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Center for Food Safety & Applied Nutrition Office of Premarket Approval January 1993 (Effective June 18, 2001, Office of Premarket Approval is now Office of Food Additive Safety. See updated contact information) |
This document supersedes the Guidelines dated July, 1986. No substantive changes have been made.
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Sanitizing solutions (sanitizers) are classified as Indirect Food additives regulated under 21 CFR 178.1010. (1) Sanitizing solutions are indirect food additives because their components are reasonably expected to become components of food through contact with the treated surfaces of food processing equipment and utensils. As food additives, sanitizers must be shown to be safe prior to their use. The conditions under which a sanitizer may be safely used on food-contact surfaces are prescribed in a regulation. A regulation may be obtained by submitting a food additive petition in accord with 21 CFR 171.1.
These quidelines are intended to amplify and explain the types of information and data needed for an adequate response to the chemistry requirements established in 21 CFR 171.1 as they pertain to sanitizing solutions. Limited reference is also made to microbiological, environmental, and toxicological requirements relating to sanitizers. Although a general set of chemistry guidelines for indirect food additive petitions is available, these guidelines are considered sufficient and complete with respect to sanitizers. For further details and information pertaining to petition format (number of copies, pagination, etc.) and requirements concerning registration of the sanitizer with the Environmental Protection Agency, write the Office of Premarket Approval (HFS-200), Food and Drug Administration, 200 C Street, S.W., Washington, D.C. 20204. (See updated contact information) The Office of Premarket Approval may also be contacted for general information regarding the type of scientific and technological data necessary for a petition for a sanitizer.
NOTE: The Agency distinguishes sanitizing solutions from disinfectants and cleaning solutions. The use of a solution as a sanitizer requires that application to a food-contact surface be followed by adequate drainage prior to contact of the surface with food (21 CFR 178.1010 (a)). A potable water rinse of the treated surface prior to food-contact negates the intended effect of the solution as a sanitizer. Thus, a product intended for treating of a food-contact surface and which is to be rinsed from the surface prior to food-contact is not considered a sanitizer. Therefore, it is unnecessary to submit a petition for a regulation under 21 CFR 178.1010 for disinfectants or cleaning solutions that are to be rinsed from food-contact surfaces.
The petition should be assembled in sections conforming, in general, to the subjects of 21 CFR 171.1(c):
A. Identity
B. Usage
C. Efficacy
D. Methods of Analysis
and Submission of Data
E. Safety
F. Tolerance
G. Amendments
H. Environmental Impact
This information is needed to characterize and identify fully the
formulation for which the petition to amend 21 CFR 178.1010 is
being submitted and to establish a list of compounds that are
potential migrants into food.
Some sanitizer concentrates may contain "precursor" components
which, upon dilution to at-use levels or upon "activation" by some
other added substance, liberate one or more functional compounds.
The reaction chemistry should be described and the liberated
substances identified and their concentrations estimated.
Chemical equations for the principal reactions involved in the
manufacture, as well as known side reactions, should be furnished.
Assay specifications for components and impurities should be
presented as a range or as a minimum or maximum amount, reflective
of the methodology employed for the determination of the
specification (e.g., "76-80%;" "not more than 5 ppm;" "98%
minimum"). All specifications should be listed in a single summary
table.
Additional data should reflect characterizing properties of the
entire formulation, e.g., pH, density, color, and freezing point.
These too should be specified as a range, where appropriate.
The analytical methodologies used to perform the assay tests should
be described in detail in the section on
"Methods
of Analysis and Submission of Data".
A clear statement of the types of food-processing systems intended
for sanitizer treatment is necessary to enable the agency to
estimate probable chronic human exposure to a sanitizer and its
components. For example, the petitioner should stipulate whether
the formulation is intended for use in public eating establishments
and institutions to sanitize eating utensils or whether its ;use
will be restricted to food plants for use on food-processing
equipment and utensils.
