![](media/image1.jpeg){width="1.6659722222222222in"
height="1.2270833333333333in"}

August 16, 2005

*BY ELECTRONIC AND REGULAR MAIL*

Marcia L. Moore

Center for Food Safety and Applied Nutrition

Food and Drug Administration

5100 Paint Branch Pkwy.,

College Park, MD 20740, 301-436-2397,

> Re: Threshold Working Group Draft Report (June 2005), *Approaches to
> Establish Thresholds for Major Food Allergens and for Gluten in Food
> (*Docket No. 2005N-0231)

Dear Ms. Moore:

The Grocery Manufacturers Association (GMA) submits these written
comments on the aforementioned June 2005 draft report on establishing
allergen thresholds prepared by the Threshold Working Group (hereinafter
the Draft Report), which was the subject of the July 13-15 meeting of
the Food Advisory Committee (FAC). GMA is the world's largest
association of food, beverage and consumer product companies. GMA's
member companies employ more than 2.5 million workers in all 50 states
and have total sales of approximately 680 billion dollars.

GMA and its member companies have been actively involved in the allergen
issue. Indeed, GMA played an instrumental role in the industry-developed
allergen labeling guidelines that have resulted in many food packages
bearing plain English names of the major allergens[^1]. The majority of
the GMA member companies voluntarily adopted these labeling practices
well before the Food Allergy Labeling and Consumer Protection Act
(FALCPA).

GMA commends the Food and Drug Administration (FDA) for its efforts in
developing the data and information that are needed to implement FALCPA.
GMA also commends FDA for convening the Food Advisory Committee (FAC) on
allergen thresholds and for the agency's efforts in preparing the Draft
Report. GMA appreciates the agency's transparency in identifying the
various methods that should be explored for establishing allergen
thresholds.

The establishment of allergen thresholds is integral to the effective
application of FALCPA. FALCPA subjects incidental additives, such as
processing aids, to the allergen labeling requirements. This provision
becomes problematic when the allergenic protein in a food is present at
such low levels that it does not pose a risk to human health. For
example, typical uses of soy lecithin---a commonly used processing
aid---result in soy protein levels in foods well under 10 parts per
million (ppm) and many uses result in levels in the parts per billion
and parts per trillion ranges.

FALCPA will fail the food allergic community if it results in allergen
labeling of foods with inconsequential levels of protein from major
allergens. The labeling of such foods would needlessly remove additional
products from the selection of food allergic consumers. FALCPA also
would lead to confusion in situations when a food label is revised to
declare a major allergen that is present at insignificant levels,
particularly when the food allergic consumer has been eating the product
safely for years without incident. By establishing thresholds, FDA would
prevent the over labeling of the many food products that currently are
being enjoyed and consumed without incident.

GMA offers the following comments on the various approaches for
establishing thresholds under consideration by FDA.

**I. Comments on Draft Report Provisions on Food Allergens**

**A. Statutorily-Derived Approach**

GMA concurs with the agency assessment that it would be appropriate to
develop interim thresholds using a statutorily-derived approach. FALCPA
specifically excludes highly refined oils from the definition of major
allergen. At the time Congress passed FALCPA, the literature contained
numerous references to the presence of detectable levels of protein in
highly refined oils. Crevel et al. (2000) published a literature review
on the levels of protein in various oils. Crevel notes "published values
vary widely, depending on the type and source of the oil as well as the
methodology used for extraction and analysis." [^2]/ Crevel reported
that the Leatherhead Food Research Association in the United Kingdom had
unpublished data revealing levels of up to 48 ppm in refined peanut oil.

FALCPA exempts highly refined oils from the major allergen definition
regardless of the level of protein in the product. Congress exempted
highly refined oils from the definition of major allergen at a time when
the literature contained reports of detectable levels of protein in
refined oils, such as 48 ppm of protein in refined peanut oil. If
Congress had intended to include all products with detectable levels of
protein in the definition of "major allergen," it would not have
exempted highly refined oils, which contain detectable levels of protein
as reported in the literature.

