AT DEPARTMENT OF HEALTH AND HUMAN SERVICES

 

UNITED STATES FOOD AND DRUG ADMINISTRATION

 

CENTER FOR FOOD SAFETY AND APPLIED NUTRITION

 

 

 

 

 

 

 

 

 

 

 

ADDITIVES AND INGREDIENTS SUBCOMMITTEE

OF THE

FOOD ADVISORY COMMITTEE

 

LATEX ALLERGY

 

 

 

 

 

 

 

Tuesday, August 26, 2003

 

9:10 a.m.

 

 

 

 

 

 

 

 

 

 

 

 

St. Regis Hotel

923 16th Street, Northwest

Crystal Ballroom

Washington, D.C.

PARTICIPANTS

 

Johanna Dwyer, D. Sci., Chair

Richard Bonnette, Executive Secretary

 

MEMBERS

 

    Jeffrey Blumberg, Ph.D.

    Goulda Downer, Ph.D.

    Lawrence Fischer, Ph.D.

    Anthony Gaspari, M.D.

    Robert Hamilton, Ph.D.

    Rachel Johnson, Ph.D.

    Brandon Scholz

    Steve Taylor, Ph.D.

    J. Antonio Torres, Ph.D.

C O N T E N T S

 

Welcome and Introductions

Committee Chair    5

 

Conflict of Interest Statements

Committee Executive Secretary    7

 

Welcome

Alan Rulis, Ph.D.    11

 

Overview of CFSAN's Office of Food Safety

George Pauli, Ph.D.    14

 

Charge and Questions

Laura Tarantino, Ph.D.    29

 

Basic Latex Allergy Background

Jay Slater, M.D.    39

 

Questions of Clarification    70

 

CDRH Proposal

Mel Stratmeyer, Ph.D.    96

 

Questions of Clarification    107

 

Safety Assessment of Food Additives

Anna Shanklin, Ph.D.    128

 

Questions of Clarification    151

 

Specific Background on Food Mediated Latex Reactions

Mark Hepp, Ph.D.    163

 

Questions of Clarification    183

 

Progress in the Management of NRL Allergy

Vesna Tomazac-Jezic, Ph.D.    200

 

Questions of Clarification    212

C O N T E N T S (cont.)

 

Invited Comment

Don Beezhold, Ph.D.    229

 

Questions of Clarification    243

 

Invited Comment from a State with Latex Food Service Glove Prohibition

Michael Heumann    260

 

Questions of Clarification    283

P R O C E E D I N G S

Welcome and Introductions

    DR. DWYER:  Good morning.  Welcome to the latex allergy discussion.  CFSAN's concern with the use of natural rubber latex gloves in retail food establishments and the food service industry is focused on whether such use may result in the production of unsafe food, and that is what we are gathered here this morning to talk about, separating the issues related to worker exposure and occupational safety from those of food safety.

    I am Johanna Dwyer and I am chairing this meeting today.  The task before this Food Advisory Subcommittee is to consider the available information related to food mediated latex allergic reactions and the use of latex food service gloves in establishments that prepare food for public consumption, so specifically, there are several issues that FDA has requested feedback from the committee on.

    The first question that we will return to over the course of the next two and a half days is has a positive relationship been established between the use of natural rubber latex gloves in food service and allergic reactions to food served in food establishments or sold at the market based on the data that are available to the committee.

    If such a relationship exists, what is the strength of that relationship and has it been shown to be causative.  Second, if a positive relationship has been established and shown to be causative, can the Advisory Committee suggest science-based options to mitigate food mediated latex allergy risk?

    Finally, if current evidence isn't sufficient to establish a relationship, what additional questions need to be addressed to adequately understand this issue?

    So, we have got a lot of work to do.  I think our main task is to keep focused on the specific questions the agency has asked us to answer rather than the broader questions that these issues raise.

    Mr. Bonnette.

Conflict of Interest Statements

    MR. BONNETTE:  Good morning.  My name is Richard Bonnette and I am the Acting Executive Secretary for the Additives and Ingredients Subcommittee of the full Food Advisory Committee.

    I will read into the record the temporary voting member appointment and conflicts of interest statement.

    By the authority granted under the Food Advisory Committee charter of July 2002, the following individuals have been appointed as temporary voting members by Joseph A. Levitt, Director, Center for Food Safety and Applied Nutrition.  Anthony Gaspari, Robert Hamilton, and Steve Taylor.

