ANNEX A
 
Guidelines for the Preparation of a Product Information File (PIF) for HTPs
 
 
 
1.
Applicants
shall
prepare
an
up-to-date
PIF
which
will
be
submitted
to
the
FDA
as
part
of
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
the application documents for a FERN.
 
 
 
 
2.
The
FDA
shall
review
and
evaluate
the
submitted
PIF
together
with
other
documentary
 
 
 
 
 
 
 
 
 
 
 
 
 
requirements
for
the
processing
of
applications
for
FERN.
However,
this
does
not
 
 
 
 
 
 
 
 
 
 
 
 
preclude
the
FDA
from
doing
​
ad-hoc
​
PIF
audits
when
required
which
may
occur
with
or
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
without notice.
 
 
 
3.
Each
brand
and
variant/model
of
HTP
refills,
cartridges
and
electronic
delivery
device
 
 
 
 
 
 
 
 
 
 
 
 
shall have its own PIF.
 
 
 
4.
Any changes in the information in the PIF shall constitute a new FERN application.
 
 
 
5.
Electronic
and/or
hard
copies
of
PIFs
shall
be
readily
accessible
at
the
address
of
the
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
marketing
authorization
holder
(MAH)
as
declared
in
the
FERN,
consistent
with
the
 
 
 
 
 
 
 
 
 
 
 
 
address
indicated
on
the
primary
or
secondary
packaging
of
the
HTP
refills
and
cartridges
 
 
 
 
 
 
 
 
 
 
 
 
 
 
and
electronic
delivery
devices
following
FDA
guidelines
on
the
packaging
and
labelling
 
 
 
 
 
 
 
 
 
 
 
 
of HTPs.
 
 
 
6.
The PIF documents shall be written in English.
 
 
 
7.
The PIF shall be arranged according to the format provided under this document.
 
 
8.
The
PIF
shall
be
kept
for
a
minimum
of
ten
(10)
years
after
the
product
has
last
been
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
placed
in
the
market
(i.e.
date
when
the
inventory
reaches
0
at
retail
level)
or
according
to
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
the
company’s
Standard
Operating
Procedure
(SOP),
whichever
provides
for
a
longer
 
 
 
 
 
 
 
 
 
 
 
retention period.
 
 
9.
The
FDA
reserves
the
right
to
request
for
additional
documents
and
product
information,
 
 
 
 
 
 
 
 
 
 
 
 
 
apart
from
the
documents
listed
in
the
specific
guidelines,
needed
during
product
 
 
 
 
 
 
 
 
 
 
 
 
evaluation.
In
such
cases,
the
MAH
shall
be
given
a
sufficient
amount
of
time
ranging
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
from fifteen to sixty (15-60) calendar days, depending on the type of document requested.
 
 
10.
Inconsistencies
between
the
actual
product
and
its
corresponding
PIF
may
result
to
the
 
 
 
 
 
 
 
 
 
 
 
 
 
institution
of
a
legal
action
directed
towards
the
FERN
of
the
subject
product
which
may
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
lead
to
its
cancellation
and
the
corresponding
product
recall
thereof
when
circumstances
 
 
 
 
 
 
 
 
 
 
 
 
so warrant.
 
 
 
 PIF Content
 
 
 
The PIF shall be composed of the following documents:
 
 
1.
PIF Part I – Administrative Documents and Product Summary
 
 
1.1
Administrative Documentation
 
 
1.1.1
Copy of the valid License to Operate (LTO) of the MAH
 
 
1.1.2
In case the MAH is a Trader
 
 
1.1.2.1
Notarized
Manufacturing
Agreement
with
Local
 
 
 
 
 
Manufacturer.
 
 
1.1.2.2
Copy of the valid LTO of the local Manufacturer
 
 
1.1.3
In case the MAH is an Importer:
 
 
1.1.3.1
In
case
the
Foreign
Supplier
is
the
manufacturer
of
the
 
 
 
 
 
 
 
 
 
 
product,
notarized
contract
of
agreement
or
notarized
letter
of
 
 
 
 
 
 
 
 
 
authorization from the manufacturer.
 
