LECTURE 3 –

CHANGE
MANAGEMENT

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Pixabay.com/images
Breda Connell – Referencing Support and Training

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ACTIVITY FROM LAST WEEK – NOT GRADED

 What sections of ISO 13485 AND CFR 820 deal with

customer complaints and feedback.
 What are the regulatory differences between the U.S.
and EU complaint handling requirements?
 What information is importance to capture when
processing a complaint and why is this information
important?

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  Change Management is a process to
manage modifications to products and
processes within a medical device
business.
 There are many triggers of change
(Planned and Unplanned)
 FDA and ISO requires that Medical Device
Companies have a formal and systematic
process to manage and control change
to ensure safe products on the market
 Change control exists to prevent
unintended consequences. A breakdown
in the change control process can result in
product recalls, regulatory penalties,
negative publicity, and in extreme cases,
injury or death to patients

WHAT IS CHANGE
MANAGEMENT?
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  FDA
 US FDA QSR (21 CFR Part 820)

 21 CFR Part 820.30 (Design

changes)

FDA AND ISO  21 CFR Part 820.40 (Document

changes)

REQUIREMENTS  21 CFR Part 820.70 (Production

and process changes)

FOR CHANGE
ISO 13485:2016
MANAGEMENT 
 Control of documents and records (4.2.4 and 4.2.5)
 Quality management system planning (5.4.2)
 Management reviews (5.6.1 and 5.6.3)
 Review of product requirements (7.2.2)
 Design and development changes (7.3.9)
 Purchasing process (7.4)
 Process validation (7.5.6 and 7.5.7)
 Need for change (8.5.1)

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 New or modified New or modified New regulations
products processes and
procedures,
documents, forms
etc
TRIGGERS OF
CHANGE
Continuous Post Market Applies to all
Improvement Feedback aspects of device
Activities lifecycle

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 Finalize the
Review the change by
Identify a need Justify the
proposed change securing
for a change proposed change
internally management
approvals

Communicate the Train employees

Document all Implement the
change to affected by the
steps above change
relevant parties change

Evaluate the
change and its
effects

BASIC STEPS INVOLVED IN CHANGE

MANAGEMENT AND CONTROL
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 CHANGE ASSESSMENT

 The change management process should begin with an

assessment.
 To even consider implementing a change, you need to have
an understanding of how it will impact your products,
processes, and your company — even small changes need
some form of assessment before being put into place.
 Specific criteria needs consideration before processing any
change to products or processes
 Throughout the entire change management process, it is
necessary to document every decision that is made
regarding the change. Your documentation may include
detailed explanations from your assessment of the change’s
scope, impact, associated risks, tasks and actions to be taken
— as well as supporting evidence to back up these claims.

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 CHANGE ASSESSMENT CRITERIA

 Scope: Is the change significant or insignificant? This will

determine the activity and resources required to implement
the change
 Change Description: Clear and concise description of the
proposed change avoids ambiguity when describing
procedures, processes, and product specifications. The
proposed change, along with how any internal procedures or
documents will be altered, will need to be described in detail
 Justification: It is imperative that the reasons for the change
can be explained, internally and externally. Depending on
the scope, a change can have far-reaching effects, and
must be able to demonstrate that it’s necessary and
appropriate to your company, your employees and your
customers. The justification should be unambiguous and to
the point and include supporting objective evidence.

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 CHANGE ASSESSMENT CRITERIA
 Impact: The impact of a change could impact one or
multiple functions or areas of the business.
 For example, let’s say that you want to change the
material in a catheter device. In this case, you’ll need to
conduct biocompatibility testing, review the existing
manufacturing specifications, reconsider the standard
operating procedures for manufacturing, and even
reassess the design in relation to the change. Mapping
out the impact in advance will allow careful planning of
the change.
 Risk: Determine whether or not follow-up activities are
necessary to assess the risk of your change. In-depth risk
assessment may be necessary to evaluate the hazardous
situations that this change could pose.
 Regulatory: Changes can, and often do, require
regulatory submissions, and this needs to be assessed in
your change process. The Regulatory Affairs function will
determine whether or not the change will require a
submission to the FDA, communication with a notified
body, or the equivalent methods in other target markets.
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 PRODUCT DESIGN CHANGES -
PREMARKET
 A pre-market design change is implemented during
product development or the design control
process. During this phase user needs, design
inputs/outputs and risk are being captured.
 During design and development, design outputs
are defined, which are essentially the “recipe” for
your device. This forms the basis for the Device
Master Record (DMR).
 During the premarket design and development
process, unforeseen obstacles, new opportunities,
fresh ideas and quality improvements related to
your device will likely appear.
 All design change decisions should be
documented
 Design Reviews should conducted at regular
intervals during the design and development
phase.
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 PRODUCT DESIGN CHANGES –
POST-MARKET
 Once the medical device reaches the market, ongoing
post-market surveillance activities are conducted, which
include customer feedback and complaint management

 Software products can also undergo post-market

changes. For example, you’ve developed an SaMD
solution intended to help detect breast cancer lesions
using a locked AI algorithm. After launch, your team may
identify enhancements to the algorithm that will assure
the recommendations being given to physicians are more
accurate, and this could trigger a post-market change in
your software.

 When making any kind of post-market change, you’ll

need to consider the impact on form, fit, and function
(FFF) at this point.

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 PRODUCT DESIGN CHANGES –
POST-MARKET
 Form, Fit, and Function
 FFF refers to the identifying characteristics of the parts or components of your device:

 Form refers to the shape, size, dimensions, and other visual or physical parameters of
components.

