1

 

                 DEPARTMENT OF HEALTH AND HUMAN SERVICES

 

                       FOOD AND DRUG ADMINISTRATION

 

               CENTER FOR FOOD SAFETY AND APPLIED NUTRITION

 

 

 

 

 

 

 

 

 

 

                     FOOD ADVISORY COMMITTEE MEETING

 

                     Advice on CFSAN'S Draft Report:

 

Approaches to Establish Thresholds for Major Food Allergens and for Gluten in Food

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

                         Wednesday, July 13, 2005

 

                          8:30 A.M. to 5:50 P.M.

 

 

 

 

                            Greenbelt Marriott

                              6400 Ivy Lane

                              Grand Ballroom

                        Greenbelt, Maryland 20770

                                                                  2

 

                         P A R T I C I P A N T S

 

       FOOD ADVISORY COMMITTEE STANDING MEMBERS:

 

       Richard A. Durst, Ph.D. - Acting Chairman

       Jeffrey A. Barach, Ph.D. (Industry Representative)

       Patrick S. Callery, Ph.D.

       Dennis Gonsalves, Ph.D., M.S.

       Jean M. Halloran (Consumer Representative)

       Douglas C. Heimburger, M.D., M.S.

       Margaret C. McBride, M.D.

       Mark Nelson, Ph.D. (Industry Representative)

       Carol I. Waslien Ghazaii, Ph.D., R.D.

 

       TEMPORARY VOTING MEMBERS:

 

       Petr Bocek, M.D., Ph.D.

       Margaret Briley, Ph.D., R.D.

       Erica Brittain, Ph.D.

       Ciaran P. Kelly, M.D.

       Soheila June Maleki, Ph.D.

       David O. Oryang

       Marc D. Silverstein, M.D.

       Suzanne Teuber, M.D.

 

       FOOD AND DRUG ADMINISTRATION:

       Catherine Copp, J.D. - Senior Policy Advisor

       Food and Drug Administration, CFSAN

 

       Steven M. Gendel, Ph.D. - Senior Scientist

       Food and Drug Administration

       National Center for Food Safety and Technology

 

       Rhonda Kane, M.S., R.D. - Consumer Officer

       Food and Drug Administration, CFSAN

 

       Michael M. Landa, J.D. - Deputy Director for Regulatory Affairs

 Food and Drug Administration, CFSAN

 

       Stefano Luccioli, M.D. - Senior Medical Advisor

       Food and Drug Administration, CFSAN

 

 Marcia Moore, Food Advisory Committee, Executive Secretary

 

       Jenny Slaughter - Director

       Food and Drug Administration Integrity and Ethics Staff

                                                                  3

 

                   P A R T I C I P A N T S (Continued)

 

       GUEST SPEAKERS:

 

       Rene Crevel, Ph.D. - Senior Scientist

 Unilever, Safety and Environmental Assurance Centre, United Kingdom

 

       Susan Hefle, Ph.D. - Associate Professor and Co-Director

 Food Allergy Research and Resource Program, University of Nebraska

       Stefano Luccioli, M.D., - Senior Medical Advisor

 CFSAN, FDA Assistant Professor, Georgetown University

 

       Anne Munoz-Furlong

 Director, Food Allergy & Anaphylaxis Network

 

       Steve Taylor, Ph.D. - Maxcy Distinguished Professor & Director

 Food Allergy Research and Resource Program, University of Nebraska

 

       Robert Wood, M.D. - Professor

 Johns Hopkins University School of Medicine

                                                                  4

 

                             C O N T E N T S

 

                                                               PAGE

 

       Call to Order, Welcome and Introductions

       Charge to the Food Advisory Committee

                 Richard Durst, Ph.D., Acting Chairman            6

 

       Conflict of Interest Statement & Other

       Instructions

                 Jenny Slaughter, FDA                            10

 

       Welcome and Opening Statement

                 Michael M. Landa, Esq., CSAN, FDA               14

 

       Use of Food allergen Thresholds

                 Catherine L. Copp, Esq., CFSAN, FDA             18

 

       Introduction to Food Allergens

                 Robert Wood, M.D.                               23

 

       Patient Perspectives on Food Allergies

                 Anne Munoz-Furlong                              72

 

       Allergenicity:  Analytical Methods

                 Susan Hefle, Ph.D.                              99

 

       Question and Answer Session                              126

 

       Oral Challenge Studies:  Purpose, Design,

       and Evaluation

                 Stefano Luccioli, M.D.