 
1.1.3.2
In
case
the
Foreign
Supplier
is
not
the
manufacturer
of
the
 
 
 
 
 
 
 
 
 
 
 
product:
 
 
1.1.3.2.1
Notarized
contract
of
agreement
or
notarized
 
 
 
 
 
 
letter
of
authorization
from
the
Foreign
Supplier
 
 
 
 
 
 
 
and
the
Valid
Supply
Agreement
between
the
 
 
 
 
 
 
 
Foreign Supplier and the Manufacturer; or
 
 
1.1.3.2.2
Valid
tripartite
agreement
between
the
MAH,
 
 
 
 
 
 
Foreign Supplier and the Manufacturer; and
 
 
2.
PIF Part II - Manufacturing Details
 
 
2.1
Details of the Manufacturer of Refill/Cartridge:
 
 
2.1.1
Company name
 
 
2.1.2
Complete address of manufacturing plant
 
 
2.1.3
Contact information
 
 
2.1.4
Organizational chart of manufacturing plant
  
2.1.5
Production line layout where the product will be manufactured
 
 
2.1.6
List of equipment used for production
 
 
2.1.7
Manufacturing Process/Procedure
 
 
2.1.8
Copy of batch coding system for the product being registered
 
 
2.2
Details of the Manufacturer of Device:
 
 
2.2.1
Company name
 
 
2.2.2
Complete address of manufacturing plant
 
 
2.2.3
Contact information
 
 
2.2.4
Organizational chart of manufacturing plant
 
 
2.2.5
Production line layout where the product will be manufactured
 
 
2.2.6
List of equipment used for production
 
 
2.2.7
Manufacturing Process/Procedure
 
 
2.2.8    Copy of batch coding system for the product being registered.
 
 
 
3.
PIF Part III – Quality Data of Raw Material
 
 
3.1
Specifications and Test Methods of Raw Materials of Refill/Cartridge
 
 
3.1.1
Technical specifications of each ingredient and/or component
 
 
3.1.2
Method
of
analysis
corresponding
to
the
technical
specifications
 
 
 
 
 
 
 
 
including the identification test for each ingredient and/or component
 
 
3.1.3
Signed
Certificate
of
Analysis
(COA)
for
each
ingredient
and/or
 
 
 
 
 
 
 
 
 
component corresponding to its technical specifications
 
 
3.1.4
Material safety data sheet (MSDS) of the ingredients
 
 
 
3.2
Specifications and Test Methods of Raw Materials of Device
 
 
3.2.1
Technical specifications of each component
 
 3.2.2
Method
of
analysis
corresponding
to
the
technical
specifications
 
 
 
 
 
 
 
 
including the identification test for each component
 
 
3.2.3
Signed
Certificate
of
Analysis
(COA)
for
each
component
 
 
 
 
 
 
 
 
corresponding to its technical specifications
 
 
3.2.4
Material safety data sheet (MSDS) of the components
 
 
4.
PIF Part IV – Quality Data of Finished Product
 
 
4.1
Qualitative and Quantitative Disclosure of Ingredients and/or Components
 
 
4.1.1
For HTP electronic delivery devices:
 
 
4.1.1.1
Complete
listing
of
components
describing
the
type
of
 
 
 
 
 
 
 
 
materials, their functions, and their countries of origin.
 
4.1.1.2
Narrative
and
summarized
projections
of
nicotine
flux
based
 
 
 
 
 
 
 
 
on
fast
(33mL/s)
and
slow
(17mL/s)
puff
velocities,
at
2s,
4s,
 
 
 
 
 
 
 
 
 
 
 
and
8s,
at
typical
operating
temperatures
of
the
heating
 
 
 
 
 
 
 
 
 
element,
when
used
as
with
the
intended
compatible
HTP
 
 
 
 
 
 
 
 
 
cartridges.
 
