1
NOMINATION
OF
THE
AEROSOL
METERED­
DOSE
INHALER
(
MDI)

AS
AN
ESSENTIAL
USE
FOR
2008
Country:
United
States
Contact
Person:
John
Thompson
Title:
Division
Director
Address:
U.
S.
Department
of
State
Washington,
DC
20520
Telephone:
202/
647­
9799
Fax:
202/
647­
5947
Email:
ThompsonJE2@
state.
gov
Expert
Contact
Person*:
Hodayah
Finman
Title:
Team
Leader
Address:
U.
S.
Environmental
Protection
Agency
Office
of
Air
and
Radiation
(
6205J)
1200
Pennsylvania
Avenue,
NW
Washington,
DC
20460
Telephone:
202/
343­
9246
Fax:
202/
343­
2338
Email:
finman.
hodayah@
epa.
gov
*
Expert(
s)
in
the
country
who
can
be
contacted
for
clarification.
2
I.
Summary
of
Nomination
A.
Please
identify
and
describe
in
detail
the
proposed
uses.
Please
indicate
for
what
disease
or
treatment
the
proposed
use
is
intended.
(
Decision
IV/
25,
pars.
2
and
3)

The
proposed
use
is
Metered
Dose
Inhalers
(
MDI)
where
the
active
ingredient
is
not
solely
salbutamol
for
the
treatment
of
asthma
and
chronic
obstructive
pulmonary
disease
(
COPD).
MDIs
are
pocket­
sized
aerosol
devices
used
to
deliver
(
orally)
precisely
measured
doses
of
medicine
directly
to
the
lungs.

CFCs
are
used
as
propellants
and
suspension
agents
in
MDIs
(
CFC­
11,12
and
114).
They
are
also
used
in
the
manufacture
of
MDI
valves
and
in
cleaning
MDI
manufacturing
equipment.

In
this
nomination,
the
U.
S.
is
not
requesting
CFCs
for
2008
for
use
in
metereddose
inhalers
where
the
sole
active
ingredient
is
salbutamol.
The
U.
S.
established
a
phaseout
date
of
December
31,
2008
for
these
products,
after
which
time
they
will
be
illegal
to
sell.

It
is
the
intention
of
the
U.
S.
government
not
to
file
a
2008
essential
use
exemption
request
for
CFCs
for
use
in
metered­
dose
inhalers
where
the
sole
active
ingredient
is
salbutamol.
However,
the
2005
and
2006
allocation
rules
that
make
CFCs
available
for
essential
uses
were
significantly
delayed
and
it
is
uncertain
at
this
time
what
impact
that
may
have
on
supplies
of
salbutamol
products
in
the
early
part
of
2008.
Therefore,
the
U.
S.
reserves
the
right
to
submit
a
2008
nomination
for
use
in
products
where
the
sole
active
ingredient
is
salbutamol
next
year
in
January
2007
should
there
be
an
essential
need
to
do
so.

B.
Please
specify
the
active
ingredient(
s)
used.
(
Decision
IV/
25,
pars.
2
and
3)

Flunisolide,
Metaproterenol,
Ipratropium
and
Salbutamol
(
in
combination),
Pirbuterol,
Epinephrine,
Triamcinolone,
Cromolyn
and,
Nedocromil.

C.
Please
identify
the
intended
market(
s)
for
sale
or
distribution
for
each
active
ingredient.
(
Decision
XV/
5,
par.
2)

Information
pursuant
to
Decision
XV/
5
will
be
submitted
by
the
United
States
under
separate
cover
for
confidentiality
reasons.
Please
note,
the
U.
S.
is
not
nominating
CFCs
for
MDIs
to
meet
export
demand.
3
D.
Please
indicate
below
the
quantity
of
CFCs1
requested
for
the
proposed
use
in
each
year
being
nominated
for
each
active
ingredient
and
for
each
intended
market
for
sale
or
distribution;
if
necessary,
the
quantities
for
intended
markets
may
be
best
estimates
from
requesting
companies.
If
more
specific
data
are
not
available,
data
aggregated
by
region
and
product
group
may
be
submitted
for
Article
5(
1)
intended
markets
for
sale
or
distribution.
(
Decision
IV/
25,
pars.
2
and
3
and
Decision
XV/
5,
par.
2)

Nominated
quantities
of
CFCs
(
metric
tonnes)
for
essential
uses
Ozone
Depleting
Substance
2008
Quantity
(
metric
tonnes)

CFC­
11,
CFC­
12,
and
CFC­
114
384.97
metric
tones
(
see
p.
15
as
well)

As
noted
above,
specific
data
on
the
amount
of
CFCs
by
active
ingredient
requested
in
Decision
XV/
5
will
be
provided
under
separate
cover
due
to
confidentiality
concerns.

II.
Substantiation
of
Nomination
A.
Role
in
Society
1.
State
whether
the
nomination
is
for
the
treatment
of
asthma
and/
or
chronic
obstructive
pulmonary
disease.
If
not,
explain
why
this
use
is
necessary
for
health
and/
or
safety
or
critical
for
the
functioning
of
society?
(
Decision
IV/
25,
p
2
and
3)

 
Describe
the
nature
of
the
disease(
s)
that
the
proposed
use
is
intended
to
treat,
e.
g.,
the
nature
and
prevalence
of
the
disease
and
the
role
of
MDIs
(
versus
other
forms
of
therapy)
in
treating
the
disease(
s).

This
nomination
requests
CFCs
solely
for
use
in
MDIs
for
the
treatment
of
asthma
and/
or
COPD.
Asthma
and
chronic
obstructive
pulmonary
diseases
(
COPD),
such
as
emphysema
and
chronic
bronchitis,
reduce
the
capacity
for
breathing.
In
asthma
and
often
in
COPD,
airways
become
inflamed
and
hyperreactive
causing
coughing
and
wheezing
that
disrupts
breathing.
These
diseases
can
also
cause
swelling
of
the
bronchi
and
produce
mucus
plugs
that
further
impede
airflow.
In
addition,
nervous
system
stimulation
can
contribute
to
further
airway
narrowing
and
worsening
symptoms.
Finally,
in
the
case
of
emphysema
and
chronic
bronchitis,
this
process
gradually
destroys
the
surface
area
of
the
lung,
reducing
its
capacity
to
exchange
oxygen
and
carbon
dioxide.