 Fit describes the way a part physically connects to or interacts with another part of your
device.

 Function refers to the action that an individual part is designed to perform.

 For a post-market change, it is necessary to understand the impact the change might
have on FFF when it comes to individual parts and their overall performance. Sometimes,
a change may be trivial in these terms; other times, a single change may require
additional changes to account for the impact on a device’s FFF.

 For example, changing from one supplier to another requires due diligence to ensure that
the new manufactured parts will be equivalent to the ones being replaced.

 It is necessary to always conduct a change assessment when modifying anything about

a device, no matter how trivial it may seem.

 It is recommended best practice for post-market changes to handle the DHF as “living”
throughout the entire product lifecycle
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 PRODUCT DESIGN CHANGES – POST-
MARKET – REGULATORY IMPACT
 When you identify making a proposed change to a
product that has already passed regulatory
clearances / approval, you may need to complete
additional regulatory documentation.
 It may also be necessary to obtain permissions from
regulatory bodies before you actually implement the
change.
 In the U.S., devices may require a 510(k) submission, a
post-market approval (PMA) supplement, or a letter to
file. The FDA guidelines on change control include a
decision tree to help you determine whether your
change will require a 510(k) submission.
 For devices certified for the European market, it may
be necessary to notify the notified body of the
proposed change prior to implementing in order to
maintain your CE mark status. 14
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 PRODUCTION PROCESS CHANGES
 Once the design is finalized, whether you are manufacturing your
device in-house or leveraging a third party contract
manufacturer, your device master record (DMR) will be affected
by any changes.
 To produce the device as designed accurately, manufacturers
need to follow the contents of the DMR, and those contents
could be subject to change for a number of reasons.
 As you gain market traction, you might scale up your
manufacturing process to mass production. Scaling in this way
will typically involve implementing changes to manufacturing
processes or materials.
 To scale to mass production, you’ll need to evaluate any
manufacturing process changes in terms of their impact and
ability to produce the same result as before. Beyond that, you’ll
often come across new suppliers or components that may have
a cost or quality advantage, and the same rationale applies
here.
 When changing parts in a device, you will also need to update
the bill of materials (BOM) in your DMR accordingly. Your BOM
identifies the suppliers that provide each individual part, as well
as the quantity and sometimes the cost. Any time you implement
a change to existing parts, or suppliers of those parts, that
change must also be updated in your BOM. 15
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 CONDUCTING A RISK ASSESSMENT
 A best practice is to conduct a risk assessment whenever there is
a manufacturing process change.

 Your manufacturing partners, whether those be internal

manufacturing facilities or external suppliers, should be involved
during the design and development process, and this should be
in motion prior to starting your verification and validation stages.

 Your manufacturing process risk assessment can be handled by

following the guidelines in ISO 14971, which can be broken down
into four components:
 Hazard: Potential source of harm

 Foreseeable event: Event leading to a hazardous situation that can

be easily imagined or predicted

 Hazardous situation: A circumstance in which people, property, or the

environment are exposed to one or more hazards

 Harm: Damage to the health of people, property, or the environment.

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 CONDUCTING A RISK ASSESSMENT
 Performing a risk assessment will provide several
benefits:

 It ensures that you have proper controls in place

so that the product is safe for end users after
you’ve implemented your change.
 It ensures that all inspection criteria and critical
characteristics are thorough and diligent enough
to avoid defects.
 It determines whether further steps, such as
manufacturing process validation, are necessary.
This would occur in the event of hazards or
hazardous situations being identified as part of a
new manufacturing process change, and the
validation process is aimed at mitigating the risks
that may emerge. 17
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 QUALITY EVENTS
 The term “quality event” refers to a situation that
could trigger product, process, or document
changes. Quality events can and do occur
sporadically throughout your product lifecycle.
 Nonconformances are an example of a quality
event in which a product or component fails to
meet the defined quality specifications at
different stages of the manufacturing process.
 Complaints are another example of a type of
quality event that can reported by end users or
partners during the feedback stages of your post-
market surveillance, and this can trigger a
change.
 Policies and procedures outlined in
nonconformance management and complaint
management dictate how you handle these
quality events. 18
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 FDA GUIDANCE ON MANAGING
CHANGE – LABELLING
 Is it a change in the indications for use statement?
 Changes in the indications for use statement raise
more Agency concern than any other aspect of
labelling. In fact, most labelling changes that affect
the substance, meaning, or scope of the indications
for use could significantly affect safety or
effectiveness and will require submission of a new
510(k).
 Changes that clarify the indications without affecting
the substance or meaning of the indications usually
do not require submission of a new 510(k).
 In addition, some changes in the indications for use
that limit use within the currently cleared indication
may occur without submission of a new 510(k). For
example, if a device was cleared for use with three
specific indications and the firm decides to market
the device for only two of those indications, this
change would not likely require submission of a new
510(k). 19
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 FDA GUIDANCE ON MANAGING
CHANGE – LABELLING
 Is it a change from a device labelled for single
use only to a device labelled as reusable?
 FDA has found that the performance and risks
associated with a reusable device can be
significantly different from the performance and
risks associated with that same device when it is
labeled for single use only.
 Therefore, changing a device labeled for single
use only to a device that is labeled as reusable
typically could significantly affect the safety or
effectiveness and would likely require submission
of a new 510(k).
 Changing a device labeled for reuse to single use
only, however, would likely not require submission
of a new 510(k) because a single use is a limitation
of the previously cleared indications for multiple
uses, and the risks of single use were inherently
considered within the risks of multiple uses. 20
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 FDA GUIDANCE ON MANAGING
CHANGE – LABELLING
 Is it a change from prescription to over the counter
(OTC) use?
 FDA has found that the directions for use necessary
for health care professionals to use a device safely
and effectively can be significantly different from
the directions for use necessary for lay users to use
that same device safely and effectively.
 Therefore, changing a device labeled for
prescription use only to a device that is labeled for
OTC use typically could significantly affect the
safety or effectiveness and would likely require
submission of a new 510(k).
 Changing a device labeled for OTC use to
prescription use, however, would likely not require
submission of a new 510(k) because it is unlikely that
the associated labelling changes could significantly
affect the safety or effectiveness of the device. 21
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 FDA GUIDANCE ON MANAGING
CHANGE – LABELLING