    With regard to the issue of conflict of interest, committee members, permanent and temporary, were screened for interests in latex glove manufacturers.  As a result of this review, in accordance with 18 U.S. Code Section 208(b)(3), Dr. Johanna Dwyer has been granted a particular matter of general applicability waiver that permits her to participate fully in the matters at issue.

    Copies of the waiver statement may be obtained by submitting a written request to the agency's Freedom of Information Office, Room 12A-30 of the Parklawn Building.

    We would also like to note that Mr. Brandon Scholz is participating in this meeting as the Industry Representative and is a non-voting participant.

    It should also be noted that Dr. Charles Reed, who will be speaking tomorrow, was invited by the latex glove industry to speak.

    With respect to all other participants, we ask in the interest of fairness that they address any current or previous financial involvement with any firm which makes latex gloves.

    I will just at this time make a few housekeeping notes especially to the committee and to the upcoming speakers.

    When you use the microphone, you have to press a little button to turn it on and then press the button again to turn it off.  That is only an issue because we can only have four mikes open at any one time.

    We will be using, for the speakers we will be using a hand-held wireless mouse, and basically what you need to know to advance your slides is there is a little trigger in the bottom that will move you onto the next slide.

    DR. DWYER:  Could we go around the table and just introduce the various members, Mr. Bonnette.

    MR. BONNETTE:  Sure.

    DR. DWYER:  Mr. Scholz, could you start off.

    MR.  SCHOLZ:  Brandon Scholz with the Wisconsin Grocer's Association.

    DR. DOWNER:  Goulda Downer, President and CEO of Metroplex Health and Nutrition Services.

    DR. JOHNSON:  I am Rachel Johnson.  I am Professor of Nutrition and Dean of the College of Agriculture and Life Sciences at the University of Vermont.

    DR. GASPARI:  I am Tony Gaspari.  I am Professor and Chair in the Department of Dermatology, University of Maryland School of Medicine.

    MR. BONNETTE:  I am Richard Bonnette.  I am the Acting Executive Secretary for this meeting.

    DR. DWYER:  Johanna Dwyer, Tufts University, Schools of Nutrition, Science and Policy, and Medicine.

    DR. BLUMBERG:  I am Jeff Blumberg.  I am a Professor of Nutrition at Tufts University.

    DR. TAYLOR:  Steve Taylor.  I am Professor and head of the Department of Food Science and Technology at the University of Nebraska.

    DR. HAMILTON:  Robert Hamilton.  I am a Professor of Medicine and Pathology at the Johns Hopkins University School of Medicine.

    DR. FISCHER:  I am Larry Fischer from Michigan State University, Director of the Institute for Environmental Toxicology.

    DR. TORRES:  I am Antonio Torres, Professor of Process Engineering, Oregon State University.

    MR. BONNETTE:  Next on the Program we have Dr. Alan Rulis from the Office of Food Additive Safety.

Welcome

    DR. RULIS:  Good morning everybody.  It is my privilege this morning to offer a few words of welcome to this first meeting of the newly created Additives and Ingredients Subcommittee of CFSAN's Food Advisory Committee.

    I am Alan Rulis.  Until recently, I was, for some years, the Director of the Office of Food Additive Safety in the Center for Food Safety and Applied Nutrition.  Now, I am working directly with our Center Director, Joe Levitt, on another area, Applied Nutrition.  But I was granted this opportunity by the Acting Director of the Office of Food Additive Safety, Laura Tarantino, to address you this morning.

    My main message to you assembled Subcommittee members, is thank you for giving generously of your time and letting us benefit of your expert knowledge in dealing with the issue of natural rubber latex in the food setting.

    During my tenure as the Director of OFAS and in other capacities in the Center, I can verify that we have, indeed, benefitted greatly from Food Advisory Committees.  Of those Food Advisory Committees that I have been directly involved with, in particular two that we held on Olestra in November, 1995 and June of 1998 and, last summer, on methylmercury in seafood, I can say that they were extremely helpful to the agency in reaching a solid decision.

    They helped ensure that our decisions of benefit of objective, public, balanced discussion and examination of all issues from all sides.  That has helped assure that we make credible decisions that are founded firmly on scientifically sound principles and evidence.  We expect no less from this meeting in its agenda on the issues of allergy and related issues surrounding the use of natural rubber latex in food service.

