Appendix II

DEVICE MASTER FILE FOR MEDICAL DEVICES OTHER THAN IN VITRO

DIAGNOSTIC MEDICAL DEVICES

Note: The manufacturer shall submit the duly signed and notarized information pertaining to
Medical Device in the following format. All information/reports/data should be in English only.
It is expected that the information submitted in the form of hard copy shall also be submitted in
the form of soft copy.

The dossier shall have an index listing the details of the documents produced as requested
hereunder and shall reflect the page numbers

1.0 EXECUTIVE SUMMARY (Not more than three A4 size pages):

An executive summary shall be provided by the manufacturer and
shall contain:
1.1 Introductory
descriptive
information on the
medical device, the
intended use and
indication for use,
Class of Device, novel
features of the device
(if any), Shelf Life of
the Device and a
synopsis on the
content of the dossier
(not more than 500
words).
1.2 Information
regarding
Sterilization of the
Device (whether it is
sterile or Non-sterile;
if sterile, mode of
sterilization)

1.3 Risk Management

Plan, Risk Analysis,
evaluation and control
documents
1.4 Clinical Evidence and
evaluation (if
applicable).
1.5 Regulatory status of
the similar device in
 India (Approved or
New Device)

1.6 Design Examination

Certificate,
Declaration of
Conformity, Mark of
Conformity
Certificate, Design
Certificate
(if applicable). Copy
of such certificate(s)
shall be enclosed.
1.7 Marketing History of
the device from the
date of introducing
the device in the
market
1.8 Domestic price of the
device in the currency
followed in the
country of origin.
1.9 List of regulatory
approvals or
marketing clearance
obtained (Submit
respective copies of
Approval Certificates)

Country Approved Approved Composition Class Date of

Indication Shelf life and/or of First
Material of Device Approval
Construction

USA

Australia

Japan

Canada

European Union
Others*
Others*-Optional

Status of market clearance pending, rejected or withdrawn

Regulatory Intended Indication Registration Reason for

Agency of use for use status and rejection/withdrawal,
the date if any
country

1.10 Safety and performance related information on the device:

a. Summary of reportable events and field safety corrective action from the date of introduction

For Serious Adverse event

S. Serious Adverse Duration Number of the Total Units Lot/Batch

No. Event SAE sold No.
(SAE) From To reported

For Field Safety Corrective Action (FSCA)

Date of FSCA Reason for FSCA Countries where Description of the

FSCA was conducted action taken
b. If the device contains any of the following then describe information on
the following need to be provided.
1. Animal or human cells
tissues and/or
derivatives there
rendered non-viable
(e.g. Porcine Heart
Valves)
2. Cells, tissues and/or
derivatives of microbial
recombinant origin
(e.g. Dermal fillers
based on Hyaluronic
acid derived from
bacterial fermentation
process)
3. Irradiating components,
ionizing or non ionizing
2.0 DEVICE DESCRIPTION AND PRODUCT SPECIFICATION,
INCLUDING VARIANTS AND ACCESSORIES

2.1 Device Description

The dossier should contain the following descriptive information for
the device:
a) A general description
including its generic
name, model name,
model no., materials of
construction, intended
use, indications,
instructions for use,
contraindications,
warnings, precautions
and potential adverse
effects;
b) the intended patient
population and medical
condition to be
diagnosed or treated
and other
considerations such as
patient selection criteria
c) principle of operation
 or mode of action,
accompanies by
animation or videos (if
available);
d) an explanation of any
novel features;
e) a description of the
accessories, other
medical device and
other product that are
not medical device,
which are intended to
be used in combination
with it and it should
also be clarified
whether these
accessories or device
are supplied as a system
or separate
components;
f) a description or
complete list of the
various configurations
or variants of the device
that will be made
available;
g) a general description of
the key functional
elements, e.g. its parts
or components
(including software if
appropriate), its
formulation, its
composition, its
functionality and where
appropriate, this will
include:
labeled pictorial
representations (e.g.
diagrams, photographs,
and drawings), clearly
indicating key parts or
components, including
sufficient explanation
to understand the
drawings and diagrams;
h) a description of the
materials incorporated
into key functional
elements and those
making either direct
contact with a human
body or indirect contact
with the body, e.g.,
during extracorporeal
circulation of body
fluids. Complete
chemical, biological
and physical
characterization of the
material (s) of the
medical device;
i) for medical devices
intended to emit
ionizing radiation,
information on
radiation source (e.g.
radioisotopes) and
the material used for
shielding of
unintended, stray or
scattered radiation from
patients, users and other
persons shall be
provided.
2.2 Product Specification The dossier should contain a list of the features,
dimensions and performance attributes of the
medical device, its variants and accessories, that
would typically appear in the product
specification made aver to the end user, e.g. in
brochures, catalogues etc.

