[Federal Register Volume 76, Number 149 (Wednesday, August 3, 2011)]
[Proposed Rules]
[Pages 46671-46677]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-19620]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 101

[Docket No. FDA-2005-N-0404; formerly Docket No. 2005N-0279]
RIN 0910-ZA26


Food Labeling; Gluten-Free Labeling of Foods; Reopening of the 
Comment Period

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule; reopening of comment period.

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SUMMARY: The Food and Drug Administration (FDA) is reopening the 
comment period for the proposed rule on the ``gluten-free'' labeling of 
foods, published in the Federal Register of January 23, 2007 (72 FR 
2795). In that document, FDA proposed to define the term ``gluten-
free,'' for voluntary use in the labeling of foods, to mean that the 
food does not contain an ingredient that is any species of wheat, rye, 
barley, or a crossbred hybrid of these grains (collectively referred to 
as ``prohibited grains''); an ingredient that is derived from a 
prohibited grain and that has not been processed to remove gluten 
(e.g., wheat flour); an ingredient that is derived from a prohibited 
grain and that has been processed to remove gluten (e.g., wheat 
starch), if the use of that ingredient results in the presence of 20 
parts per million (ppm) or more gluten in the food; or 20 ppm or more 
gluten. FDA also announced in the proposed rule that we intended to 
conduct a safety assessment for gluten exposure and seek comments on 
the safety assessment and its potential use in defining the term 
``gluten-free'' in the final rule. A report by FDA discussing a health 
hazard assessment we conducted, which included a safety assessment for 
gluten exposure in individuals with celiac disease, has been peer 
reviewed by an external group of scientific experts, and we revised the 
assessment, as appropriate, based upon expert comments. FDA is 
reopening the comment period for the proposed rule on the ``gluten-
free'' labeling of foods to, in part, announce the availability of and 
solicit comments on the report entitled ``Health Hazard Assessment for 
Effects of Gluten Exposure in Individuals with Celiac Disease: 
Determination of Tolerable Daily Intake Levels and Levels of Concern 
for Gluten'' (``Gluten Report''), which discusses the Agency's gluten 
safety assessment. The Agency also seeks comments on whether and, if 
so, how, the safety assessment should affect FDA's proposed definition 
of ``gluten-free'' in the final rule, and on a number of related 
issues. Finally, FDA seeks comments on the Agency's tentative 
conclusions that the safety assessment-based approach may lead to a 
conservative, highly uncertain estimation of risk to individuals with 
celiac disease associated with very low levels of gluten exposure; and 
that the

[[Page 46672]]

final rule should adopt the proposed rule's approach to defining the 
term ``gluten-free,'' because that approach takes into account the 
availability of reliable analytical methods and also considers other 
practical factors related to the needs of individuals with celiac 
disease and their food consumption.

DATES: Submit electronic or written comments by October 3, 2011.

ADDRESSES: You may submit comments, identified by Docket No. FDA-2005-
N-0404 (formerly Docket No. 2005N-0279) by any of the following 
methods:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments.

Written Submissions

    Submit written submissions in the following ways:
     Fax: 301-827-6870.
     Mail/Hand delivery/Courier (for paper, disk, or CD-ROM 
submissions): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
    Instructions: All submissions received must include the Agency name 
and docket number and Regulatory Information Number (RIN) for this 
rulemaking. All comments received may be posted without change to 
http://www.regulations.gov, including any personal information 
provided. For additional information on submitting comments, see the 
``Comments'' heading of the SUPPLEMENTARY INFORMATION section of this 
document.
    Docket: For access to the docket to read background documents or 
comments received, go to http://www.regulations.gov and insert the 
docket number, found in brackets in the heading of this document, into 
the ``Search'' box and follow the prompts and/or go to the Division of 
Dockets Management, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Rhonda R. Kane, Center for Food Safety 
and Applied Nutrition (HFS-820), Food and Drug Administration, 5100 
Paint Branch Pkwy., College Park, MD 20740-3835, 240-402-2371, FAX 301-
436-2636; e-mail: [email protected].

SUPPLEMENTARY INFORMATION: 