 Is it a change to the device name or a change

solely to improve readability or clarity?
 Changes to the device name or description that
are consistent with the cleared indications for use
typically do not significantly affect the safety or
effectiveness and would likely not require
submission of a new 510(k).
 Changes that are solely to improve readability or
clarity that are consistent with the cleared
indications for use typically do not significantly
affect the safety or effectiveness and likely would
not require submission of a new 510(k)

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 FDA GUIDANCE ON MANAGING
CHANGE – LABELLING
 Does the change describe a new disease, condition, or
patient population that the device is intended for use in
diagnosing, treating, preventing, curing or mitigating?
 Differences in indications for use should be analyzed to
explain how they are or are not critical to the intended
therapeutic, diagnostic, prosthetic, or surgical use of the
device, and how the differences do or do not affect the
safety and effectiveness of the device.
 Specific changes that could significantly affect the safety
and effectiveness include describing a new disease,
condition, or patient population that the device is
intended for use in diagnosing, treating, preventing,
curing or mitigating (or an anatomical site from which a
new disease, condition, or population may be inferred).
 The criticality of these types of changes and their direct
effect on safety and effectiveness means that a change
to add a new disease, condition, or patient population
likely requires submission of a new 510(k).
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 FDA GUIDANCE ON MANAGING
CHANGE – LABELLING
 Does a risk-based assessment of the changed device
identify any new risks or significantly modified existing
risks?
 if a change is intended to significantly affect safety or
effectiveness, particularly those meant to significantly
improve clinical outcomes, to mitigate a known risk, or in
response to adverse events, that change likely requires
submission of a new 510(k); this includes changes to the
indications for use for:
 Change creates new risks or significantly modifies existing
risks.
 Changes to the labelling can affect a device’s risk profile by
affecting how, when, where,or by whom the device is used.
As part of the risk-based assessment of a labelling change,
manufacturers should consider whether the change could
introduce human factors or usability issues that could
significantly affect users’ understanding of the labelling and
use of the device.
 Changes that significantly affect a device’s risk profile likely
require submission of a new 510(k). 24
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 FDA GUIDANCE ON MANAGING
CHANGE – LABELLING
 Changes in user or use environment: How a change of this type affects
a device’s risk profile depends on the differences in use environment
and environmental specifications.
 For example, a change from use in a surgical suite to use in a hospital
recovery room, both of which will have professional healthcare
supervision, may not significantly affect the device’s risk profile.
Similarly, changes between users with similar training on a specific
device, such as changes between a general physician and a
specialist using basic medical equipment may not significantly affect a
device’s risk profile.
 However, changes from professional use to home use or hospital use
to ambulatory transport are more likely to affect the device’s risk
profile and require submission of a new 510(k) because the different
environments have different levels of professional healthcare
supervision and offer different environmental challenges, such as
presence of other electronic devices that can cause electromagnetic
interference, different levels of cleanliness, or shocks and vibrations
associated with patient travel or ambulatory use.
 Similarly, changes from professional use to home use, hospital use to
ambulatory transport, or between any other healthcare providers with
different levels of training on specific devices are more likely to affect
the device’s risk profile and require submission of a new 510(k)
because the different level of training could significantly affect the
safe and effective use of the device
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 FDA GUIDANCE ON MANAGING
CHANGE – LABELLING

 Changes in frequency or duration of use:

 Changes in the frequency or duration of use of a
device include changes indicating that a device
can or should be used more or less often, changes
indicating that a device can perform a task or
treat a condition in or for a different duration of
time, or changes between periodic and
continuous monitoring.
 Manufacturers should evaluate the effect such
changes could have on the performance of a
device, and whether such changes significantly
affect the device’s risk profile