The legislative history also establishes Congressional intent that
ingredients with insignificant levels of allergens should not be subject
to the allergen labeling requirements. During legislative discussions,
the Senate Committee reporting the bill out of Committee to the full
Senate expressly stated that it "encourages FDA to adopt a reasonable
standard for determining whether a food ingredient "does not contain an
allergenic protein" \... for example, ingredients containing allergenic
proteins below \[a future\] established threshold would be eligible for
the notification procedure." [^3]/ The Senate Committee further directed
FDA to provide "guidance to industry on the information that would be
useful for making a determination that foods that contain protein
derived from one of the eight food allergens do not cause an allergic
response that poses a risk to human health" and create a "process
...that minimizes the burden on the food manufacturer." [^4]/

GMA believes the language of FALCPA and the legislative history support
the establishment of a statutorily-based threshold until sufficient data
are available to conduct a safety or risk assessment approach. GMA does
not believe it is necessary, however, as explained in the Draft Report,
to set the threshold level on the basis of the "average protein" level
in highly refined oils. FALCPA exempts all highly refined oils from the
definition of major allergen regardless of the level of protein in the
oil. Because the published literature contained reports of up to 48 ppm
of protein in refined peanut oils at the time Congress passed FALCPA, it
would be reasonable to establish the statutorily based threshold at 48
ppm. GMA, however, believes that 10 ppm would be a more reasonable level
for a threshold based on the statutorily-derived approach.

The food industry has long taken the position, on the basis of advice
from leading experts, that an allergenic protein that is present at
levels below 10 ppm in the finished food should not be subject to
ingredient labeling because such levels are unlikely to trigger a
response in food allergic consumers. GMA collected data on food allergic
complaints from various member companies that did not label the presence
of soy lecithin and fish gelatin when present at levels below 10 ppm.
The data summarized in the chart below reveal similar levels of consumer
complaints in the control products, which did not contain any allergens,
and the products with undeclared soy lecithin and fish gelatin.

  ----------------------- -------------------------- --------------------
  **Product**             **Complaints per Million   **Complaints Per
                          Units/Packages**           Million Servings**

  Control                 0.058                      0.05500

  Soy Lecithin            0.077                      0.00700

  Fish Gelatin            0.001                      0.00002
  ----------------------- -------------------------- --------------------

The data generated by GMA identified an absence of credible complaints
when consuming food products with very low levels of undeclared soy
lecithin and fish gelatin. Given the prevalence of food allergies in
this country and the significant number of units and servings sold, a
higher incident of allergic consumer complaints would have been expected
if the products had a high enough level of allergenic protein to trigger
an adverse reaction. The absence of credible consumer complaints to
products with very low levels of undeclared major allergens provides
further support for the establishment of 10 ppm as an interim level
based on the statutorily-derived approach.

GMA concurs with the Draft Report assessment that thresholds established
under the statutorily-derived approach should be viewed as "interim
levels." As more data become available, the statutorily-derived
threshold should be replaced with a method based on a safety or risk
assessment approach as recommended in the Draft Report.

**B. Method of Analysis Derived Approach**

GMA does not support the use of a method of analysis approach when
setting thresholds for major allergens. We question the utility of this
approach because commercially-available methods of analysis have not
been developed for all of the major allergens. Indeed, the peanut method
is the only method that has been validated. Moreover, the analytical
approach can be complicated by the development of increasingly more
sensitive analytical methods, which could result in a continually
changing threshold level. Limits of detection well below 1 ppm could
easily be obtained through advances in analytical technology.

In the event the agency ultimately decides to use the methods of
analysis approach, GMA concurs with Draft Report recommendations that
such thresholds should be considered interim and replaced with
thresholds that are established under the safety or risk assessment
approaches.

