FDA CIRCULAR
 
No. ___________
 
 
 
            TO               :
ALL MANUFACTURERS/ TRADERS/ IMPORTERS OF VAPOR
 
PRODUCTS
 
 
 
SUBJECT   :
 
PROCEDURE FOR THE ISSUANCE OF PRE-APPLICATION
 
 
DOCUMENTARY EVALUATION (PADE) VAPOR PRODUCTS
 
SEEKING REGISTRATION UNDER FERN 1 WITH THE
 
CENTER FOR COSMETICS REGULATION AND RESEARCH
 
 
 
I.
BACKGROUND
 
 
Pursuant
to
Republic
Act
No.
11467,
Republic
Act
9711,
and
Executive
 
 
 
 
 
 
 
 
 
 
 
Order
No.
106,
the
Food
and
Drug
Administration
(FDA)
is
mandated
to
regulate
vapor
 
 
 
 
 
 
 
 
 
 
 
 
 
 
products
and
Heated
Tobacco
Products
(HTPs)
consistent
with
evolving
medical,
public
 
 
 
 
 
 
 
 
 
 
 
health,
and
scientific
evidence.
As
such,
the
FDA
has
established
a
regulatory
 
 
 
 
 
 
 
 
 
 
 
 
framework
which
includes
the
issuance
of
marketing
authorizations
for
vapor
products
 
 
 
 
 
 
 
 
 
 
 
prior
to
sale
in
the
Philippines.
Product
authorizations
are
a
crucial
step
in
ensuring
 
 
 
 
 
 
 
 
 
 
 
 
 
 
traceability,
accountability
of
the
product
owner,
and
the
mitigation
of
potential
health
 
 
 
 
 
 
 
 
 
 
 
 
risks of the products sold in the market.
 
 
II.
OBJECTIVE
 
 
This
Circular
is
being
issued
to
provide
the
supplemental
procedures
and
 
 
 
 
 
 
 
 
 
 
 
guidelines
for
the
issuance
of
a
Pre-application
Documentary
Evaluation
(PADE)
 
 
 
 
 
 
 
 
 
 
certificate
as
part
of
the
requirements
for
vapor
product
refills
and
cartridges
under
FDA
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Electronic Registration Number Category (FERN 1) authorization.
 
 
 
III.
SCOPE AND COVERAGE
 
 
This
Circular
shall
apply
to
all
manufacturers,
traders,
and
importers
 
 
 
 
 
 
 
 
 
 
seeking to apply for a FERN 1 certification of their vapor product refills and cartridges.
 
 
IV.
GENERAL GUIDELINES
 
 
1.
Manufacturers,
traders,
and
importers
of
vapor
products
shall
submit
an
application
 
 
 
 
 
 
 
 
 
 
 
for PADE certification with the FDA prior to applying for FERN 1.
 
 
2.
Submissions
for
PADE
documents
shall
be
done
at
least
one
hundred
twenty
(120)
 
 
 
 
 
 
 
 
 
 
 
 
 
calendar
days
prior
to
the
application
for
FERN
1
through
the
FDA
E-portal
system
 
 
 
 
 
 
 
 
 
 
 
 
 
 
for vapor products.
 
 3.
The
FDA
reserves
the
right
to
disapprove
applications
that
are
incomplete
or
are
 
 
 
 
 
 
 
 
 
 
 
 
 
with deliberately redacted data.
 
 
4.
The
Center
for
Cosmetics
Regulation
and
Research
(CCRR)
may
request
for
 
 
 
 
 
 
 
 
 
 
 
specific
research
and
journal
articles
from
the
applicants
in
aid
of
a
more
rigorous
 
 
 
 
 
 
 
 
 
 
 
 
 
 
evaluation.
 
 
5.
The
final
disposition
on
the
evaluations
shall
lie
solely
with
the
Director
General
of
 
 
 
 
 
 
 
 
 
 
 
 
 
 
the FDA upon the recommendation of the Director IV of the CCRR.
 
 
6.
Under
no
circumstances
shall
evaluations
with
favorable
dispositions
be
deemed
as
 
 
 
 
 
 
 
 
 
 
 
an
imprimatur
of
FDA
approval
nor
shall
it
mean
the
approval
of
a
product
claim.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Any
industry
promotion,
advertisement,
or
communication,
explicit
or
implicit,
 
 
 
 
 
 
 
 
 
contrary
to
this
provision
shall
be
grounds
for
immediate
disapproval
of
active
 
 
 
 
 
 
 
 
 
 
 
 
vapor product FERN 1 applications.
 
