a lot of general

9 grocery products that people don\'t think of right

10 away as containing gluten, deli meats, snack foods,

11 spices, mixes. A lot of times when I am getting

12 initially diagnosed people write to me, I inform

13 that these products are available in our stores and

14 it is more often the smaller producers that will

15 make products, like potato chips, that don\'t have

16 gluten in the spice mix that goes on them.

17 I think that although perhaps our

18 ignorance in this country about celiac disease may

19 be a reason why there are cross contamination

20 issues, especially in oats. I also think it might

21 be because I get the general impression that we

22 process our foods a little bit more than the rest

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1 of the world and gluten is really useful in

2 processing, not only to tie things together like in

3 baking but also to keep spices from clumping in

4 production. I think that is it. Thank you.

5 DR. SCHNEEMAN: Great! Thank you.

6 MR. BLANK: My name is James Blank. I am

7 a member of CSA. I just wanted to bring out that

8 the gluten-free labeling is going to help some

9 people that are very vulnerable, and those are the

10 very elderly people and the very young. Most of

11 the time that has to do with the caregivers and

12 families that have to try to figure out this whole

13 thing about gluten-free or not.

14 I was diagnosed 12 years ago and I was

15 doing fine. Eight months ago my father was

16 diagnosed with celiac disease. Now I have to teach

17 my family and, you know, his wife how to look for

18 gluten-free products and it is very difficult,

19 especially when you have some family members that

20 don\'t understand celiac disease and how difficult

21 it is and how dangerous it can be for people. When

22 I was diagnosed I lost 50 lbs. and I almost died

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1 from this disease. I think that is the thing, and

2 when you are diagnosed with something and you get

3 very sick from it, you know, it really matters.

4 Now, with my father, 78 years old now, it is hard.

5 I have to train him, 78 years old and now he has to

6 learn how to eat all over again.

7 I think these are the people that the

8 gluten-free labeling is going to help. Those and

9 also people in hospitals. You know, people are

10 afraid. They are afraid to go to the hospital

11 because they don\'t know what they are going to eat.

12 So, that is all I have to say and I just want to

13 thank the FDA for having this meeting.

14 DR. SCHNEEMAN: Great! Thank you. Do we

15 have any other presenters?

16 \[No response\]

17 Again, on behalf of FDA, I want to really

18 sincerely express my appreciation to all of you who

19 have been here today for your participation and

20 involvement. I appreciate the fact that you have

21 respected our time schedule; you have respected the

22 fact that we had very specific questions that we

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1 are trying to address and I think you have provided

2 us with a real wealth of information. Again,

3 hearing from both the industry as well as

4 consumers, plus the analytical piece of it, those

5 are all important inputs for our decision-making.

6 Before we adjourn, I do want to remind

7 everyone of the docket number, 2005N-0279 that

8 corresponds to this meeting. The ten questions

9 that we cited in the Federal Register Notice will

10 remain there and that docket is open until

11 September 19. Obviously, we have heard in just

12 short presentations that some of you do have

13 additional data, references, reference material and

14 perhaps some additional comments. So, we encourage

15 you to submit material to that docket and that is

16 one of the best ways to make sure that FDA

17 considers your input in its decision-making as it

18 goes forward with this very important initiative.

19 So, again, thank you for being here.

20 Thank you for sticking to the very end so that we

21 had the opportunity to hear everyone who wanted to

22 make a comment. I just want to express my sincere

294

1 appreciation to the staff at FDA who really worked

2 hard to put all of this together, to gather the

3 speakers, arrange the meeting. I know that Rhonda

4 Kane has spent a substantial amount of time, and

5 Geraldine June has also put in a huge effort to

6 make sure that this meeting would come off very

7 well and that FDA would be able to gather the type

8 of information that is most useful to us. We had a

9 lot of volunteers from our office who have helped

10 with the registration desk. That is just extra

11 effort on their part because they view this

12 information as important. So, again, thank you for

13 being here.

14 \[Whereupon, at 4:08 p.m., the proceedings

15 were adjourned.\]

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