    We expect your deliberations will help us greatly.  So, again, welcome and all the best to you in your deliberations today and in the coming day or two.

    Thank you.

    MR. BONNETTE:  Next on the program, I would like to welcome Dr. George Pauli also from the Office of Food Additive Safety.

    DR. DWYER:  Dr. Rulis, while we are waiting for the projection, could you tell us where the methylmercury final decision is posted or published.

    DR. RULIS:  Of course, as with all such public advisory committees, there is a transcript available of that meeting.  There were recommendations that resulted from the meeting.  There was a decision to incorporate in the Center for Food Safety and Applied Nutrition's Priority Program, that is, the so-called Yellow Book that is the publication of the Center's priority activities for any given year, an element that is directly related to that advisory committee to examine the messages that are on labels of fish that will be supplied when fish is offered for sale.

    We are to look at that carefully and decide, based on what we know at the moment and what other organizations are doing, not only federally, but at the state level, to derive an appropriate method for marine seafood that is in interstate commerce relative to the methylmercury issues.

    So, we are in the process of doing that.  We are currently, in this fiscal year, working on that recommendation, and I expect that something public will happen soon, but I can't predict when.

Overview of CFSAN's Office of Food Additive Safety

    DR. PAULI:  Thank you.  Let me also join Alan in thanking you for being here to help us weave through these tricky and sometimes controversial issues.

    I am George Pauli, the Associate Director for Science and Policy in the Office of Food Additive Safety.

    I thought I would take this slide just to acknowledge something that--the name of the subcommittee Additives and Ingredients, most people would probably think isn't that the same thing, but one of the things I want to do today is mention a few of the differences and also, because the Office of Food Additive Safety is responsible for our statutory obligations under the Food, Drug, and Cosmetic Act for both additives and ingredients, I will start by introducing you to the Office of Food Additive Safety, which will give some of you an orientation for future meetings, as well as this one.

    Looking at our mission statement, if I can emphasize a few of those bullets, we evaluate new applications for new ingredients or new additives.  We want to make sure that everything we do meets a high performance standard based on science, and we want to, as we are doing today, monitor safety over time because any decision is made with the information you have, and we are in the business of making decisions, so have to continue to monitor to find if there is any new information that would cause us to rethink some of our decisions.

    We also have a modest research program to try to support this monitoring effort.

    A little introduction to what the office looks like.  I will just emphasize some of the different functions.  The Division of Food Contact, Substance Notification, we have responsibility for anything that becomes a component of food because food is touching it or somehow it is getting in the food even though nobody intends for that to happen.

    We have a Division of Petition Review for essentially new food ingredients and color additives where there is a formal process to get an approval.

    We have a Division of Biotechnology and GRAS Notice Review, which refers to many ingredients don't require approval, but we have to know whether they are ingredients that don't require approval or if they are additives that must be approved through the Division of Petition Review.

    Finally, our research wing on the far right.

    One of the things that is related to this meeting and other meetings we will be having in the future, one of things that has come into context as being very important in recent years is the issue of allergies.  So, we now have for the first time, for about a year now, an allergist in our office, Dr. Luccuoli, who is sitting at the side table over there.

    Food Additive Decision Framework.  I will have to recognize that under the law, different approaches are used for distinction segments or components of food.  Sometimes people are concerned that everything should have the same standard, but there is a higher standard for those substances that are used intentionally in a manner whereby human have a choice to use it or don't use it, or to use it with controls or don't use it with controls.

    So, from that standpoint, food additives, color additives, food contact substances require a pre-market approval of a very high standard of safety.  Ingredients that are generally recognized as safe have essentially already met that safety in the scientific community at large and put in a separate category.

    Dietary ingredients and dietary supplements are under a new framework since 1994, and contaminants, of course, nobody wants, but it is a question of how hard you control it that have to have a different standard, as well.

    Now, one of the things I think that is important is that all authority that we, at the Food and Drug Administration, have to control and enhance the safety of food is derived from the authority that has been given to us by Congress, primarily through the Federal Food, Drug, and Cosmetic Act.

