• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

Food

  • Print
  • Share
  • E-mail

FDA's Responses to Public Comments on the Draft Report "Approaches to Establish Thresholds for Major Food Allergens and for Gluten in Food"

March 2006
 

  A notice of availability of the draft report "Approaches to Establish Thresholds for Major Food Allergens and for Gluten in Food" was published in the Federal Register (70 FR 35258) on June 15, 2005, and the report was made available through the FDA Docket and the CFSAN web site. FDA requested that interested persons submit comments, scientific data, and information to FDA Docket No. 2005N-0231 during a 60-day period, ending August 16, 2005. Eighteen letters were received, including comments from consumer groups, the food industry, trade associations, experts on food allergens and gluten, and individual consumers.

Previously, in the Federal Register of May 23, 2005 (70 FR 29528), FDA announced a meeting of the Food Advisory Committee to be held on July 13, 14, and 15, 2005. Members of the public were invited to participate in the meeting. The Committee was asked to consider whether the draft report was scientifically sound in its analyses and approaches and whether the report adequately considered available relevant data on food allergens and on gluten. The Food Advisory Committee meeting included presentations on issues related to the diagnosis and treatment of food allergies and of celiac disease, the quality of life for affected consumers, analytical methods to measure allergens and to measure gluten in food, and clinical studies to characterize dose-response relationships. The complete transcript of the meeting is available on the FDA web site.

All public comments received at the Food Advisory Committee meeting and in the public docket are summarized below with a brief indication as to how the revised report responds to each comment. As noted below, many of the public comments addressed issues beyond the scope of the report and thus, these issues were not addressed in the report.

 

Table 1. Allergen-Related Comments Presented at the Food Advisory Committee (FAC) Meeting
Topic AreaCommenterSummary of CommentResponse
Analytical methods-based approachIndustry AssociationThe use of the analytical methods-based approach appears not to be appropriate as it would result in an unnecessarily low threshold. FDA should avoid the establishment of artificially low thresholds with the "intent" of adjusting them later - historically this has not taken place despite good intentions. Future adjustments would be confusing for the consumer and disruptive to the food industry.This is discussed in the report and the Committee's comments.
Analytical methods-based approachIndustry Association RepresentativeIt would not be appropriate to use the analytical methods-based approach because we have only one validated method and new methodologies would set a lower threshold which would be consistently changing.The limitations of the analytical methods-based approach are discussed in the report. The issue of the impact of new, improved methods is also discussed in the report.
Endpoint of concernIndividual consumerThe draft report fails to consider sensitization as a health endpoint of concern.This is discussed in the report and Committee's comments. This is currently not a viable endpoint of concern because there are no methods available to assess sensitization.
Limitations of challenge studiesIndividual consumerThe oral challenge data are unacceptably biased because they are likely to only represent the least allergic individuals excluding not only the most sensitive individual but also average allergic individual.This is discussed in the report and the Committee's comments. For the safety assessment-based approach, this would be considered in determining appropriate uncertainty factors.
FALCPA implementationIndustry AssociationThe draft report is excellent and covers a complicated, complex area. The association does not believe that enzymes fit within the scope of allergen labeling as defined by FALCPA. Enzymes are processing aids and do not need to be labeled. The enzyme industry uses some of the 8 allergens as food for the microorganisms during production of enzymes. Both the EU and Japan have concluded that enzymes are not required to have allergen labeling.The issue of the status of enzymes is outside the scope of this report.
FALCPA implementationIndustry AssociationFDA must have a clear timetable for the establishment of these thresholds.This issue is outside the scope of this report which is focused on scientific approaches to establish thresholds. FALCPA does not require FDA to establish thresholds for allergens in foods.
FALCPA implementationIndustry Association representativeIncidental additives such as processing aids (soy lecithin) that result in inconsequential levels of protein from major allergens should not require labeling.While soy lecithin is discussed with the report, this specific issue is outside the scope of this report. FALCPA includes procedures for obtaining an exemption from labeling where certain conditions are satisfied.
FALCPA implementationIndividual ConsumerIn addition to food labels, FDA must consider skin and hair items including toothpaste. Often the type of flavoring in items like toothpaste and medicine is not detailed as an ingredient. Threshold levels must be set at zero.This issue is beyond the scope of this report. FALCPA addresses food and food ingredients.