2.3 Reference to predicate and/or previous generations of the device

Where relevant to demonstrating conformity to the Essential Principles,
and to the provision of general background information, the dossier should
contain an overview of:

a) the manufacturer’s
previous generation(s)
of the device, if such
exist; and/or
b) Predicate devices
 available on the local
and international
markets.
c) Comparative analysis to
prove substantial
equivalence to the
predicate device(s) as
claimed.
3.0 LABELLING

The dossier should typically contain a complete set of labeling associated

with the device as per the requirements of Chapter VI of these rules.
Information on labeling should include the following:-
(a) Copy of original label of the device, including accessories if any,
and its packaging configuration;
(b) Instructions for use (Prescriber’s manual);
(c) Product brochure; and
(d) Promotional material.
4.0 DESIGN AND MANUFACTURING INFORMATION

4.1 Device Design The dossier should contain information to allow

a reviewer to obtain a general understanding of
the design stages applied to the device. The
information may take the form of a flow chart.
Device design valid data should be submitted.

4.2 Manufacturing The dossier should contain information to allow

Processes a reviewer to obtain a general understanding of
the manufacturing processes. The information
may take the form of a process flow chart
showing, an overview of production,
manufacturing environment, facilities and
controls use for manufacturing, assembly, any
final product testing, labelling & packaging and
storage of the finished medical device. If the
manufacturing process is carried out at multiple
sites, the manufacturing activities at each site
should be clearly specified.

5.0 ESSENTIAL (i) The dossier should contain the following:-

PRINCIPLES (EP) (a) the essential principles;
CHECKLIST (b) whether each essential principle applies to the
device and if not, why not;
(c) the method used to demonstrate conformity
with each essential principle that applies;
(d) a reference for the method employed (e.g.,
 standard); and
(e) the precise identity of the controlled
document that offers evidence of conformity
with each method
used.
(ii) Methods used to demonstrate conformity
may include one or more of the following:
(a) conformity with standards as referred to in
rule 7;
(b) conformity with an in-house test method;
(c) the evaluation of pre-clinical and clinical
evidence;
(d) comparison to a similar device already
available on the market.
(iii) The essential principles checklist should
incorporate a cross-reference to the location of
such evidence both within the full technical
documentation held by the manufacturer and
within the dossier. A template for a checklist is
shown in as under:

A template for a checklist is shown in as under

Essential Relevant Specification/standard Complies Document

Principle Yes/No Sub-clause/reference Yes/No Reference
Justification
and/or
comments

6.0 RISK ANALYSIS AND The dossier should contain a summary

CONTROL SUMMARY of the risks identified during the risk
analysis process and how these risks
have been controlled to an acceptable
level. This risk analysis should be
based on recognized standard s e.g.
ISO 14971 and be part of the
manufacturer’s risk management plan
based on complexity and risk class of
the device. The technique used to
analyze the risk must be specified, to
ensure that it is appropriate for the
medical device and risk involved. The
 risks and benefits associated with the
use of the medical device should be
described. The risk analysis mitted
shall have periodic updating of the
risks identified as per risk management
plan.
7.0 PRODUCT VERIFICATION AND VALIDATION of Medical Device

