Management of Changes to a

Medical Device

Regulatory Affairs
Cochlear Limited

Change Management

Regulatory Position
Cochlears implementation of change management
Change Scope
The concept of significant vs non-significant change
Approval requirements for significant changes
Differences between jurisdictions
Reference material

Key Principles
A device shall have clinical benefits
A device shall be as safe as
practicable
The benefit/risk ratio of a device
should be larger than one

The focus of Regulatory Controls

Regulatory Audit
Quality Management System

Premarket
Classification Conformity Assessment

Essential Principles
Standards
Device Specification
Design Control
Design verification and validation
Clinical Evidence
STED
Declaration of conformity

Risk Management
Postmarket Surveillance
Conformity Assessment (continued)

Registration
Listing

Adverse Event Reporting

Complaint Management
Maintenance and Service
Corrective and Preventive Actions
Postmarket clinical follow up

New products to the market,

while recognising that changes occur,

Regulatory Baseline

Medical Devices are approved on the basis

of the information submitted to the
regulators and the assumed design and
manufacturing status at that time

Changes post submission must be

assessed for requiring approval and/or
reporting

Change Management at Cochlear

Changes are assessed using

CHANGE ASSESSMENT PROCEDURE
12654AG
which identifies the regulatory implication
of the change.

Assessment of changes
Product status covered by change control

Product on the market

Product submitted for regulatory approval
Product submitted for clinical trials

Changes requiring considerations

Manufacturing processes, facilities, equipment

Manufacturing requirements, procedures
Design and performance specifications
Materials
Labelling

Generic Change Process

Proposed Change

Change Request
Review

Change
Assessment
Advisory

Change Design

Change Note
Review

Change
implementation

Change complete

Change
Assessment
Binding

A systematic and documented assessment is performed by Cochlear Q&R

Assessment of changes
CHANGE ASSESSMENT PROCEDURE E12654AG
SIGNIFICANT CHANGE means a change that could potentially affect the
safety or effectiveness of a medical device. It includes a change to any of the
following:
the manufacturing process, facility or equipment;
the manufacturing quality control procedures, including the methods, tests or
procedures used to control the quality, purity and sterility of the device or of
the materials used its manufacture;
the design of the device, including its performance characteristics, principles
of operation and specifications of materials, energy source, software or
accessories;
the intended use of the device, including any new or extended use, any
addition or deletion of a CONTRA-INDICATION for the device, and any
change to the period used to establish its expiry date, and
major changes to the facilities such as an additional operational location

Changes - Japan
Minor changes in a medical device are exempted from an application for partial
change as long as such changes do not directly affect the effectiveness and
safety of the medical device such changes would be:
a)
b)
c)

d)
e)
f)

Changes not related to the medical device itself

Changes which affect the structural materials, external appearance etc but
which does not affect the performance, electrical rating, safety etc
Change, addition or elimination of auxiliary equipment or accessories
which are not stand-alone medical devices, as the change does not affect
the performance, electrical rating, safety etc
Changes in material, form, dimensions, or position of parts not contacting
the patient body
Minor changes which do not affect the safety, performance or essence of
the device
Minor changes in the method of operation or use of the medical device
due to any of the changes (a) to (e)

Prerequisites for Assessement

Clear and unambiguous description

Reason why is the change important?
Impact analysis what is affected?
Incremental risk analysis which tests?

Generic Change Assessment Process

A systematic and documented
assessment is performed by
Cochlear Q&R

Generic Change Process

MAIN CHART

A systematic and documented

assessment is performed by
Cochlear Q&R

File Changes - CLTD

Regional Report ?

No
Change to a
device or its
manufacturing
processes

M2
M1
due to Field
Action ?

Assess change. Is it significant?

Is the safety and effectiveness of
the device potentially affected?

Yes

Yes

Approval required

No

M3

M4

M6

M5
in design or design
specifications ?
Mechanical
Electrical
Software, etc

in manufacturing
processes?

in indication
for use /
labelling?

in Facilities?