FALCPA implementationHealth ProfessionalReading food labels are part of a life-and-death decision for the food-allergic consumer. Precautionary labeling - "may contain," "processed on the same line" - forces families and patients to contact the manufacturers to try to gauge the risk. Most families decide on zero tolerance, limiting dietary choices. We know that severity of reaction and the dose required to elicit reactions varies from person to person. If thresholds are established, health care professionals need to know what to tell patients. If food-allergic consumers lose faith in the integrity of the labels, they will be left with a practice called "trial and error."Labeling issues are outside the scope of this report, as are issues about outreach and education should any threshold be established.
FALCPA implementationIndividual consumerConsumers count on manufacturers' voluntary labeling to assist with complete avoidance. In favor of label statements such as: "may be manufactured in the same plant." Hopes that mandatory labeling will be better and more thorough. Has greater confidence in accuracy of labels from the same company when some labels show allergens and others do not. Thankful to industry efforts on labeling.Labeling issues are outside the scope of this report.
FALCPA implementationIndustry AssociationThe draft report provides a reasonable perspective of pros and cons of various options towards establishing allergen thresholds and helps to keep the public informed of the deliberative process. FDA should consider a temporary (3-yr) exemption for certain food ingredients derived from major allergens such as fish gelatin; as was done by European Commission directive on the basis of EFSA finding that these food ingredients are extremely unlikely to induce allergic reaction. Data are available to conclude that thresholds for certain allergens are finite, measurable and above zero; zero is unnecessary and unachievable burden on the industry. Declaration of biologically insignificant amounts on labels will cause confusion. Thresholds will allow industry to optimize their quality control efforts.FALCPA includes procedures for obtaining an exemption from labeling where certain conditions are satisfied.
FALCPA implementation, LabelingIndividual ConsumerExplained the difficulty in making food choices when the label of a product consumed in the past has a new label such as a "may contain" statement. It is difficult to decide whether to continuing purchasing the product or removing it from one's diet. The process of establishing thresholds must be transparent and all manufacturers must be held to the same standard. Disclaimers on packaging should be consistent, especially when the level of the allergen is below the threshold.We agree that the application of any approach to establish a threshold should be transparent. The specific issue concerning labeling is outside the scope of this report.
Research needsIndustry AssociationFDA must be prepared to provide financial support for studies where critical gaps exist in the current database.This issue is outside the scope of this report.
Safety assessment methodologyIndividual consumerThe use of initial objective symptom is not generally protective.This issue is discussed in the report and in the Committee's comments. We note that the initial objective symptom is the only widely used biomarker reported in the literature.
Sensitive populationsIndividual ConsumerMilk products are main ingredients and fillers for flavor enhancers, making avoidance difficult. It is impossible to eat prepared foods and in restaurants. Threshold levels must consider the most sensitive populations.The issue of which populations should be considered in establishing a threshold is discussed in the report. In the safety assessment-based approach, sensitive populations would be considered in determining appropriate uncertainty factors.
Statutorily-derived approachIndustry Association representativeThe statutorily derived approach would support the establishment of 10 ppm as an interim threshold level. Marketing data previously provided to FDA demonstrates that the presence of undeclared soy lecithin, fish gelatin, and wheat starch contribute 10 ppm or less to the diet and do not result in a measurable increase in allergenic responses. Some highly refined oils have levels of 48 ppm, while most have less than 20 ppb.This issue is outside the scope of this report because the intent of the report is to identify approaches that could be used to establish thresholds, not to evaluate specific threshold levels.
Statutorily derived approachIndividual consumerThe proposed methodology for the statutory-based threshold does not meet minimum data quality requirements. The data on oils with no detectable protein were arbitrarily excluded and the data on protein levels included in the paper appear unrelated to highly refined oil.These considerations were discussed in the report and the Committee's comments. Data from studies reporting no detectable protein were not reported in Appendix 3 of the report because these studies did not provide sufficient information to determine the accuracy and sensitivity of the assays used.
ThresholdsIndustry AssociationThresholds should not be unduly or unnecessarily restrictive. They should be based on the best possible scientific data and the effect of the allergen on the allergenic individual. Thresholds should not be set at zero.The strengths and limitations of each approach are discussed in the report.
