1

FOOD ADVISORY COMMITTEE AND DIETARY

SUPPLEMENTS SUBCOMMITTEE

THE ROLE OF GLUCOSOSAMINE AND CHONDROITIN

SULFATE IN OSTEOARTHRITIS

Monday, June 7, 2004

8:03 a.m.

Bethesda Marriott

5151 Pooks Hill Road

Bethesda, Maryland

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

Sanford A. Miller, Ph.D., Chair

Linda Reed, Acting Executive Secretary

Douglas L. Archer, Ph.D.

Patrick S. Callery, Ph.D.

Annette Dickinson, Ph.D.

Goulda A. Downer, Ph.D.

Johanna Dwyer, D.Sc., R.D.

Jean M. Halloran

Norman I. Krinsky, Ph.D.

Daryl B. Lund, Ph.D.

Margaret C. McBride, M.D.

Mark F. Nelson, Ph.D.

Robert M. Russell, M.D.

Carolyn I. Waslien, Ph.D., R.D.

Edward Blonz, Ph.D.

Edward D. Harris, Ph.D.

Harihara M. Mehendale, Ph.D.

Steven Zeisel, M.D., Ph.D.

Temporary Voting Members

Steven Abramson, M.D.

John J. Cush, M.D.

Luis Espinoza, M.D.

David Felson, M.D., M.P.H.

Scott A. Kale, M.D., J.D., M.S.

Nancy E. Lane, M.D.

Also Present:

Jeanne Latham, Executive Secretary, Dietary

Supplements Subcommittee

C O N T E N T S

AGENDA ITEM PAGE

Call to Order, Introductions - Dr. Miller 4

Administrative Matters and Conflict of Interest

Statement - Ms. Reed 9

Opening Remarks, Robert E. Brackett, Ph.D.,

Director, Center for Food Safety and Applied

Nutrition (CFSAN) 20

Background and Questions to Committee - Laura M.

Tarantino, Ph.D. 22

Questions and Clarifications 30

Overview of Legal Framework, Louisa Nickerson,

Office of General Counsel, FDA 33

Questions and Clarifications 38

Overview of petitions: FDA's Review Process and

Issues - Dr. Craig Rowlands, Biologist,

FDA/ONPLDS/CFSAN 42

Questions and Clarifications 57

Petitioner: Weider Nutrition International, Inc.,

Luke R. Bucci, Ph.D., Vice President of Research,

Weider Nutrition Group 69

Questions and Clarifications 105

Petitioner: Rotta Pharmaceutical, Inc.

- Dr. Lucio C. Rovati, Executive Medical Director,

Rotta Research Laboratory 136

- Dr. Roy D. Altman, Professor of Medicine and

Rheumatology, University of Miami and University of

California-Los Angeles 156

Questions and Clarifications 174

Lunch 207

Questions and Comments 250

C O N T E N T S (Continued)

AGENDA ITEM PAGE

Current State of the Science on Etiology of OA and

Modifiable Risk Factors for OA - Dr. Lee Simon,

Harvard University 209

Questions and Clarifications 250

The Role of Animal and in vitro Models in OA Risk

Reduction - Dr. James Witter, Center for Drug

Evaluation and Research, FDA 256

Questions and Clarifications 287

Public Comment 291

- Jason Theodasakis, M.D. 291

- Gayle E. Lester, Ph.D. 299

- Robert Arnot, M.D. 304

- Jose Verges, M.D. 317

- Todd Henderson, D.V.M. 332

- Chuck Filburn, Ph.D. 334

Questions and Clarifications 341

Adjournment 352

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

2 DR. MILLER: Good morning. I want to take

3 this opportunity of welcoming you to this meeting

4 of the Food Advisory Committee. Today and tomorrow

5 the committee is going to deal with two topics, one

6 dealing with the role of glucosamine and

7 chondroitin sulfate in osteoarthritis, and the

8 other having to do with furan contaminants in

9 foods.

10 For that reason, in order to expand the

11 expertise of the committee, we've invited some

12 temporary members to join the committee, several

13 dealing with the glucosamine and chondroitin

14 sulfate issue and several having to do with the

15 issues concerned with furans.

16 As always, we have much too full a

17 schedule, and as always, I'm going to insist that

18 we stick to our time. We have to give everybody an

19 opportunity to speak and speak for the time limits

20 that they've been assigned, and we also have to

21 provide enough time for us to discuss the issues to

22 the extent that the committee needs and feels that

1 discussion is needed. Towards that end, as you

2 make your presentations and you have exceeded your

3 time, I'll let you know. And I'm not sure exactly

4 what I'll do if you continue to talk, but--

5 [Laughter.]