 
V.
SPECIFIC GUIDELINES
 
 
1.
The Pre-Application Documentary Evaluation shall contain the following parts:
 
 
1.1.
Administrative Data of MAH
 
1.1.1.
Marketing Authorization Holder (MAH)
 
1.1.1.1.
Name
of
MAH
as
reflected
in
the
License
to
Operate
 
 
 
 
 
 
 
 
 
 
(LTO)
 
1.1.1.2.
Declared address of MAH
 
1.1.1.3.
LTO number of MAH
 
1.1.2.
Name
and
address
of
the
manufacturer
(if
MAH
is
not
the
 
 
 
 
 
 
 
 
 
 
 
manufacturer)
 
1.1.2.1.
LTO number (for local manufacturers)
 
1.1.3.
Name and address of the supplier (for imported products)
 
 
1.1.4.
Authorization
for
the
FDA
to
use,
copy,
store,
and
distribute
 
 
 
 
 
 
 
 
 
 
digital
and
physical
copies
of
all
documents
submitted
to
FDA
for
 
 
 
 
 
 
 
 
 
 
 
the
purposes
of
(1)
review
and
evaluation
of
the
application;
(2)
 
 
 
 
 
 
 
 
 
 
 
enforcement;
and
(3)
conduct
of
research
for
the
development
of
 
 
 
 
 
 
 
 
 
 
regulatory
standards
and
public
health
policies.
All
information
 
 
 
 
 
 
 
 
 
and
documents
submitted
to
the
FDA
shall
be
deemed
as
 
 
 
 
 
 
 
 
 
 
Confidential
Information
and
shall
be
protected
in
accordance
 
 
 
 
 
 
 
 
with
the
Data
Privacy
Act
​
with
respect
to
personal
data,
the
 
 
 
 
 
 
 
 
 
 
 
Department
of
Health’s
Freedom
of
Information
Manual,
and
also
 
 
 
 
 
 
 
 
 
in
accordance
with
other
applicable
laws,
rules
and
regulations,
 
 
 
 
 
 
 
 
 
and existing jurisprudence protecting Confidential information
​
.
 
 
Confidential
Information
for
purposes
of
this
Circular
shall
 
 
 
 
 
 
 
 
include
personal
data,
trade
secrets,
intellectual
property,
business,
 
 
 
 
 
 
 
 commercial,
financial,
or
proprietary
information,
or
any
other
 
 
 
 
 
 
 
 
information or date that by its nature should be kept confidential.
 
 
1.1.5.
An
attestation
from
the
manufacturer,
trader,
or
importer
that
the
 
 
 
 
 
 
 
 
 
 
information
contained
in
the
bundle
is
complete,
accurate,
and
 
 
 
 
 
 
 
 
 
unredacted, under the penalties of all relevant legislation.
 
 
1.2.
Data on Raw Materials
 
1.2.1.
Administrative Data and Information
 
1.2.1.1.
Name and address of the manufacturer
 
1.2.1.2.
Name and address of the supplier
 
 
1.2.2.
Chemistry, Manufacturing and Controls
 
1.2.2.1.
General properties
 
1.2.2.2.
Schematic
flow
diagram
and
sequential
procedural
 
 
 
 
 
 
narrative of the manufacturing process
 
1.2.2.3.
Materials used in the manufacture of the components
 
1.2.2.4.
Technical specifications
 
1.2.2.5.
Analytical Procedures
 
 
1.3.
Data on Finished Product
 
1.3.1.
Chemistry, Manufacturing and Control
 
1.3.1.1.
Technical specifications of the product
 
1.3.1.1.1.
Appearance (color, odor, physical state)
 
1.3.1.1.2.
Flammability
 
1.3.1.1.3.
pH
 
1.3.1.1.4.
Viscosity
 
1.3.1.1.5.
Known incompatibilities with other product
 
1.3.1.2.
Qualitative and quantitative composition of the product
 
1.3.1.3.
Compatibility of the ingredients
 
1.3.1.4.
Schematic
flow
diagram
and
sequential
procedural
 
 
 
 
 
 
narrative of the manufacturing process
 
1.3.1.5.
Complete
list
of
equipment
used
during
the
manufacturing
 
 
 
 
 
 
 
 
process
 
1.3.1.6.
Process validation
 
1.3.1.7.
Analytical procedures
 
1.3.1.8.
Validation of analytical procedures
 
1.3.1.9.
Batch analyses
 
1.3.1.10.
Characterization of impurities
 
1.3.1.11.
Packaging Materials Specifications
 
1.3.1.12.
Stability/Shelf life
 
1.3.1.13.
Certificate
of
Analysis
containing
the
manufacturing
date,
 
 
 
 
 
 
 
batch
number,
name
and
signature
of
the
laboratory
 
 
 
 
 
 
 
 
analyst and manager.
 