Uncertainty factorsIndustry AssociationA reasonable-certainty-of-no-harm standard should be applied towards establishing threshold levels. Uncertainty factors that are reasonable should be applied and only when needed. The uncertainty factor of 10 for intraspecies variation for peanuts is not needed because multiple studies were done in both male and female and adults and children. A standard uncertainty factor of 10 should not be applied to the sensitive populations since children and sensitive subjects were included in clinical trials. Since the lowest, not the mean, dose for an objective symptom is being used, an uncertainty factor of 2 may be justifiable to give added protection to the highly sensitive subpopulation.The uncertainty factors discussed in the report are examples only. The selection of specific uncertainty factors is beyond the scope of this report.


 

Table 2. Gluten-Related Comments Presented at the Food Advisory Committee (FAC) Meeting.
Topic AreaCommenterPublic CommentResponse
LabelingConsumer AssociationDifficult to adhere to gluten-free lifestyle and diet, especially because there is no standard for how much is too much and reliable, evidence-based guidelines are needed. Food labels that include warnings that the food is made in facilities that also manufacture gluten-containing foods would be helpful. An industry standard of 20 to 100 ppm would be safe and reasonable.Labeling issues are outside the scope of this report as are specific threshold levels for gluten.
Research needs, LabelingConsumer AssociationClear, unambiguous labeling of food is important. The strict definition of a gluten-free diet remains controversial due to the lack of accurate method to detect gluten in food products and the lack of scientific evidence for what constitutes a safe amount of gluten ingestion. An approach to setting thresholds is premature without more data. FDA should request (in its report to Congress) that NIH fund further research in this area with the goal of defining an appropriate and healthful threshold level. Analytical methods are needed to enable food processors to determine the level of gluten present in food because of potential cross-contamination issues. Labeling of foods as either gluten-free or low-gluten would allow the consumer choice.Labeling and funding issues are outside the scope of this report. The detection and measurement of gluten is discussed in the report and the Committee's comments.
Research needs, FALCPA implementationIndividual ConsumerDescribed lifestyle and difficult food choices. Research is needed to establish a threshold. A threshold would help with food choices.The report identifies gaps in the data that would be required to establish a threshold for gluten.
Risk assessment-based approach, LabelingConsumer AssociationThe risk assessment based method is best and is the process that patients use. Labeling along with information from manufacturers about their products has helped patients make food choices. Patients want reliable information that they can use to make choices for themselves.Labeling issues are beyond the scope of this report. The strengths and limitations of the risk assessment-based approach are discussed in the report.
Analytical methods-based approachAcademiaThe test kit commercially available from R-Biopharm detects prolamins (the prolamins and gliadin from wheat, secalin from rye, and hordein from barley) but does not detect oats. It is sufficiently reliable for the food industry to use to determine whether products are gluten-free; but a zero-level is not attainable. There are no technical limitations that prevent the development of an ELISA test for oats. It would be better to develop the test than to argue whether oats are safe or not.Information on test kits is included in Appendix 4.
FALCPA exemptionAcademiaRaw agricultural commodities are exempt from FALCPA, once they are converted into milled products they are no longer exempt.This is in essence a legal issue that is beyond the scope of this report.
Thresholds, LabelingAcademiaLevel of <20 ppm (similar to that used in Italy and Canada) allows production of safe and effective gluten-free products. It costs $50-75 to test a sample, and a testing system should be strategically designed depending on the specifics of a particular facility.The report discusses the strengths and limitations of various approaches to establish thresholds but does not address specific thresholds for gluten.


 

Table 3. Public Comments Submitted to the FDA Docket 2005N-0231.
Topic AreaCommenterPublic CommentResponse
Analytical methods based-approach, AllergensAcademiaDoes not agree with the statement that "most test systems do not detect specific allergenic proteins" (See section II.Food Allergy G. Exposure 3 Detecting and measuring proteins). Cites: Nogueira et al. (2004). Can commercial peanut assay kits detect peanut allergens? JAOAC Int.; 87:1480-1484. Many kits detect Ara h 1 and 2 (known peanut allergens), beta-lactoglobulin, soy Kunitz trypsin inhibitor, shrimp tropomyosin, casein, etc..The text of the report was revised to respond to this comment.
Analytical methods based-approach, AllergensAssociationValidated analytical methods for allergens must be available before thresholds are implemented. Acceptable methods must be available to test whether allergens are present above or below the thresholds. Methods must be accepted by FDA or another independent authoritative body (such as AOAC), before the food industry can be held to threshold levels.Analytical method issues are discussed in the report.
