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Supplemental Recommendations
DIS/TSS-2 Jan 25, 1979
EFFICACY DATA REQUIREMENTS
Supplemental Recommendations
When an antimicrobial Agent is intended for a use pattern
that is not reflected by the test conditions specified in the Recommended
Methods, one or more test conditions specified in the method must be modified
and/or supplementary data developed in order to provide meaningful results
relative to the conditions of use. The following basic information is
critical to the development and submission of appropriate data.
1. EXPOSURE PERIOD
All products tested by the recommended methods may be tested
at the exposure periods prescribed in those methods. However, if the product
is intended for use at exposure periods shorter or longer than those specified
in the method, the method must be modified, in a manner acceptable to
the Agency, to reflect the deviation in exposure intended. A modification
to provide a shorter exposure period is restricted by the manipulative
limitations inherent in the method, while a modification to provide a
longer exposure period is restricted by the conditions applicable to the
use pattern. If a ten-minute exposure period is necessary for the antimicrobial
agent to be effective against the test microorganism the product cannot
be represented as an "instantly active" product, or cannot be
represented as being "effective in 30 seconds, "one minute,"
or at any time period shorter than 10 minutes. Also, the product cannot
be recommended for use in a manner which is inconsistent with the exposure
period necessary for effectiveness (as, for example, "Spray on surface,
and immediately wipe with clean cloth") unless the standard method
has been modified and reflects efficacy under such conditions of use.
In any case, the exposure period or manner of use necessary to provide
efficacy must be featured prominently on the product label.
2. TYPE OF SURFACE
When an antimicrobial agent is intended to be effective
in treating a hard porous surface, some of the Recommended Methods may
be modified to simulate this more stringent condition by substitution
of a porous surface carrier (such as a porcelain penicylinder or unglazed
ceramic tile) for the non-porous surface carrier (stainless steel cylinder
or glass slide) specified in the method. In addition, control data, described
below in Supplemental Recommendation No. 6, must be developed to assure
the validity of the test results when this modification of the method
is employed. In no case may a surface carrier which represents a less
stringent condition be substituted for a surface carrier which is specified
in the Recommended Method.
3. HARD WATER
The Recommended Methods may be modified to demonstrate the
effectiveness of an antimicrobial agent in hard water. The hard water
tolerance level may differ with level of antimicrobial activity claimed.
To establish disinfectant efficacy in hard water, all microorganisms (bacteria,
fungi, viruses) claimed to be controlled must be tested by the appropriate
Recommended Method at the same hard water tolerance level.
4. ORGANIC SOIL
An antimicrobial agent identified as a "one-step"
cleaner-disinfectant, cleaner-sanitizer, or one intended to be effective
in the presence of organic soil must be tested for efficacy by the appropriate
method(s) which have been modified to include a representative organic
soil such as 5% blood serum. A suggested procedure to simulate in-use
conditions where the antimicrobial agent is intended to treat dry inanimate
surfaces with an organic soil load involves contamination of the appropriate
carrier surface with each test microorganism culture containing 5% v/v
blood serum (e.g., 19 ml test microorganism culture $ 1 ml blood serum)
prior to the specified carrier-drying step in the method. Control data,
described below in Supplemental Recommendation No. 6, must also be developed
to assure the validity of the test results when this modification is incorporated
into the method. The organic soil level suggested is considered appropriate
for simulating lightly or moderately soiled surface conditions. When the
surface to be treated has heavy soil deposits, a cleaning step must be
recommended prior to application of the antimicrobial agent. The effectiveness
of antimicrobial agents must be demonstrated in the presence of a specific
organic soil at an appropriate concentration level when specifically claimed
and/or indicated by the pattern of use. A suggested procedure for incorporating
organic soil load where the antimicrobial agent is not tested against
a dry inanimate surface, such as the AOAC Fungicidal Test involves adding
5% v/v blood serum directly to the test solution (e.g., 4.75 ml test solution
+ 0.25 ml blood serum) before adding 0.5 ml of the required level (5 X
106 /ml) of conidia.
5. RE-USE
The Recommended Methods are designed to demonstrate efficacy
of a freshly prepared antimicrobial solution intended for a single application.
When the same use solution is intended for repeated applications, testing
must be conducted in accordance with a test protocol specially designed
to demonstrate retention of the claimed level(s) of antimicrobial activity
in the use solution after repeated microbial and other appropriate challenges
(such as supplemental recommendations indicated above) and stress conditions
(such as an inadvertent or incidental dilution inherent in the use pattern)
over the period of time or number of times specified in the directions
for use.
6. MICROORGANISM SURVIVAL AFTER DRYING ON A HARD
SURFACE
Quantitative determinations of the viable microbial concentration
on the untreated control carrier after drying are required in order to
determine the validity of the test results obtained with treated carriers
when the Recommended Methods are modified to include such elements as
(i) test microorganisms not specified in the method, (ii) substitution
of a porous surface (e.g., porcelain penicylinder, unglazed ceramic tile)
for the specified nonporous surface (stainless steel cylinder, glass slide),
and/or (iii) an organic soil load. The detailed protocol for this testing
must include: (i) preparation of inoculum, (ii) application of inoculum
to the carrier, (iii) the time/temperature and relative humidity conditions
for drying the microorganisms on the carrier, (iv) the technique for removal
of the microorganisms from the carrier, and (v) the specific assay procedure
indicating such details as replication, subculture media/diluents, and
the incubation time/temperature conditions for the enumeration procedure
employed. The test results must include the individual counts obtained
by the method.
7. NEUTRALIZATION
For each antimicrobial product, procedures must be employed
that will preclude residual effects of the active ingredient(s) in the
subculture medium. A specific medium capable of neutralizing the antimicrobial
effects of a product (whenever one is known) should be employed prior
to the microbiological assay. Some of the Recommended Methods rely solely
upon the selection of an appropriate subculture medium to neutralize the
antimicrobial effects of certain general types of chemical compounds (active
ingredients). However, to document absence of residual effects of the
active ingredient(s) in the subculture medium, the following testing is
necessary: (i) secondary subcultures must be performed to demonstrate
that antimicrobial effects were overcome, or (ii) at the conclusion of
the incubation period specified or employed in the method, the primary
culture medium with test carrier must be inoculated with approximately
10 microorganisms/ml of the specific culture under test (documented by
actual plate counts) and re-incubated for the specified period to demonstrate
that the subculture medium was capable of supporting bacterial growth.
8. BATCH REPLICATION FOR MODIFIED TESTS
Where the required batch replication has already been
performed and accepted for a product registration with unmodified
tests by the Recommended Methods, additional testing at the same use concentration
under modified conditions (e.g., different exposure period, presence of
organic soil or hard water, porous surface carrier, etc.) may be conducted
with reduced batch replication, as follows: (i) for basic efficacy claims
(e.g., sterilizers, disinfectants, or sanitizers), 2 samples, representing
2 different batches, instead of 3, and (ii) for supplemental efficacy
claims (e.g., fungicides, virucides, or tuberculocides), one sample instead
of 2.
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