                 Senior Medical Advisor, CFSAN, FDA             133

 

       Question and Answer Session                              161

 

       Threshold Modeling Approach

                 Rene Crevel, Ph.D.                             170

 

       Food Allergen Thresholds

                 Steve Taylor, Ph.D.                            189

 

       Overview of Approaches to Establishing

       Thresholds:  Allergens

                 Steven M. Gendel, Ph.D., FDA                   218

                                                                  5

 

                       C O N T E N T S (Continued)

 

                                                               PAGE

 

       Public Comments:

 

                 Tracy Atagi                                    228

 

                 John Carroll                                   232

 

                 Diane Castiglione                              242

 

 

                 Will Duensing                                  247

 

                 Martin J. Hahn, Esq.                           250

 

                 Peggy Mockett                                  254

 

                 Kim Mudd                                       257

 

                 Kim Mulherin                                   260

 

                 Linda Webb                                     264

 

                 Jupiter Yeung                                  268

 

       Committee Discussion:

 

                 Panel Discussion with Guest Speakers

                 Thresholds for Food Allergens - Questions      272

 

       Adjournment

 

                 Richard Durst, Ph.D., Acting Chairman          414

                                                                  6

 

                          P R O C E E D I N G S

 

                CALL TO ORDER, WELCOME, AND INTRODUCTIONS

 

                  CHARGE TO THE FOOD ADVISORY COMMITTEE

 

                 CHAIRMAN DURST:  I would like to call the

 

       meeting to order.

 

                 Good morning.  I am Dick Durst, professor

 

       of chemistry in the Food Science and Technology

 

       Department at Cornell University.  I was asked to

 

       chair this meeting over the next two and a half

 

       days.  I would like to make a few announcements

 

       before we begin our meeting this morning.

 

                 I would appreciate it if everyone would

 

       turn off their cell phones, unless they are

 

       expecting a call of a super emergency nature.  I

 

       would also like to ask if the guest speakers could

 

       make themselves available for the discussion this

 

       afternoon, I would really appreciate it.  We may

 

       have some additional questions.

 

                 We have received a charge from the FDA to

 

       give our evaluation of the draft report prepared by

 

       the Threshold Working Group.  I assume all of the

 

       members have read that thoroughly.  In my opinion,

                                                                  7

 

       I it was fascinating.

 

                 It was an excellent article and I commend

 

       the Committee for coming up with it.  It was very

 

       educational.  Not being an expert on food allergens

 

       myself, it was extremely educational, and I was

 

       able to follow it quite clearly.

 

                 Our charge is to evaluate this report to

 

       determine whether the approaches that are presented

 

       in there are the only ones or the better ones,

 

       which of the ones that are in there might be the

 

       most appropriate.  This is the focus of our meeting

 

       today, both on the food allergens and on gluten.

 

 

                 Let me also begin by asking the committee

 

       members to introduce themselves.  We will start

 

       with Dr. Silverstein.

 

                 Marc, would you start it off?

 

                 DR. SILVERSTEIN:  Good morning.  My name

 

       is Marc Silverstein, and I'm a general internist

 

       and geriatrician at Baylor Health Care System in

 

       Dallas.

 

                 DR. TEUBER:  Good morning.  My name is

 

       Suzanne Teuber, I am an allergist at UC-Davis.

                                                                  8

 

                 MR. ORYANG:  Good morning.  I am

 

       David Oryang.  I am a risk analyst and agricultural

 

       engineer at the United States Department of

 

       Agriculture, Animal and Plant Health Inspection

 

       Service.

 

                 DR. KELLY:  I am Ciaran Kelly, and I am a

 

       gastroenterologist at the Harvard Medical School in

 

       Boston.

 

                 DR. MALEKI:  I am Soheila Maleki.  I am a

 

       scientist with the USDA.

 

                 DR. BRITTAIN:  Erica Brittain, I am a

 

       statistician at the National Institute of Allergy

 

       and Infectious Disease.