Analytical methods-based approach. Gluten.AssociationThe analytical methods-based approach is not recommended because the detection limit may become lower than the level at which celiac patients have negative reactions as the tests become more sensitive and capable of detecting small levels of gluten.This limitation is acknowledged in the report.
Analytical methods-based approach, AllergensFood AssociationIf the analytical methods-based approach is used for interim thresholds, it should be replaced as soon as possible with thresholds based on safety or risk assessments.We concur. This is noted in the Findings of the report.
Analytical methods-based approach, AllergensAssociationThe analytical methods-based approach could be implemented more quickly than the other approaches. This approach should not be used in the long-term. If it is used in the short-term, the levels derived from analytical methods should apply to only the allergen tested by that specific method (e.g., the method for peanut should only be used to establish a threshold for peanut protein and should not be used for hazelnut or cashew). Potential problems with this approach are that: (1) there is currently only one validated method (peanut protein); (2) as sensitivity of the tests improve, eventually, the detection limit could be lower than the levels at which allergic individuals react.These limitations of the analytical methods-based approach are acknowledged in the report.
Analytical methods-based approach, AllergensFood AssociationDoes not support the use of the analytical methods-based approach because commercially-available methods have not been developed for all major allergens. Also, development of increasingly more sensitive analytical methods could result in a continually changing threshold level. Limits of detection well below 1 ppm could easily be obtained through advances in analytical technology.These limitations of the analytical methods-based approach are acknowledged in the report.
Analytical methods-based approach, GlutenFood AssociationIt would be appropriate to set a gluten threshold based on the method of analysis approach to define "gluten free" for use on products that contain no detectable levels of gluten. However, when data become available, thresholds should be based on a safety or risk assessment. This approach is consistent with current use of the term "free" - such as "alcohol free" that can be used when a product contains "no detectable alcohol." However, the commenter questions whether any products would qualify as gluten-free with this approach, given the commingling of grains.This comment is consistent with the report findings.
Analytical methods-based approach, AllergensAcademiaAssays designed to detect whole allergenic foods are most meaningful to the food-allergenic patient and food industry as supported by the following: 1) Very specific detection of allergenic proteins is not required for an assay to be specific and sensitive for the allergenic food. 2) Not all allergens in the major food allergens have been discovered or characterized. 3) LOAELS and NOAELS are determined with oral challenges using whole foods.This comment is consistent with the report findings.
Celiac disease.Health ProfessionalSection III, Celiac Disease, B. Pathogenesis: The damage is not "self-perpetuating" in celiac disease and it resolves when gluten is avoided (unlike refractory sprue where the T cell activation is indeed self perpetuating).The text of the report was revised to respond to this comment
Celiac diseaseHealth ProfessionalSection III, Celiac Disease, C. Adverse Effects: Suggest adding: "The reasons for this spectrum of clinical presentations are unknown but may result the age and immunol...."The text of the report was revised to respond to this comment
Celiac diseaseHealth ProfessionalSection III. Celiac Disease. C. Adverse Effects Are the quoted relative risks correct? I thought that the relative risk for lymphomas was greater than for small bowel carcinomaThe text of the report was revised to respond to this comment
Celiac disease.Health ProfessionalSection III, Celiac Disease, C. Adverse Effects "Silent" celiac disease is characterized by the absence of symptoms or nutritional deficiency states, not by the degree of intestinal involvement.The text of the report was revised to respond to this comment
Celiac diseaseHealth ProfessionalSection III, Celiac Disease, C. Adverse Effects. Silent and latent celiac disease are not characterized by atypical disease manifestations but instead by the absence of symptoms or other disease manifestations (other than the mucosal abnormalities present in silent disease)The text of the report was revised to respond to this comment
Celiac diseaseHealth ProfessionalSection III, Celiac Disease, D. Prevalence, page 32, line 2. I believe the prevalence reported by Talley in 1994 was ~1:5,000The text of the report was revised to respond to this comment
Celiac diseaseHealth ProfessionalSection III, Celiac Disease, D. Prevalence, page 32, line 11. Celiac disease is rarely misdiagnosed as Crohn's disease so I suggest "The disease is often misdiagnosed as another gastrointestinal disorder (e.g., lactose intolerance, irritable bowel syndrome) due to similarities in..."The text of the report was revised to respond to this comment
Celiac diseaseHealth ProfessionalSection III, Celiac Disease, B. Pathogenesis, page 30 line 2. "and specifically targets" is inaccurate--suggest "and is characterized by damage to"The text of the report was revised to respond to this comment
Challenge studiesConsumer GroupThere are no studies on the long-term effects of the ingestion of low levels of gluten by a diagnosed celiac patient. Long-term studies that examine the cumulative effect of gluten consumption are needed to set a reasonable threshold. A single, short-term study with a limited number of patients, no peer review, no publication, and no replication should not be the basis for establishing the threshold for a chronic, lifelong, lifestyle changing disease.This limitation is noted in the report.