    That is certainly true of the Office of Food Additive Safety where the Federal Food, Drug, and Cosmetic Act is the main authority we have to do anything.  For that reason, we have to look at two standpoints.  Statutory standards, are we doing something we would like to do, or have we actually been given authority to do that, to make that kind of decision.

    The decision we make has to be consistent with the statutory standard that Congress gave us.  One of the good things of the statutory standard is it relies on scientific principles, so we can use our science to get the facts right, but those two parts are so fundamental you can't ignore either one.

    Now, this advisory committee, we bring together scientists to emphasize the scientific principles part, but we just have to recognize that what the ultimate regulatory decision is depends also on the statutory standard.

    Now, the Food, Drug, and Cosmetic Act of 1938, a part of the New Deal legislation, was amended several times, but four times that is particularly important to us.  In 1958, it was amended with the Food Additives Amendment requiring pre-market approval for food additives.

    In 1960, it was amended with the Color Additive Amendments for color additives and foods, drugs, and cosmetics.

    In 1994, it was amended with the Dietary Supplement Health and Education Act that exempted certain ingredients in dietary supplements from the food additive provisions.

    In 1997, with the Food and Drug Administration Modernization Act, the regulation of food contact substances is modified to make it streamlined through a notification program.  However, the safety standard with the notification program for food contact substances is the same as it was before, the data we require are the same as before.  It is just the procedure that we follow to get approvals is a little bit different.

    We look at some of the basic principles of these amendments, defines a food additive with an exemption for those ingredients that are already generally recognized as safe.  I always use my favorite example - no one is ever going to ask us to approve the use of water in soda population.  That is a no-brainer, everyone knows that one.

    Or vitamin C as a nutrient supplement in many foods, however, when you have a new ingredient where there isn't a consensus in the scientific community, where the knowledge of it isn't widely known, then, we have the food additive.

    As I mentioned, there is also an exemption in the food additive definition now for dietary ingredients and dietary supplements.  If something meets the food additive definition, you must have pre-market approval before the product is sold in the U.S.

    The statute establishes the standard of review, establishes the standard of safety, establishes formal rulemaking procedures whereby we can issue requirements or issue approvals.

    Now, the statutory definition is a very broad one, and I do not have all the words of the definition on this slide.  There are several examples given which would run onto about two more slides if I gave them all.

    But we will get very broad.  Any substance which because of how it is being used, intended to be used, not accidentally, but intended to be used results or may reasonably be expected to result, directly or indirectly, in its becoming a component of food or otherwise affecting the characteristics of any food.

    The definition goes on with some examples, such as sources of irradiation equipment which can affect the characteristics of food or food additive, substances used in the packaging, manufacture of food, and that is what we are dealing with this week.

    You have the big exemption for those substances whose use is generally recognized as safe, and let emphasize the word "use."  We do not evaluate the safety of substances, we evaluate the safety of how substances are used.  So, it is very much a safe under intended conditions of use standard.

    Examples of the universe that we are responsible for in our office - direct food ingredients, sweeteners, preservatives, and the like.  That would be generally food additives, but not always.  Color additives are generally recognized as safe ingredients uses, which overlaps with the direct food ingredients certainly, and it also overlaps with food contact substances, such as iron pans for cooking.  Some of that iron is going to get into food, but no one is concerned about that.

    Food ingredients produced using modern biotechnology to ensure that it is still the same food and you haven't come up with something new that we don't understand, in which case it could come in under the food additive provisions.

    Processing aids that may be in contact with food for a short time or that may be used in food, but then are decomposed by heat or something, so that they are no longer in the final product.  As mentioned before, food irradiation equipment and what we are focusing on this week, food packaging and food contact substances.

    Standard for safety, which comes out of the legislative history of the food additive amendment, is reasonable certainty of no harm, and we look at that in the words of Congress there, "The concept involves the question of whether a substance is hazardous to the health of man or animal."

    So the harm we are talking about is harm to health.  It says "man or animal" because the same applications apply to ingredients in packaging used for animal feed for pets or food-producing animals.

    "Safety requires proof of a reasonable certainty that no harm will result from the proposed use of an additive."  You will hear this a few more times before this week is over.

    I have to also note--again, it's the words of Congress--"It does not--and cannot--require proof beyond any possible doubt that no harm will result under any conceivable circumstances."