 

                 DR. BRILEY:  Margaret Briley, University

 

       of Texas at Austin, nutritionist.

 

                 DR. BOCEK:  Good morning.  I am

 

       Petr Bocek, medical officer in NIH's National

 

       Institute of Allergy and Infectious Diseases.

 

                 MRS. MOORE:  I am Marcia Moore.  I am with

 

       the FDA as the executive secretary of the Food

 

       Advisory Committee.

 

                 DR. WASLIEN:  I am Carol Waslien.  I am a

                                                                  9

 

       nutritional epidemiologist at the University of

 

       Hawaii.

 

                 DR. McBRIDE:  I am Margaret McBride.  I am

 

       a child neurologist at Akron Children's Hospital.

 

                 DR. CALLERY:  I am Patrick Callery, a

 

       pharmaceutical scientist from West Virginia

 

       University.

 

                 DR. GONSALVES:  I am Dennis Gonsalves, a

 

       scientist with USDA in Hawaii.

 

                 DR. HEIMBURGER:  I am Doug Heimburger, a

 

       physician and nutrition specialist at the

 

       University of Alabama at Birmingham.

 

                 DR. BARACH:  Jeff Barach with Food

 

       Products Association, vice president for special

 

       projects and regulatory affairs.

 

                 DR. NELSON:  Mark Nelson with the Grocery

 

       Manufacturers Association responsible for

 

       regulatory and scientific policy.

 

                 MS. HALLORAN:  Jean Halloran from the

 

       Consumers Union where I am director of food policy

 

       initiatives.

 

                 CHAIRMAN DURST:  Thank you very much.

                                                                 10

 

                 One other item is that we may have some of

 

       our members leave early on Friday, depending on the

 

       amount of time we can spend.  What I propose is

 

       that today and tomorrow that we anticipate having

 

       to go perhaps till 6 o'clock so that we can be sure

 

       that we have enough time for all of our

 

       discussions.

 

                 Okay.  Let me introduce our first speaker.

 

       This will be Jenny Slaughter, director of Ethics

 

       and Integrity Staff at the FDA, to describe the

 

       "Conflict of Interest Statement" and other

 

       instructions.

 

                      CONFLICT OF INTEREST STATEMENT

 

                          AND OTHER INSTRUCTIONS

 

                 MS. SLAUGHTER:  Well, good morning and

 

       welcome.  The Food and Drug Administration is

 

       convening today's meeting of the Food Advisory

 

       Committee under the authority of the Federal

 

       Advisory Committee Act of 1972.

 

                 With the exception of the industry

 

       representatives, all members of the Committee are

 

       special government employees or regular Federal

                                                                 11

 

       employees from other agencies subject to Federal

 

       conflict of interest laws and regulations.

 

                 FDA has determined that members of this

 

       Advisory Committee are in compliance with Federal

 

       ethics and conflict of interest laws including, but

 

       not limited to, 18 U.S.C. 208 and 21 U.S.C. 355 and

 

       354.

 

                 Under 18 U.S.C., Section 208, applicable

 

       to all government agencies, and 21 U.S.C. 355,

 

       applicable to only FDA, Congress has authorized FDA

 

       to grant waivers to special government employees

 

       who have financial conflicts when it is determined

 

       that the Agency's need for particular

 

       interventional services outweighs the potential

 

       conflict of interest.

 

                 Members who are special government

 

       employees at today's meeting including special

 

       government employees appointed as temporary voting

 

       members, have been screened for potential financial

 

       conflicts of interest of their own as well as those

 

       of their spouse, minor child, and employer, which

 

       are related to the discussions of today's and

                                                                 12

 

       tomorrow's and Friday's meeting regarding the "FDA

 

       Draft Report: Approaches to Establish Thresholds

 

       for Major Food Allergens and for Gluten in Foods."

 

                 These interests may include investments,

 

       consulting, expert witness testimony, contracts,

 

       grants, research and development agreements, public

 

       speaking, writing, patents, royalties, and primary

 

       employment.

 

                 In accordance with 18 U.S.C. 208(b)(3),

 

       full waivers have been granted to the following

 

       participants, Dr. Suzanne Teuber and Dr. Soheila

 

       Maleki, please note that all of the interests in

 

       the firms that could potentially be affected by the

 

       Committee's decisions.