 
4.1.2
For HTP refills and cartridges
 
 
4.1.2.1
Complete
ingredient
list
of
the
HTP
refill
with
their
 
 
 
 
 
 
 
 
 
corresponding
function,
gross
weight
(in
grams,
g)
and
 
 
 
 
 
 
 
 
percentage
(%)
content.
Ingredients
shall
be
named
using
the
 
 
 
 
 
 
 
 
 
nomenclatures
from
approved
references,
namely:
(1)
British
 
 
 
 
 
 
 
Pharmacopeia;
(2)
United
States
Pharmacopeia;
(3)
Chemical
 
 
 
 
 
 
 
Abstract
Service.
Botanical
ingredients
shall
be
identified
by
 
 
 
 
 
 
 
 
their genera, species, and specific strain.
 
 
4.1.2.2
Complete
listing
of
components
describing
the
type
of
 
 
 
 
 
 
 
 
materials used and their function.
 
 
4.2
Product Presentation
 
 
 
4.2.1
Clear
facsimile/layout
of
the
immediate
and/or
secondary
packaging
 
 
 
 
 
 
 
 
and
other
informative
materials
that
are
used
(i.e.
inserts,
leaflets,
 
 
 
 
 
 
 
 
 
 
hangtags) for the HTP refill/cartridge and device.
 
 
4.2.2
Clear
photo
of
the
actual
products
showing
the
principal
display
 
 
 
 
 
 
 
 
 
 
panel.
 
 4.3
Technical
Specifications
of
the
Finished
Product
and
their
Corresponding
 
 
 
 
 
 
 
 
 
Test Methods
 
 
 
4.3.1
Technical specifications of the finished product.
 
 
4.3.2
Test
methods
used
corresponding
to
the
technical
specifications
of
the
 
 
 
 
 
 
 
 
 
 
finished product.
 
 
 
4.3.3
Signed
COA,
by
laboratories
not
owned,
partially
owned,
or
otherwise
 
 
 
 
 
 
 
 
 
 
controlled
by
the
tobacco
industry
or
its
representatives,
of
the
 
 
 
 
 
 
 
 
 
 
finished product corresponding to its technical specifications
 
 
 
4.3.3.1
For HTP electronic delivery devices:
 
 
4.3.3.2.1 Migration of specific metals
 
 
4.3.3.2.2 QC test on device temperature output consistency
 
 
4.3.3.2
For HTP refills and cartridges:
 
 
4.3.3.4.1 Nicotine content
 
 
4.3.3.4.2
Test
for
harmful
and
potentially
harmful
 
 
 
 
 
 
 
constituents
 
(HPHCs)
 
 
4.3.3.4.3 Other chemical substances including trace elements
 
 
4.4
Certificate
of
Analysis
of
Emission
Testing
for
the
US
FDA
panel
of
HPHCs
 
 
 
 
 
 
 
 
 
 
 
 
 
in
tobacco
products,
as
tested
under
the
World
Health
Organization
WHO
 
 
 
 
 
 
 
 
 
 
 
Tobacco
Laboratory
Network
(TobLabNet)
or
Health
Canada
protocols,
as
 
 
 
 
 
 
 
 
 
applicable,
by
laboratories
not
owned,
partially
owned,
or
otherwise
 
 
 
 
 
 
 
 
 
controlled by the tobacco industry or its representatives.
 
 
4.5
Product
Safety
Data
Sheet
following
the
Guidelines
under
the
Globally
 
 
 
 
 
 
 
 
 
 
Harmonized
System
for
the
Classification
and
Labelling
of
Chemicals
 
 
 
 
 
 
 
 
 
(GHS)
Annex
4
–
Guidance
on
the
Preparation
of
Safety
Data
Sheets
(SDS)
 
 
 
 
 
 
 
 
 
 
 
 
 
for refills and cartridges.
 
 
 
4.6
Product Stability
 
 
 
4.6.1
The
stability
study
shall
be
part
of
the
PIF
to
support
the
product’s
 
 
 
 
 
 
 
 
 
 
 
 
 
claimed
shelf-life.
The
stability
study
conducted
on
the
product
may
 
 
 
 
 
 
 
 
 
 
be accelerated or long-term.
 
 4.6.1.1
Accelerated stability study; or
 
 
4.6.1.2
Long-term stability study shall be provided.