1
The
Parties
decided
in
Decision
X/
6
to
approve
CFCs
in
the
aggregate
rather
than
by
individual
compound.
Therefore,
Parties
need
only
provide
the
total
requested
quantity
of
CFC­
11,
CFC­
12,
CFC­
113,
and/
or
CFC­
114
in
the
aggregate.
4
Asthma
and
COPD
greatly
diminish
the
quality
of
life
for
patients
and
their
families,
and
in
severe
cases
may
cause
death.

Asthma
is
a
chronic
and
debilitating
respiratory
disease
with
sudden,
unpredictable
and
potentially
life­
threatening
effects.
The
treatment
of
asthma
requires
constant
vigilance
and
the
active
involvement
of
patients,
families,
physicians
and
other
care­
givers
in
a
comprehensive
program
to
monitor,
anticipate
and
promptly
respond
to
the
onset
of
asthmatic
attacks.

Patients
with
asthma
may
be
restricted
from
normal
physical
activity,
may
be
limited
in
their
choice
of
work,
afflicted
by
the
side
effects
of
some
medications,
and
subject
to
unpredictable
and
sudden
asthma
attacks
which
disrupt
their
daily
activities
and
may
even
threaten
their
lives.

Chronic
obstructive
pulmonary
disease
produces
inflammation,
swelling,
and
mucus
in
the
human
airway,
and
gradually
destroys
the
surface
area
of
the
lung.
COPD
is
progressive
and
generally
irreversible,
and
severely
restricts
the
capacity
for
respiration.

In
its
April
1999
report,
the
Technology
and
Economic
Assessment
Panel
stated
that:
"
there
is
international
consensus
that
primary
treatment
of
[
asthma
and
COPD]
should
be
by
the
inhaled
route.
This
permits
treatment
to
be
delivered
quickly
and
efficiently
to
the
airways,
which
minimizes
risk
of
adverse
reactions.
Therapy
necessitates
regular
treatment,
often
with
more
than
one
drug.
MDIs
remain
the
dominant
inhaled
delivery
system
in
most
countries
and
for
all
categories
of
drugs."

The
American
Lung
Association
has
issued
a
publication
entitled
"
Lung
Disease
Data
2000"
which
contains
statistics
concerning
the
prevalence,
mortality,
and
treatment
of
asthma
and
COPD
in
the
United
States.
The
report
states
that:

 
There
are
approximately
17
million
asthma
sufferers
in
the
U.
S.
Asthma
is
now
the
sixth­
ranking
chronic
condition
and
the
leading
serious
chronic
illness
in
children.
(
p.
5
).

 
"
Asthma
is
unquestionably,
and
unaccountably,
on
the
rise".
Between
1982
and
1995,
the
prevalence
rate
(
the
rate
per
thousand
persons)
of
asthma
rose
from
34.8
to
56.8,
a
63%
increase.
The
prevalence
of
pediatric
asthma
rose
from
40.1
to
74.9,
a
72.3%
increase.
(
p.
5)

 
There
were
5,434
deaths
from
asthma
recorded
in
1997.
This
represents
more
than
a
two­
fold
increase
since
1979.
(
p.
7)

 
Asthma
attacks
bring
an
estimated
1.9
million
Americans
to
emergency
rooms
each
year
and
account
for
one
in
six
of
all
pediatric
emergency
room
visits
in
the
U.
S.
(
p.
5)
5
 
Asthma
cost
the
U.
S.
an
estimated
$
11.3
billion
in
1998.
This
amount
includes
direct
health
care
expenses
($
7.5
billion)
and
indirect
costs
such
as
lost
productivity
($
3.8
billion).
(
p.
5)

 
In
addition
to
those
with
asthma,
more
than
16
million
Americans
are
estimated
to
suffer
from
COPD,
and
it
is
the
fourth­
ranking
cause
of
death
in
the
United
States.
(
p.
22)

 
COPD
was
responsible
for
the
death
of
over
103,000
Americans
in
1997.
This
is
a
new
high
in
a
steadily
increasing
toll
(
the
1980
figure
was
just
over
53,000).
(
p.
22)

 
COPD
costs
the
nation
approximately
$
26.0
billion
each
year,
which
includes
both
health
care
expenditures
($
13.6
billion)
and
indirect
costs
($
12.4
billion).
(
p.
22­
23)

 
COPD
is
the
third­
ranking
condition
necessitating
at­
home
care.
(
p.
23)

The
problem
is
not
limited
to
the
Unites
States.

 
The
total
incidence
of
asthma
is
estimated
to
be
around
5­
8%
worldwide.

 
According
to
the
World
Health
Organization
(
WHO),
worldwide
rates
of
asthma
are
rising,
on
average,
by
50%
every
decade.
(
WHO
Fact
Sheet
No.
206)

 
COPD
is
estimated
to
affect
up
to
15%
of
the
population
and
is
the
fifth
leading
cause
of
death
worldwide.

 
Asthma
and
COPD
result
in
approximately
3
million
deaths
annually.
(
World
Health
Report
1997,
WHO)

There
have
been
significant
advancements
in
the
development
of
alternatives
since
the
beginning
of
the
essential
use
exemption
program.
As
a
result,
the
U.
S.
government,
for
the
first
time
since
the
inception
of
the
exemption
program,
is
not
nominating
CFC
MDIs
where
the
sole
active
ingredient
is
salbutamol
for
an
exemption.
The
United
States
has
begun
rulemaking
processes
this
year
to
examine
the
essentiality
of
MDIs
where
the
sole
active
ingredient
is
not
salbutamol
that
use
CFCs
as
well.

The
need
for
an
essential
use
exemption
remains
while
we
develop
suitable
alternatives
for
certain
uses
or
complete
the
transition
to
CFC­
free
alternatives
in
other
products.
Exempted
CFC
consumption
for
products
to
treat
asthma
and
COPD
in
the
United
States
is
necessary
in
2008
for
the
health,
safety
and
critical
functioning
of
society
due
to
the
prevalence
and
seriousness
of
these
diseases.

2.
Does
this
use
include
any
MDI
product
approved
after
31
December
2000
for
the
treatment
of
asthma
and/
or
chronic
obstructive
pulmonary
disease?
(
Decision
II/
2,
par.
2)

No.
6
B.
Description
of
Transition
Status
The
following
elements
should
be
addressed
or
updated
in
each
year's
nomination:

1.
Has
a
transition
strategy
applicable
to
the
intended
market(
s)
for
sale
or
distribution
and
a
plan
of
action
been
submitted
to
the
UNEP
Ozone
Secretariat
under
Decision
XII/
2,
or
IX/
19,
and
XV/
5?
(
Decisions
IX/
19,
par.
5,
XII/
2,
par.
5(
c)),
and
XV/
5,
par.
4.