 

                 A copy of the written waiver statements

 

       may be obtained by submitting a written request to

 

       the Agency's Freedom of Information Office, Room

 

       12A-30 of the Parklawn Building.

 

                 In addition, the following individuals are

 

       participating as FDA's invited guest speakers,

 

       July 13th: Dr. Rene Crevel, Dr. Susan Hefle,

 

       Anne Mun[MLM1] oz-Furlong, Dr. Steve Taylor, and

                                                                 13

 

       Dr. Robert Wood.

 

                 The following individuals will be

 

       participating as FDA invited guest speakers

 

       tomorrow, July 14th: Dr. Pekka Collin,

 

       Dr. Alessio Fasano, Dr. Donald Kasarda,

 

       Dr. Cynthia Kupper, and Dr. Joseph Murray.

 

                 Lastly, I would like to report that

 

       Dr. Jeffrey Barach and Dr. Mark Nelson are serving

 

       as the industry representatives on the Committee at

 

       today's meeting.  They are acting on behalf of all

 

       regulated industry.

 

                 Dr. Jeffrey Barach is employed by the

 

       National Food Processors Association and

 

       Dr. Mark Nelson is employed by the Grocery

 

       Manufacturers of America.

 

                 A copy of this document will be placed on

 

       the back table, if anybody wishes to take a look at

 

       it.  I thank you.

 

                 CHAIRMAN DURST:  Thank you very much.

 

       We will now go on to the welcome and opening

 

       statement by Dr. Michael Landa, the deputy director

 

       for Regulatory Affairs at CFSAN, the FDA.

                                                                 14

 

                 Mike.

 

                      WELCOME AND OPENING STATEMENT

 

                 MR. LANDA:  Thank you, Dr. Durst.  You

 

       will be pleased to learn that I don't have a

 

       doctorate or an M.D.  I'm just a plain, old J.D.

 

                 (General laughter.)

 

                 MR. LANDA:  Thanks again.  Good morning to

 

       everyone.  Welcome to the members of the committee,

 

       to the guest speakers, to members of the public who

 

       have joined us today, and to my fellow FDA

 

       employees.

 

                 I would like to give a special thanks to

 

       the Committee members for your willingness to take

 

       time from busy schedules to help us with your

 

       expertise for a meeting that will be several days

 

       long.  We are all here today, tomorrow and a fair

 

       chunk of Friday.

 

                 Let me just add that Dr. Brackett had

 

       hoped to be here this morning, but he wasn't able

 

       to make it.  I am hopeful that he will be here for

 

       some portion of the meeting.  He was called

 

       downtown for a meeting this morning.

                                                                 15

 

                 I am going to refer to a couple of points

 

       on the food allergens, but the points I'm making

 

       apply to celiac disease as well.  It is just less

 

       cumbersome to start with the food allergens.  The

 

       agenda has been making, I think, an opening

 

       statement, of course I'm really not going to do

 

       that.

 

                 There are just a few points I want to make

 

       as you go into your inquiry today.  The first is

 

       virtually every FDA speaker makes at this kind of

 

       proceeding which is what we do really is based on

 

       science.

 

                 We talk about being a science-based

 

       agency.  It is the bedrock; it is the foundation.

 

 

       In that context, I am going to paraphrase what may

 

       be a rather obscure 19th century Senator, Karl

 

       Shrews from Pennsylvania.

 

                 The paraphrase essentially is, Our science

 

       correct or incorrect, when it is correct, help us

 

       keep it correct; when it is incorrect, help us to

 

       correct it.  That is as much as anything else what

 

       we want from you here in terms of your expertise in

                                                                 16

 

       the science.

 

                 If with respect to the threshold in the

 

       Draft Report, we have gotten it right, we want to

 

       know from you that we have gotten it right.  We

 

       want your help in keeping it right.  If we have

 

       gotten it wrong, we want your help in getting it

 

       right.  That includes, as you will hear, if we have

 

       not considered an approach that we should have

 

       considered, we want to know that from  you.