DataAssociationFDA should review the information on allergens from other countries, such as Canada's database on adverse reactions and the European Union's directive on exemptions of certain food ingredients. This information could be helpful to determine what data are needed to set thresholds.We did consider the available public information from these sources in the report.
FALCPA exemptionPrivate IndustryAllergens used in manufacturing of packaging should be excluded from FALCPA labeling requirement.This issue is beyond the scope of this report.
Thresholds, AllergensAssociationDairy processors are prepared to label ingredients that could cause an allergic individual to have a reaction. Reformulation or labeling changes have a significant economic impact on the industry and should be done only if there is a health benefit.This issue is beyond the scope of this report.
Thresholds, AllergensFood AssociationFDA should also consider approaches for establishing thresholds for allergens such as that used by the American Academy of Pediatrics in setting a threshold for hypoallergenic infant formulas. That is, an infant formula can be labeled as hypoallergenic if it is documented using double-blind, placebo-controlled conditions, that at a minimum, there is 95% certainty that 90% of the cow's milk allergic population will not react.This process is addressed in the report; see Section IV, A. 3. Risk Assessment-Based Approach.
Thresholds. AllergensAssociationThe approach used for each allergen should be determined independently based on what works best for that allergen, and reevaluated when new data become available, with the ultimate goal of using safety or risk assessments. For example: initially exempt an ingredient if it contains a non-detectable level of protein from a major food allergen. As more data become available, conduct a safety or risk assessment to set a threshold.This comment is consistent with the report findings.
Thresholds, GlutenAssociationGluten is a concern for cheese-makers. Ingredients used in very small amounts in cheeses (e.g., anti-caking agents) may be derived from wheat. Some cheese cultures are grown on bread or wheat-based media.This issue is beyond the scope of this report.
Thresholds, GlutenAssociationThe international community may be able to provide resources and models for setting a gluten threshold. Canada, Australia, New Zealand have set thresholds for gluten. There is also work by the Codex Committee on Nutrition and Foods for Special Dietary Uses.We considered the public information available from these sources in preparing the report.
Thresholds, GlutenFood AssociationSupports the draft report recommendations on establishing thresholds for gluten for the purposes of establishing definitions for gluten-freeNo response required.
Gluten, Oats sensitive PopulationHealth ProfessionalSection IV Discussion and recommendation, D.1.c Foods of Concern: The percentage of individuals with celiac disease that are sensitive to oats has not been determined but is likely to be <1%.The text of the report was revised to respond to this comment
Labeling, Gluten-free foodsInternational AssociationData needed to establish a definition for the term "gluten-free" are limited at the current time. This was also the conclusion of the National Institute of Health conference on celiac disease (June 2004). However, data from the Italian Microchallenge study and from dietary survey studies in Finland may allow a provisional threshold for labeling gluten-free foods. The maximum level of gluten for wheat starch-based gluten-free foods can be safely set at 200 ppm. A second category of naturally gluten-free products, with guaranteed lower gluten content will fulfill the needs for the most sensitive celiac people. A summary of study results and references were provided: Catassi et al.; 1993, Catassi et al., 2004; Collin et al., 2004; Kaukinen et al., 2004; and Peräaho et al., 2003.Discussion of specific thresholds is beyond the scope of this report. The references provided in the comment have been included in the report.
Analytical Methods, AllergensFood IndustryProvided information for Appendix 1 on LOD, LOQ, etc for ELISA Systems test kits.The information provided in the comment has been included in the report.
GeneralAcademiaFDA should be applauded for the effort made to prepare the document and develop methods to establish minimal eliciting doses for major allergenic foods.No response required.
GeneralConsumer GroupThe draft report was complete, organized, and readable.No response required.