I. The Proposed Rule

    In the Federal Register of January 23, 2007 (72 FR 2795), FDA 
proposed to define the term ``gluten-free'' for the voluntary use in 
the labeling of foods to mean that the food does not contain: (1) An 
ingredient that is any species of wheat, rye, barley, or a crossbred 
hybrid of these grains (collectively referred to as ``prohibited 
grains''); (2) an ingredient that is derived from a prohibited grain 
and that has not been processed to remove gluten (e.g., wheat flour); 
(3) an ingredient that is derived from a prohibited grain and that has 
been processed to remove gluten (e.g., wheat starch), if the use of 
that ingredient results in the presence of 20 ppm or more gluten in the 
food; or (4) 20 ppm or more gluten. FDA stated in the proposal that 
establishing a definition of the term ``gluten-free'' and uniform 
conditions for its use in the labeling of foods is necessary to ensure 
that individuals with celiac disease are not misled and are provided 
with truthful and accurate information with respect to foods so labeled 
and to respond to a directive of the Food Allergen Labeling and 
Consumer Protection Act of 2004 (FALCPA) (Title II of Pub. L. 108-282).
    In response to FALCPA, FDA convened an internal, interdisciplinary 
group to review the available literature and evaluate the current state 
of knowledge about scientifically sound approaches to establishing 
labeling thresholds for gluten (as well as for the major food 
allergens), including the data needs and advantages and disadvantages 
of each approach, among other issues. The resulting FDA report, 
entitled ``Approaches to Establish Thresholds for Major Food Allergens 
and for Gluten in Food,'' revised March 2006 (``Thresholds Report'') 
(Ref. 1), described four approaches that the Agency might consider 
using to establish a gluten threshold level, if the Agency chose to do 
so (Ref. 1 at pp. 2 and 42-45). As stated in the preamble to the 
proposed rule, the Thresholds Report concluded that an analytical 
methods-based approach and a safety assessment-based approach were the 
two viable approaches that FDA could use to establish a gluten 
threshold level to define the food labeling term ``gluten-free'' (72 FR 
2795 at 2803).
    Based upon the analytical methods-based approach, FDA proposed in 
2007 a gluten threshold level of < 20 ppm (i.e., a food labeled 
``gluten-free'' cannot contain 20 ppm or more gluten) as one of the 
criteria to define the term ``gluten-free.'' Under this approach, the 
gluten threshold would be determined by the sensitivity of the 
analytical method(s) used to verify compliance.
    FDA stated in the proposed rule (72 FR 2795 at 2803) that the 
Agency had tentatively determined that enzyme-linked immunosorbent 
assay (ELISA)-based methods can be used reliably and consistently to 
detect gluten at the level of 20 ppm in a variety of food matrices. We 
further stated that FDA was tentatively considering using < 20 ppm as 
the threshold gluten level, for purposes of enforcing a regulatory 
definition of ``gluten-free,'' based on the results of a method 
validation trial published in the peer-reviewed scientific literature 
(Ref. 2). Since the publication of our proposed rule, FDA has become 
aware that this method, which is known as the ``R5-Mendez Method'' 
(alternatively, also referred to as the ``ELISA R5 Mendez Method'') 
(Refs. 3 and 4), has received a Certificate of Performance Tested\SM\ 
Status from the AOAC Research Institute (Certificate No. 12061) (Ref. 
5). This method is recommended for determining the gluten content of 
foods by the Codex Alimentarius Commission in the 2008 revised ``Codex 
Standard for Foods for Special Dietary Use for Persons Intolerant to 
Gluten (Codex Stan 118-1979)'' (Ref. 4).
    In the proposed rule (72 FR 2795 at 2803), we mentioned two other 
validated ELISA-based methods that also can be used to detect gluten 
(Ref. 6). Although these ELISA-based methods have not been certified by 
AOAC International, the results of their multi-laboratory validation, 
which were published in the peer-reviewed scientific literature, 
indicate that they can reliably and consistently detect gluten at 20 
ppm in a variety of food matrices. Similar to the R5-Mendez Method, 
these two ELISA-based methods are designed to detect the prolamin 
called ``gliadin'' in wheat (which represents approximately half the 
total gluten proteins in wheat) and to cross-react with the prolamins 
in the other gluten-containing grains rye and barley. These methods 
were validated in Japan and are official methods of the Japanese 
Ministry of Health, Labor and Welfare (Ref. 6). Of the two ELISA-based 
methods validated in Japan, FDA is considering for use the one that is 
currently commercially available in the United States (``Morinaga 
method'') (Ref. 7).
    If FDA includes in its final rule a gluten threshold level of < 20 
ppm as one of the criteria for defining the term ``gluten-free,'' the 
Agency has tentatively concluded that it would use both the ELISA R5-
Mendez Method and the Morinaga method that are discussed in this 
Federal Register document (Refs. 5 and 7) to assess compliance with 
such gluten threshold level for foods bearing ``gluten-free'' labeling 
claims. By requiring concurrence between two validated, peer-reviewed 
ELISAs that

[[Page 46673]]

