STANDARD OPERATING PROCEDURE Ref.

:P /RISKA

Edition No. : 1
RISK ANALYSIS Revision No. : 00
Date : 15/05/2023

1. RISK ANALYSIS
1. Method used to analyze risk
The risk analysis method is based on 4 steps:

1. Identification of safety features, hazards associated with the device, hazardous situations,
or possible harm to the patient or users or environment (4.3). The list of hazards provided
in annex E of the standard may be used for hazard identification.
2. Evaluation of the probability of occurrence of each hazardous situation, and the severity of the
resulting harm (4.4 and 4.5)
3. Description of the control options (by design, protective measures, information for safety)
(6.2 and 6.3)
4. Residual risk evaluation and risk/benefit analysis (6.4, 6.5 and 6.6)

The 4 steps are documented in an Excel file TF-520 Risk analysis matrix, allowing the risk project
team to follow the entire risk assessment process.

Note: one hazardous situation may cause more than one type of harm. The most serious harm is always
considered when performing risk evaluation.

2. Risk control options

There are three risk control options used to reduce risk (listed in order of priority):

1. Inherent safety by design;

2. Protective measures in the medical device itself or in the manufacturing process;
3. Information for safety.

Evidence must be provided to demonstrate the efficacy of risk control options.

According to the EU Directive 93/42/EEC, control measures are put in place in order to reduce the risks
as far as possible (i.e. the AFAP method: As Far As Possible).

According to the EU Directive 93/42/EEC and Annex ZA 7.c) of the EN ISO 14971:2012 standard, the
information given to users does not solely allow for additional risk reduction.

If needed, an action plan may be written regarding the application of risk control methods.

3. Risk quotation criteria

Risk is defined as the combination of the severity of possible harms to the patient or user and the
probability of occurrence of each harm.

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Edition No. : 1
RISK ANALYSIS Revision No. : 00
Date : 15/05/2023

4. The severity scale

Severity is the measure of the possible consequences (damage, harm or
adverse health effect) of a hazard. Here, a ranking scale from 1 to 4 is used to
rank the severity of a potential harm.

Severity level Description Possible harm to user/patient

• Discomfort
Reversible alteration without
1: Negligible • Dissatisfaction, loss of time
medical care
• Infinitesimal local warmth

Reversible light alteration • Minor skin injury

2: Moderate
requiring medical care • Minor local skin irritation
• Major skin/bone injury
• Allergic skin reaction
• Respiratory tract irritation
• Other limited health risks due
to inhalation/ingestion of
3: Significant Reversible severe alteration
harmful chemical component
• Viral or bacterial infection
• Wrong diagnostic leading to
inadequate treatment or
unnecessary additional tests

5. The probability of occurrence scale

The likelihood ranking, also a scale from 1 to 4, indicates the probability of occurrence of a
harm.

Probability level Qualitative likelihood Quantitative likelihood

An event that is very unlikely < 1 in 1000 devices
1: Improbable
to happen < 0.1%
Unlikely to occur during total
Between 1 in 1000 and less than 1 in
operational life but may
2: Rare 100 devices
rarely occur when
0.1% - 1%
considering all
devices
Between 1 in 100 and less than 1 in 10
May occasionally occur
3: Probable devices
when considering all
1% - 10%
devices
Likely to occur at least once
≥ 1 in 10 devices
4: Frequent during operational life of
≥ 10%
the device
The probability of harm is inferred from the number of devices put on the

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Edition No. : 1
RISK ANALYSIS Revision No. : 00
Date : 15/05/2023

market and not from the total number of uses. Indeed, most risks will occur
only once, making the product is useless and requiring its return to the
manufacturer.

In fact, the probability of occurrence of harm is computed as the product of two different
probabilities:
- The probability of a hazardous situation occurring (P1)
- The probability of hazardous situation leading to harm (P2)

P1 and P2 are estimated separately and the overall probability of occurrence

P1xP2 is then determined following the table below.

P2
P1 x P2 Low Moderate High
0-1% 1-10% 10-100%
Low
1: Improbable 1: Improbable 2: Rare
0-1%
Moderate
P1 1: Improbable 2: Rare 3: Probable
1-10%
High
2: Rare 3: Probable 4: Frequent
10-100%

Since we have no historical, production or PMS data, probabilities are initially

estimated based on expert knowledge and common sense, always considering a
worst-case scenario (highest possible probability of occurrence). Experimental
data, analytical techniques or simulation may be used in this assessment.
Probabilities will be re-evaluated using historical, production and PMS data.