 

                 The third point I will make is that

 

       Americans suffer from food allergies, particularly

 

       children.  There is some evidence that the number

 

       is increasing.  If you add to that family members,

 

       you really have tens of millions of folks who are

 

       involved.  At the moment their principle means of

 

       protection really is exquisite attention to the

 

       food label.  That is their pathway to safety I

 

       suppose.

 

                 We are hoping that eventually thresholds

 

       will provide another path to safety.  This is the

 

       beginning of the inquiry into thresholds, that is,

 

       the approaches that are outlined in the report.  It

                                                                 17

 

       is the first step in a very important process.

 

                 The last point I will make is just that

 

       this is as much as anything else for members of the

 

       public, the docket is going to remain open until

 

       about the middle of August.

 

                 If people have comments, based on what

 

       they have heard today, for example, they should

 

       feel free to submit those comments to the docket.

 

       Again, it is until about, I don't remember the

 

       precise date, but it is the middle of August.

 

                 In that connection, I should say we are

 

       especially interested, as I think is always the

 

       case, in data.  In this case, data of the type

 

       outlined in the report.

 

                 Thank you.

 

                 CHAIRMAN DURST:  Thank you, Mike.  Since

 

       Mr. Landa didn't want me conferring a doctorate

 

       degree on him, I will not do it with Catherine

 

       Copp, who is the policy advisor at CFSAN, also the

 

       FDA, who will discuss the use of food allergens

 

       thresholds.

 

                     USE OF FOOD ALLERGENS THRESHOLDS

                                                                 18

 

                 MS. COPP:  I was hoping.  Oh, well.

 

                 (General laughter.)

 

                 MS. COPP:  Thank you, Dr. Durst.

 

                 Good morning.  As you know, the focus of

 

       this meeting today and tomorrow and the discussion

 

       on Friday is the Draft Report of CFSAN's Threshold

 

       Working Group:  Approaches to Establish Thresholds

 

       for Major Food Allergens and For Gluten in Food.

 

                 I have been asked to provide a context for

 

       the Draft Report in terms of CFSAN's programmatic

 

       efforts.  This is one thing that if I were a real

 

       doctor I could do.  Lawyer's don't do this.

 

                 (Slide.)

 

                 MS. COPP:  Last August, Congress enacted

 

       the Food Allergen Labeling and Consumer Protection

 

       Act, which we refer to in-house by the somewhat

 

       awkward acronym "FALCPA."

 

                 This new law amends the Federal Food, Drug

 

       and Cosmetic Act, the principle statute

 

       administered by FDA by requiring that the label of

 

       a food product that is or contains an ingredient

 

       that bears or contains a major food allergen

                                                                 19

 

       declare the presence of the allergen as specified

 

       in the law.  In shorthand, the declaration is to be

 

       in "consumer friendly" terms.

 

                 FALCPA defines a "major food allergen" as

 

       one of the eight foods or food groups or a food

 

       ingredient that contains protein derived from one

 

       of these foods.  Those are listed on the bottom of

 

       this slide.  By "food groups," I mean fish, tree

 

       nuts and crustacean shellfish, which were

 

       identified by Congress in the law.

 

                 (Slide.)

 

                 MS. COPP:  The possible existence of

 

       threshold levels for food allergens is an important

 

       scientific issue, as Mr. Landa has pointed out,

 

       associated with our implementation of FALCPA.

 

                 Although the law does not require FDA to

 

       establish thresholds for any food allergen, there

 

       are three possible ways, which are listed on this

 

       slide, that such thresholds could be used to

 

       implement the new law, these are: administering the

 

       petition process provided for in FALCPA,

 

       administering its notification process, and

                                                                 20

 

       addressing the issue or the occurrence of

 

       cross-contact.

 

                 (Slide.)

 

                 MS. COPP:  FALCPA provides two processes

 

       by which an ingredient may be exempt from the

 

       FALCPA labeling requirements, a petition process

 

       and a notification process.  I'm trying to read my

 

       own slides (laughter).  No, okay.

 

                 Under the petition process, an ingredient

 

       may be exempt, if the petitioner demonstrates that

 

       the ingredient does not cause an allergenic

 

       response that poses a risk to human health.

 

                 Given this language for the petition

 

       exemption standard, we believe it will be very

 

 

       important for us to both understand food allergen

 

       thresholds and to have a sound scientific framework

 

       for evaluating the existence of such thresholds.