Yes

Yes

Go to
Chart E

Go to
ChartG

Yes
Yes
Go to
Chart
C

Go to
Chart A
A1

Yes

Yes

Identical to present?
eg. replacement or for
capacity.

Yes

in control
mechanism?

Chart C

No

No

Yes
No

A4
Go to
Chart B

new equipment or
materialbeing
added?

No

C1

A3

A2
only changes
to the quality
control criteria?

Chart A

C2

A7

to a quality control
procedure, criteria or
validation test
specification?

No

D1
in operating
principle?

Could the
change affect
the process where
used?

Yes

No

E1
of animal or
human origin?

Chart D

Yes

Approval Required

No
C3

Go to
Chart C

Yes

A6

D2

in design or
performance
specifications?

No

Could the
process change affect
the safety and effectiveness
of the device?

in the design?

A6

Yes

in materials?

Yes

Chart D

No

From
Chart D

Yes

Yes

in material supplier?

in software or
firmware?

Yes

effectiveness?
better assurance of safety and
Is there equivalent or

of the device?
the safety and effectiveness
Could the change affect

Yes

No

No

Yes

E4

Is clinical evidence
requierd?

Yes

Approval Required

improvement of
clarity?

Extension of expiry
date?

No

No

No

File Changes - CLTD

Regional Report ?

File Changes - CLTD

Regional Report ?

File Changes - CLTD

Regional Report ?

No
Could the change affect
the safety and effectiveness
of the device?

No

Yes

Approval Required

No

Approval Required

F5
No

Are any critical

process locations
changed

Yes

No

Could the change affect

the safety and effectiveness
of the device?

E6
Could the change affect
the safety and effectiveness
of the device?

Yes

C9

Yes

Could the change affect

the safety and effectiveness
of the device?

No
E5

No

No

B1

Are high risk product

processes affected?

Yes

D10

C8

No

F3

Yes

D9

Yes

Yes

Yes

Yes

changes in design
or performance
specifications?

Yes

Is the present facility

expanded?

Yes

addition or
deletion of
contraindications?

No

Yes
ChartB

ordered to the same

specifications/

affect indication for

use?

Yes

No

Yes

Go to
Chart C

No

F4

E3
are additional
biocompatibility
tests required?

No

C7

B3

No

D5

No

D7

No

Regional Report ?
File Changes - CLTD

in contact with
the body?

D6

C6

No

Yes

No

No

No

in the performance
specifications?

specifications?
performance
in design or

Yes
No

D4
in the type or
formulation?

C5

B2

Yes

No
F2

is it to existing
warnings and
precautions?

Yes
D3

in packaging

Approval Required

Yes

absorbed or remain in
body > 30 days?

No

C4

Chart C
Go to

E2

Yes

No

Yes

is new
manufacturing
facility
being added?

Chart F

No

No
A5

F1
affect indication
for use?

Chart E

File Changes - CLTD

Regional Report ?

No

Could the change affect

the safety and effectiveness
of the device?

Yes

Approval Required

File Changes - CLTD

Regional Report ?

No

FDA Change Assessment Process

Identify the modification and
the reason for it

Conduct risk analysis

Define testing that will assess

the impact of the modification
an safety and effectiveness

Choose the regulatory

pathway from the options
below

New clinical
and new
preclinical

New clinical
and ptentially
some new
preclinical

New original
PMA

Panel track
Supplement

Preclinical and
potentially limited
confirmatory
clinical

Preclinical
only

Manufacturing
change
affecting S&E

180 day
supplement

Real-Time
Supplement

30-Day/135Day
Supplement

Change(s)
that enhance
the S&E

Manufact.
Site
Change
Supplement

Special
supplement
Changes
Being
Effected

Change(s)
that does not
affect S&E

Annual
Report

Summary
New Products must be approved

Changes to current products must be

assessed for regulatory implications
Changes must be properly executed and
documented