Consistent
with
the
request
of
the
Parties
in
Decision
VIII/
12,
the
United
States
has
submitted
to
the
UNEP
Ozone
Secretariat
its
transition
strategy
in
the
form
of
regulations
developed
by
the
U.
S.
Food
and
Drug
Administration
(
USFDA).
These
regulations
describe
the
criteria
that
USFDA
will
use
to
determine
when
it
is
appropriate
to
remove
the
essential
use
designation
from
products
that
use
ozone­
depleting
substances.
The
final
regulations
were
published
in
the
Federal
Register
on
July
24,
2002.2
The
rule
may
be
accessed
on
the
USFDA
website
at
http://
www.
accessdata.
fda.
gov/
scripts/
oc/
ohrms/
index.
cfm
by
searching
for
rules
published
on
July
24,
2002.
The
USFDA
issued
a
final
rule
on
April
4,
2005
(
70
FR
17169)
that
sets
the
date
to
remove
the
essential
use
designation
for
CFC
MDIs
whose
active
ingredient
is
salbutamol,
reflecting
substantial
progress
towards
phaseout
of
essential
uses
in
the
U.
S.
Please
see
Section
5
of
this
document
for
more
information
on
the
USFDA
rulemaking
process.

2.
Explain,
if
known,
how
any
such
transition
strategy
applies
to
the
active
ingredients(
s)
for
each
intended
market
for
sale
or
distribution
as
set
forth
above.
(
Decision
XV/
5,
par.
3)

Decision
XV/
5
requests
the
TEAP
to
provide
recommendations
to
the
Parties
with
reference
to
a
national
transition
strategy
covering
the
intended
market.
The
United
States
is
nominating
CFCs
solely
for
domestic
use
and
therefore
our
transition
strategy
as
a
whole
applies
to
the
entire
intended
market.

3.
Describe
progress
in
the
transition
to
alternatives
pursuant
to
the
national
or
regional
transition
strategy
submitted
to
the
Secretariat
in
the
domestic
market.
(
Decision
XII/
2,
par.
5(
c))

2
"
Use
of
Ozone­
Depleting
Substances;
Essential­
Use
Determinations."
67
Federal
Register
48370.
7
Significant
progress
has
been
made
in
recent
years
to
facilitate
an
orderly
transition
to
safe
and
effective
CFC­
free
alternatives.
Following
substantial
investment
in
research
and
development
by
U.
S.
firms,
and
completion
of
the
required
safety
tests
for
new
drug
products,
USFDA
has
approved
several
new
treatments
for
asthma
and
COPD
that
do
not
rely
on
CFCs
(
see
the
table
below).
Additional
alternatives
are
under
review
by
USFDA.
Also,
the
U.
S.
Government
has
overseen
the
consistent
application
of
Decisions
by
the
Parties
regarding
the
allocation
of
essential
use
allowances
by
ensuring
that
the
amount
granted
by
the
Parties
is
not
allocated
if
it
is
not
needed
nationally.
In
2002
USFDA
issued
the
final
regulations
that
provide
the
framework
for
the
transition
to
CFC­
free
alternatives
in
the
United
States.
These
regulations
describe
the
criteria
for
determining
if
a
product
using
ODSs
is
no
longer
medically
essential.
The
USFDA
finalized
their
first
action
to
remove
the
essentiality
of
a
medical
device
in
2004
with
the
ban
on
the
sale
and
distribution
of
CFC
salbutamol
MDIs
effective
December
31,
2008.
The
accelerating
shift
by
U.
S.
firms
to
CFC­
free
products,
as
well
as
the
success
of
these
products
in
the
U.
S.
market,
is
reflected
in
the
more
than
50%
reduction
in
the
2008
U.
S.
nomination
as
compared
to
the
total
approved
by
the
Parties
for
the
U.
S.
for
consumption
in
2007
(
the
2008
amount
is
approximately
one
third
of
the
U.
S.
2007
nomination).

There
are
several
factors
that
affect
the
timetable
for
the
introduction
of
alternatives
and
substitutes
including:

 
The
length
of
time
necessary
for
research
and
development
of
alternate
products;

 
The
time
required
to
seek
USFDA
approval
of
new
therapies;

 
The
regulatory
process
to
determine
that
a
medical
device
is
no
longer
essential.

The
process
for
determining
the
essentiality
of
a
product
is
described
in
a
final
rule
developed
by
the
USFDA.
The
final
rule
was
published
in
the
Federal
Register
of
July
24,
2002
(
67
FR
48370)
(
the
2002
final
rule)
(
corrected
in
67
FR
49396,
July
30,
2002,
and
67
FR
58678,
September
17,
2002).
The
rule
set
standards
that
FDA
would
use
for
determining
whether
the
use
of
an
ODS
in
a
medical
product
is
no
longer
essential.

All
CFC
MDI's
where
the
sole
active
ingredient
is
not
salbutamol
currently
marketed
in
the
United
States
do
not
have
acceptable
alternatives
with
the
same
active
moieties.
The
standard
to
remove
an
essential­
use
designation
for
products
where
there
are
not
adequate
alternatives
available
with
the
same
active
moiety
provide
that
FDA
must
find
that:
 
Substantial
technical
barriers
do
not
exist
to
formulating
the
product
without
ODS;
 
The
product
does
not
provide
an
unavailable
important
public
health
benefits;
and
8
 
Use
of
the
product
releases
cumulatively
significant
amounts
of
ODS
into
the
atmosphere
or
the
release
is
warranted
in
view
of
the
unavailable
important
public
health
benefits.

This
is
the
standard
that
is
being
used
in
the
current
rulemakings
regarding
the
essential
use
status
of
MDIs
where
the
sole
active
ingredient
is
not
salbutamol.