6 DR. MILLER: The very least would be to

7 turn off your microphone and ask questions

8 concerning the meaning of your data.

9 To begin the meeting, I'd like to

10 introduce--or have them introduce themselves, the

11 members of the committee. This morning we will

12 deal with the glucosamine and chondroitin sulfate

13 issues, and tomorrow we'll deal with furans.

14 I'll begin by introducing myself. My name

15 is Sandy Miller. I'm a senior research associate

16 at the Center for Food Nutrition Policy at Virginia

17 Tech University.

18 DR. RUSSELL: I'm Robert Russell. I'm

19 director of the USDA Human Nutrition Research

20 Center on Aging at Tufts.

21 DR. DICKINSON: Annette Dickinson,

22 president of the Council for Responsible Nutrition.

1 DR. ARCHER: I'm Doug Archer, professor,

2 Food Science and Human Nutrition at the University

3 of Florida.

4 DR. CALLERY: Patrick Callery,

5 pharmaceutical chemist, from West Virginia

6 University.

7 DR. DOWNER: Goulda Downer, president and

8 CEO, Metroplex Health and Nutrition Services,

9 Washington, D.C.

10 DR. McBRIDE: Margaret McBride, child

11 neurologist at Akron Children's Hospital.

12 DR. BLONZ: Edward Blonz, nutritional

13 biochemist, from Kensington, California.

14 DR. ABRAMSON: Steve Abramson, Director of

15 Rheumatology at NYU and the Hospital for Joint

16 Diseases and Dean for Clinical Research at NYU.

17 DR. FELSON: David Felson, rheumatologist,

18 from Boston University.

19 DR. ESPINOZA: Luis Espinoza, Chief of

20 Rheumatology, LSU, New Orleans.

21 DR. KALE: Scott Kale. I'm a

22 rheumatologist at Rush Presbyterian and St. Luke's

1 in Chicago.

2 DR. LANE: Nancy Lane, rheumatologist,

3 University of California-San Francisco.

4 DR. ZEISEL: Steve Zeisel. I'm professor

5 and Chair of the Department of Nutrition at the

6 University of North Carolina at Chapel Hill.

7 DR. MEHENDALE: Hari Mehendale, professor

8 of toxicology at the University of Louisiana at

9 Monroe.

10 DR. HARRIS: I'm Ed Harris, professor of

11 biochemistry and nutrition, Texas A&M University.

12 DR. NELSON: Mark Nelson, Vice President

13 for Scientific and Regulatory Policy, Grocery

14 Manufacturers of America.

15 DR. WASLIEN: Carol Waslien, Chair and

16 professor, Nutritional Epidemiology, University of

17 Hawaii.

18 DR. LUND: Daryl Lund, University of

19 Wisconsin-Madison, Food Science, and Executive

20 Directors of the North Central Regional

21 Association.

22 DR. DWYER: Johanna Dwyer, professor at

1 Tufts University, and Director of the Frances Stern

2 Nutrition Center and New England Medical Center,

3 and I'm spending the year in Washington.

4 DR. KRINSKY: Norman Krinsky, emeritus

5 professor of biochemistry, Tufts University School

6 of Medicine.

7 MS. LATHAM: Jeanne Latham, Food and Drug

8 Administration, Executive Secretary of the Dietary

9 Supplements Subcommittee.

10 MS. REED: Linda Reed, Acting Executive

11 Secretary of the Food Advisory Committee.

12 DR. MILLER: Next we have certain

13 administrative things that we need to go through,

14 and Linda Reed, who is the Acting Executive

15 Secretary of the Food Advisory Committee, will

16 present those rules of the road and issues

17 concerning conflict of interest.

18 MS. REED: Good morning, everyone. As

19 you've heard, I'm Linda Reed, the Acting Executive

20 Secretary of the Food Advisory Committee. I was

21 asked to take a few minutes to refresh everyone's

22 memory about a few rules of the road, if you will,

1 in terms of Advisory Committee operations.

2 It is my understanding that all of the

3 committee members have been provided a copy of a

4 Committee Member Guide to FDA Advisory Committees.

5 There is a copy of the Member Guide at the

6 registration desk for anyone who may be interested

7 in looking through it. The Committee Member Guide

8 is in need of updating, but, by and large, it does

9 provide good operational review.

10 FDA relies on Advisory Committees to

11 provide the best possible scientific advice

12 available to assist us in making complex decisions.