employ different antibodies and different methods of sample preparation 
of foods for analysis, the probability of erroneous results (e.g., 
false positives and false negatives) is diminished, which increases the 
confidence level of any conclusions made based on the results (Ref. 8). 
FDA seeks comments on this tentative conclusion.
    FDA's proposed codified language in the proposed rule (72 FR 2795 
at 2817) pertaining to the addition of a new Sec.  101.91(c) states: 
``Compliance. When compliance with paragraph (b) of this section is 
based on an analysis of the food, FDA will use a method that can 
reliably detect the presence of 20 ppm gluten in a variety of food 
matrices, including both raw and cooked or baked products.'' FDA 
tentatively concludes that the specific analytical methods that we will 
use to assess compliance with the < 20 ppm gluten threshold level in 
foods labeled ``gluten free'' should be specified in codified language. 
Doing so would clarify for interested stakeholders what methodology FDA 
intends to use for enforcement purposes. FDA recognizes that for some 
food matrices (e.g., fermented or hydrolyzed foods), there are no 
currently available validated methods that can be used to accurately 
determine if these foods contain < 20 ppm gluten. In such cases, FDA is 
considering whether to require manufacturers of such foods to have a 
scientifically valid method \1\ that will reliably and consistently 
detect gluten at 20 ppm or less before including a ``gluten-free'' 
claim in the labeling of their foods. FDA is requesting comments on 
this proposed approach as well as on whether FDA also should require 
these manufacturers to maintain records on test methods, protocols, and 
results and to make these records available to FDA upon inspection.
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    \1\ A scientifically valid method for purposes of substantiating 
a ``gluten-free'' claim for foods matrices where formally validated 
methods (e.g., that underwent a multi-laboratory performance 
evaluation) do not exist is one that is accurate, precise, and 
specific for its intended purpose and where the results of the 
method evaluation are published in the peer-reviewed scientific 
literature. In other words, a scientifically valid test is one that 
consistently and reliably does what it is intended to do.
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II. Health Hazard/Safety Assessment for Gluten Exposure in Individuals 
with Celiac Disease

    The second possible approach deemed in the Thresholds Report to be 
feasible for establishing a gluten threshold level is the safety 
assessment-based approach. Under the safety assessment-based approach, 
the labeling threshold is determined at least in part on the basis of a 
``safe'' level or ``tolerable daily intake'' (TDI) of a substance as 
calculated using the No Observed Adverse Effect Levels (NOAELs) and the 
Lowest Observed Adverse Effect Levels (LOAELs) from available dose-
response data in animals or humans and applying one or more appropriate 
``uncertainty factors'' to account for gaps, limitations, and 
uncertainty in the data and for inter-individual difference (i.e., 
variability among individuals within the target population) (Ref. 1 at 
pp. 42-43). In the proposed rule, we stated that FDA would conduct a 
safety assessment for gluten exposure consistent with the safety 
assessment-based approach described in the Thresholds Report (72 FR 
2795 at 2803).
    We completed a health hazard assessment of the adverse health 
effects of gluten exposure in individuals with celiac disease that 
included a safety assessment for gluten. We submitted a report on this 
health hazard assessment, the Gluten Report (Ref. 9), to a group of 
external scientific experts for peer review, and revised the document, 
as appropriate, considering the experts' comments. The report 
concerning the external peer review is available for public review, and 
can be accessed at the Agency's Web site http://www.fda.gov/downloads/Food/ScienceResearch/ResearchAreas/RiskAssessmentSafety Assessment/
UCM264150.pdf.
    FDA is now reopening the comment period on the proposed rule, in 
part, for the purpose of announcing the availability of, and soliciting 
comments on, our Gluten Report. The Agency also invites comments on 
whether and, if so, how the safety assessment should affect FDA's 
proposed definition of the food labeling term ``gluten-free'' in the 
final rule, and on a number of related issues.
    FDA's assessment of the adverse health effects of gluten exposure 
in individuals with celiac disease presented in the Gluten Report 
followed established hazard assessment components and approaches used 
within the Center for Food Safety and Applied Nutrition (CFSAN) to 
determine TDIs for chemical and natural toxin contaminants in foods. 
The assessment combined safety and risk assessment principles, and the 
determination of TDIs relied primarily on human dose-response data from 
prospectively-designed challenge studies in which NOAELs and/or LOAELS 
are available. In the Gluten Report, FDA examines and provides an 
overview of the nature and characteristics of the adverse effects 
associated with celiac disease found in susceptible individuals, and an 
overview of gluten proteins involved in inducing these effects.
    The Gluten Report also describes the nature of the evaluation FDA 
performed on the available dose-response and adverse health effects 
data associated with celiac disease. As explained in the Gluten Report, 
the Agency conducted a review of relevant gluten challenge and other 
dose-response studies and assessed these studies for routes of 
exposure, type of challenge material, timing of adverse response, type 
of adverse response, age groups of subjects, and other relevant dose-
response characteristics. Based on the timing of adverse responses to 
gluten exposure, studies were delineated and assessed in the following 
reaction timeframes: Acute (hours up to and including 14 days), 
subchronic (greater than 14 days up to and including 3 months), and 
chronic (greater than 3 months). The types of adverse responses from 
dose-response studies characterized and assessed were the following: 
Morphological and/or physiological adverse health effects (e.g., 
adverse changes in the small intestinal mucosa, gastrointestinal 
absorption measures, or immune response) and clinical adverse health 
effects (e.g., diarrhea, constipation, abdominal pain, or fatigue). 
Also, gluten dose-response data were divided based on age of the 
subjects participating in the studies with children, represented by 
individuals from 1 year up to and including 18 years of age, and 
adults, represented by individuals greater than 18 years of age. These 
different categorizations allowed for characterization and comparison 
of TDIs and other safety assessment determinations from a variety of 
studies based on adverse health response type (i.e., morphological and/
or physiological or clinical), duration of gluten exposure (i.e., 
acute, subchronic, or chronic) and age (i.e., children or adults) of 
sensitive subjects with celiac disease. We calculated the TDI levels 
for gluten in both children and adults with celiac disease to be 0.4 
milligrams (mg) gluten/day for adverse morphological and/or 
physiological adverse health effects and 0.015 mg gluten/day for 
clinical adverse health effects (regardless of the duration of gluten 
exposure). Further details about this calculation are available in the 
safety assessment itself.
    In cases where more than one appropriate study was available for a 
given assessment category (e.g., acute gluten exposures leading to 
morphological health effects in children), this assessment identified a 
``critical study'' of high quality in line