4.
Briefly
describe
the
action
plan
adopted
by
the
Party
pursuant
to
paragraphs
4
and
5
of
decision
XV/
5
(
providing
for
plans
of
action
including
a
specific
phase­
out
date
for
salbutamol
CFC
MDIs
sold
or
distributed
in
non­
Article
5
Parties,
specific
measures
and
actions
sufficient
to
deliver
the
phase­
out;
and
actions
and
measures
needed
to
ensure
continuing
access
to
or
supply
of
CFC­
containing
MDIs
by
Article
5
Parties,
where
appropriate).
(
Decision
XV/
5,
pars.
4
and
5)

As
indicated
previously
in
this
document,
the
United
States
has
established
a
phase­
out
date
for
the
sale
of
CFC
salbutomol
products
effective
December
31,
2008.
The
U.
S.
has
not
traditionally
exported
CFC
salbutamol
products
to
A5
countries
but
the
EPA
is
currently
evaluating
the
amount
of
CFCs
needed
to
meet
demand
for
MDIs
in
Article
5
Parties
as
part
of
the
U.
S.
regulations
on
production
for
basic
domestic
needs.

5.
Describe
progress
made
towards
determining
and
submitting
a
specific
date
by
which
time
the
Party
will
cease
making
nominations
for
essential
use
exemptions
for
CFCs
for
metered­
dose
inhalers
where
the
active
ingredient(
s)
is
not
solely
salbutamol
and
the
metered­
dose
inhalers
are
expected
to
be
sold
or
distributed
on
the
market
of
any
Party
not
operating
under
paragraph
1
of
Article
5.
(
Decision
XV/
5,
par.
6)

The
United
States
has
begun
rulemaking
processes
this
year
to
examine
the
potential
phaseout
of
CFC
MDIs
where
the
active
ingredient
is
not
solely
salbutamol.
USFDA
makes
a
determination
on
the
essentiality
of
a
product
through
a
public
advisory
process
and
accompanying
notice
and
comment
rulemaking.
This
process
may
be
a
lengthy
one
taking
years
to
complete
and
is
required
by
domestic
law
to
ensure
that
an
essentiality
determination
is
made
with
due
consideration.
The
USFDA
has
already
held
two
advisory
council
meetings,
which
are
a
preliminary
step
for
the
agency
to
begin
consideration
of
this
issue.
As
per
Decision
XVII/
5,
the
United
States
will
inform
the
Ozone
Secretariat
as
to
the
estimated
dates
for
publication
of
these
proposed
rules
prior
to
the
18th
MOP
if
the
proposed
rules
have
not
published
by
that
time
or
an
essential
use
is
not
the
subject
of
one
of
the
current
rulemakings.

6.
Explain
what
substitutes
and
alternatives
to
the
proposed
use
are
currently
available
in
the
domestic
market
and,
to
the
extent
known,
in
each
intended
9
market
for
sale
or
distribution.
(
Decision
IV/
25,
pars.
1(
a)(
ii),
1(
b)(
i),
2
and
3(
d))

Below
is
a
list
of
CFC­
free
MDI
and
DPI
products
approved
for
the
treatment
of
asthma
and
COPD
in
the
U.
S.
domestic
market:

Product
Drug
Delivery
System
Active
Moiety
Product
Approval
Date
Proventil
HFA
HFA
MDI
Salbutamol
15/
08/
96
Ventolin
HFA
HFA
MDI
Salbutamol
19/
04/
01
Proais
HFA
HFA
MDI
Salbutamol
29/
10/
04
Xepenex
HFA
HFA
MDI
Levalbuterol
11/
03/
05
Q­
Var
HFA
MDI
Beclomethasone
15/
09/
00
Advair
Diskus
DPI
Fluticasone/
salmeterol
24/
08/
01
Flovent
Diskus
DPI
Fluticasone
29/
09/
00
Flovent
HFA
HFA
MDI
Fluticasone
14/
05/
04
Pulmicort
Turbuhaler
DPI
Budesonide
24/
06/
97
Serevent
Diskus
DPI
Salmeterol
19/
09/
97
Asmanex
Twisthaler
DPI
Mometasone
30/
03/
05
Atrovent
HFA
HFA
MDI
Ipratropium
27/
11/
05
In
addition
to
the
MDI
and
the
DPI,
three
other
forms
of
therapy
exist
for
the
treatment
of
asthma
and
COPD:

 
orally
administered
drugs
 
injectable
drugs
 
nebulizers
Orally
administered
and
injectable
drugs
are
prescribed
for
some
patients
but
rarely
offer
adequate
relief
by
themselves.
As
noted
elsewhere
in
the
nomination,
there
is
"
international
consensus
that
primary
treatment
of
these
diseases
should
be
by
the
inhaled
route."
Nebulizers
are
currently
impractical
replacements
for
MDIs
due
to
issues
of
portability
and
ease
of
use.
In
its
April
1999
report,
the
Technology
and
Economic
Assessment
panel
stated,
"
Novel
oral
compounds
(
leukotriene
modifiers)
for
the
treatment
of
asthma
have
been
introduced
in
some
countries.
These
may
be
of
value
to
a
certain
number
of
those
with
asthma,
but
it
is
unlikely
that
these
will
be
a
full
substitute
for
current
effective
inhaled
preventive
therapy"
(
p.
191).
10
7.
Explain
steps
being
taken
to
implement
these
substitutes
and
alternatives
in
the
domestic
market.
(
Decision
IV/
25,
pars.
1(
a)(
ii),
1(
b)(
i),
2
and
3(
d))

List
and
describe
in
detail
the
education
efforts
being
undertaken
to
accomplish
the
transition.

Regulatory
Actions
to
Facilitate
Transition
Substantial
progress
has
been
made
in
recent
years
to
facilitate
an
orderly
transition
to
safe
and
effective
CFC­
free
alternatives.
Following
substantial
investment
in
research
and
development
by
U.
S.
firms,
and
completion
of
the
required
safety
tests
for
new
drug
products,
USFDA
has
approved
several
new
treatments
for
asthma
and
COPD
that
do
not
rely
on
CFCs
(
see
the
table
under
question
6).
Additional
alternatives
are
under
review
by
USFDA.
In
2002
USFDA
issued
the
final
regulations
that
provide
the
framework
for
the
transition
to
CFC­
free
alternatives
in
the
United
States.
These
regulations
describe
the
criteria
for
determining
that
a
product
using
ODSs
is
no
longer
medically
essential.
Lastly,
the
U.
S.
Government
has
overseen
the
consistent
application
of
Decisions
by
the
Parties
regarding
the
allocation
of
essential
use
allowances
by
ensuring
that
the
amount
granted
by
the
Parties
is
not
allocated
if
it
is
not
needed.
The
accelerating
shift
by
U.
S.
firms
to
CFC­
free
products,
as
well
as
the
success
of
these
products
in
the
U.
S.
market,
is
reflected
in
the
more
than
50%
reduction
in
the
2008
U.
S.
nomination
as
compared
to
the
total
approved
by
the
Parties
for
consumption
in
the
U.
S.
in
2007.
In
fact,
depending
on
the
outcome
of
the
ongoing
rulemaking
process,
the
EPA
allocation
of
CFCs
to
manufacturers
for
2008
may
be
substantially
lower.