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 FDA GUIDANCE ON MANAGING
CHANGE – LABELLING
 Changes concerning the compatibility or interoperability of a device
with other devices, components, or accessories: Two examples of such
changes would include
 1) changes indicating an IVD reagent for use with a new system,
 2) changes that describe how to use an infusion pump with inputs
from other devices not described in the previously cleared 510(k),
such as a pulse oximeter or blood pressure monitor.
 To evaluate whether these changes significantly affect the device’s
risk profile, manufacturers should carefully consider the following
factors:
 Differences between the other devices, components, or accessories
referred to in the previously cleared indications and the ones referred to in
the modified indications.
 Manufacturers should be able to clearly identify and analyze the risks
associated with such differences, including whether the change may affect
biocompatibility, performance, connectivity, etc. If the change is to
indicate compatibility with a type of device, component, or accessory that
was not indicated as compatible previously, that change will likely require
submission of a new 510(k).
 The criticality of the other device, component, or accessory; the more
critical the other device, component, or accessory is to overall system
function, the more likely a labelling change regarding compatibility or
interoperability could significantly affect safety or effectiveness.
 The labelling of the other device, component, or accessory. If the change is
to indicate compatibility or interoperability with another device that is
labeled for use with the subject device or device type, it is less likely that the
change introduces a compatibility or interoperability issue that could
significantly affect safety or effectiveness.
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 FDA GUIDANCE ON MANAGING
CHANGE – LABELLING
 Does the change add or delete a
contraindication?
 Changes in the labelled contraindications for
device use generally could significantly affect
safety or effectiveness of a device and should
typically be reviewed by the Agency;
 FDA recognizes that, in general, the addition of a
contraindication based on new information is
important to public health. Thus, FDA does not
intend to object if manufacturers add new
contraindications to their labelling and notify
existing users of their device as expeditiously as
possible whenever a pressing public health need
arises. In this situation, the new labelling should be
submitted to FDA as part of a new 510(k) that is
prominently labelled “change being effected”
 Manufacturers should ensure they are thoroughly
familiar with the definition of a contraindication in
such situations. 28
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 FDA GUIDANCE ON MANAGING
CHANGE – LABELLING

 Is it a change in warnings or precautions?

 In order to facilitate a continuous upgrading in
device labelling, manufacturers should monitor
device usage and promptly revise the warnings
and precautions section(s) based on user
experience.
 Events that precipitate changes of this type may
be those reported under the medical device
reporting regulation (MDR), 21 CFR Part 803.
Submission of new 510(k)s for such labelling
changes are generally not required.

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 FDA GUIDANCE ON MANAGING
CHANGE – LABELLING

 Could the change affect the directions for use of

the device?
 Device labelling may be changed for a multitude
of reasons. Many labelling changes result from
attempts to clarify labelling. Manufacturers should
consider whether the change is intended to or
could affect how the device is used in practice.
 Manufacturers should evaluate labelling changes
to determine whether the change affects the
directions for use of the device, including IVD
labelling required under 21 CFR 809.10.
 If the change could not affect the directions for
use of the device, submission of a new 510(k) is
likely not required based on the labelling change.
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 FDA GUIDANCE ON MANAGING
CHANGE – LABELLING
 Examples of changes that affect the directions
for use of the device:
 Adding additional or new instructions on how to
interpret diagnostic data from a diagnostic
device.
 Adding a new procedural technique not
described in the original labelling.
 Use of a product for a duration/frequency that is
different than what is described in the labelling of
the cleared device.
 Changing from labelling a device as non-sterile to
labelling it as sterile or vice versa.
 Adding instructions for device use in a new patient
population not described in the original
indications for use.
 Adding instructions for device use in a different
type of joint, organ, bone, vasculature, or tissue. 31
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 FDA GUIDANCE ON MANAGING CHANGE –
TECHNOLOGY, ENGINEERING, AND PERFORMANCE
CHANGES

 These types of changes encompass a broad

span of design activities, from minor engineering
changes in a circuit board layout to a change
from electromechanical to microprocessor
control of device function
 These changes should be evaluated using this
scheme, and then the changes should be
verified and/or validated according to the QS
requirements (21 CFR 820.30(i)).
 If the results of the verification and/or validation
raise any unexpected issues, the decision of
whether submission of a new 510(k) is required
should be re-evaluated
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 FDA GUIDANCE ON MANAGING CHANGE –
TECHNOLOGY, ENGINEERING, AND PERFORMANCE
CHANGES
 Is it a control mechanism, operating principle, or energy type
change?
 Control mechanism changes: A control mechanism, is the
manner by which the actions of a device are directed. Almost all
changes in the control mechanism for a device could
significantly affect safety and effectiveness.
 Therefore, such changes will usually require submission of a new
510(k). This is also true for changes in operating principle as well
as for changes in energy type Changes of these types tend to be
more revolutionary than evolutionary.
 One example of a control mechanism change would be a
change from analog to digital control of a medical device. While
the change to digital control can markedly improve device
performance specifications and effectiveness, the integration of
a digital control into a previously all-analog system is complex
and usually undertaken only as part of a major redesign of a
product.
 Thus, it would be rare that submission of a new 510(k) would not
be required. Most often, such changes in control mechanism
represent the introduction of a new product line.
 Another example of a change that would likely require
submission of a new 510(k) is the change from pneumatic to
electronic control of a respiratory care device 33
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 FDA GUIDANCE ON MANAGING CHANGE –
TECHNOLOGY, ENGINEERING, AND PERFORMANCE
CHANGES