    I have to say we are in the business of making decisions.  We cannot expect absolute certainty in any decision, but when are you to the reasonable stage, when are you going over the edge, or where don't you have enough information to proceed at all is part of the judgment that comes in here and where we ask for help.

    For a new food additive, petitioner has the burden to demonstrate this reasonable certainty of no harm, and again I have emphasize from the intended use of the additive.  We find that there are some things that we regulate that may cause health problems when used in a totally different manner, and we just can't address other uses outside of the intended use with food.

    From doing that, we look at whether we have adequate data to say reasonable certainty of no harm has been demonstrated.

    Now, part of understanding what reasonable certainty is, is today's food--and I have put in quotation marks, "New" and "Today" because this has been going on for 45 years now--there is an underlying assumption in the food additives amendment that unprocessed food from the farm is safe and that no one should be allowed to use some substance in a manner to make that food less safe.

    So, it gives us a little bit of an idea of what we mean by "safe" and "certainty."  We are looking at food as being the gold standard.  Of course, one thing we know today, that we didn't know in 1958, is that is again not absolute safety.

    The olden days, which I define as from 5 to 30 years ago, we managed to do everything in our office by strong control.  We had food additive petitions, we had color additive petitions, and if something did not require approval because it was generally recognized as safe, we had GRAS affirmation petitions even when approval was not required.

    Now, the petition review process, just to give you an idea of what we were looking at, it is not an academic inquiry or academic research.  Many times one sees data and say this is interesting, I would like to explore that more, but if it doesn't get right at the food safety decision, we don't go there.

    It will have to be focused on safe under conditions of use, not on interesting things that are beyond that.  Therefore, it is not a search for complete knowledge, can't assure safety with absolute certainty, does not weigh risks and benefits.

    People are often surprised at that, but as I mentioned before, there is an underlying assumption that food is safe, if that's the case, why would you take a risk with something, what benefits are there?  You already have a safe food.

    Again, I think we are looking at things maybe a little different in some ways today, but that still is what the law is.  That is still the standard.  We don't weigh risks and benefits, and it is not intended to enforce or limit consumer or producer choices among safe foods.  There is no need base here.

    We sometimes see in some countries of whether there is a need to use something.  That is not one of our standards.  The standard is, is it safe under the conditions of use.  The marketplace will decide whether they need it, the consumer will decide whether to buy it, the producer will decide whether or not it is in their interests to use that substance, that material.

    The food additive decision process does, in fact, ensure safety as we look through what we have done for the last 45 years.  We have a good track record.  Occasionally, uncertainty comes in, but we haven't really seen safety issues with things that have been approved.  The safety issue is more with ingredients that were used prior to that time.

    It is a consensus decision.  No individual is ever responsible for the decision.  We share that responsibility, we argue with each other, and eventually, someone, possibly the Commissioner or possibly the Secretary of Health and Human Services may make the ultimate decision.  The ultimate decision rests with the Secretary of Health and Human Services, but that authority is delegated down for decision.  That doesn't require such a high level of person.

    Today and sort of the shape of the future, we have had consultations on modifications of food through bioengineering actually since 1994.  We now have programs where people who conclude that the way they intend to use an ingredient is generally recognized as safe because the law doesn't require approval.

    We do have a program where they can notify us just to make sure that we don't have people working at cross purposes, one person concluding one thing and FDA concluding something else and saying we will meet you in court, so we have a program where companies do let us know, for those ingredient uses that they think do not require approval, and we have food contact substance notification, which as I mentioned before require all the data of the old petitions, but under a current law, since 1997, a law which took effect a few years later, we get notifications with the data why the use of a food contact substance is safe, and we at FDA have 120 days to disagree with that if we believe that they have not met their burden.

    Now, a final little issue of looking back at everything we look at.  If you look at whole foods, you have to evaluate those differently than you do ingredients.  You don't get 100-fold safety factors from toxicity data for whole foods.

    As we go from the bottom working upward in the slide, we get to human exposure that gets less and less, and where we generally require less data, but we can apply safety factors, we are looking at things that are used at levels faro below where they would cause any harm, and now again, as we are reminding ourselves this week, we are even getting into the allergy area where one question, how low do you have to go when you are considering the safety of something that may be allergenic.

    That is not on this chart, but I would put that up sort of at the top end of the very small amounts of things that we are concerned with.