Removing
Information
Barriers:
Government
and
Industry
Activities
To
encourage
doctor
and
patient
acceptance
and
use
of
CFC­
free
MDIs,
MDI
companies
in
the
U.
S.
will
undertake
national
promotional
campaigns
that
include,
among
other
things,
meetings
with
and
letters
to
health
care
professionals,
information
booths
at
medical
conferences,
advertisements,
and
distribution
of
educational
materials
introducing
these
products
into
the
market.
These
steps
will
be
taken
in
accordance
with
relevant
regulations
of
USFDA.

U.
S.
pharmaceutical
companies
have
undertaken
a
number
of
education
efforts.
The
International
Pharmaceutical
Aerosol
Consortium
(
IPAC),
to
which
many
U.
S.
MDI
manufacturers
belong,
has
undertaken
the
following
education
efforts,
some
with
the
assistance
of
the
U.
S.
Environmental
Protection
Agency
(
U.
S.
EPA).
Some
of
these
education
efforts
include:

 
World
Wide
Web
Sites
USEPA
and
USFDA
have
websites
with
information
on
the
transition
to
CFC­
free
metered
dose
inhalers.
They
are
located
at
www.
fda.
gov/
cder/
mdi/
and
11
http://
www.
epa.
gov/
ozone/
title6/
phaseout/
mdi/
index.
html.

The
International
Pharmaceutical
Aerosol
Consortium
(
IPAC),
to
which
several
companies
operating
in
the
U.
S.
belong,
also
has
a
World
Wide
Web
site
(
www.
ipacmdi.
com).
The
purpose
of
the
web
site
is
to
provide
patients
and
physicians
with
information
on
the
transition
to
CFC­
free
MDIs.
The
web
site
showcases
IPAC
brochures,
newsletters,
fact
sheets,
and
publications
that
IPAC
distributes
at
medical
conferences
and
symposia.

 
Brochure
on
the
Transition
A
group
of
parties
 
USEPA,
USFDA,
the
US
National
Institutes
of
Health,
IPAC,
the
National
Asthma
Education
and
Prevention
Program
of
the
National
Heart,
Lung,
and
Blood
Institute
 
collaborated
in
the
publication
of
a
brochure
entitled
"
Your
Metered­
Dose
Inhaler
Will
Be
Changing.
.
.
Here
are
the
Facts."
This
brochure
explains
the
reasons
why
the
CFC
MDI
is
being
replaced,
the
effort
being
made
to
develop
and
introduce
the
CFC­
free
MDI,
the
ways
in
which
the
CFC­
free
MDI
may
differ
from
the
CFC
MDI,
and
a
list
of
organizations
from
which
patients
and
physicians
may
receive
further
information.

 
Outreach
The
U.
S.
Government
maintains
an
ongoing
dialogue
on
the
MDI
transition
with
a
range
of
stakeholder
organizations
(
pharmaceutical
companies,
public
health
organizations,
and
patient
and
provider
advocacy
organizations).
USEPA
and
USFDA
participate
in
meetings
of
the
US
Stakeholders
Group
on
the
MDI
Transition,
which
meets
under
the
auspices
of
the
American
Lung
Association.

In
addition
to
the
activities
conducted
by
IPAC,
individual
companies
in
the
pharmaceutical
industry
promote
respiratory
education
in
many
ways.
MDI
companies
often
play
a
supporting
role
in
the
development
of
respiratory
symposia.
MDI
pharmaceutical
companies
assist
medical
professionals
through
in­
service
education
programs,
and
by
providing
reprints
of
articles
and
reports,
as
well
as
copies
of
educational
aids
for
distribution
to
patients.
Finally,
MDI
companies
support
respiratory
patient
organizations
through
financial
grants
and
the
distribution
of
educational
aids.

Advertisements
and
other
promotional
materials
are
placed
in
medical
journals
and
circulated
to
prescribing
physicians
by
pharmaceutical
companies
to
heighten
medical
professionals
awareness
of
new
respiratory
care
products
on
the
market,
including
MDIs
and
DPIs.

International
professional
associations
such
as
the
American
Thoracic
Society
12
(
ATS),
the
American
Academy
of
Allergy,
Asthma,
and
Immunology
(
AAAAI),
and
the
European
Respiratory
Society
(
ERS)
support
medical
professionals
active
in
the
treatment
of
asthma
and
COPD.
These
associations
publish
medical
journals,
reports
and
newsletters
and
organize
medical
congresses.
These
activities
are
designed
to
inform
medical
professionals
about
the
management
of
asthma
and
COPD,
and
the
range
of
treatment
options
available
for
their
patients.

Addressing
Economic
Barriers
To
facilitate
the
transition
away
from
CFC
based
salbutamol
MDIs,
a
number
of
U.
S.
pharmaceutical
companies
are
creating
programs
to
distribute
free
or
low
cost
HFA
based
alternatives
to
underserved
populations.
GSK
has
established
a
"
Bridges
to
Access"
program
which
provides
GSK
drugs
at
very
low
cost
to
lower
income
individuals
and
families.
In
addition,
GSK's
"
Orange
Card
Program"
and
the
"
Together
Rx"
program
offer
eligible
Medicare
patients
the
ability
to
purchase
drugs
at
significantly
reduced
prices.
Lastly,
GSK
intends
to
annually
distribute
2
million
VENTOLIN
HFA
MDIs
to
physicians
as
samples.
A
second
major
pharmaceutical
company,
Schering
Plough,
established
the
"
SP
Cares"
program,
which
is
similar
to
GSK's
Bridges
to
Access
program
to
distribute
free
drugs,
including
PROVENTIL
HFA,
to
low­
income
uninsured
patients.
These
patient
assistance
programs
have
the
potential
to
alleviate
difficulties
that
lower
income
patients
may
have
in
obtaining
the
higher­
priced
salbutamol
HFA
MDIs.
These
activities
were
factored
into
the
USFDA
determination
that
salbutamol
CFC
MDIs
will
no
loner
be
"
essential"
as
of
the
end
of
2008
and
represent
significant
progress
in
the
transition
away
from
CFCs
for
essential
uses
in
the
United
States.