 Is it a control mechanism, operating principle, or energy

type change?
 Operating principle changes: Similar to a control mechanism
change, a change in operating principle would also usually
require submission of a new 510(k).
 An example of a new operating principle for a device would
be changing the image reconstruction algorithm used in a
computed tomography x-ray system from simple back
projection to a new, more radiation-efficient method. In this
case, testing both at the bench and in the clinic would be
necessary to support a finding of substantial equivalence for
the new device.
 Another example would be a change in a water droplet
dispersal method used by a respiratory gas humidifier from
piezoelectric material to a wick and fan method. The two
mechanisms use the same design principle, but apply it in
different ways. The differences between the two could
significantly affect safety and effectiveness.
 Such changes may also be accompanied by significant
labelling changes and, sometimes, by a need for operator
retraining to ensure continued safe and effective operation.
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 FDA GUIDANCE ON MANAGING CHANGE –
TECHNOLOGY, ENGINEERING, AND PERFORMANCE
CHANGES
 Is it a control mechanism, operating principle, or
energy type change?
 Energy type changes: Submission of a new 510(k) will
usually be required for energy type changes. These
changes include both energy output and input
changes.
 A change from emitting microwave energy to
radiofrequency (RF) energy would be an example of
an energy output change; this type of change would
likely be part of a significant redesign.
 An example of an energy type input change is a
change from AC to battery power; this type of
change is usually part of a redesign to provide a
portable device that can be used under different
environmental conditions than the original device.
Such a change would normally be accompanied by
significant labelling changes, including a new or
expanded indication for use
 Such changes should be considered changes in
performance specifications or device design 35
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 FDA GUIDANCE ON MANAGING CHANGE –
TECHNOLOGY, ENGINEERING, AND PERFORMANCE
CHANGES

 Is it a change in sterilization, cleaning, or

disinfection?
 Changes in sterilization, cleaning, or disinfection
should be carefully assessed.
 If the sterility assurance level (SAL) is lowered,
manufacturers should consider whether device
safety or effectiveness may be compromised by
the new level. In general, reductions in SAL require
submission of a new 510(k) unless the SAL remains
better than 10-6

36
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 FDA GUIDANCE ON MANAGING CHANGE –
TECHNOLOGY, ENGINEERING, AND PERFORMANCE
CHANGES

 Could the change significantly affect the

performance or biocompatibility of the device?
 Changes in the method of sterilization, cleaning, or
disinfection have the potential to change material
or performance characteristics of a device.
 This is particularly true of the properties of
polymeric materials or surface coatings,
resorbable materials, or animal-derived materials.
 When manufacturers make changes in sterilization,
cleaning, or disinfection methods, they should
consider whether the properties or specifications
of the device could be significantly affected.

37
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 FDA GUIDANCE ON MANAGING CHANGE – MATERIAL
CHANGES

 Medical device manufactures making changes

to the materials from which their device is
manufactured should also consider the other
types of changes discussed and their impact on
the decision regarding submission of a new
510(k).
 For example, a material change,, might also lead
to a change in the labelling of the device (e.g.,
the removal of a contraindication or the addition
of a new warning), or a change in specifications
(e.g., a reduction in the strength of the device).
 These collateral changes should be considered
also
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 FDA GUIDANCE ON MANAGING CHANGE – MATERIAL
CHANGES

 Is this a change in material type, material

formulation, chemical composition, or the material’s
processing?
 If there is any change in material type, formulation, or
chemical composition, the answer to this question
should be yes.
 Additionally, if there is any change in supplier or
manufacturer material processing or finishing steps,
the answer should also be yes.
 The biocompatibility and physical properties of a
finished device depend not only on the materials, but
also on the processing of the materials,
manufacturing methods (including the sterilization
process), and the manufacturing residuals that may
be present on the finished device.
 Changes of this type should be further evaluated for
their potential impact on safety and effectiveness. 39
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 FDA GUIDANCE ON MANAGING CHANGE – MATERIAL
CHANGES
 Will the changed material directly or indirectly
contact body tissues or fluids?
 Both direct and indirect patient and user contact
should be considered in answering this question.
Direct contact is when a material comes into
physical contact with a patient or user while the
material is still in or on the patient or user. A
material with indirect contact is a material through
which a fluid or gas passes, prior to the fluid or gas
coming into physical contact with body tissue (i.e.,
the device or device component itself does not
physically contact body tissue).
 For example, materials in a catheter hub (the part
of the catheter which is external to the patient)
can contact the patient indirectly if fluids or drugs
are infused through the hub and directly into the
patient.
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 FDA GUIDANCE ON MANAGING CHANGE – MATERIAL
CHANGES

 Does a risk assessment identify any new or

increased biocompatibility concerns?
 Manufacturers should conduct a biocompatibility risk
assessment, which may include an assessment of the
device’s toxicological and physical properties, of any
changed materials that may contact the patient or
user to determine if there are any new or increased
biocompatibility concerns.
 An example of a new concern would be a material
change that requires a new type of biocompatibility
test, such as an implantation test, that was not
required for the original device.
 An example of an increased concern would be
where a new chemical component added to a
material requires a genotoxicity analysis of that
component (because, for instance, the particular
component is noted in the literature as potentially
genotoxic), but the original device already required
a genotoxicity analysis. FDA have specific guidance
for manufacturers on determining this. 41
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 FDA GUIDANCE ON MANAGING CHANGE – MATERIAL
CHANGES