Change Assessment
References

Europe - NB-MED/2.5.2/Rec2 Reporting of

design changes and changes of the quality
system

GUIDANCE FOR INDUSTRY, Guidance for the

Interpretation of Significant Change of a Medical
Device, Health Canada , 2003/03/02

USA, FDA - Guidance for Industry,

Modifications To Devices Subject to Premarket
Approval The PMA Supplement Decision
Making Process Draft Guidance

Key Regulations for Cochlear

Regulations

Reference to changes

FDA 21CFR14 Premarket

Yes
Approval of Medical Devices
EUROPE AIMD& MD
no - see guidance
Directives 90/385/EEC,
93/45/EEC
Australia Therapeutic
yes
Goods (Medical Devices)
Regulation 2002
Canada Medical Device
yes
Regulation

????

FDA 21CFR814

Sec. 814.39 PMA supplements.

(a) After FDA's approval of a PMA, an applicant shall submit a PMA supplement for review and
approval by FDA before making a change affecting the safety or effectiveness of the device for which
the applicant has an approved PMA, unless the change is of a type for which FDA, under paragraph
(e) of this section, has advised that an alternate submission is permitted or is of a type which, under
section 515(d)(6)(A) of the act and paragraph (f) of this section, does not require a PMA supplement
under this paragraph. While the burden for determining whether a supplement is required is primarily
on the PMA holder, changes for which an applicant shall submit a PMA supplement include, but are
not limited to, the following types of changes if they affect the safety or effectiveness of the device:
(1) New indications for use of the device.
(2) Labeling changes.
(3) The use of a different facility or establishment to manufacture, process, or package the device.
(4) Changes in sterilization procedures.
(5) Changes in packaging.
(6) Changes in the performance or design specifications, circuits, components, ingredients, principle
of operation, or physical layout of the device.
(7) Extension of the expiration date of the device based on data obtained under a new or revised
stability or sterility testing protocol that has not been approved by FDA. If the protocol has been
approved, the change shall be reported to FDA under paragraph (b) of this section.

FDA 21CFR814 contd

(b) An applicant may make a change in a device after FDA's approval of a PMA for the device without
submitting a PMA supplement if the change does not affect the device's safety or effectiveness and
the change is reported to FDA in postapproval periodic reports required as a condition to approval of
the device, e.g., an editorial change in labeling which does not affect the safety or effectiveness of the
device.
(c) All procedures and actions that apply to an application under 814.20 also apply to PMA
supplements except that the information required in a supplement is limited to that needed to support
the change. A summary under 814.20(b)(3) is required for only a supplement submitted for new
indications for use of the device, significant changes in the performance or design specifications,
circuits, components, ingredients, principles of operation, or physical layout of the device, or when
otherwise required by FDA. The applicant shall shall include information relevant to the proposed
changes in the device. A PMA supplement shall identify each change and explains the reason for
each such change.

FDA 21CFR814 contd

(f) Under section 515(d) of the act, modifications to manufacturing procedures or

methods of manufacture that affect the safety and effectiveness of a device subject to
an approved PMA do not require submission of a PMA supplement under paragraph (a)
of this section and are eligible to be the subject of a 30-day notice.
A 30-day notice shall describe in detail the change, summarize the data or information
supporting the change, and state that the change has been made in accordance with the
requirements of part 820 of this chapter.
The manufacturer may distribute the device 30 days after the date on which FDA
receives the 30-day notice, unless FDA notifies the applicant within 30 days from receipt
of the notice that the notice is not adequate. If the notice is not adequate, FDA shall
inform the applicant in writing that a 135-day PMA supplement is needed and shall
describe what further information or action is required for acceptance of such change.
The number of days under review as a 30-day notice shall be deducted from the 135day PMA supplement review period if the notice meets appropriate content requirements
for a PMA supplement.