Explain
why
alternatives
and
substitutes
are
not
sufficient
or
appropriate
to
eliminate
the
proposed
use.

MDIs
possess
numerous
characteristics
that,
taken
together,
set
them
apart
from
other
inhalation
delivery
systems.
MDI
propellants
provide
the
energy
needed
for
drug
delivery
independent
of
any
external
power
source
or
extra
inspiratory
effort
on
the
part
of
the
patient.
In
MDIs,
the
delivered
dose
depends
significantly
on
the
metering
valve
and
formulation,
not
entirely
on
patient
inspiration.
A
patient
who
must
take
multiple
medications
can
operate
a
variety
of
MDIs
using
the
same
technique.
MDIs
provide
very
good
protection
from
atmospheric
humidity
and
patient
exhalation.
MDIs
can
be
used
for
the
inhalation
of
all
of
the
most
commonly
used
respiratory
medications
and
are
widely
available
for
use
with
these
medications.
They
can
be
adapted
to
meet
the
needs
of
special
patient
populations,
including
young
children
and
infants.

Although
seven
MDIs
with
an
alternative
(
non­
CFC)
propellant
are
available
in
the
U.
S.,
these
products
represent
only
a
fraction
of
the
many
drugs
currently
13
available
in
an
MDI
format.
USFDA
regulations
published
in
2002
describe
the
criteria
that
the
Agency
uses
to
determine
when
it
is
appropriate
to
remove
the
essential
use
designation
from
products
that
use
ozone­
depleting
substances.
One
element
of
these
criteria
is
the
availability
of
at
least
two
alternatives
for
a
given
use.
In
some
instances,
such
as
the
essential
use
designation
for
salbutamol
MDIs,
there
are
at
least
two
alternatives
available
to
patient
and,
therefore,
the
USFDA
established
a
date
for
a
ban
on
the
sale
of
CFC
salbutamol
MDIs.
While
other
CFC­
free
MDIs
may
be
introduced
in
the
next
few
years,
it
is
clear
that
CFC
MDIs
will
still
be
vital
for
the
treatment
of
asthma
and
COPD
in
the
U.
S.
for
the
near
future.

The
1993/
94
UNEP
Technical
Options
Report
lists
reasons
why
the
MDI
is
a
vital
therapy
option.
These
reasons
remain
pertinent
today:

Nebulizers
(
1993/
94
UNEP
Technical
Options
Report,
p.
49)

 
Most
nebulizers
"
require
a
source
of
electricity
or
compressed
gas,
and
are
very
bulky
and
complicated
to
set
up
and
use."
 
Currently
available
hand­
held
nebulizers
are
"
inefficient."
 
Dose
reproducibility
in
nebulizers
"
is
not
reliable."
 
Electric
nebulizers
require
"
10­
20
minutes
to
deliver
a
dose."

Oral
Medication
(
1993/
94
UNEP
Technical
Options
Report,
p.
50)

 
Oral
medication
usually
produces
"
more
side
effects
than
inhaled
medication."
 
Some
drugs
which
are
effective
by
inhalation
"
are
not
absorbed
as
oral
therapy."
 
Treatment
guidelines
"
have
favoured
a
move
from
oral
to
inhaled
route
for
the
treatment
of
respiratory
diseases."

Injectable
Therapy
(
1993/
94
Technical
Options
Report,
p.
50)

 
Injectable
therapy
"
is
not
practical
for
general
use
in
ambulatory
patients
and
is
therefore
reserved
for
the
treatment
of
hospitalized
patients."

Dry
Powder
Inhalers
(
1993/
94
UNEP
Technical
Options
Reports,
pp.
48­
49)

 
DPIs
are
"
difficult
for
patients
with
low
inspiratory
flow
rates,
"
e.
g.
small
children,
COPD
patients,
and
asthmatics
suffering
from
an
acute
asthma
attack.
 
DPIs
require
"
special
packaging
for
use
in
humid
climates."
 
Patient
acceptance
of
DPIs
"
is
not
uniform."
14
Describe
how
MDI
manufacturers
or
distributors
differentiate
the
packaging
of
non­
CFC
MDIs
from
CFC­
driven
MDIs
and
describe
what
marketing
strategies
are
being
taken
to
assure
that
their
non­
CFC
MDIs
are
used,
and
describe
the
steps
that
companies
applying
for
essential
use
exemptions
have
taken
to
obtain
approval
for
CFC­
free
alternatives
in
their
domestic
and
export
markets.

MDI
companies
have
and
will
continue
to
differentiate
the
packaging
for
CFCfree
MDIs
from
the
packaging
of
CFC
MDIs
through
the
use
of
shapes,
sizes,
colors,
trademarks,
logos,
and
other
design
features.
In
addition,
leaflets
have
been
and
will
be
included
in
the
packages
containing
CFC­
free
MDIs
which
inform
patients
of
the
differences
between
the
CFC­
free
MDI
and
the
CFC
MDI.
These
steps
have
been
and
will
continue
to
be
taken
in
accordance
with
relevant
regulations
of
the
U.
S.
FDA
(
for
example,
21
Code
of
Federal
Regulations
(
CFR)
Part
201
(
dealing
with
labeling
requirements
for
drugs)
and
Part
314
(
dealing
with
approval
of
new
drugs).
Also,
all
CFC
MDIs
sold
in
the
U.
S.
carry
a
USEPA
notification
that
the
contents
of
the
MDI
includes
CFCs.

To
encourage
doctor
and
patient
acceptance
and
use
of
CFC­
free
MDIs,
MDI
companies
in
the
U.
S.
will
undertake
national
promotional
campaigns
that
include,
among
other
things,
meetings
with
and
letters
to
health
care
professionals,
information
booths
at
medical
conferences,
advertisements,
and
distribution
of
educational
materials
introducing
these
products
into
the
market.
These
steps
will
be
taken
in
accordance
with
relevant
regulations
of
USFDA.

Describe
what
steps
have
been
taken
to
ensure
that
companies
manufacturing,
distributing,
or
selling
CFC
MDIs
and
non­
CFC
alternatives
do
not
engage
in
false
and
misleading
advertising
targeted
at
non­
CFC
alternatives
or
CFC
MDIs.