 Has the manufacturer used the same material in

a similar legally marketed device?
 Manufacturers who have identified possible
biocompatibility concerns in their risk assessment
should consider whether they have used the same
material, in its final, finished state, in another one
of its own legally marketed devices that has been
cleared or approved by the FDA.
 If the manufacturer has used the same material in
a similar device that has been cleared or
approved by the FDA (this would typically involve
a biocompatibility evaluation), and there is no
post-market evidence of biocompatibility issues
with the device, that may provide evidence that
the material will be biocompatible in its new
application in the changed device as well and
the manufacturer can answer yes to this question. 42
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 FDA GUIDANCE ON MANAGING CHANGE – MATERIAL
CHANGES
 Could the change affect the device’s performance
specifications?
 Manufacturers should consider whether the material
change could affect the performance of the device
by affecting its mechanical properties, such as
strength, hardness, etc.
 Manufacturers should also consider whether the new
material could be affected by any labeled cleaning,
disinfection, and/or sterilization process of the device.
 If the answer to this question is yes, manufacturers
should consider whether the change could
significantly affect the safety or effectiveness of the
device.
 If the change could not affect the device’s
performance specifications, it is unlikely the change
could significantly affect safety or effectiveness, and
the manufacturer should document the change.
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FDA GUIDANCE ON MANAGING CHANGE – CONSIDERATIONS FOR
RISK-BASED ASSESSMENTS OF MODIFIED DEVICES
 FDA recommends that manufacturers use an accepted
method of risk assessment, such as ISO 14971, which is an
FDA-recognized standard that provides a framework for
systematically managing risks of medical devices
throughout the total product life cycle.
 In general, the assessment of risk in deciding whether to
submit a new 510(k) should identify all possible risks
associated with the changed or modified device, and
then focus on risks whose existence and characteristics
are supported by objective scientific evidence.
 It is not necessary to focus on hypothetical risks that are
not supported by scientific evidence or those that are
determined to be negligible due to both the low
probability of occurrence and low severity of harm.
 The manufacturer should then explore the severity and
probability of occurrence of the harm to determine
whether the device change could significantly affect
safety or effectiveness and require submission of a new
510(k).
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FDA GUIDANCE ON MANAGING CHANGE – EXAMPLES OF
LABELLING CHANGES

 Change: The manufacturer of a device adds a

precaution stating that the device must be properly
sterilized prior to use for patient safety. The modified
labelling does not modify the previously validated
cleaning, disinfection, or sterilization instructions.
 Relevant questions:
 Is it a change in the indications for use statement?
No. This is not a change in the indications for use
statement of the device.
 Is it a change in warnings or precautions? Yes.
 Does a risk-based assessment of the changed
device identify any new risks or significantly
modified existing risks? No.
 The added precaution simply emphasizes proper
sterilization and does not affect the device’s risk
profile.
 Decision: Documentation. 45
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FDA GUIDANCE ON MANAGING CHANGE – EXAMPLES OF
LABELLING CHANGES

 Change: The original directions for use for a surgical laser

intended to treat stones in the urinary tract only included
instructions on lithotripsy modes. The instructions are modified
to provide instructions on ablating soft tissue.

 Relevant questions:
 Is it a change in the indications for use statement? No. This is
not a change in the indications for use statement of the
device.
 Could the change affect the directions for use of the device?
Yes.
 Does the change describe a new disease, condition, or
patient population that the device is intended for use in
diagnosing, treating, preventing, curing or mitigating? Yes.
 The revised instructions would result in the device being
intended for use for ablation of soft tissue, which is a new
disease or condition that the device is intended for use in
treating, preventing, curing or mitigating, as compared to the
treatment of stones in the urinary tract.
 Decision: New 510(k). 46
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FDA GUIDANCE ON MANAGING CHANGE – EXAMPLES OF DESIGN
CHANGES

 Change: The manufacturer changes the packaging

for their device, which is provided sterile, from one
variant of polyethylene to another due to a
material supplier change. An analysis shows the
new polyethylene has no impurities that could
affect the device’s biocompatibility.
 The manufacturer will use the same package
integrity test protocol as the one described in its
previously cleared 510(k) to support the change.
 Relevant questions:
 Is there a change in packaging or expiration
dating? Yes.
 Is the same method or protocol, as described in a
previously cleared 510(k) used to support the
change? Yes.
 Decision: Documentation. 47
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FDA GUIDANCE ON MANAGING CHANGE – EXAMPLES OF DESIGN
CHANGES

 Change: The manufacturer of a urinary drainage (Foley)

catheter reduces the diameter of the catheter. The new
diameter is outside of the range of previously cleared
diameters for this device. The new diameter is also smaller
than what is typically used or has been shown to be
functionally appropriate for adult patients, and is of a size
that is typically used and shown to be functional for
paediatric patients. The device is not cleared for paediatric
use.
 Relevant questions:
 Is it any other change in design (e.g., dimensions,
performance specifications, wireless communication,
components or accessories, or the patient/user interface)?
Yes.
 Does the change significantly affect the use of the device?
Yes.
 Even if the indications for use and labelling are not changed,
this new diameter significantly affects the use of the device
by rendering the device non-functional in an adult and
changing it from adult use to paediatric use. This could
significantly affect the safety and effectiveness of the device.
 Decision: New 510(k). 48
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FDA GUIDANCE ON MANAGING CHANGE – EXAMPLES OF MATERIAL
CHANGES