6. Risk acceptability Criteria

The acceptability criteria are defined using the matrix below.

According to the EU Directive 93/42/EEC, all risks should be considered

and reduced as far as possible (even if the risk is in a broadly acceptable
region).

The matrix is used to evaluate risks before and after risk control measures are implemented.

Severity
Probability 1: Negligible 2: Moderate 3: Significant

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1: Improbable 1 5 7
2: Rare 2 6 10
3: Probable 3 8 11
4: Frequent 4 9 12

Negligible risk (1-7)

Acceptable risk (8-11)

acceptable risk (12)

7. Risk-benefit evaluation criteria

According to EN ISO 14971:2012, a risk-benefit analysis is not required for
every risk. However, as stated in point 4 of Annex ZA of the EU Directive
93/42/EEC, it is required that the manufacturer performs a risk-benefit analysis
for the individual risk and the overall risk-benefit analysis in all cases.

The risk-benefit ratio is evaluated by the risk management team who establish
the acceptability of the risk as a function of the expected performance of the
device and the actual experience. The benefits determined in the clinical
evaluation report are used as the basis of the evaluation.

Medical Device Benefits are:

- Performance 1: homogenization and enhancement of the transmit

1 B +

field in the temporal lobes in the vicinity of the pads.

A risk-benefit analysis is used to justify a risk once all practicable measures to

reduce the risk have been applied. If, after applying these measures, the risk is
still below acceptability level, a risk/benefit analysis is needed to establish
whether the medical device is likely to provide more benefit than harm.
Generally, if all practicable risk control measures are insufficient to satisfy the risk
acceptability criteria in the risk management plan, the design or the
manufacturing steps shall be modified.

Verification and evaluation of overall residual risk

The overall residual risk evaluation process occurs subsequent to
implementation and verification of individual risk reduction measures. During
the design and development cycle, the risk management process is focused on
individual risks and associated risk reduction measures. During the overall
residual risk evaluation process, the device must be evaluated as a “whole” with
all individual risk reduction measures implemented and tested.

At least once per year, a risk management review is performed; it reviews the

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risk management plan, the risk analyses, and all clinically obtained data.

A team is put together to perform the risk review. Note that it is possible to have
an external person on the team.

At the end of the review, a new risk management report is written and archived.

7.1 Review of all residual risks

During the risk management review, all risk analyses and risk control measures
(reports, technical documents, instructions for use, etc.) are reviewed. A
column is filled in on the day of the review for the group to ensure that the
evidence for each risk control measure is available.

If there is a lack of evidence, an action plan shall be established and a

provisional deadline to obtain the required evidence will be indicated. A
summary, in the form of two risk acceptability tables, is then made based upon
the risk analysis files. These two tables provide an overview of risk reduction
through risk control methods. The types of risks are described and it is ensured
that these risks are considered in the clinical evaluation. These tables are part
of the risk management report.

It should be noted that a decrease in the risk score is only effective if the
associated evidence is available; in the absence of this evidence, the initial risks
core applies.

7.2 Method used to analyze overall residual risk

Evaluation of the overall residual risk is the step in which the residual risk is
examined from a broad perspective. In accordance with annex D.7 of EN ISO
14971:2012, the methods below will be used to evaluate overall residual risk.

7.3 Review for conflicting requirements

Risk control measures that are appropriate for individual risks can result in
conflicting requirements when all the risks are evaluated.

During the risk review, special attention should be focused on evaluating any
conflicting requirements between the control options chosen.

If one conflicting requirement is found during the review, the risk controls
should be reviewed and a new risk analysis must be performed until no to
eliminate conflicting requirements are found.

7.4 Review of warnings in the manuals/ instructions for use

A warning considered on its own may provide adequate risk reduction;
however, too many warnings can reduce the effect of individual warnings.

During the risk analysis review, the team in charge should determine if the
warnings are adequate, and easy to understand, in order to have an acceptable
overall residual risk. The team must also ensure that all risk control measures

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related to information for safety specified in the risk analysis are included in the
instructions for use.