[[Page 46674]]

with the safety assessment procedure from which to estimate TDIs for 
the respective category. Once the NOAELs and/or LOAELs of the critical 
studies were determined from these data, a single 10-fold uncertainty 
factor was applied to account for inter-individual variability. In 
cases in which only LOAELs were available, a second 10-fold uncertainty 
factor to extrapolate from LOAEL values to NOAEL values was applied, 
which resulted in a 100-fold (i.e., 10 x 10) reduction in the estimated 
TDI gluten levels.
    As described in the Gluten Report, FDA also used the U.S. 
Department of Agriculture Continuing Survey of Food Intake by 
Individuals (CSFII) for the combined survey years of 1994 to 1996 and 
1998 (Ref. 10) to conduct an exposure assessment in which a number of 
estimates of gluten consumption from food products are determined and 
presented (Ref. 9). Due to the absence of sufficient study data on 
actual dietary intakes of individuals with celiac disease, FDA had to 
make certain assumptions about how foods labeled ``gluten-free'' might 
be used by these persons. For example, in our gluten exposure 
assessment, we assumed that Americans with celiac disease would 
substitute ``gluten-free'' versions of the same types and quantities of 
foods that represent major sources of gluten consumed by persons who do 
not have celiac disease. Also, we assumed that all of the ``gluten-
free'' versions of these foods would contain a uniform trace amount of 
gluten, representing the different estimated gluten levels of concern 
(LOCs) for these foods corresponding to the different TDIs of gluten we 
identified.
    Based upon CSFII data, at the 90th percentile level of intake of 
``all celiac disease grain foods,'' the estimated gluten LOC values for 
individuals with celiac disease presented in the Gluten Report range 
from 0.01 ppm to 0.6 ppm, depending upon the corresponding age group 
and whether the type of adverse health effects are clinical or 
morphological and/or physiological in nature. The lowest gluten and 
most conservative LOC value associated with a TDI that we estimated, 
0.01 ppm gluten, would: (1) Be protective of the vast majority of 
individuals with celiac disease ages 1 year and older, including those 
most sensitive to gluten and (2) not cause clinical, morphological, 
and/or physiological adverse health effects. FDA tentatively concludes 
that, based on the LOCs identified in the safety assessment-based 
approach, the Agency should not use that approach in defining ``gluten-
free'' because the estimation of risk to individuals with celiac 
disease associated with very low levels of gluten exposure may be 
conservative and highly uncertain.
    Specific details with regard to the methodologies used, data 
considered, and conclusions can be found in the Gluten Report. FDA is 
interested in receiving public comments on the safety assessment and, 
in particular, comments concerning: (1) The assessment approach used, 
(2) the assumptions made, (3) the data considered, and (4) the 
transparency and clarity of the Gluten Report.