7.1 General
A) The dossier should contain product verification and validation documentation.
As a general rule, the dossier should summaries the results of verification and
validation studies undertaken to demonstrate conformity of the device with
the Essential Principles that apply to it. Such information would typically
cover wherever applicable:
a) engineering tests;

b) laboratory tests;

c) simulated use testing;

d) any animal tests for

demonstrating feasibility or proof
of concept of the finished device;

e) any published literature

regarding the device or
substantially similar devices.
B) Such summary information may include:

a) Declaration or certificate of
conformity to a recognized
standard and summary of the
data if no acceptance criteria are
specified in the standard;
b) Declaration or certificate of
conformity to a published
standard that has not been
recognized, supported by a
rationale for its use, and summary
of the data if no acceptance
criteria are specified in the
standard;
c) Declaration or certificate of
conformity to a professional
guideline(s), industry method(s),
or in-house test method(s),
supported by a rationale for its
use, a description of the method
used, and summary of the data in
sufficient detail to allow
assessment of its adequacy;
d) a review of published literature
regarding the device or
substantially similar devices.

C) In addition, where applicable to the device, the dossier should contain detailed
information on:
a) biocompatibility studies data as
per recognized standards e.g. ISO
10993 requirements

b) medicinal substances
incorporated into the device,
including compatibility of the
device with the medicinal
substance
c) biological safety of devices
incorporating animal or human
cells, tissues or their derivatives;

d) sterilization;

e) software verification and

validation;

f) animal studies that provide direct

evidence of safety d performance
of the device, especially when no
clinical
investigation of the device was
conducted;

g) clinical evidence.

D) Detailed information will describe test design, complete test or study

protocols, methods of data analysis, in addition to data summaries and test
conclusions. Where no new testing has been undertaken, the dossier should
incorporate a rationale for that decision, e.g. biocompatibility testing on the
 identical materials was conducted when these were incorporated in a previous,
legally marketed version of the device. The rationale may be incorporated into
the Essential Principle checklist.
7.2 Biocompatibility i). The dossier should contain a list of
all materials in direct or indirect
contact with the patient or user.
ii).Where biocompatibility testing has
been undertaken (as per recognized
standards e.g. ISO 10993) to
characterize the physical, chemical,
toxicological and biological response
of a material, detailed information
should be included on the tests
conducted, standards a end, test
protocols, the analysis of data and the
summary of results. At a minimum,
tests should be conducted on samples
from the finished, sterilized (when
supplied sterile) device.
iii).Depending on nature and intended
use of the investigational medical
device, device performance for its
actions (including mechanical,
electrical, thermal, radiation and any
other of this type) and safety should be
assessed in healthy or diseased animal
model (intended to be treated by such
medical device), as appropriate,
demonstrating reaction to active and
basic parts of the devices on absolute
tissue, local tissue as well as whole
organ, clearly recording local, general
and systemic adverse reactions, risks
or potential risks and performance of
device in line with intended use.
Wherever possible, histopathology,
pathophysiology and path anatomy
should be carried out.
iv). ISO-10993, Biological Evaluation
of Medical Devices, should be
followed for conducting bio-
compatibility study for invasive
medical devices should be carried out.
A report of biocompatibility study
along with rationale for selecting
specific tests carried out should be
 prepared including conclusion of the
study.
7.3 Medicinal Substances Where the medical device incorporates
a medicinal substance(s), the dossier
should provide detailed information
concerning that me final substance, its
identity and source, the intended
reason for its presence, and its safety
and performance in the intended
application.