The
regulations
of
the
USFDA
prohibit
advertisements
which
are
false,
lacking
in
fair
balance,
or
otherwise
misleading
(
21
CFR
202(
e)(
5)).
An
advertisement
shall
be
so
deemed
if,
for
example,
it
contains
a
"
representation
or
suggestion,
not
approved
or
permitted
for
use
in
the
labeling,
that
a
drug
is
better,
more
effective,
useful
in
a
broader
range
of
conditions.
.
.
than
has
been
demonstrated
by
substantial
evidence
or
substantial
clinical
experience.
.
."
(
21
CFR
202.1(
e)(
6)(
i)).
The
USFDA
has
a
variety
of
means
at
its
disposal
to
enforce
this
requirement.
See
generally
sections
301,
502,
and
505
of
the
Federal
Food,
Drug,
and
Cosmetic
Act
(
21
U.
S.
C.
351,
352,
and
355)
and
21
CFR
Parts
202
and
314.
U.
S.
Federal
regulations
may
be
accessed
at
http://
www.
access.
gpo.
gov/
su_
docs/
index.
html.

Describe
what
steps
have
been
taken
to
ensure
that
companies
applying
for
MDI
essential
use
exemptions
participate
in
regulatory
proceedings
with
a
view
toward
legitimate
environmental,
health
and
safety
concerns.
15
FDA
regulations
governing
participation
in
regulatory
proceedings
generally
prohibit
any
company,
including
any
MDI
company,
from
advancing
environmental,
health
and
safety
concerns
that
are
illegitimate,
or
from
otherwise
engaging
in
conduct
that
misleads
or
obfuscates.
These
regulations
require,
among
other
things,
that:

 
"
All
submissions
to
the
Dockets
Management
Branch
[
of
the
USFDA]
are
representations
that,
to
the
best
of
the
knowledge,
information,
and
belief
of
the
person
making
the
submission,
the
statements
made
in
the
submission
are
true
and
accurate.
All
submissions
are
subject
to
the
False
Reports
to
the
Government
Act
(
18
U.
S.
C.
1001)
under
which
a
willfully
false
statement
is
a
criminal
offense"
[
21
CFR
§
10.20(
i)];

 
Any
company
filing
a
"
citizen
petition"
with
the
USFDA
must
certify
that
the
petition
"
includes
representative
data
and
information
known
to
the
petitioner
which
are
unfavorable
to
the
petition"
[
21
CFR
§
10.30(
b)];
and
 
Knowingly
and
willingly
making
a
materially
false
statement
or
representation
at
a
hearing
that
is
part
of
a
USFDA
rulemaking
process
is
a
felony
under
U.
S.
criminal
law
[
18
U.
S.
C.
1001(
a)].

8.
Assure
that
each
company
requesting
essential
use
allocations
has
fully
complied
with
Decision
VIII/
10.1
to
demonstrate
ongoing
research
and
development
of
alternatives
to
CFC
MDIs
with
all
due
diligence
and/
or
collaborate
with
other
companies
in
such
efforts.
(
Decision
VIII/
10,
par.
1)

All
companies
requesting
essential
use
exemptions
submitted
information
to
the
U.
S.
government
demonstrating
their
ongoing
research
and
development
of
alternatives
to
CFC
MDIs.

9.
Describe
the
steps
to
minimise
emissions
of
CFCs
during
the
manufacture
of
the
essential
use
products.
(
Decision
IV/
25,
pars.
1(
b)(
i),
2
and
3(
b);
Decision
VI/
9,
par.
4;
and
Decision
VIII/
10,
pars.
6
and
7)

The
waste
minimization
strategies
employed
in
the
manufacture
of
MDIs
include:

 
Use
of
a
vapor
return
hose
Vapor
return
hoses
minimize
emissions
during
the
transfer
of
16
CFCs
from
tank
trucks
to
on­
site
storage
tanks.
These
hoses
ensure
that
CFC
vapor
from
the
top
of
the
storage
tank
flows
back
into
the
delivery
vehicle
rather
than
being
vented
to
the
atmosphere.

 
Trucks
and
canisters
dedicated
to
a
single
material
Delivery
trucks
and
canisters
are
dedicated
to
a
single
type
of
material.
Refilling
of
a
truck
or
canister
results
in
reduced
emissions
through
emission­
controlled
sampling
and
testing
of
the
refilled
truck
or
canister
for
quality
and
purity
of
the
CFC.
The
need
to
vent
and
clean
multiple­
use
trucks
and
canisters
is
eliminated,
thereby
decreasing
associated
emissions.

 
Installation
of
permanent,
hard
piping
Temporary,
flexible
hosing
for
CFC
transfer
is
replaced
with
permanent,
hard
piping.
The
piping
reduces
CFC
vapor
emission
because
it
does
not
need
to
be
drained,
disconnected,
or
vented
between
runs.

 
Detection
and
prevention
of
pump
failure
Electronic
sensors
and
automatic
valves
are
installed
in
order
to
close
off
and
isolate
a
pump
in
the
event
of
pump
failure.
Listening
devices
are
also
installed
to
detect
imminent
pump
failure.

 
Detection
and
prevention
of
leaks
Inspection
and
maintenance
programs
are
employed
to
minimize
the
risk
of,
and
promptly
detect
and
remedy,
leaks
in
transfer
networks.

 
Minimization
of
mixing
vessel
waste
material
The
blending
of
CFCs
and
pharmaceutical
active
ingredient(
s)
results
in
an
extremely
small
amount
of
CFC­
containing
waste
material.
A
process
has
been
developed
to
minimize
this
waste
product.

 
Destruction
or
reclamation
of
CFC­
containing
waste
material
CFC­
containing
waste
material
from
blending
and
cleaning
operations
is
destroyed.
The
possibility
of
reclaiming
the
CFCs
in
this
waste
material
is
being
explored.

 
Minimization
of
leaks
during
blending
Seals
on
blending
vessels
have
been
redesigned
and
improved
to
minimize
emissions
during
the
formulation
blending
process.
Hermetically
sealed
vessels
are
drained
and
cleaned
without
venting
to
the
environment.
Programs
are
in
place
to
check
for
17
leaks
during
the
blending
process.

 
Replacement
of
rubber
elastomers
in
MDIs
New
elastomers
have
been
employed
to
reduce
the
number
of
rejected
lots
and
the
leak
rate
of
MDIs.

 
In­
line
stainless
steel
filters
CFC
filters
are
used
more
efficiently
and
replaced
less
frequently,
thereby
reducing
the
release
of
CFCs
during
each
filter
change.