Europe - NB-MED/2.5.2/Rec2

The Medical Devices Directives variously require in different Annexes that where a
Notified Body has been involved in the approval of the quality system or the device
design / type, the manufacturer must inform the Notified Body of substantial changes
to the quality system and/or changes to the device which could affect compliance with
the essential requirements or the intended use.
It is not practicable to specify in general terms what types of change are or are not
substantial. For instance, a change in colour may be purely cosmetic in some cases,
yet be substantial in other cases where it is the means for drawing attention to
warnings, functions etc. Instead, it is recommended that the manufacturer have a
system for categorising changes as substantial or not and informing the Notified Body as
appropriate, and that the Notified Body reviews the operation of this system as part of
routine surveillance.
The manufacturer should establish, maintain and apply a procedure for categorizing and
documenting any changes to the design / device and/or quality system as either
substantial or not substantial.

Europe contd
There is a recognition of Substantial Changes per below:
Changes are substantial and (depending on the chosen conformity assessment route)
the manufacturer must inform the Notified Body where:
(i) for product changes, the change would affect conformity with
(a) the essential requirements and/or
(b) the conditions prescribed for the intended use of the device.
The matters for the manufacturer to consider when deciding whether or not particular
changes are substantial include the following:
- for device changes
- does the change introduce new hazards which have not been previously addressed?
- does the change adversely affect the risk associated with existing hazards?
- does the change alter the details on intended use and/or compliance with the essential
requirements given in the design / type approval dossier submitted to the Notified Body?
- does the change mean that the device will have different end users or be used in a
different manner?
- does the change mean that the clinical data for the original device is not sufficient to
confirm conformity of the changed device with the required characteristics and
performance?

Canada
"significant change" means a change that could reasonably be expected to affect
the safety or effectiveness of a medical device. It includes a change to any of
the following:
(a) the manufacturing process, facility or equipment;
(b) the manufacturing quality control procedures, including the methods, tests or
procedures used to control the quality, purity and sterility of the device or of
the materials used in its manufacture;
(c) the design of the device, including its performance characteristics, principles of
operation and specifications of materials, energy source, software or
accessories; and
(d) the intended use of the device, including any new or extended use, any
addition or deletion of a contra-indication for the device and any change to the
period used to establish its expiry date.

Canada contd
Application for a Medical Device Licence Amendment
34. If the manufacturer proposes to make one or more of the following changes,
the manufacturer shall submit to the Minister, in a format established by the
Minister, an application for a medical device licence amendment including the
information and documents set out in section 32 that are relevant to the
change:
(a) in the case of a Class III or IV medical device, a significant change;
(b) a change that would affect the class of the device;
(c) a change in the name of the manufacturer;
(d) a change in the name of the device;
(e) a change in the identifier of the device, including the identifier of any medical device
that is part of a system, test kit, medical device group, medical device family or
medical device group family;
(f) in the case of a Class II medical device, a change in the medical conditions,
purposes or uses for which the device is manufactured, sold or represented.

Canada contd
Obligation to Inform
43. (1) Every manufacturer of a licensed medical device
shall, annually before November 1 and in a form
authorized by the Minister, furnish the Minister with a
statement signed by the manufacturer or by a person
authorized to sign on the manufacturer's behalf
(a) confirming that all the information and documents supplied by the
manufacturer with respect to the device are still correct; or
(b) describing any change to the information and documents supplied
by the manufacturer with respect to the device, other than those to
be submitted pursuant to section 34.

Australia
(3) For the purpose of enabling the examination to be carried out, the
manufacturer must have available:
(a) information, in writing, in relation to the following matters in relation to the
kind of medical device:
(i)
the design;
(ii) the production process;
(iii) the intended performance; and
(4) If, after examination by the Secretary of the design of a kind of medical device,
the manufacturer makes a substantial change to the design, or the intended
performance, of the kind of device, the manufacturer must:
(a) notify the Secretary, in writing, of the change; and
(b) arrange for examination of the change by the Secretary to assess
whether the design, or the intended performance, of the medical device, as
changed, complies with the applicable provisions of the essential principles.