The manner in which the sanitization is performed (e.g., CIP
(clean-in-place), immersion, spray-application, etc.) and the types
of equipment intended for treatment (e.g., bottles, utensils,
conveyer belts, tanks, flat work surfaces, etc.) should also be
indicated. The food industries expected to use the sanitizer and
the foods expected to contact the treated surfaces should also be
specified, e.g., beverage industry (beer, wine, fruit juices,
carbonated soft drinks), dairy industry (milk, cheese), egg
products industry (mayonnaise).
Instructions to the end-user for dilution of the formulation, if
sold as a concentrate, should be provided along with the
corresponding "at-use" concentrations of each component (in ppm).
These values (for the non-GRAS ingredients) will be written into
the final regulation. They are also necessary for the estimation
of consumer exposure. The Agency may also require a compliance
method for analysis of "at-use" concentrations of one or several
components of the formulation. Guidelines for the development and
submission of compliance methods are provided in
Section D of these guidelines.
Facsimile labels on which it is clearly indicated that treatment of
a surface should not be followed by a water rinse prior to its
contact with food should also be submitted. The labels should
comply with 21 CFR 178.1010(a): "Such sanitizing solutions are
used, followed by adequate draining, before contact with food."
A sanitizing solution must be shown to be effective at the minimum
concentrations to be encountered under all proposed conditions of
use as stated on label declarations. Sanitizers that may be
affected by water hardness, e.g., anionic detergent-acid
formulations, chlorinated trisodium phosphates and quaternary
ammonium compounds, must be tested for effect or water hardness on
end-point reduction of organisms under the Association of Official
Analytical Chemists (AOAC) germicidal and detergent sanitizer test
to a level of 500 ppm synthetic water hardness.
The Office of Premarket Approval may be consulted for additional
information concerning the appropriate microbiological protocols
for establishing the effectiveness of the sanitizer formulation.
Report all analytical data in a clear and concise manner.
analytical results should be accompanied by the raw data so that
the significance of the conclusions and confidence in the results
can be evaluated. Raw data should include copies of instrument
recordings, notebook pages, sample calculations, calibration
curves, and computer printouts. Label or caption all tables and
figures with enough detail to be essentially independent of text
material. Include sufficient information so that all computations
and calculations can be understood and evaluated. Express all
units of measurement in appropriate metric quantities. English
units may accompany their metric equivalents. Conversion factors,
where used, should also be explicitly presented.
To assess precision, analyses should be performed in triplicate.
Usually, good intra-laboratory precision is indicated by a relative
standard deviation of less than 10% for analytical values above 0.1
ppm and less than 20% for analytical values below 0.1 ppm. For
values well above the ppm range, relative standard deviations are
generally expected to be significantly better than 10%. For
analyses of lots or batches, five or more samples should be
analyzed to indicate variation among samples. Analyses of blanks
and any appropriate control samples should also be reported.
A petitioner may submit through the Office of Premarket Approval,
for review and comment, descriptions of analytical protocols prior
to initiating the collection of data.
It should be noted that in many instances, common standard assays
such as those in the Food Chemicals Codex,
3rd ed.,(2)
need only be referenced.
It is recommended that validation samples be fortified at levels of
one-half of, equal to, and two times (if possible) the nominal
concentration for a given component. Results of fortification
experiments typically are expected to show recovery between 80 and
110% for levels above 0.1 ppm. For levels well above the ppm
range, as generally expected for an ingredient in a sanitizer
concentrate, recovery is expected to be significantly better than
80%. Recoveries defined as the amount of the substance measured in
the fortified sample minus the amount measured in the unfortified
sample, divided by the amount added in the fortified sample, times 100.
The compliance methodology should be validated using fortification
and recovery experiments as discussed above. It is recommended that
the limit of detection of the method be established.