GeneralFederal GovernmentThe report did an excellent job of reviewing a difficult subject.No response required.
GeneralFood AssociationAppreciates FDA's transparency in identifying the various methods that should be explored for establishing allergen thresholds, commends FDA for its efforts in developing the data and information needed to implement FALCPA, for convening the FAC on allergen thresholds, and efforts in preparing the draft threshold report.No response required.
Thresholds, GlutenConsumer GroupCeliac patients that set as their goal no wheat, barley, rye, oats or any of their derivatives, to manage their medically required lifestyle do not know what the "safe" number is and it doesn't matter.Discussion of specific thresholds is beyond the scope of this report.
FALCPA exemptionFood IndustryAgency should exclude food packaging and food-contact substances from the scope of FALCPA regulation (labeling) if they contain de minimis levels of allergens.This issue is beyond the scope of this report.
FALCPA implementationFood AssociationBy establishing thresholds, FDA would prevent the over-labeling of the many food products that currently are being enjoyed and consumed without incident.This issue is beyond the scope of this report.
FALCPA implementationFood AssociationFDA should adopt a scientific standard when determining whether there are sufficient data to support the establishment of thresholds under the safety assessment approach that is based on the FALCPA definition for exempting an ingredient - which is a demonstration that the ingredient "does not cause an allergic response that poses a risk to human health."The report addresses the strengths and limitations of the safety assessment-based approach.
FALCPA implementationFood IndustryRequiring declaration of every de minimis amount of an allergen in food could produce consumer confusion and be contrary to the purposes of FALCPA and the Agency's goal of protecting public healthThis issue is beyond the scope of this report.
Labeling, GlutenIndividual ConsumerFood labels should disclose all gluten, including wheat, barley, malt, rye or oats. Some manufacturers no longer indicate whether or not a food is actually "gluten-free". The food labeling law should be changed to appropriately require "gluten" not just "wheat" on labels.Labeling issues are beyond the scope of this report.
FALCPA exemptionAssociationLow levels of food allergen-derived materials are used in paperboard food packaging. These substances should be excluded from FALCPA's labeling requirements. No allergic reactions attributable to food allergens in packaging or food contact substances have ever been reported. FDA has the authority to exempt food packaging and food contact substances from FALCPA.This issue is beyond the scope of this report.
FALCPA exemptionAssociationRequiring declaration of every de minimis amount of an allergen would be contrary to the purposes of FALCPA and public health goals. Low levels of food allergen-derived materials are used in the vast majority of paperboard food packaging. No incidents of allergic reactions attributable to food packaging or food contact substances have ever been reported. FDA should categorically exclude food packaging and food contact substances from the scope of FALCPA. The FALCPA petition and notification processes are not viable for the paperboard food packaging and food contact substance industry because there are a broad range of allergen-derived substances and a variety of types of packaging; use of recycled materials also adds complications - which means that a large number of individual petitions or notifications would need to be submitted, imposing an immense burden upon manufacturers of paperboard food packaging and food contact substances.This issue is beyond the scope of this report.
FALCPA exemptionFood IndustryNot aware of any reported incidence of single-use packaging or single-use food-contact substances being cited as causing an allergenic reaction.No response needed.
FALCPA exemptionFood IndustryThe FDA should exclude food packaging and food contact substances from the scope of FALCPA. Some of the major food allergens are ubiquitous presences in the primary materials used for conversion into corrugated products and in the substances used in the converting process.This issue is beyond the scope of this report
FALCPA implementationIndividual ConsumerFALCPA does not require FDA to establish threshold levels for ingredient labeling. FDA has no obligation to set levels or otherwise grant exemptions from labeling requirements and the burden is on the petitioner to provide adequate scientific evidence.The requirements of FALCPA are discussed in the report.
FALCPA exemptionIndustry, Private FoodAny fermentation ingredient that is a minor component of the fermentation media (<10%) is requested to be exempt from labeling in the finished ingredient. Commenter claims that these are not the major food allergens that the law was intended to address.This issue is beyond the scope of this report..
Risk assessment-based approach, AllergensAssociationStrongly encourages FDA to carry out an allergen risk assessment to determine (1) the levels of allergenic protein that cause reactions in allergic individuals and (2) whether there are some ingredients that may contain trace levels of protein from allergenic sources but do not cause reactions (e.g., soy lecithin, fish gelatin).We agree that the risk assessment-based approach provides the strongest, most transparent scientific analysis to establish thresholds for the major food allergens. The report discusses limitations to implementing this approach.
