tific literature reporting that these ingredients bound milk-specific IgE and
caused reactions in milk-allergic individuals was further evidence that these ingredients contained allergenic protein.
Some submissions based their entire
argument for exemption on the notion
or standard that the ingredient had undergone sufficient hydrolysis or other
manufacturing method to reduce protein content. By having a reduced protein content, the notifiers or petitioners
claimed that the allergenicity of the ingredient would therefore be negligible.
However, none of these submissions
provided clear evidence that all allergenic proteins had been eliminated,
since there was still evidence of residual
protein content in most cases. Furthermore, there was no clear evidence provided that the residual protein content
posed no allergenic risk. The teams frequently observed that commercial
ELISA test kits, which are generally designed to detect allergen residues found
in foods due to cross-contact, were inappropriately applied to address the question of whether or not allergenic protein
was present in an ingredient. Such kits
do not necessarily detect all allergenic
proteins from an allergenic source. In addition, these kits may have both qualitative and quantitative limitations with
respect to validated detection of low levels of allergenic proteins, making them
inappropriate for establishing the absence of such proteins.
The appropriateness or specificity of
animal studies was also an issue in some
submissions. Studies with animal models
were sometimes presented to make conclusions about the absence of protein
content in the ingredient(s). Although
the teams recognized the potential of animal models, the submissions did not
provide a clear explanation of why the
studies would be appropriate or adequate to address the criteria established
for FALCPA submissions. Moreover, no
animal model of food allergy has yet
been validated to answer questions regarding allergenicity of food proteins in
Failure to incorporate a comprehensive
overview of the relevant information. In
some cases, literature reports of allergenic reactions to the ingredient(s) were
“New food proteins and the presence of
allergenic ingredients in the food supply present
unique assessment issues and approaches for
either not mentioned or were not adequately addressed. Evidence of known
(or lack of) reactions to the ingredient(s)
following repeated challenges or exposures in sensitive individuals may highlight important information with regards
to the ingredient’s allergenic potential.
Moreover, some submissions presented
scientific evidence on only one analytical approach or one type of testing
method, and failed to examine other potential questions or existing scientific information, which made it difficult for
the review teams to conclude that the exemption standard had been satisfied. Finally, the teams observed that the
notifiers and petitioners did not take the
opportunity to provide their own scientific statement about what studies, assays, and criteria would be sufficient to
meet the FALCPA exemption standards
or to present their own understanding of
these standards. Lack of a clear scientific
argument therefore made it difficult to
attain demonstration of sufficient “
scientific evidence” for labeling exemption.
gredients. However, no exemptions have
been granted in response to the FALCPA
notifications or petitions submitted and
reviewed to date. Absent defined thresholds for any major allergenic food, FDA
is considering whether agency guidance
on notification or petition standard criteria would further assist notifiers and
petitioners to include more complete
data in their submissions and to present
a clear and valid scientific argument for exemption from labeling requirements.
Conclusions and Future
New food proteins and the presence
of allergenic ingredients in the food supply present unique assessment issues and
approaches for regulators. The approach
to date has taken into consideration a
variety of factors on a case-by-case basis
using a weight-of-evidence approach
which looks at the type and origin of
protein, chemical, structural, or biological properties, estimated exposure to allergen, and relevant challenge history
data or other epidemiological data.
Nonetheless, difficulties in assessment of
food allergens remain.
The FALCPA notification and petition processes are available to industry
to request exemptions from required labeling for certain allergen-containing in-
Stefano Luccioli, M.D., is a scientific advisor and reviewer for activities related to
food allergies and hypersensitivity disorders. He is a member of CFSAN’s Office of
Food Additive Safety.
Jeremiah Fasano, Ph.D., is a consumer safety officer in the Office of Food
Additive Safety’s Division of Biotechnology
and GRAS Notice Review at CFSAN. He
has coordinated and participated in numerous reviews of food ingredient safety assessments, including some of the FALCPA
submissions received by FDA.
Sue Challis is a writer/editor with
CFSAN’s Office of Food Defense, Communication and Emergency Response.
2. “Food Labeling; Current Trends in the
Use of Allergen Advisory Labeling: Its use,
Effectiveness, and Consumer Perception;
Public Hearing” FDA Dockets #FDA–
2008–N–0429, September 16, 2008.
4. Gendel SM, Dennis SB, and Buchanan
R. (December 2006–January 2007) The
Challenge of Regulating Allergens in
Food. Food Safety Magazine.
5. American Academy of Pediatrics Committee on Nutrition. (2000) Hypoallergenic
infant formulas. Pediatric 106:346-349.