A review of the Agency's accumulation of experimental residue data
has led to the conclusion that a "worst case" assumption for
residual sanitizer solution of one milligram per square centimeter
of treated surface (1 mg/cm²) is a reasonably conservative
estimate that reflects the body of data. Therefore, the petitioner
may elect for the Agency to use this value for the exposure
calculation or may provide its own experimental data having
determined that the assumption of 1 mg residue/cm² is excessively
high as an approximation for its formulation. In the absence of
residue information, however, the Agency will perform an exposure
estimate assuming this "worst case" value.
If the petitioner chooses to rely on the 1 mg/cm² of residual
sanitizer solution, the petitioner should calculate the residues
of the individual components of the formulation based on the
assumption that each is present in the residual sanitizer in
proportion to its "at-use" concentration; special circumstances, e.g.,
volatility, gas evolution, reaction, etc., should be taken into
account.
If petitioners choose to perform their own residue measurements,
the results must be accompanied by a detailed description of the
analytical methodology along with validation data. The highest
sanitizer residuals--approaching 1 mg/cm²--have been observed
for sanitized bottles (e.g. milk bottles) and glass tumblers (which
have rims) used in public eating establishments. For such uses, it
may prove feasible to obtain reasonable residue data by weighing a
glass tumbler before and after treatment. The following protocol
is suggested: use 8 oz. (ca 240 mL) glass tumblers and carry
out experiments with varying vertical drain time (30 sec, 2 min, 5
min). Glasses should be initially dried, then weighed, filled to
the brim with the sanitizer solution, inverted to drain on a
suitably designed wire rack for the predetermined time, and
righted. The outer surfaces should be carefully and quickly dried
(wipe or blot--do not heat), and the glass reweighed. A minimum
of five measurements and two water "controls" for each drain time
should be satisfactory.
When application of the sanitizer will be restricted, for example,
to Clean-In-Place equipment, direct measurements of residual
sanitizer solution may not be feasible because the quantity of
residual solution may be much less than 1 mg/cm². This may also
be the case if flat steel, glass, or plastic test panels are used
as surrogates for actual plant equipment. In such instances,
development of an alternative physico-chemical measurement for one
or more components may be necessary. It is recommended that prior
to initiating data collection the petitioner submit for review a
protocol describing the intended methodology, including sample
collection.
The safety requirements depend on the chemical constituents of the
sanitizer formulation and on the extent to which these constituents
or their reaction products from food contact may reasonably be
expected to become a part of food. The Agency will determine the
toxicological studies needed to provide a reasonable assurance of
no harm to the public from use of the sanitizer after establishing
the probable daily intake of sanitizer residue.
To estimate probable daily intakes three types of information are
usually required: (1) sanitizer residues--discussed above, (2)
the mass and/or volume of food contacting a unit area of treated
surface, and (3) an estimate of an individual's daily intake of
foods assumed to have contacted the sanitized surfaces. The
Agency's calculations are intended to reflect a reasonable, yet
conservative, "worst case" situation. Therefore, the nature of the
exposure estimate will depend on the particular usages requested by
the petitioner.
The broadest coverage includes use of the sanitizer in
institutional or public eating facilities. In this case, the
Agency's worst-case estimate assumes that all food consumed by an
individual in a single day has contacted 4000 cm² of sanitized
non-porous food-contact surfaces. This contact area represents the
summation of the surface area of silverware, china, and glass used
by a person who regularly eats three meals per day in an
institutional or public facility. Assuming, for example, a
sanitizer residue of 1 mg/cm² and an "at-use" concentration of
200 ppm for component X, the estimated daily intake (EDI) for
residual X would be:
EDI = (1 mg/cm²)(200 µg X/1000 mg)(4000 cm²/person/day)
= 800 µg X/person/day
Generally, the estimated consumer exposure for a given "at-use"
concentration of a sanitizer intended for use in public eating
establishments for exceeds the estimated exposure when application
is restricted to "food processing equipment and utensils."