7.5 Residual risk interactions

The overall residual risk must be evaluated in terms of potential combinations
of individual residual risks as well as their frequency and gravity.

A combined risk is a new risk resulting from the simultaneous or concomitant

appearance of two or more dangerous situations.

During the risk management review, the team will separate residual risks that are «
combinable » from those that are « impossible to combine ».

The team must then evaluate if the residual risks can be combined, by asking two main
questions:

1. Does a new risk emerge from the combination of the residual risks?

2. Does the combination of the residual risks lead to a higher risk level than
each individual residual risk?

If the answer to one of the two questions is YES, a new risk-benefit analysis of
the combined residual risks must be conducted.

If the answer is NO for both questions, there is no need for a further risk-benefit analysis.

7.6 Global residual risk

Considering 16 risk values placed in the table of §6.4.

At the time of the review, the working group will ensure that:

 There is no longer any unacceptable risk (no risk > 11)

 The average risk is acceptable (average risk ≤ 7)

Average risk: Ar = ∑ Rn / N with N total number of risks and Rn the individual risk value.

7.7 Overall residual risk acceptability criteria

The table below summarizes the acceptability criteria used to assess the overall residual risk.

Acceptability criteria Answers given during the

review
Residual risk interaction
New risk identified YES/ NO
Risk with a higher risk YES /
level NO
Conflicting requirements YES / NO
Review of warnings
Inadequate warning in instruction
YES / NO
manual

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Comparison of risks
New risks or higher-level risks YES / NO
ACCEPTABILITY of OVERALL
UNACCEPTABLE(*)/ ACCEPTABLE
RESIDUAL RISK
(*): the overall residual risk is judged unacceptable if one or
more of the answers in the right column is YES.
If a new risk or a higher risk is identified, new risk control options must be
applied in order to reduce the risk to an acceptable level, and a new risk
analysis performed.

If conflicting requirements are found, the team in charge of the review must find a
way to reduce them until the associated risk becomes acceptable

If inadequate warnings are found in the manual, or the instructions are difficult
to understand or incoherent, the team in charge of the review must modify the
manual such that no inadequate warnings remain.

If no solutions can be found to reduce risks to acceptable levels, the design

and/or the production should be modified or stopped.

N.B.: In accordance with Article 7 of the standard EN ISO 14971:2012, in the

case where the overall residual risk is deemed to be unacceptable according to
the criteria set out in the Article, the team must establish whether the medical
advantages of the intended usage of the device outweigh the overall residual
risk.

The risk-benefit ratio for the overall residual risk is evaluated with the help of
the clinical evaluation. This risk-benefit ratio is qualitative and is based on the
literature about the product itself and similar products.

If the medical benefit outweighs the overall residual risks, then the latter are deemed to be
acceptable.

3. Risk Management report & updates

3.1.1 Frequency of reviews/reports
At least once a year, a risk management review is carried out. This is a review of
the risk management plan, the risk analyses, the PMS file and the clinical
evaluation.

Any corrective and preventative actions implemented are evaluated using the
product review (PMS) to verify that the agreed actions are effective.

Additional risk management reviews may take place as required upon the
occurrence of particular events: customer complaints, adverse events, ANSM
website alerts, literature reviews, etc.

A team must be established for this additional review; afterwards, a new risk
management report is written and archived.

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3.1.2 Contents of the review / risk management report

Prior to the first placing of the product on the market, and in accordance with
the risk management procedure, a risk management review is performed. After
this review, the risk management report makes it possible to guarantee and
ensure:

1. The risk management plan has been appropriately implemented

2. The overall residual risk has been reviewed and is acceptable

3. Appropriate methods are in place to obtain relevant production and post-production

information

Once the product is on the market, a review of the risk management file is carried
out on a yearly basis or whether a change occurs that could impact patient
safety (field feedback, adverse events, changes in the design, etc.).

4. Method of collecting production and post production information

Procedure is followed to collect production and post-

production information. At a minimum, the collected

data must include:

 Product and supplier non-conformities

 Customer complaints
 Customer satisfaction
 Changes in the literature
 Adverse events of similar products
 Production information directly related to the product
These data are part of the post market surveillance and allow regular updating of risk
management.

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