13 Our goal is to do that in as open and transparent a

14 manner as possible. Part of that openness carries

15 with it a request that the members try to avoid

16 even the appearance that issues are being decided

17 or conclusions are being reached outside of the

18 meeting.

19 We understand that issues raised during

20 the meeting may well lead to conversation over

21 breaks and during a meal. In fact, we hope the

22 discussions are thought-provoking.

1 We have had instances where members have

2 come back from a break and said, "You know, we were

3 talking over the break, and we would like to

4 request that the FDA provide us with some

5 additional information so we can better understand

6 thus and such." That is perfectly acceptable.

7 What we don't want is to have a situation

8 where, after the break, the members come back and

9 say, "We were talking over the break and decided

10 that an answer to a question is..." From our

11 perspective, that would be particularly troublesome

12 because neither the agency nor the public would

13 have had the benefit of listening to the entire

14 discussion, the question raised, and the responses.

15 In fact, FDA has adopted a policy that

16 only the matters can be reached by a show of hands,

17 procedure matters, for example--I read all that

18 wrong. Excuse me.

19 In fact, FDA has adopted a policy that the

20 only matters that can be decided by a show of hands

21 are procedure matters, for example, break times.

22 All other votes and comments must be placed on the

1 record, attributed to the member making that

2 statement. The policy goes even further. If a

3 member has to leave the meeting early, the member

4 waives that right to vote. You may wonder why the

5 person may lose their right to vote, but the answer

6 is fairly simple. FDA believes that all parts of

7 the meeting and discussions are important.

8 Consequently, voting on issues without having the

9 benefit of the discussion would be premature.

10 The issue of openness is larger than what

11 transpires during the course of the meeting. I

12 would like to call your attention to the section in

13 the Member Guide titled "Member Interaction Before,

14 During, and After a Meeting." In essence, this

15 section underscores the fact that all

16 communications with the members should be routed

17 through the committee's Executive Secretary. That

18 would be myself. No one, not even FDA staff, with

19 the exception of the Executive Secretary, should be

20 contacting the members about upcoming meetings,

21 topics, et cetera. This same guidance applies to

22 consultations between members prior to a meeting.

1 If a member receives an inappropriate

2 contact, the member should feel free to notify

3 myself and/or refer the person making the contact

4 to me. Our goal in having all contacts routed

5 there the Exec. Sec. is to minimize any situations

6 that could be misinterpreted.

7 Appearance issues are always difficult,

8 because, as is true of many things, appearances can

9 be deceiving. We ask that our members, guest

10 speakers, liaisons, and everyone attending the

11 meeting be mindful of how an interaction between a

12 member--and anyone, for that matter--might be

13 perceived.

14 Please let me be clear. It is not my

15 intention to question anyone's integrity or

16 motives. But I'm very sensitive to the issue

17 because I have--and I imagine you all have, too--seen highly

18 respected individuals become an object

19 of negative attention based on a misperception.

20 And I certainly wouldn't want anyone in this room

21 to become such a target.

22 I'm confident that everyone here today is

1 sensitive to these issues and can appreciate that

2 my comments are intended as a gentle reminder.

3 Lastly, as you settle in, please take this

4 opportunity to silent any cell phones or other

5 devices that ring, beep, or play show tunes. And I

6 appreciate your attention for that statement.

7 Now I'd like to read the conflict of

8 interest statement into the record.

9 DR. MILLER: Just to be certain that there

10 are no mistakes, does anybody need any

11 clarification?

12 [No response.]

13 DR. MILLER: If not, why don't we go on.

14 MS. REED: Okay. As Dr. Miller mentioned,

15 we have the pleasure of having two of our

16 subcommittees and several members of our sister

17 center Advisory Committee serving throughout the

18 meeting, and we thank you for being here.

19 And with that, I would like to read the

20 conflict of interest statement into the meeting

21 record. And as with the rules of the road, this is

22 a rather long one, so please bear with me.

1 The authority to appoint temporary voting

2 members to the Food Advisory Committee is granted

3 to the Center Director. Relying on that authority,

4 Dr. Robert Brackett, Director, Center for Food

5 Safety and Applied Nutrition, has signed letters

6 appointing Dr. Luis Espinoza, Dr. Scott Kale, and

7 Dr. Nancy Lane as temporary voting members of the

8 Food Advisory Committee of the June 7-8, 2004,

9 committee meeting. These members will serve on the

10 committee for the first portion of the meeting, the

11 subject of which is osteoarthritis.

12 The authority to grant permission to