 1.4.
Toxicological Risk Assessment
 
1.4.1.
Safety Data Sheet (SDS) of the Finished Product
 
1.4.1.1.
In
accordance
with
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
 
 
1.4.2.
Toxicity profile
 
1.4.2.1.
Acute Toxicity Tests
 
1.4.2.1.1.
Acute Oral Toxicity
 
1.4.2.1.2.
Acute Dermal Toxicity
 
1.4.2.1.3.
Acute Inhalation Toxicity
 
1.4.2.2.
Allergy/Sensitization Test
 
1.4.2.3.
Sub-chronic Toxicity Tests
 
1.4.2.4.
Reproduction Effects Studies
 
1.4.2.5.
Teratogenicity Studies
 
1.4.2.6.
Neurotoxicity Studies
 
1.4.2.7.
Mutagenicity Studies
 
1.4.2.8.
Carcinogenicity Tests and Chronic Toxicity in Rats
 
1.4.2.8.1.
In Vitro Studies
 
1.4.2.8.1.1.
Neutral Red Uptake (NRU) Assays
 
1.4.2.8.1.2.
Bacterial Reverse Mutation (Ames) Test
 
1.4.2.8.1.3.
Mouse Lymphoma Assay (MLA)
 
 
1.4.2.9.
Systems Toxicology Studies
 
1.4.2.9.1.
Acute
and
Repeated
Exposure
Studies
with
Human
 
 
 
 
 
 
 
Organotypic Tissues
 
1.4.2.9.2.
ApoE-/- Mouse Switching Study
 
 
1.4.2.10.
Summary of Toxicological Findings
 
 
1.5.
Emission Testing
 
 
Emission
testing
guidelines/requirements
for
vapor
products
shall
 
 
 
 
 
 
 
be implemented three (3) years after the issuance of regulatory guidelines.
 
 
1.6.
Laboratory Competency
 
1.6.1.
A
complete
list
of
relevant
certifications
held
by
the
laboratory
 
 
 
 
 
 
 
 
 
 
conducting the in vitro, in vivo, and systems toxicology studies.
 
1.6.2.
An
attestation
from
the
said
laboratory
of
the
exact
make,
model,
 
 
 
 
 
 
 
 
 
 
 
and
brand
of
the
smoking
robot
used
in
the
conduct
of
the
in
vitro
 
 
 
 
 
 
 
 
 
 
 
 
 
 
studies.
 
1.6.3.
A
complete
declaration
of
interest
of
all
researchers
conducting
 
 
 
 
 
 
 
 
 
the
clinical
and
behavioral
pharmacology
evaluation
and
their
 
 
 
 
 
 
 
 
relevant qualifications and affiliations.
  
VI.
APPROVAL
 
 
Approval
of
the
PADE
shall
mean
that
the
MAH
may
apply
for
FERN
under
the
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
licensing and registration schemes defined in relevant policy instruments of the FDA.
 
 
VII.
FEES
 
 
 
Per submission shall have a fee of Php 50,000.00 plus a legal research fee of 1%.
 
 
 
VIII.
PENALTIES
 
 
Violation
to
any
provisions
of
this
Circular
shall
be
subject
to
the
 
 
 
 
 
 
 
 
 
 
 
 
penalties/sanctions
provided
under
Book
III,
Article
XI
of
the
Rules
and
Regulations
 
 
 
 
 
 
 
 
 
 
 
 
Implementing
Republic
Act
No.
9711,
Republic
Act
No.
11467,
Executive
Order
No.
 
 
 
 
 
 
 
 
 
 
 
 
106 and other penalties provided by other applicable laws.
 
 
IX.
SEPARABILITY CLAUSE
 
If
any
provision
in
this
Circular,
or
application
of
such
provision
to
any
 
 
 
 
 
 
 
 
 
 
 
 
 
circumstances,
is
held
invalid,
the
remainder
of
the
provisions
in
this
Circular
shall
not
be
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
affected.
 
X.
EFFECTIVITY
 
This Circular shall take effect immediately.