III. Discussion

A. Gluten Threshold Level of < 20 ppm To Define, in Part, the Term 
``Gluten-Free''
    We proposed to use an analytical methods-based approach to adopt a 
gluten threshold level of < 20 ppm as one of the criteria for defining 
the term ``gluten-free.'' Were we to move forward with this analytical 
methods-based approach, FDA is considering using both the two ELISA-
based methods discussed in this Federal Register document (Refs. 5 and 
7) when analysis of a food would be necessary in order to determine 
regulatory compliance with FDA's definition of ``gluten-free'' for a 
food bearing such a labeling claim. For the reasons discussed in this 
section, FDA tentatively concludes that, in the final rule, the 
definition of ``gluten-free'' should follow the proposed rule's 
analytical methods-based approach, which takes into account the 
availability of reliable analytical methods and also considers other 
practical factors related to the needs of individuals with celiac 
disease and their food consumption.
    In the Thresholds Report, as well as in the proposed rule, FDA 
noted that the Agency's decisions in setting a threshold for gluten 
would require consideration of factors, such as ``ease of compliance 
and enforcement, stakeholder concerns (i.e., industry, consumers, and 
other interested parties), economics (e.g., cost/benefit analysis), 
trade issues, and legal authorities'' (Ref. 1 at p. 45 and 72 FR 2795 
at 2800). First, in order to enforce a regulatory definition of 
``gluten-free,'' it is essential that the Agency have analytical 
methods that have been validated to detect the level of gluten at the 
cutoff point that the Agency uses to establish a gluten threshold level 
as a criterion to define the term ``gluten free.'' At the current time, 
FDA is not aware of any analytical methods that have been validated to 
reliably and consistently detect gluten below 20 ppm.
    We also note that the proposed analytical methods-based threshold 
level of < 20 ppm gluten would be consistent with international 
standards currently in place. In 2008, after the issuance of the 
proposed rule, the Codex Alimentarius Commission adopted a revised 
``Codex Standard for Foods for Special Dietary Use for Persons 
Intolerant to Gluten (Codex Stan 118-1979)'' (Ref. 4). This Codex 
standard established a threshold of 20 mg gluten per kilogram (kg) 
product (which is equivalent to 20 ppm gluten) for foods labeled 
``gluten-free.'' \2\ In 2009, the Commission of European Communities 
issued a regulation (Ref. 13), in part, requiring that foods labeled 
``gluten-free'' not contain more than 20 ppm gluten. This regulation is 
binding and applicable in all Member States of the European Union, 
which currently represents 27 countries in Europe (Refs. 13 and 14).
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    \2\ The Foreign Agriculture Organization and World Health 
Organization jointly created the Codex Alimentarius Commission, in 
part, to develop food standards and guidelines as well as related 
codes of practice to protect the health of consumers and to 
facilitate international trade (Ref. 11). There are currently more 
than 185 countries, including the United States, that are eligible 
to participate in the decision-making process to develop Codex 
standards (Ref. 12).
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    The European Union level of 20 ppm is consistent with statements by 
some celiac disease researchers and some epidemiologic evidence 
suggesting that variable trace amounts and concentrations of gluten in 
foods can be tolerated by most individuals with celiac disease without 
causing adverse health effects (Refs. 15 through 20). These statements 
and studies were considered in the safety assessment, but because these 
do not provide dose-response data necessary for development of a 
hazard/safety assessment, they were not factored into that analysis. 
FDA seeks comments on this research, conducted in Europe, much of which 
was focused on identifying a maximum threshold value for trace amounts 
of gluten in ``gluten-free'' diets. In their research report, a group 
of Spanish researchers described the importance of identifying such a 
maximum tolerable level of gluten in ``gluten-free'' foods to people 
with celiac disease:

    Although alternative therapies are now being researched * * *, 
the only treatment available nowadays for those suffering from 
celiac disease is to adhere to a strict gluten-free diet for life. 
This includes a combination of consumption of naturally gluten-free 
foods, such as meat, fish, fruit, vegetables, legumes, eggs and 
dairy products with gluten-free substitutes of bread, cookies, pasta 
and other cereal-based foods. Gluten-

[[Page 46675]]

free products intended for dietary use have two main roles. On the 
one hand, they are essential for achieving a balanced diet and on 
the other, they minimize the differences with the diet of noncoeliac 
patients. These two roles should not be underestimated, the former 
should provide the appropriate energy and nutrients required for a 
healthy diet and the latter improves socialization of celiac 
patients, preventing them from looking different, from feeling 
deprivation and consequently from committing transgression. This is 
particularly important for the newly diagnosed as they are often 
undernourished, especially in cases in which a late diagnosis has 
occurred. This is also crucial during adolescence, widely documented 
as the most difficult stage to manage a strict gluten-free diet. 
Considering the important role of gluten-free products in the diet 
of coeliac patients, the quality of these products should be 
carefully assessed and reviewed. (Ref. 19).