7.4 Biological Safety i). The dossier should contain a list of

all materials of animal or human origin
used in the device. For these materials,
detailed information should be
provided concerning the selection of
sources/donors; the harvesting,
processing, preservation, testing and
handling of tissues, cells and
substances of such origin should also
be provided Process validation results
should be included to substantiate that
manufacturing procedures are in place
to minimize biological risks, in
particular, with regard to viruses and
other transmissible agents. TSE/BSE
Certificates should also be submitted.
ii). The system for record-keeping to
allow traceability from sources to the
finished device should be fully
described
7.5 Sterilization i). Where the device is supplied sterile,
the dossier should contain the detailed
information of the initial sterilization
validation in lauding sterilizer
qualification, disburden testing,
pyrogen testing, testing for sterilant
residues (if applicable) and packaging
validation as per recognized standards
e.g. ISO 11607.
Typically, the detailed validation
information should include the method
used, sterility assurance level attained,
standards applied, the sterilization
protocol developed in accordance with
 recognized standards e.g. ISO 11137,
and a summary of results.
ii) Evidence of the ongoing
revalidation of the process should also
be provided. Typically this would
consist of arrangements for, or
evidence of, revalidation of the
packaging and sterilization processes.
7.6 Software Verification and The dossier should contain information
Validation on the software design and
development process and evidence of
the validation of the software, as used
in the finished device. This
information should typically include
the summary results of all verification,
validation and testing performed both
in-house and in a simulated or actual
user environment prior to fin l release.
It should also address all of the
different hardware configurations and,
where applicable, operating systems
identified in the labeling.

7.7 Animal Studies i). Where studies in an animal model

have been undertaken o provide
evidence of conformity with the
Essential Principles related to
functional safety and performance,
detailed information should be
contained the dossier.
ii). The dossier should describe the
study objectives, methodology, results,
analysis and conclusions and document
conformity with good Laboratory
Practices. The rationale (and
limitations) of selecting the particular
animal model should be discussed.
7.8 Shelf Life/Stability Data If available, real-time aging data shall
be submitted to support the claimed
shelf life. However, if real-time data is
not available, accelerated stability data
shall be submitted to support the
claimed shelf life. Such a provisional
claimed shelf life may be approved
provided that the manufacturer
immediately initiates real-time stability
 testing to validate the proposed shelf
life. After completion of the real time
stability analysis, real-time stability
data shall be submitted in support of
the claimed shelf life.
7.9 Clinical Evidence The dossier should contain the clinical
evidence that demonstrates conformity
of the device with the Essential
Principles that apply to it. It needs to
address the elements contained in the
Clinical Investigation, as specified
under the Seventh Schedule. If a
predicate device is available, the
manufacturer needs to submit the
substantial equivalence evaluation
along with relevant published literature
in accordance with these rules.
7.10 Post Marketing Surveillance Data The dossier should contain the Post
(Vigilance Reporting) Marketing Surveillance or Vigilance
Reporting procedures and Data
collected by the manufacturing
encompassing the details of the
complaints received and corrective and
Preventive actions taken for the same.
NOTE:

1. All reports submitted as a part of the dossier should be signed and dated by the
responsible person.
2. Batch Release Certificates and Certificate of Analysis of finished product for minimum 3
consecutive batches should be submitted.
3. All certificates submitted must be within the validity period.
4. Any information which is not relevant for the subject device may be stated as ‘Not
Applicable’ in the relevant Sections/Columns of the above format, and reasons for non-
applicability should be provided.

Place:
Date: Signature of the manufacturer
Name:
Designation:
Seal / Stamp
 Part IV

Information required to be submitted with the Application Form for import

or manufacture of medical devices which does not have predicate device.

A. Data to be submitted along with the application (for medical devices

other than new in vitro diagnostic):-
1 Design Analysis data including, (whichever applicable)-
a. design input and design output documents;
b. mechanical and electrical tests;
c. reliability tests;
d. validation of software relating to the function of the device;
e. any performance tests;
f. in vitro tests.
2 Bio-compatibility tests data, Report of bio-compatibility
tests along with rationale for selecting these tests.
Summary report of the biocompatibility study including
the conclusion of the study.
3 Risk Management data
4 Animal Performance study data;
5 Pilot or Pivotal Clinical Investigation data, including that
carried out in other countries if any;
6 In case, if waiver from clinical investigation is claimed in
accordance with the provisions of Medical Device Rules,
2017, the information or supporting data shall be
submitted.
7 Regulatory status and Restriction on use in other countries
(if any) where marketed or approved
8 Proposed Instruction for use and labels