Risk assessment-based approach, AllergensFood AssociationAgrees with FDA that there are insufficient data and information at this time to set thresholds using the risk assessment-based approach. As more data become available either the safety or risk assessment approaches should be used.This is discussed in the report.
Risk assessment-based approach, GlutenFood AssociationAdditional research should be conducted before the risk assessment-based approach is used.The need for additional research is addressed in the report,.
Safety assessment-based approach, AllergensIndividual ConsumerThe report does not consider sensitization as a health endpoint of concern. Sensitization as a health endpoint is good public policy--if labeling helps children avoid or outgrow allergies, there would be significant economic and health benefits.This is discussed in the report and Committee's comments. This is currently not a viable endpoint of concern because there are no methods available to assess sensitization.
Safety assessment-based approach, AllergensIndividual ConsumerCommenter does not support the recommendation of the report to only include data on objective reactions. Data on subjective reactions that could be significant indicators of risk to human health should not be excluded.This is discussed in the report and the Committee's comments. Objective reactions are the only widely used biomarkers reported in the literature.
Safety assessment-based approach, AllergensIndividual ConsumerThe report includes studies where subjects reacted to the lowest administered dose and incorrectly characterizes those doses as LOAELs. If a study shows a reaction at the first dose, it is not usable for the purpose of setting threshold levels.The report acknowledges and discusses the difficulties associated with LOAELs from publications that do not establish NOAELs.
Safety assessment-based approach, GlutenAssociationThere appears to be enough scientific data for the LOAEL to set a threshold for gluten. It should be updated as additional data become available.The comment is consistent with the report findings.
Safety assessment-based approach, Gluten, Uncertainty factorAssociationA 100-fold uncertainty factor that allows for intraspecies differences and extrapolation from the LOAEL should protect individuals while also allowing the food industry to actually produce foods that can be labeled "gluten free"These issues are discussed in the report. If the safety assessment-based approach is implemented, decisions on uncertainty factors will be based on the available data.
Safety assessment-based approach, AllergensIndividual ConsumerSome findings do not separate science and policy. Example, in Finding 3, the term "viable" is based on policy interpretation that is contrary to the intent of FALCPA. "Finding 3. The safety assessment-based approach, based on currently available clinical data, is a viable way to establish thresholds for the major food allergens."The term "viable way" refers only to the scientific viability and not policy decisions.
Safety assessment-based approach, AllergensAssociationData are sufficient to set thresholds for peanuts, egg and milk but not for the other allergenic foods, using this approach. LOAELs : peanut (0.25-66 mg), egg (0.13-200mg), and milk (0.6-180 mg). Data collection on the other allergens should continue in order to develop NOAEL/LOAELS and threshold levels.Specific threshold levels are beyond the scope of this report.
Safety assessment-based approach, Allergens, Uncertainty factorAssociationAn uncertainty factor of 100 should allow for intraspecies differences with extra allowance for particularly sensitive individualsThis issue is discussed in the report. If the safety assessment-based approach is implemented, decisions on uncertainty factors will be based on the available data.
Safety assessment-based approach, AllergensAssociationIt is not appropriate to set threshold levels for all allergens using the LOAEL of the most potent allergen. This would set the threshold level lower than required for the majority of food allergens and unnecessarily limit foods available to allergic consumers.The strengths and limitations of this approach are discussed in the report and in the Committee's comments.
Safety assessment-based approach, AllergensFood AssociationThis approach is appropriate for establishing thresholds.This is noted in the Findings of the report.
Safety assessment-based approach, Allergens, Uncertainty factorFood AssociationIt is not possible to set one uncertainty factor that can be applied across all studies. Therefore, the commenter does not agree that the factor of 100 (10-fold for intraspecies and 10-fold for severity of response and sensitivity of the population). Some studies may not require an uncertainty factor to be applied.This issue is discussed in the report and the Committee's comments. If the safety assessment-based approach is implemented, decisions on uncertainty factors will be based on the available data.
Safety assessment-based approach, AllergensFood AssociationUse the first objective symptom when determining the LOAEL or NOAEL. Subjective responses do not "pose a risk to human health"This issue is discussed in the report and the Committee's comments.