 Change: The manufacturer of a catheter changes the material of its

catheter from polymer A to polymer B. The manufacturer has not
previously used polymer B in any of its devices, but knows of another
catheter on the market from a different manufacturer with the same
cleared indications for use that uses polymer B.
 Relevant questions:
 Is this a change in material type, material formulation, chemical
composition, or the material’s processing? Yes.
 Will the changed material directly or indirectly contact body tissues or
fluids? Yes.
 Does a risk assessment identify any new or increased biocompatibility
risks? Yes.
 Polymer B has a different chemical formulation than polymer A. The
risk assessment identifies that the new formulation presents a new
biocompatibility risk.
 Has the manufacturer used the same material in a similar legally
marketed device? No, the manufacturer has not used the same
material before. Even though there is another catheter from a
different manufacturer on the market made of polymer B, the other
device may have a different formulation or different manufacturing or
finishing processes that could affect the biocompatibility or
performance.
 Decision: New 510(k) 49
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FDA GUIDANCE ON MANAGING CHANGE – EXAMPLES OF MATERIAL
CHANGES
 Change: A manufacturer decides to change the material of a catheter
from material A to material B. Material B is used in another of the
manufacturer’s own cleared catheters, which has the same type and
duration of patient contact, as well as the same performance
specifications. Both materials A and B are molded and are sterilized by
ethylene oxide.
 Relevant questions:
 Is this a change in material type, material formulation, chemical
composition, or the material’s processing? Yes.
 Will the changed material directly or indirectly contact body tissues or
fluids? Yes.
 Does a risk assessment identify any new or increased biocompatibility risks?
Yes. Material B has a different chemical formulation than material A. The risk
assessment identifies that the new formulation presents a new
biocompatibility risk.
 Has the manufacturer used the same material in a similar legally marketed
device? Yes. The manufacturer has used material B in another cleared
catheter, and the processing is the same. In addition, the size and geometry
of the new device would not affect curing of the polymer or result in more
material in the new device, and there are no differences in how material B
is joined to other components of the catheter (e.g., type of adhesive, or
conditions of heat welding) that could result in different interactive
chemistries.
 Could the change affect the device’s performance specifications? No. The
manufacturer has used the same material B in another model of catheter
with the same performance specifications, which is processed in the same
manner.
 Decision: Documentation. 50
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FDA GUIDANCE ON MANAGING CHANGE – DOCUMENTATION

 Whenever a manufacturer changes its device, it

must take certain actions to comply with the QS
regulation, 21 CFR Part 820, unless a regulatory
exemption exists. The QS regulation requires that
design changes and production and process
changes be documented prior to
implementation.
 21 CFR 820.30(i) and 820.70(b). If a manufacturer
determines that the device change(s) does not
require submission of a new 510(k), it should
document the decision-making process and the
basis for that conclusion. The documentation
should be prepared in a way that an FDA
investigator or other third party can understand
what the change is and the rationale underlying
the manufacturer’s conclusion that submission of
a new 510(k) is not required. 51
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FDA GUIDANCE ON MANAGING CHANGE – DOCUMENTATION
 Documentation should include the following:
 Product name
 Date of change assessment
 Description of the device
 Description of the change(s)
 Reason why the change(s) is being made
 Applicable regulatory history, including the 510(k) number of
the most recently cleared version of the device
 Comparison of the modified device to the most recently
cleared version of the device (consider including a table)
 Applicable elements of the FDA guidance, including the
applicable questions from the body of the guidance
document
 Analysis and assessment of the elements on this list and a
conclusion of whether submission of a new 510(k) is required
 Reference to related documents, particularly those that
support the decision whether or not submission of a new
510(k) is required (e.g., risk analysis)
 Signature(s) 52
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CONSEQUENCES OF NOT MANAGING AND CONTROLLING CHANGE

 In the summer of 2018, the U.S. Food and Drug

Administration (FDA) announced a voluntary
recall of a single-use resuscitation device
produced by Vyaire Medical, Inc.
 Vyaire recalled the resuscitation device due to a
manufacturing error which may cause extra
plastic material in the oxygen output connection
that reduces or blocks the flow of oxygen to the
patient.
 The FDA noted than an undeclared change to
the manufacturing process of the resuscitation
device likely led to this production error.
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CONSEQUENCES OF NOT MANAGING AND CONTROLLING CHANGE

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EU – MDCG GUIDANCE - MDCG 2020-3 - GUIDANCE ON SIGNIFICANT CHANGES
REGARDING THE TRANSITIONAL PROVISION UNDER ARTICLE 120 OF THE MDR WITH
REGARD TO DEVICES COVERED BY CERTIFICATES ACCORDING TO MDD OR AIMDD

 On 16 March 2020, the long-awaited guidelines

on “significant change” were published by the
Medical Device Coordination Group (MDCG),
under guidance document MDCG 2020-3.
 This guidance document is intended to provide
clarification on the changes to a device that
should be considered a “significant change in
design or a significant change in the intended
purpose” under MDR Article 120(3).
 This guidance document does not elaborate on
the process for manufacturers’ submission and
notified bodies’ assessment of such changes as
these should be part of the conformity
assessment process and surveillance defined by
the relevant notified 55
MDCG 2020-3 – EU Commission
EUROPE – MDCG GUIDANCE - MDCG 2020-3 - GUIDANCE ON SIGNIFICANT
CHANGES REGARDING THE TRANSITIONAL PROVISION UNDER ARTICLE 120 OF THE MDR
WITH REGARD TO DEVICES COVERED BY CERTIFICATES ACCORDING TO MDD OR AIMDD

 MDCG 2020-3 builds upon two relevant

references:
 The Notified Body’s best practice guide NBOG
BPG 2014-3 on the type of medical device design
and Quality Management System (QMS) changes
that would require reporting to the Notified Body,
under the former MDD.
 The types of software changes triggering a new
UDI, as provided for in Annex VI Part C, section 6.5
of the same EU MDR.
 This guidance document becomes a valuable
basis for manufacturers to assess the significance
of device changes in a consistent manner.
56
MDCG 2020-3 – EU Commission
EUROPE – MDCG GUIDANCE - MDCG 2020-3 - GUIDANCE ON SIGNIFICANT
CHANGES REGARDING THE TRANSITIONAL PROVISION UNDER ARTICLE 120 OF THE MDR
WITH REGARD TO DEVICES COVERED BY CERTIFICATES ACCORDING TO MDD OR AIMDD

