ANNEX A
 
 
Guidelines for the Preparation of a Product Information File (PIF) for Vapor Products
 
 
1.
Applicants
shall
prepare
an
up-to-date
PIF
which
will
be
submitted
to
the
FDA
as
part
of
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
the documentary requirements for vapor product FERN applications.
 
 
 
2.
The
FDA
shall
review
and
evaluate
the
submitted
PIF
together
with
other
documentary
 
 
 
 
 
 
 
 
 
 
 
 
 
requirements
for
the
processing
of
applications
for
product
marketing
authorization.
 
 
 
 
 
 
 
 
 
 
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
of
vapor
product
refills
and
cartridges,
and
model
electronic
 
 
 
 
 
 
 
 
 
 
 
 
 
delivery device shall have its own PIF.
 
 
4.
Any
changes
in
the
information
in
the
PIF
shall
constitute
a
new
application
for
product
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
marketing authorization.
 
 
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
product
marketing
 
 
 
 
 
 
 
 
 
 
authorization,
consistent
with
the
address
indicated
on
the
primary
or
secondary
 
 
 
 
 
 
 
 
 
 
 
packaging
of
the
vapor
product
refill
and
cartridges
and
electronic
delivery
devices
 
 
 
 
 
 
 
 
 
 
 
 
following FDA guidelines on the packaging and labelling of vapor products.
 
 
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
zero
(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
product
marketing
authorization
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:
 
 
2.1.1
Company name
 
 
2.1.2
Complete address of manufacturing plant
 
 
2.1.3
Contact information
 
 
2.1.4
Copy of valid LTO of manufacturer (for local manufacturer)
 
  
2.1.5
Organizational chart of manufacturing plant
 
 
2.1.6
Production line layout where the product will be manufactured
 
 
2.1.7
List of equipment used for production
 
 
2.2
Manufacturing Process/Procedure for product being registered
 
 
2.3
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
 
 
 
3.1.1
Technical specifications of each ingredient and/or components
 
 
 
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
(for
refills
and
 
 
 
 
 
 
 
 
 
 
 
cartridges)
 
 
4.
PIF Part IV – Quality Data of Finished Product
 
 
4.1
Qualitative and Quantitative Disclosure of Ingredients and/or Components
 
 
4.1.1
For  electronic delivery devices:
 
4.1.1.1
Complete
listing
of
components
describing
the
type
of
 
 
 
 
 
 
 
 
materials and its function.
 
 
4.1.2
For vapor product refills and cartridges
 
 
4.1.2.1
Complete
ingredient
list
of
the
vapor
product
refill
with
their
 
 
 
 
 
 
 
 
 
 
corresponding
function
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
its
genus
and
 
 
 
 
 
 
 
 
 
species.
 
 
 
 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 product.
 
 
4.2.2
Clear photo of the actual product 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
of
the
finished
product
corresponding
to
its
technical
 
 
 
 
 
 
 
 
 
 
specifications
 
 
4.3.3.1
For electronic delivery devices:
 
4.3.3.1.1
Migration of Specific Metals
 
 
4.3.3.2
For vapor products refills and cartridges:
 
4.3.3.2.1
Nicotine content
 
 
4.4
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
 
 
4.5
Product Stability
 
 
 
4.5.1
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.
 
 
 
4.5.1.1
Accelerated stability study; or
 
 
4.5.1.2
Long-term stability study shall be provided.