**C. Safety Assessment Approach**

GMA believes it would be appropriate to establish thresholds on the
basis of the safety assessment approach outlined by the agency. We
question, however, whether it is appropriate to use an uncertainty
factor of 100, with a 10-fold factor to account for intraspecies
differences and another 10-fold factor to account for severity of the
response and sensitivity of the population. GMA concurs with the FAC
recommendations that it is not possible to set one uncertainty factor
that can be applied across all studies. The scientific community must
evaluate each study independently, identify its strengths and
weaknesses, and make an informed assessment of the uncertainty factor,
if any, that should be applied in a study. Indeed, an uncertainty factor
may not be necessary when evaluating studies involving a sufficient
number of patients with various sensitivities when there are no symptoms
reported at the lowest tested doses and objective symptoms reported at
higher doses.

Another issue that must be considered in any safety assessment is the
scientific standard that will be used by the agency when developing the
threshold. FALCPA does not specifically address this issue in the
context of thresholds. FALCPA does recognize, however, that an
ingredient should be exempt from the major allergen definition under the
petition process if the petitioner can demonstrate that the use of the
ingredient "does not cause an allergic response that poses a risk to
human health." GMA believes it is reasonable for FDA to adopt this
standard when determining whether there are sufficient data to support
the establishment of thresholds under the safety assessment.

GMA also believes it is appropriate, as recommended in the Draft Report,
to use the first objective symptom when determining the lowest observed
adverse effect level (LOAEL) or the no observed adverse effect level
(NOAEL). Because subjective responses are not the type of responses that
"pose a risk to human health," objective symptoms should be used when
setting NOAELS and LOAELS. GMA does not believe, as suggested during the
FAC deliberations, that the uncertainty factor should be increased to
accommodate the first subjective symptom. The scientific community
should evaluate each study and make an informed decision on whether the
first subjective symptom in the study is indicative of a true allergic
response or a psychologically-induced response. In instances when a
subject reports a first subjective response at a very low level and
there is no evidence of an objective response until a significantly
higher level, it would be seemingly inappropriate to use the first
subjective response as the basis for the uncertainty factor.

GMA also believes FDA should consider approaches such as that used by
the American Academy of Pediatrics (AAP) in setting a threshold for
hypoallergenic infant formulas. The AAP determined that infant formulas
can be labeled hypoallergenic if it is documented under double-blind,
placebo-controlled conditions that, at a minimum, there is 95 percent
certainty that 90 percent of the cow's milk allergic population will not
react. [^5]/ This approach could be used, modified as necessary for
specific allergens and populations, to address thresholds for other
allergens.

**D. Risk Assessment Approach**

GMA concurs with the agency assessment that there are insufficient data
and information at this time to set thresholds using the risk-assessment
approach. As more data become available, GMA believes it would be
appropriate for the agency to set allergen thresholds using either the
safety or risk assessment approaches.

**II. Comments on Draft Report Provisions on Gluten**

GMA supports the Draft Report recommendations on establishing threshold
levels for gluten for purposes of establishing definitions for gluten
free and offers the following brief comments.

**A. Method of Analysis Approach**

GMA believes it would be appropriate to set the gluten threshold based
on the method of analysis approach, although we question whether any
products would qualify for the claim given the commingling of gluten and
non-gluten containing grains. Corn, wheat, soybeans, oats and other
grains are grown on the same farms in the United States and farmers use
the same combines to harvest, wagons to transport, and grain bins to
store these various grains. The grain elevators receiving the grains
also may use the same catch basin and augers to transport different
types of grains. The grains then can be transported in containers by
truck and rail that are used to transport other grains. There are many
opportunities for gluten and non-gluten containing grains to be
commingled. Indeed, the USDA grade standards specifically recognize that
up to 10 percent of "other grains" can be found in corn, soybeans, wheat
and canola and that up to 25 percent of "other grains" can be found in
oats and barley. [^6]/

While the milling industry may try to separate unwanted grains during
the milling process, it simply is not possible with the current
technology to separate all wheat from oats, corn, soybeans and other
grains. The flours milled from non-gluten containing grains and the
products made from such flours, therefore, can be expected to have very
low levels of gluten. GMA, therefore, suspects that very few products
would be eligible for a gluten-free claim if the threshold is based on
the analytical method.