Safety assessment-based approach, Allergens, Uncertainty factorFood AssociationDoes not agree with the FAC deliberations. The uncertainty factor should not be increased to accommodate the first subjective symptom. Each study must be evaluated to decide whether the first subjective symptom is indicative of a true allergic response or a psychologically-induced response. It would be inappropriate to use the first subjective response as the basis for the uncertainty factor if there is no evidence of an objective response until a significantly higher level than reported for the first subjective response.This issue is discussed in the report and the Committee's comments. If the safety assessment-based approach is implemented, decisions on uncertainty factors will be based on the available data.
Safety assessment-based approach, Gluten, Uncertainty factorFood AssociationObjective rather than subjective response should be used when setting LOAELs and NOAELs. It is inappropriate to set a single uncertainty factor for all studies; the quality of the underlying study must be the basis for the uncertainty factor.This issue is discussed in the report and the Committee's comments.
Safety assessment-based approach, Allergens, Uncertainty factorIndividual ConsumerThe currently available clinical data deliberately exclude the populations that are most likely to be of concern. There is no scientific evidence that a 10-fold uncertainty factor would be protective.This issue is discussed in the report and the Committee's comments. If the safety assessment-based approach is implemented, decisions on uncertainty factors will be based on the available data.
Statutorily derived approach, AllergensAssociationThere appear to be significant problems with accurately determining the level of protein found in highly refined oils. There will not be a strong basis for using the statutorily derived approach without an accurate quantification of the allergenic protein in ingredients that are already exempted from labeling. This approach should not be used unless there is a way to accurately assess the level of protein in highly refined oils.The comment is consistent with the report findings.
Statutorily-derived approach, AllergensFood AssociationIt would be appropriate to develop interim thresholds using the statutorily derived approach, until sufficient data are available to conduct a safety or risk assessment. At the time Congress passed FALCPA, the literature contained numerous references to the presence of detectable levels of protein in highly refined oils (e.g., Crevel et al. (2000) reported levels up to 48 ppm in refined peanut oil.)The comment is consistent with the report findings.
Statutorily-derived approach., AllergensIndividual ConsumerThe report does not explain how the statutorily derived approach would ensure that an ingredient would not cause an allergic response that poses a risk to human health. To meet information quality requirements for clarity, the report should provide information on the protein in oils on the same matrices as on health-based thresholds so that the reader can compare the two.The limitations of this approach are discussed in the report.
Statutorily-derived approach, AllergensIndividual ConsumerExcluding studies (without explanation) with data on oils with no detectable amounts of protein, fails the information quality requirements of objectivity and clarity. Oils with no detectable protein are likely the only ones that would meet Congress's intent in exempting highly refined oils. Instead of using protein levels in different oils to define a threshold, FDA should use the lack of protein to define whether an oil was "highly refined." The range of protein concentrations (see section IV.C.2.d) should not exclude studies that reported levels "not detected".This is discussed in the report and the Committee's comments. Data from studies reporting no detectable protein were not reported in the appendix because these studies did not provide sufficient information to determine the accuracy and sensitivity of the assays used.
Thresholds, AllergensFood AssociationA threshold level should not be based on the average levels of protein (as per FDA's statutorily-derived approach). The published literature contains reports up to 48 ppm. However, an interim level of 10 ppm is more reasonable. As evidence, information was provided on the level of consumer complaints in control products and in products with undeclared soy lecithin and fish gelatin.Specific threshold values and methods to calculate them are beyond the scope of this report.
Use of non-peer reviewed dataConsumer GroupNon-peer reviewed, non-published studies should not be used in consideration for establishing a threshold for celiac disease in the US.This issue is discussed in the Committee's comments.
Wheat allergiesFederal GovernmentNot much information was included in the report on allergies to wheatSome additional information was added. The revised report reflects the current state of knowledge about wheat allergies.
Wheat allergiesFederal GovernmentStatement in Section 2- Food Allergens "whereas the principal wheat allergenic proteins are albumins" is not necessarily true. Many wheat flour proteins have been implicated in allergic responses to wheat.The text of the report was revised to respond to this comment
Wheat allergiesFederal GovernmentResearch is needed to determine if proteins in barley and rye can induce the same responses in subjects who are allergic to wheat.This is discussed in the report.

March 2006 Approaches to Establish Thresholds for Major Food Allergens and for Gluten in Food