For applications limited to use of the sanitizer on food processing
equipment and utensils, the Agency has determined that estimates of
sanitizer exposure from use in dairy processing plants
significantly exceed estimates based on other uses with food
processing equipment and utensils. Depending on the available
safety data, the petitioner may either submit a petition for the
broader use of its sanitizer on "food processing equipment and
utensils including dairy processing plants" or for the more limited
use on "food processing equipment and utensils excepting use in
dairy processing plants."
The following simplified example will illustrate the calculation of
the EDI of residual sanitizer solution in milk from sanitizer use
in a dairy processing plant. Although in practice consideration of
all the components of a milk handling system must be included as
sources of sanitizer residue in milk, for this example the only
source is assumed to be a sanitized tank truck used to transport
the milk. It is further assumed that the milk undergoes no
additional dilution prior to reaching the consumer. Assuming a
cylindrical model for the tank truck (4000 gallon capacity) with a
length of 19.9 feet and cross-sectional diameter of 6 feet, an
internal surface area of 413 ft² is calculated for the tank.
Assuming that the sanitizer treatment leaves a residue of 1 mg/sq
cm and the "at-use" concentration of component X is 200 ppm, the
concentration of component X is 200 ppm, the concentration of X in
the milk residing in the tank would equal:
(413 ft²/1 truck)(1 truck/4000 gal)(1 mg/cm²)(200 µg/1000 mg)
(929 cm²/1 ft²)(0.264 gal/1 L)
To compute the probable daily exposure to X for a consumer of milk
requires information on the quantity of milk consumed on a daily
basis. The Agency relies on dietary surveys for this information.
For example, the average and 90th percentile (high consumer) intakes
of milk are approximately 125 and 320 g/person/day (g/p/d),
respectively (Market Research Corporation of America, 1982-87 five
year Menu Census, DHHS/FDA contract No. 223-87-2088). Therefore,
the EDIs of X from milk would be:
average EDI: (125 g milk/p/d)(5.1 ng X/g milk)
= (638 ng X/p/d) or (0.64 µg X/p/d)
90th percentile EDI: (320 g milk/p/d)(5.1 ng X/g milk)
= (1632 ng X/p/d) or (1.6 µg X/p/d)
The same type of calculations would be performed for residues on
food processing equipment and utensils in other food processing
plants (e.g. breweries).
In summary, once the Agency has considered the exposure estimate
from all petitioned uses, the Agency can establish the level of
toxicological testing needed for the safety evaluation. Consult
the Office of Premarket Approval for information.
At times, a tolerance (maximum permitted level in a food) for a
food additive is needed to ensure its safe use. Tolerances for
components of sanitizer formulations have not been required. The
limitations set forth in 21 CFR 178.1010(c) are not tolerances.
These limitations reflect minimum and/or maximum permitted "at-use"
concentrations of sanitizer components. The minimum values
typically refer to concentrations below which efficacy of the
formulation has not been demonstrated. The upper limit is
established on the basis of safety considerations.
Amendments are intended to effect changes in an existing regulation
(see 21 CFR 171.1(c)). Petitions to amend sanitizer solution
regulations must include full information on each proposed change
in the existing regulation.
Environmental information requirements are contained in 21 CFR 25
(see also 50 FR 16636). Additional information may be requested
from the Office of Premarket Approval.
Hypertext updated by dms/hrw 2004-JAN-06 A. Identity, Manufacture, Properties, & Specification of the
Formulation
B. Usage
C. Efficacy
D. Methods of Analysis and Submission of Data
E. Safety
= 5.1 µg X/L milk ~ 5.1 ppb
F. Tolerance
G. Amendments
H. Environmental Assessment
* Office of Premarket Approval, Center for Food Safety and
Applied Nutrition (HFS-200), Food and Drug Administration,
200 C St., SW., Washington, DC 20204 (See updated contact information)
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