If FDA chooses to use the method of analysis as the basis for defining
gluten free, GMA believes that such a position would be consistent with
agency precedent on the use of "free." FDA has taken the position that
the term "free," when used outside the context of nutrient content
claims, should be limited to products with no detectable levels of the
substance. For example, FDA takes the position that "alcohol free" only
may be used in instance when a product contains "no detectable
alcohol." [^7]/ GMA similarly believes it would be appropriate for FDA
to define "gluten free" for use on products that contain no detectable
levels of gluten. Very few products, however, likely would qualify for
such a claim. GMA would encourage FDA to set the threshold for gluten
free claims on the basis of the safety or risk assessment approach as
soon as the data are available.

**B. Safety Assessment Approach**

GMA supports the use of the safety assessment approach when setting
thresholds for gluten. For the same reasons discussed in more detail
above, GMA believes that FDA should consider the objective rather than
subjective response when setting LOAELS and NOAELS. GMA also believes it
would be inappropriate to set a single uncertainty factor for all
studies. FDA must evaluate the quality of the underlying study and set
the uncertainty factor on the basis of the study design.

**C. Risk Assessment Approach**

GMA concurs with the agency assessment that there are insufficient data
and information at this time to set thresholds using the risk-assessment
approach. As more data become available, GMA believes it would be
appropriate for the agency to set gluten thresholds using either the
safety or risk assessment approaches.

\* \* \* \* \*

GMA appreciates the opportunity to comment on this very important issue.
The FALCPA labeling requirements become effective on January 1, 2006. We
urge FDA to establish, in as expeditious a manner as possible,
thresholds for major allergens. The industry needs this information so
it will know whether it will be necessary to label major allergens when
they are present at minor and inconsequential levels.

In conclusion, GMA believes the statutorily derived method is
appropriate for the establishment of interim threshold levels for major
allergens and urges the agency to adopt an interim threshold as soon as
possible. For the reasons noted above, GMA believes that 10 ppm is an
appropriate statutorily-derived threshold. GMA agrees with the Draft
Report recommendation that interim thresholds should be replaced using
the safety or risk assessment approach as the relevant data become
available.

GMA believes the method of analysis approach may be appropriate for
setting interim levels for "gluten free'', but questions whether any
products would qualify given the commingling of grains. GMA also
supports the risk and safety assessments for setting thresholds on
gluten free.

If you have any questions on this or other matters, please contact us.

Sincerely,

![](media/image2.png){width="2.5in" height="0.7798611111111111in"}

Alison Kretser\
Sr. Director, Scientific and Nutrition Policy

[^1]: Food Allergen Labeling Guidelines
    http://www.gmabrands.com/publicpolicy/docs/whitepaper.cfm?DocID=770&

[^2]: / Crevel, R.W.R. et al., *Allergenicity of Refined Vegetable
    Oils*, 38 Food and Chemical Toxicology, 385, 389 (2000).

[^3]: / S. Rep. No. 108-226 at p.7 (2004).

[^4]: / *Id*.

[^5]: / Policy Statement on Hypoallergenic Infant Formulas, American
    Academy of Pediatrics Committee on Nutrition, PEDIATRICS Vol. 106
    No. 2, pp. 346-349 (Aug. 2000) (accessed on Aug. 16, 2005 at
    <http://aappolicy.aappublications.org/cgi/content/full/pediatrics;106/2/346>).

[^6]: / *See., e.g.,* 7 CFR §§  810.401(corn), 810.1001(oats),
    810.1601(soybeans) and 810.2202(wheat).

[^7]: / FDA Compliance Policy Guide, Sec. 510.400, Dealcoholized Wine
    and Malt Beverages\--Labeling (CPG 7101.04) (March 1995).