 
Special
gassing
adapters
Gassing
adapters
specially
designed
for
the
MDI
minimize
the
release
of
propellant
during
the
filling
of
each
MDI
canister.

 
Use
of
CFC­
free
solvents
CFC­
free
solvents
are
used
for
many
elements
of
the
cleaning
process.

10.
Describe
the
steps
being
taken
to
provide
a
continuity
of
supply
of
asthma
and
chronic
obstructive
pulmonary
disease
treatments
to
importing
non­
Article
5(
l)
countries,
Article
5(
l)
countries
and
CEIT.
Also
describe
the
steps
being
taken
by
companies
to
assist
their
MDI
manufacturing
facilities
in
Parties
operating
under
Article
5(
l)
and
CEIT
in
upgrading
the
technology
and
capital
equipment
needed
for
manufacturing
non­
CFC
asthma
and
chronic
obstructive
pulmonary
disease
treatments.
(
Decision
VIII/
10,
pars.
9
and
10)

Many
U.
S.
pharmaceutical
companies
have
a
multinational
presence,
and
have
introduced
CFC­
free
alternatives
in
other
countries.
As
reformulation
programs
are
completed,
and
necessary
regulatory
approvals
secured,
CFC­
free
alternatives
will
be
introduced
in
both
domestic
and
export
markets.

III
Substantiation
of
Volumes
1.
Please
indicate
below
the
actual
or
estimated
quantities
of
CFCs
used
in
years
prior
to
the
first
year
for
which
an
exemption
is
requested.

CFCs
Used
for
MDIs
Prior
to
Nomination
(
metric
tonnes)

Ozone
Depleting
Substance
1993
1994
1995
CFC­
l1,
12,
113,
114
(
aggregate)
2981.55
3044.61
3300.2
18
Data
for
years
1995­
2006
are
provided
in
the
U.
S.
Reporting
Accounting
Framework
for
Essential
Uses
which
is
provided
to
the
Secretariat
on
an
annual
basis.

2.
For
the
nominated
quantities
intended
for
use
in
MDIs
for
export,
assure
that
the
Secretariat's
list
of
CFC
MDI
active
ingredients
and/
or
category
of
products
determined
to
be
non­
essential
by
an
importing
Party
has
been
consulted,
and
that
none
of
the
volumes
requested
shall
be
used
for
items
posted
on
that
list.

No
nominated
quantities
will
be
used
for
a
product
determined
to
be
nonessential
by
an
importing
Party.

3.
Provide
details
of
the
management
of
the
stockpile
and
any
surplus.
(
Decision
IV/
25,
par.
1(
b)(
ii))

The
USFDA
examines
data
on
holdings
of
CFCs
and
recommends
adjustments
to
the
amounts
nominated
and
to
the
amounts
subsequently
allocated
to
reflect
the
need
for
a
cushion
of
a
one
year
operational
supply.
The
Montreal
Protocol's
Technology
and
Economic
Assessment
Panel
(
TEAP)
has
recommended
a
12­
month
level
of
reserves
as
reasonable
to
guard
against
unforeseen
events.
Decision
XVI/
12,
taken
by
the
Parties
at
their
Sixteenth
Meeting
in
November
2004,
instructed
nominating
countries
to
"
give
due
consideration
to
existing
stocks,
whether
owned
or
agreed
to
be
acquired
from
a
metered­
dose
inhaler
manufacturer,
of
banked
or
recycled
controlled
substances
as
described
in
paragraph
1(
b)
of
decision
IV/
25,
with
the
objective
of
maintaining
no
more
than
one
year's
operational
supply."
Any
amounts
nominated
by
the
Party
reflect
the
level
of
essential
need
in
accordance
with
Decision
XVI/
12
taking
into
account
the
availability
of
recycled
and
stockpiled
ODS.
The
calculation
of
a
one
year's
operational
supply
includes
both
pre­
1996
CFCs
and
essential
use
CFCs.

4.
Provide
details
of
the
existing
stock
of
pharmaceutical­
grade
CFCs
(
preand
post­
1996)
held
by
the
Party
requesting
an
essential
use
exemption,
describing
the
quantity
(
metric
tonnes),
the
quality
and
the
availability
for
the
year
prior
to
the
nomination.
Describe
how
this
stockpile
will
be
utilised
in
coming
years.
(
Decision
IV/
25,
par.
1(
b)(
ii)
and
Decision
XVI/
12,
par.
3)

Data
on
aggregate
stocks
of
CFCs
held
by
MDI
companies
will
be
provided
with
the
2005
accounting
framework
under
separate
cover.

5.
Confirm
that
the
nominating
Party
has
given
due
consideration
to
the
following.
That:
19
a.
Each
company's
existing
stock
of
pharmaceutical­
grade
CFCs
(
including
CFCs
the
company
possesses
or
has
title
to,
preand
post­
1996)
aims
not
to
exceed
one
year's
operational
supply
(
the
amount
used
by
the
company
to
produce
CFC
MDIs
in
the
preceding
year);

b.
The
Party's
aggregate
stocks
of
pharmaceutical­
grade
CFCs
(
pre­
and
post­
1996)
aim
not
to
exceed
one
year's
operational
supply
for
that
Party;

c.
The
Party's
nomination
has
been
reduced,
if
necessary,
with
the
objective
of
the
Party's
aggregate
stocks
of
available
preand
post­
1996
pharmaceutical­
grade
CFCs
not
exceeding
one
year's
operational
supply;
and
d.
All
available
pre­
1996
stockpiles
have
been,
or
will
be,
depleted
by
companies
before
drawing
on
essential
use
quantities
and
thereby
assure
that
pre­
1996
stockpiles
are
taken
into
account
in
making
essential
use
requests.
(
Decision
IV/
25,
par.
1(
b)(
ii)
and
Decision
XVI/
12,
par.
3)

A
description
of
the
how
the
United
States
treats
stocks
is
provided
above.
The
United
States
aims
to
ensure
no
more
than
a
one
year
operational
supply
of
stocks
(
aggregate
pre
and
post
1996)
available
to
MDI
companies
and
makes
reductions
to
the
amount
of
CFCs
nominated
and
allocated
to
reflect
this
calculation
in
accordance
with
the
language
in
Decision
IX/
6
and
related
decisions.
20
IV.
Reporting
Accounting
Framework
for
Essential
Uses
Other
than
Laboratory
and
Analytical
Applications
Accounting
framework
to
be
forwarded
to
the
Ozone
Secretariat
under
separate
cover
after
January
31,
2006.