 Medical device manufacturers shall assess all

changes against the criteria in MDCG 2020-3 in
order to determine whether or not they are
“significant changes” within the meaning of EU
MDR Article 120.
 For devices other than Class I, the changes and
their implementation will be verified by the
Notified Body at audits or upon change
notification submissions, where applicable.
 The Notified Body verification will determine
whether an existing MDD/AIMDD certificate
remains valid, per EU MDR Article 120, or a new
certificate under EU MDR is required. Such
verification will be confirmed in writing by the
Notified Body. 57
MDCG 2020-3 – EU Commission
EUROPE– CHANGES THAT DO NOT TRIGGER UPGRADING OF
CERTIFICATION IN EU

 Administrative changes, in principle, are considered

non-significant. This would include a change in EU
Authorized Representative (EAR) for a non-EU
based manufacturer, or changes in legal
manufacturer’s name, address or legal form for a
given legal entity. However, a change in legal
manufacturer (to a different legal entity) would not
be considered an administrative change.
 QMS process changes that do not impact design or
intended purpose, e.g. relocation or addition of a
manufacturing sites (incl. for subcontractors and
suppliers), and certain changes to the quality
management system that do not impact the
conditions of the existing MDD/AIMDD certificate.
 Device (incl. labelling) changes not restricted by
MDCG 2020-3 flowcharts, e.g. certain like-for-like
material changes, appearance changes without
usability impact. 58
MDCG 2020-3 – EU Commission
EUROPE – WHAT ARE “SIGNIFICANT CHANGES IN DESIGN OR
INTENDED USE”?

 MDCG 2020-3 introduces 6 sequential flowcharts

to guide the decision making, i.e. a main chart
and 5 topic-specific secondary charts.
 Main Chart and Seconding Charts A-E (See
MDCG document and read the charts)

59
MDCG 2020-3 – EU Commission
Main Chart

60
EUROPE – SECONDARY CHARTS – CHART A
 Chart A – Intended purpose changes

 Significant changes include:

 intended purpose extension or change (other
than limitation, which is not considered
significant),
 new patient/user population,
 change in clinical use (e.g. change in
anatomical/access site, change in clinical
deployment method).
 NOTE: Labelling changes should be assessed to
ensure they do not qualify as significant relative
to the intended use (e.g. modifications to
contraindications or warnings). 61
MDCG 2020-3 – EU Commission
EUROPE – SECONDARY CHARTS – CHART B
 Chart B – Design/performance specification
changes

 Significant changes include:

 changes that require further clinical/usability data to

support safety/performance,
 new risks requiring mitigation or negative impact on
existing risks,
 change in built-in controls,
 change in operating principle, source of energy or
alarms.
 NOTE: Changes in design/performance should be
assessed regardless of how they are achieved (i.e.
hardware, software,…). 62
MDCG 2020-3 – EU Commission
EUROPE – SECONDARY CHARTS – CHART C
 Chart C – Software changes

 Significant changes include:

 changes of operating system or any component,

 new or modified architecture/database structure/algorithm,
 user input replaced by closed loop algorithm,
 new diagnostic/therapeutic feature,
 new channel of interoperability,
 new user interface,
 new presentation of medical data (e.g. in new format, new
dimension or measuring unit).
 NOTE: Examples of minor changes without impact to
diagnostic/treatment would include: bug fixes (for errors
that do not pose a safety risk), security updates (e.g.
cybersecurity enhancements, longevity calculations),
appearance/enhancement of the user interface without
performance changes, or operating inefficiencies. 63
MDCG 2020-3 – EU Commission
EUROPE – SECONDARY CHARTS – CHART D
 Chart D – Material changes

 Significant changes include:

 any changes to materials of human/animal origin

 any changes to medicinal substances contained (or
to any process affecting the quality, safety or
efficacy of such medicinal substances),
 new suppliers for other types of material/ingredient
where the existing specifications are not met.
However, if the existing specifications are met, the
change in supplier needs to be assessed in terms of
impact to the device design/performance
specifications.
 NOTE: Like-for-like material changes (same supplier
and same specifications) are not considered
significant. 64
MDCG 2020-3 – EU Commission
EUROPE– SECONDARY CHARTS – CHART E
 Chart E – Sterilization changes

 Significant changes include:

 changes in sterilization method (including from
non-sterile to sterile, but excluding change in
cycle parameters),
 changes in sterility assurance level (per the
corresponding international standards),
 changes in a sterile device’s packaging design
affecting functionality, safety, stability or seal
integrity,
 changes in a sterile device’s shelf life (extension of
shelf-life, in principle, is not considered significant).
65
MDCG 2020-3 – EU Commission
EUROPE – WHAT DO MEDICAL DEVICE MANUFACTURERS NEED
TO DO?

 Manufactures are required to:

 Integrate the significant change decision-making process

from MDCG 2020-3 in their QMS. This would typically mean
updating the change management procedure,
accordingly. It might also require links/updates to the
notification/reporting procedure, regulatory strategy
procedure (relative to the upgrading of “legacy devices”
to EU MDR certification), and design control or software
lifecycle procedures, as applicable.
 Collect all Notified Body confirmation letters relative to
changes implemented, and store them along with the
existing MDD/AIMDD certificates, as proof of their validity,
per the transitional provisions in EU MDR Article 117.
 Document the justification relative to the significance of a
change affecting Class I medical devices. 66
MDCG 2020-3 – EU Commission