 

                 Under the notification process, an

 

       ingredient may be exempt, if the notification

 

       contains scientific evidence that demonstrates that

 

       the ingredient does not contain allergenic protein,

 

       or, if FDA has previously determined under the food

                                                                 21

 

       additive approval process that the food ingredient

 

       does not cause an allergenic response that poses a

 

       risk to human health.

 

 

 

                 (Slide.)

 

                 MS. COPP:  Given this language for the

 

       notification exemption standard, we also believe

 

       that it will be very important for us to understand

 

       food allergen thresholds and to have a sound

 

       scientific framework for evaluating the existence

 

       of such thresholds.

 

                 (Slide.)

 

                 Finally, the FALCPA directs FDA to prepare

 

       and submit a report to Congress.  This report will

 

       focus principally on the issue of cross-contact of

 

       foods with food allergens and is to describe the

 

       types, current use of, and consumer preferences

 

       with respect to so-called "advisory labeling."

 

       Processed in a facility that also processes tree

 

       nuts is an example of such labeling.

 

                 Cross-contact may occur during food

 

       production when residues of an allergenic food are

                                                                 22

 

       present in the manufacturing environment and are

 

       unintentionally incorporated into a food.  Because

 

       the food is not intended to contain the allergen,

 

       it is not declared as an ingredient on the food's

 

       label.  In some cases, however, the potential

 

       presence of the food allergen is declared by a

 

       voluntary advisory statement.

 

                 We also believe that understanding food

 

       allergen thresholds and developing a sound

 

       scientific framework for evaluating the existence

 

       of such thresholds may also be useful to us in

 

       evaluating and addressing food allergen

 

       cross-contact and the use of advisory labeling.

 

                 Thank you.

 

                 CHAIRMAN DURST:  Thank you very much.

 

                 Does the Committee have any questions or

 

       discussion of this presentation?

 

                 (No verbal response.)

 

                 CHAIRMAN DURST:  If not, I think we will

 

       proceed.

 

                 The next speaker is Dr. Robert Wood,

 

       professor at Johns Hopkins University School of

                                                                 23

 

       Medicine, who will give us an introduction to food

 

       allergens.

 

                      INTRODUCTION TO FOOD ALLERGENS

 

                 DR. WOOD:  Thank you very much.  It is a

 

       pleasure to be here.  What I was asked to do is to

 

       provide an overview of food allergens and food

 

       allergy leading into the discussion that is going

 

       to go on over these next couple of days.

 

                 (Slide.)

 

                 DR. WOOD:  The beginning of this, any talk

 

       about food allergy really requires that we have

 

       some common definition that we can all agree on.

 

       This is something that is not as easy as it might

 

       sound and often generates a lot of confusion.  The

 

       reality is that a lot of what is called food

 

       allergy is really not food allergy and may fall

 

       under more of a food intolerance category.

 

                 When we are talking about food allergy,

 

       there are a couple of key ingredients.  One of them

 

       is that there is an immunologic component to the

 

       reaction.  The reaction is typically to the protein

 

       component of the food as opposed to a food

                                                                 24

 

       intolerance that is more often related to the

 

       carbohydrate component of the food.  Importantly to

 

       this meeting, exquisitely small amounts may cause a

 

       reaction and that these reactions can be severe and

 

       even life threatening.

 

                 (Slide.)

 

                 DR. WOOD:  The pathophysiology of the

 

       allergic response is sort of very schematically

 

       diagramed here.  What we are thinking about is a

 

       process that begins with exposure and with most

 

       allergy, probably all allergy, you have to have

 

       some prior exposure to develop your sensitivity.

 

                 (Slide.)

 

                 DR. WOOD:  There is a genetic

 

       predisposition that makes some people particularly

 

       more prone to develop allergy in general, whether

 

 

       it be food allergy or respiratory allergy, than

 

       others.   There are some people who no

 

       matter what, how, when and where they are exposed

 

       they will never develop an allergy, and others who

 

       with very trivial exposure may develop a severe

 

       allergy.

                                                                 25

 

                 If you are in this group who is

 

       genetically predisposed, your immune system then