Page
1
of
3
October
2,
2003
Questions
for
the
Panel
I.
Performance
Standards
The
Agency
plans
to
adopt
the
Performance
Standards
developed
by
the
Interagency
Coordinating
Committee
on
the
Validation
of
Alternative
Methods
(
ICCVAM)
as
a
means
of
communicating
the
basis
by
which
each
of
three
validated
in
vitro
test
methods,
Corrositex
®
,
EPISKIN
 
/
EpiDerm
 
,
and
Transcutaneous
Electrical
Resistance
(
TER),
are
deemed
acceptable
for
providing
dermal
corrosivity
data.
Performance
Standards
consist
of
descriptions
of
(
1)
essential
test
method
components,
which
are
the
essential
structural,
functional,
and
procedural
elements
of
a
validated
test
method
that
should
be
included
in
the
protocol
of
a
proposed
mechanistically
and
functionally
similar
test
method;
(
2)
a
minimum
list
of
Reference
Chemicals,
which
is
used
to
assess
the
accuracy
and
reliability
of
the
similar
test
method;
and
(
3)
comparable
accuracy
and
reliability
values
that
should
be
achieved
by
the
proposed
test
method
when
evaluated
using
the
minimum
set
of
Reference
Chemicals.

Question
1.
Please
comment
on
the
provisions
in
the
Performance
Standards
for
each
of
the
three
methods
to
demonstrate
mechanistic
similarity
of
"
me­
too"
methods.
Do
the
essential
test
method
components
for
each
method
adequately
describe
the
unique
characteristics
of
the
method
necessary
to
determine
whether
a
test
is
mechanistically
and
functionally
similar.

Question
2.
In
its
evaluation
of
any
mechanistically
similar
test
system,
the
Agency
plans
to
use
the
generic
criteria
used
by
ICCVAM
for
selecting
subsets
of
the
Reference
Chemicals
for
all
three
ICCVAM
Performance
Standards
documents.
The
criteria
specify
that
chemicals
should
be
selected
in
such
a
way
that
the
subset:
includes
representatives
of
applicable
chemical
classes,
measures
a
range
of
corrosive
strengths,
includes
well­
defined
chemicals
that
are
currently
available
commercially,
and
has
unequivocal
animal
or
other
in
vivo
evidence.
Please
comment
on
the
strengths
or
weaknesses
of
this
approach
and
identify
and
discuss
any
modifications
to
the
criteria
that
should
be
considered.

Question
3.
The
ICCVAM
approach
for
demonstrating
functional
similarity
of
"
me­
too"
test
methods
to
validated
methods
includes
the
use
of
wellcharacterized
Reference
Chemicals
and
specifies
the
accuracy
and
reliability
that
should
be
achieved
by
"
me­
too"
test
systems
when
tested
in
intra­
and
inter­
laboratory
studies.
Please
comment
on
whether
"
me­
too"
test
systems
should
be
demonstrated
to
be
effective
for
evaluating
the
testing
Page
2
of
3
endpoint
for
all
of
the
chemicals
in
the
Performance
Standard.
Please
comment
on
the
value
of
including
chemicals
with
range
of
potencies
in
the
Performance
Standard.
Under
what
circumstances
might
testing
of
"
metoo
systems
within
one
laboratory
ever
be
sufficient
to
demonstrate
functional
equivalence?

II.
Quality
Control
The
Agency
is
proposing
quality
control
measures
that
should
be
considered
when
evaluating
the
reliability
of
test
kits
for
regulatory
purposes.
Please
address
the
following
specific
issues.

Question
4.
Subsets
of
the
Reference
Chemicals
used
in
test
method
validation
may
be
used
as
training
or
calibration
sets
by
testing
laboratories
using
in
vitro
systems.
Please
discuss
the
utility
of
and
necessity
for
training
or
calibration
sets
in
assuring
data
quality.
Please
comment
on
the
chemicals
selected
by
ICCVAM
for
use
as
a
calibration
set
for
TER
for
this
purpose.
Please
comment
on
the
ranges
of
chemical
classes
and
potencies
of
these
chemicals.
How
might
other
chemicals
be
selected
for
possible
use
in
the
calibration
sets?
Please
comment
on
the
value
of
identifying
chemicals
that
might
be
used
by
laboratories
as
training
sets
to
demonstrate
proficiency
in
performing
the
test.

Question
5.
Anticipating
the
use
of
systems
using
tissue
constructs,
ex
vivo
systems,
microarrays
or
genetically
modified
cells,
please
discuss
aspects
of
the
quality
control
criteria
that
are
necessary
for
assuring
the
integrity
of
such
systems
over
time
and
from
lot­
to­
lot.
Please
comment
on
whether
and
how
the
type
of
system
­
tissue
constructs,
ex
vivo
systems,
or
genetically
modified
cells
or
animals
­
should
affect
the
criteria
for
quality
control
for
assuring
the
integrity
of
such
systems,
both
over
time
and
from
lot­
to­
lot.

Question
6.
Please
comment
on
the
advantages
and
disadvantages
of
including
concurrent
positive
and
negative
controls
with
in
vitro
assays
when
used
as
alternatives
to
animal
testing.
What
are
the
important
characteristics
of
positive
and
negative
controls
for
in
vitro
studies?
What
aspects
of
positive
control
characteristics
allow
them
to
be
used
as
part
of
the
quality
control
process?
When
might
confirmation
that
positive
controls
are
performing
within
expected
or
historical
limits
be
sufficient
to
demonstrate
that
the
Proprietary
Test
Method
or
non­
proprietary
assay
system
is
functioning
properly?
When
might
additional
quality
control
measures
be
needed?

Question
7.
Does
the
Panel
agree
that
the
benchmark
controls
serve
a
useful
purpose
to
Page
3
of
3
demonstrate
the
level
of
response
that
can
be
expected
for
each
chemical
class
for
each
lot
of
Proprietary
Test
Method
assays?
Can
the
Panel
suggest
criteria
for
choice
of
appropriate
benchmark
controls?

sapquestions10/
02/
03.
wpd