FDA considers the points made by Gilbert and her colleagues to be 
important considerations in defining the term ``gluten-free.'' To the 
extent it is possible to do so and protect public health, we believe 
that we should set a gluten threshold level for ``gluten free'' 
labeling that best assists most individuals with celiac disease in 
adhering life-long to a ``gluten-free'' diet without causing adverse 
health consequences. If the prevalence of persons with celiac disease 
not following a ``gluten-free'' diet increases because there are fewer 
foods labeled ``gluten-free'' to choose from (because the criteria for 
making ``gluten-free'' labeling claims are too stringent for most food 
manufacturers to meet) or such foods become more expensive (because any 
changes made by manufacturers to enable them to meet more stringent 
criteria to make foods labeled ``gluten-free'' may increase their 
production costs), then these individuals could be at a higher risk of 
developing serious health complications and other diseases associated 
with celiac disease. In other words, moving to a definition of 
``gluten-free'' that adopts a criterion that is much lower than < 20 
ppm gluten could have an adverse impact on the health of Americans with 
celiac disease.
    A consequence of using the analytical methods-based approach is 
that the words ``gluten-free'' could be used on a product that is not, 
in fact, entirely free of gluten. There is precedent in FDA regulations 
on defined ``free'' nutrient content labeling claims to allow up to a 
specified measurable amount of the substance that is the subject of 
each of those claims to be present in the food. For example, per 
reference amount customarily consumed or per labeled serving, a food 
labeled ``fat free'' could contain < 0.5 gram (g) of fat (Sec.  
101.62(b)(1)(i) (21 CFR 101.62(b)(1)(i))), a food labeled ``cholesterol 
free'' could contain < 2 mg cholesterol (Sec.  101.62(d)(1)(i)(A)), and 
a food labeled ``sodium free'' could contain < 5 mg sodium (21 CFR 
101.61(b)(1)(i)). FDA seeks comments regarding whether, in light of 
FDA's safety assessment and the data underlying it, the possible 
presence of more than 0.01 ppm but < 20 ppm gluten in a food bearing a 
``gluten-free'' labeling claim would be a material fact that must be 
disclosed on the label in order to prevent a ``gluten-free'' claim from 
being false or misleading under the statutory definitions of 
misbranding found at 21 U.S.C. 321(n) and 343(a).
    FDA also seeks comments, data, and any other information related to 
the issue of whether a ``gluten-free'' claim on foods that contain a 
trace level of gluten greater than 0.01 ppm but < 20 ppm should be 
qualified in a way to ensure that the claim is truthful and not 
misleading. In the proposed rule (72 FR 2795 at 2803 and 2804), the 
Agency discussed and requested comments on whether the addition of 
qualifying language would be necessary in order to inform individuals 
with celiac disease that a food labeled ``gluten-free'' nonetheless 
could contain the amount of gluten permitted by whatever labeling 
threshold level FDA established in a final rule. For example, an 
asterisk could be placed immediately after the term ``gluten-free'' 
(i.e., ``gluten-free*'') on a food label or in food labeling, with a 
clarifying statement located in close proximity to that claim in a 
print size no smaller than \1/16\ of an inch (e.g., ``does not contain 
20 ppm or more gluten'' or ``does not contain 20 micrograms or more 
gluten per 100 grams food''). In light of the safety assessment, and 
because FDA previously received very few comments on this issue, we are 
soliciting public comments again on whether it would be necessary to 
accompany any ``gluten-free'' labeling claim with the addition of 
qualifying language. Also, we request comments on the wording for any 
qualifying language and on its proximity to a ``gluten-free'' claim 
appearing on a food label or in food labeling.
B. Gluten Threshold Lower Than < 20 ppm To Define, in Part, the Term 
``Gluten-Free''
    FDA is considering whether and how the results of the safety 
assessment should alter the Agency's proposed definition of ``gluten-
free.'' We recognize that there are highly sensitive individuals with 
celiac disease who may not be fully protected if they consume foods 
containing a trace level of gluten above 0.01 ppm but below 20 ppm. 
Therefore, we are seeking comments on whether a ``gluten free'' claim 
based on a < 20 ppm threshold should be accompanied by a qualifying 
statement. FDA has tentatively concluded, however, that < 20 ppm gluten 
is the appropriate threshold level to use as a criterion to define the 
food labeling term ``gluten-free.'' As previously noted, FDA is 
concerned that adoption of a gluten threshold level that is lower than 
< 20 ppm may have the unintended and unwanted effect of making it more 
difficult for those with celiac disease to adhere to a life-long 
``gluten-free'' diet, thereby putting those individuals at increased 
risk of developing serious health complications and other diseases 
associated with celiac disease.
    FDA's concern is based on questions about whether food 
manufacturers of multi-ingredient foods, especially grain-based 
products, could comply with a gluten threshold level much lower than < 
20 ppm. Even if a lower gluten threshold level could be enforced, we do 
not know if it would: (1) Influence some U.S. food manufacturers to 
discontinue labeling their products ``gluten-free'' because they cannot 
consistently and reliably meet a lower gluten threshold level, (2) 
discourage other U.S. food companies from becoming manufacturers of 
foods labeled ``gluten-free,'' (3) result in a significant increase in 
the cost of foods labeled ``gluten-free,'' or (4) negatively affect 
international trade of foods labeled ``gluten-free,'' thereby affecting 
the availability of certain foods to those individuals with celiac 
disease.
    Therefore, FDA invites comments, supported by data and any other 
information, on the potential impact the adoption a gluten threshold 
level lower than < 20 ppm as a criterion to define the term ``gluten-
free'' might have on manufacturers of foods labeled ``gluten-free'' and 
on celiac disease consumers of those foods.
    FDA seeks to define the term ``gluten-free'' to assist as many 
individuals with celiac disease as possible in identifying foods that 
they can eat without experiencing adverse health effects. If FDA adopts 
the proposed < 20 ppm gluten threshold level as one of the criteria to 
define the term ``gluten-free'' in the final rule, the Agency will 
remain open to the feasibility and desirability of revising this 
criterion as more sensitive methods to detect gluten become available 
or if FDA determines in the future that further research on celiac 
disease indicates that the adoption of a lower gluten threshold level 
for foods labeled ``gluten-free'' is warranted to be