    I hope this gives you a little understanding of the responsibilities of our office, and, hence, the responsibilities of this subcommittee that we are going to be looking for advice.

    If anyone has any particular questions, I would be happy to try to answer them; otherwise, we will move on to our next speaker.

    DR. DWYER:  Thank you very much.

    Two things, just a quick one.  Does everyone have the handout on the committee?  Okay.  Could you please see to it that everybody has all the handouts.

    Secondly, are there any questions after that illuminating introduction?  Any questions from the committee?

    Thank you for setting this process in context.

    Since there are no questions, I think we can proceed to Dr. Tarantino, who is at the Office of Food Safety and Quality, and she is going to give the committee its charge and review the questions.

    Dr. Tarantino.

Charge and Questions

    DR. TARANTINO:  Thank you, Dr. Dwyer and members of the Additives and Ingredients Subcommittee.  Good morning.

    As she said, I am Laura Tarantino, and as Alan said, I am currently Acting Director of the Office of Food Additive Safety, and my job here is to go from the very general introduction to begin to outline your task that we are going to ask you about for the next couple of days and to amplify a little bit on the charge and questions and what we are after that Dr. Dwyer read to you earlier.

    I am going to join George and Alan in also thanking you for taking time out of what I know are busy schedules to come to D.C. and to help us with what I think you are going to find to be a challenging and a little bit of a vexing issue, at least it has been for us, so we are looking forward to your help.

    That issue obviously has to do with latex allergy and I know we are aware and you are all aware that allergy and response to natural rubber latex is a very real, very significant public health issue, and a very serious and sometimes actually life-altering concern for those that are affected.

    Those that are affected, as you know, are particularly groups that have had prolonged heavy exposure to natural rubber allergens, such as healthcare workers, people in the rubber industry, and patients, particularly young patients who have been subject to a number of surgeries.

    The latex allergy resulting from that occupational exposure or medical exposure has been the subject of a lot of study, a lot of work over the last decade or so, and there has been a variety of government agencies, professional organizations, patient groups, other groups that have been very involved with taking steps to try to reduce the risks associated with that occupational or medical exposure risk.

    You are going to hear about some of those steps at this meeting, but as you heard a few minutes ago, our authority and our focus here is specifically on latex allergy as it relates to food safety and food additive safety.

    As noted in the background materials that you have had, I think, natural rubber is an approved food additive.  It is approved for a variety of uses actually including some food contact applications, and George mentioned those food contact applications being, well, food contact, one of which is latex gloves that are used in food service applications.

    The pertinent regulations that allowed this use were actually promulgated in the 1960s through the process that was outlined by Dr. Pauli, that is, there were petitions.  There were petitions that had data and information which allowed and supported a finding of safety, a finding of reasonable certainty of no harm for those uses.

    Well, why are we here?  What happened since to come before this committee?  Obviously, one of the things that has happened is the use of natural rubber latex particularly for gloves has increased dramatically both in the medical care setting to try to quell the transfer of microorganisms and infectious disease, and in the food setting as we attempted to try to control foodborne illness.

    So, during this period, then, there was an increase in exposure to latex by a number of people and during that time, then, there is a population of individuals who are sensitized to natural rubber latex allergens in the population, this population started to appear.

    Then, we at CFSAN started getting reports of people who were sensitized to natural rubber latex allergen, who are allergic to latex, who believed that they were having a reaction to food that had been handled and touched and worked on by food safety workers using latex gloves.

    So, now, then, the question for us becomes what is the evidence that the use of natural rubber latex and contact with food may render the food unsafe.  If you want to put it another way, this use of natural rubber latex, is it possible that that use may no longer reach reasonable certainty of no harm.

    As you are going to hear over the next day or two, this isn't a simple or straightforward question, or maybe I should say the answers to the question aren't simple or straightforward.

    So,  with this background, then, let me return then to the charge and questions that were provided to you this morning and read to you early.

    To repeat what we mentioned, our concern is that this use is focused on whether such use may result in the production of unsafe food and that it is important to separate issues related to worker exposure and occupational safety from those of food safety while not minimizing the issues that are related with that worker safety and occupational use, but that is different from where we want you to focus your attention right now.

    So, the task before you is to consider the available information relating to food mediated latex allergic reactions and the use of latex food service gloves and establishments that prepare food for public consumption.