[[Page 46676]]

adequately protective of the celiac disease population. FDA is 
interested in receiving data and comments that will help identify the 
proportion of the population of individuals with celiac disease that 
may experience adverse health effects as a result of exposure to gluten 
at levels between 0.01 ppm and < 20 ppm.
C. Gluten Threshold to Define, in Part, the Term ``Low-Gluten''
    In the proposed rule (72 FR 2795 at 2804), we noted that Australia 
and New Zealand have developed a two-tiered approach to gluten-related 
food labeling by setting regulatory standards for ``gluten-free,'' 
meaning no detectable gluten, and ``low-gluten,'' meaning no more than 
20 mg gluten per 100 g of the food (which is equivalent to no more than 
200 ppm gluten in the food). In the Preliminary Regulatory Impact 
Analysis section (72 FR 2795 at 2811 and 2812) and the Regulatory 
Flexibility Analysis section (72 FR 2795 at 2813) of the proposed rule, 
we evaluated an alternative regulatory option (referred to as ``Option 
6''), under which we would define and allow in food labeling both of 
the claims ``low gluten'' and ``gluten free.'' The ``Option 6'' 
analysis used < 20 ppm gluten as a criterion for defining the term 
``gluten-free,'' with the suggestion that an amount higher than 20 ppm 
would be specified as a criterion for defining the term ``low-gluten.'' 
The proposed rule did not identify any specific amount of gluten to 
define the term ``low-gluten'' because we did not have sufficient 
scientific data to recommend such a level, nor does FDA have such data 
today.
    In light of the findings of FDA's safety assessment and the 
discussion in this Federal Register document of factors that could 
influence the Agency's decision on how to define the term ``gluten-
free,'' FDA believes that it would be helpful to again solicit comments 
about any reasons that would support a gluten threshold level to 
define, in part, the food labeling claim ``low-gluten.'' If such 
reasons exist, FDA is also seeking comments on the specific gluten 
threshold level and any other criteria that the Agency should use to 
define the term ``low-gluten.''

IV. Request for Comments

    In addition to comments on the issues raised elsewhere in this 
Federal Register document, we are interested in any data and 
information not identified in this Federal Register document, the 
Gluten Report, or the proposed rule, that we should consider in 
establishing a gluten threshold level as one of the criteria to define 
the food labeling term ``gluten free.''

V. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) either electronic or written comments regarding this 
document. It is only necessary to send one set of comments. It is no 
longer necessary to send two copies of mailed comments. Identify 
comments with the docket number found in brackets in the heading of 
this document. Received comments may be seen in the Division of Dockets 
Management between 9 a.m. and 4 p.m., Monday through Friday.

VI. Electronic Access

    Persons with access to the Internet may obtain FDA's report on the 
health hazard assessment it conducted, the Gluten Report, at http://www.fda.gov/downloads/Food/ScienceReseacrh/ReseacrhAreas/RiskAssessmentSafetyAssessment/UCM264152.pdf.

VII. References

    The following references have been placed on display in the 
Division of Dockets Management (see ADDRESSES) and may be seen by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday. 
(FDA has verified the Web site addresses but FDA is not responsible for 
subsequent changes to the Web sites after this document publishes in 
the Federal Register.)

1. The Threshold Working Group, ``Approaches to Establish Thresholds 
for Major Food Allergens and for Gluten in Food,'' Revised Report, 
Center for Food Safety and Applied Nutrition, Food and Drug 
Administration, College Park, MD, March 2006, accessible at http://www.fda.gov/Food/LabelingNutrition/FoodAllergensLabeling/GuidanceComplianceRegulatoryInformation/ucm106108.htm and http://www.fda.gov/downloads/Food/LabelingNutrition/FoodAllergensLabeling/GuidanceComplianceRegulatoryInformation/UCM192048.pdf.
2. M[eacute]ndez, E., V. Carmen, U. Immer, et al., ``Report of a 
Collaborative Trial to Investigate the Performance of the R5 Enzyme 
Linked Immunoassay to Determine Gliadin in Gluten-Free Food,'' 
European Journal of Gastroenterology & Hepatology, 17(10):1053-1063, 
2005.
3. R-Biopharm Gliadin AG Web site, ``Ridascreen[supreg] Gliadin'' 
(Product Code R7001) Web page, http://www.r-biopharm.com/product_site.php?product_id=252&product_class_one=QWxsZXJnZW5z&product_class_two=R2xpYWRpbg==&product_class_three=&product_class_four=&product_range=Food%20and%20Feed%20Analysis&, accessed July 1, 
2011.
4. Codex Alimentarius Commission, ``Codex Standard for Foods for 
Special Dietary Use for Persons Intolerant to Gluten (Codex Stan 
118-1979),'' Rome, Italy, pp. 1-3, 2008; accessible at http://www.codexalimentarius.net/download/standards/291/cxs_118e.pdf.
5. AOAC Research Institute, ``Certificate of Performance Tested\SM\ 
Status, Certificate No. 120601,'' AOAC International, Gaithersburg, 
MD, 2010; accessible at http://www.aoac.org/testkits/2010_120601_Certificate.pdf.
6. Matsuda, R., Y. Yoshioka, H. Akiyama, et al., ``Interlaboratory 
Evaluation of Two Enzyme-Linked Immunosorbent Assay Kits for the 
Detection of Egg, Milk, Wheat, Buckwheat, and Peanut in Foods,'' 
Journal of AOAC International, 89(6):1600-1608, December 2006.
7. Morinaga Institute of Biological Science, Inc., Web page: 
``Product: Food Allergen Kits: Food Allergen ELISA Kits,'' http://www.miobs.com/english/product/food_allergen_elisa_kits/index.html, and Information Sheet Download ``Wheat Protein ELISA Kit 
(Gliadin),'' http://www.miobs.com/english/product/food_allergen_elisa_kits/dl/gdrev1.pdf accessed July 1, 2011.
8. Garber, E, Memorandum, ``ELISA Methods Used to Detect Gluten in 
Foods,'' Center for Food Safety and Applied Nutrition, Food and Drug 
Administration, College Park, MD, July 15, 2011.
9. Office of Food Safety, ``Health Hazard Assessment for Gluten 
Exposure in Individuals with Celiac Disease: Determination of 
Tolerable Daily Intake Levels and Levels of Concern for Gluten,'' 
Center for Food Safety and Applied Nutrition, Food and Drug 
Administration, College Park, MD, May 2011; accessible at http://www.fda.gov/downloads/Food/ScienceReseacrh/ReseacrhAreas/RiskAssessmentSafetyAssessment/UCM264152.pdf.
10. U.S. Department of Agriculture, Agricultural Research Service, 
Beltsville Human Nutrition Research Center, Food Surveys Research 
Group (Beltsville, MD), ``Continuing Survey of Food Intakes by 
Individuals 1994-96, 1998 and Diet and Health Knowledge Survey 1994-
96: Documentation'' (csfii9498--documentationupdated.pdf) or Data 
Files (csfii9498--data.exe); accessible at http://www.ars.usda.gov/Services/docs.htm?docid=14531.
11. Codex Alimentarius Web site, ``Welcome'' Web page, http://www.codexalimentarius.net/web/index_en.jsp, accessed July 1, 2011.
12. Codex Alimentarius Web site, ``Membership of the Commission'' 
Web page, http://www.codexalimentarius.net/web/members.jsp?lang=EN, 
accessed July 1, 2011.
13. The Commission of the European Communities, ``Commission 
Regulation (EC) No 41/209,'' Official Journal of the European Union, 
Brussels, Belgium, pp. L 16/3-L 16/5, January 20, 2009; accessible 
at http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2009:016:0003:0005:EN:PDF.
14. Europa: Gateway to the European Union Web site, ``Countries'' 
Web page, http://

[[Page 46677]]

europa.eu/about-eu/countries/index--en.htm, July 1, 2011.
15. Collin, P., L. Thorell, K. Kaukinen, et al., ``The Safe 
Threshold for Gluten Contamination in Gluten-Free Products. Can 
Trace Amounts Be Accepted in the Treatment of Coeliac Disease?'' 
Alimentary Pharmacology & Therapeutics, 19(12):1277-1283, June 2004.
16. Kaukinen, K., P. Collin, K. Holm, et al., ``Wheat Starch-
Containing Gluten-Free Flour Products in the Treatment of Coeliac 
Disease and Dermatitis Herpetiformis: A Long-Term Follow-up Study,'' 
Scandinavian Journal of Gastroenterology, 34(2):163-169, January 
1999.
17. Per[auml]aho, M., K. Kaukinen, K. Paasikivi, et al., ``Wheat-
Starch-Based Gluten-Free Products in the Treatment of Newly Detected 
Coeliac Disease: Prospective and Randomized Study,'' Alimentary 
Pharmacology & Therapeutics, 17(4):587-594, February 2003.
18. Hischenhuber, C., R. Crevel, B. Jarry, et al., ``Review Article: 
Safe Amounts of Gluten for Patients With Wheat Allergy or Coeliac 
Disease,'' Alimentary Pharmacological & Therapeutics, 23(5):559-575, 
March 2006.
19. Gibert, A., M. Espadaler, M. Canela, et al., ``Consumption of 
Gluten-Free Products: Should the Threshold Value for Trace Amounts 
of Gluten Be at 20, 100 or 200 p.p.m.?'' European Journal of 
Gastroenterology & Hepatology, 18(11):1187-1195, 2006.
20. Akobeng, A. and A. Thomas, ``Systematic Review: Tolerable Amount 
of Gluten for People With Celiac Disease,'' Alimentary Pharmacology 
& Therapeutics, 27(11):1044-1052, June 2008.

    Dated: July 28, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-19620 Filed 8-2-11; 8:45 am]
BILLING CODE 4160-01-P