Risk Management Report

Herpes Simplex Virus -Ⅰ/Ⅱ IgM (HSV-Ⅰ/Ⅱ IgM) Assay

Reagent Kit (CMIA)

Drafted by: Hu Yong

Date: 2021.08.21

Reviewed by: Liu Gang

Date: 2021.08.23

Approved by: Ding Pengfei

Date: 2021.08.25

<Hangzhou Realy Tech Co., Ltd.>

1/34
 Revision history

Revised
Revised content Revised reason Revised date Revisor
chapter

2 / 34
1.Summary
1.1 Purpose and Scope
The usage of the devices would not cause any direct risk to patients or users, however in some
conditions, hazards concerning in vitro diagnostic medical devices which lead to or contribute to
incorrect decision, would pose indirect risks. The risk management report was applied to identify the
risks of the product series, define the risk acceptability, control risks to meet the safety requirements of
products.
The risk management analyzed and evaluated the risks related product intended use, safety
characteristic and apparent or potential hazards, took measures to control the risks, meanwhile,
evaluated the acceptability of residual risks after risk control. It is confirmed that the product risks
were managed and controlled within acceptable ranges.
1.2 Product Introduction
1.2.1 Test principle
The HSV-Ⅰ/Ⅱ IgM assay is a two-step immunoassay for the qualitative measurement of HSV-Ⅰ IgM
antibodies in human serum and plasma using CMIA technology, with flexible assay protocols.
In the first step, sample and HSV recombinant antigen coated paramagnetic microparticles are
combined. HSV-Ⅰ IgM and HSV-Ⅱ IgM present in the sample binds to the HSV recombinant antigen
coated microparticles. After that, ALP-labeled mouse anti-human IgM antibody conjugate is added to
create a reaction mixture in the second step. Following wash cycle, substrate is added to the reaction
mixture. The resulting chemiluminescent reaction is measured as relative light units (RLUs). A direct
relationship exists between the amount of both HSV-Ⅰ IgM and HSV-Ⅱ IgM in the sample and the
RLUs detected by the System optics.
1.2.2 The main components
Materials provided:
1.HSV-Ⅰ/Ⅱ IgM Test Device 2. Product Insert
3. Calibration Solution (optional) 4. Control Solution (optional)
Materials required but not provided
1. Analyzer
1.2.3 Intended use
The Herpes Simplex Virus -Ⅰ/Ⅱ IgM (HSV-Ⅰ/Ⅱ IgM) Assay Reagent Kit (CMIA) a chemiluminescent
microparticle immunoassay (CMIA) for the qualitative determination of herpes simplex virus IgM
(HSV-Ⅰ/Ⅱ IgM) antibodies in human serum and plasma.
1.2.4 Product Storage Condition and Validity Period
1. Store the kit at 2-8°C and avoid light, with a stable period of 18 months.
2. The HSV-Ⅰ/Ⅱ IgM Reagent Kit (CMIA) must be used immediately after removal from 2-8℃ storage
or the device was opened.
1.3 Basis information
1.3.1 Related basis
(1)ISO 14971-2019 Medical devices — Application of risk management to medical devices
(2)EN ISO 13485-2016 Medical devices — Quality management systems — Requirements for
regulatory purposes
(3)ISO/TR 24971:2020 Medical devices — Guidance on the application of ISO 14971
1.3.2 Information about the product
(1)Product technical requirements

3
(2)Product instruction for use
(3)The use of similar products, customer complaints records, etc
(4)Articles and other information in professional literature
1.4 Risk Management Team Related users
Risk management group and responsibilities.
users Title Department Responsibility
Management Coordinating of product risk management and
Wujianghai Management Level
Representative approving of risk management files.
Organizing of risk management group,
activities and writing of risk management
report.
LiuGang Dept. Manager R&D
Participate in risk analysis and evaluation,
formulation and implementation of risk
control measures, and residual risk evaluation.
Hongchuny Risk analysis and risk control in production
Dept. Manager Production Dept.
ong stages of product.
Quality Control Risk analysis and risk control in quality
Yangxiao Dept. Manager
Dept. control stages of product.
Responsible for providing legal basis for risk
Regulatory Affairs
Zhouyinyan Dept. Manager management and reviewing risk management
Dept.
activities.
Risk analysis and risk control in sale stages of
Duxiaoning Dept. Manager Marketing Dept.
product.
2. Risk Management Review Input
2.1 Risk acceptance criteria
In accordance with the requirements of the risk Management Control Procedure, the Risk Management
Team has developed a risk management plan in which the risk acceptance criteria are established by
rating the probability and severity of the injury in accordance with the company’s risk control policy,
as follows:

4
2.1.1 Probability Level of Risk (P)
Level Code Frequency (per year)
Improbable 1 ＜10-6and ≥10-7
Remote 2 ＜10-5and ≥10-6
Occasionally 3 ＜10-4and ≥10-5
Probable 4 ＜10-3and ≥10-4
Frequent 5 ≥10-3
2.1.2 Severity level of risk(S)
Level Code System risk definition
Negligible 1 Inconvenience or temporary discomfort or no danger (source)
Cause temporary injury or injury that does not require professional medical
Minor 2
intervention

Serious 3 Cause injuries or injuries that require professional medical intervention

Critical 4 Cause permanent damage or life-threatening injury

2.1.3 Risk Acceptance Criteria

Severity
S1 Negligible S2 Minor S3 Serious S4 Critical

Probability
P5 Frequent A U U U

P4 Probable A U U U

P3 Occasionally A A U U

P2 Remote A A A U

P1 Improbable A A A A

Note: A - Acceptable U - Unacceptable

2.1.4 Risk Acceptable Criteria Coefficient Value Analysis
Based on the 5×4 risk assessment matrix of the above-mentioned risk assessment criteria, identify the
acceptable areas of risks.
Acceptable coefficient Ac=Pi×Si
2.1.4.1 Acceptable risk
Ac＜8
While the risks are acceptable, the feasibility of accepting further reductions in risk needs to be
considered, and any risk should be reduced to a feasible minimum.
2.1.4.2 Unacceptable risk
Ac≥8
In this region, risk control measures should be analyzed to reduce risks. If the risk after adopting
control measures are still unacceptable, the benefit of accepting the risk should be analyzed, and the

5
risk should be compared with the benefit. If the benefit exceeds the risk, the risk is acceptable; If the
risk is not exceeded, the risk is unacceptable.
2.2 Risk management documentation
1) Risk management plan;
2) List of safety characteristics and possible hazards (source) analysis table;
3) Risk analysis table;
4) Risk assessment and control list;
5) Production and post-production risk analysis record sheet.
3.Risk management review
3.1 Completion of the risk management plan
The review team reviewed the risk management documentation and concluded that it basically met the
requirements of risk management and completed the risk management plan.
3.2 Comprehensive residual risks assessment
The review team evaluates the identified risks in the design and development phase and the previous
risk management activity cycle, the production and post-production risks identified in this cycle one by
one, and conducts a comprehensive analysis of all residual risks, considering the common impact of all
individual residual risks According to the review result, the comprehensive residual risk of the product
is acceptable. The following are the specific evaluation aspects:
1) Have all the production and post-production risks related to the product been identified at this stage?
The conclusion is: Yes
2) Are there conflicting requirements for the risk control of a single risk?
Conclusion: There is no contradiction in the existing risk control.
3) Will risk control measures trigger new risks?
Conclusion: No.
4) Conclusion of the review
Conclusion: After analyzing the above aspects, the risk management review team unanimously
evaluated that the comprehensive residual risk of this product is acceptable.
3.3. Review the approved risk management documentation
1) Annex1:List of safety features and possible hazards (source) analysis table;
2) Annex2:Risk analysis table ;
3) Annex3:risk assessment and control list;
4) Annex4:Production and post-production risk analysis record sheet.
4. Risk management review conclusions
The risk management review team reviewed the risk management process by checking risk
management documents, and concluded that:
-The risk management plan has been properly implemented;
-The comprehensive residual risk of the product is within the acceptable range of the risk acceptance
criteria, and the benefit exceeds the risk.
The product’s effectiveness and safety meet relevant requirements.
Continue to carry out risk management activities after the product post-product in accordance with the
requirements of the “Risk Management Control Procedures”.

6
Annex 1: List of safety features and possible hazards (source) analysis table;
Identification of intended uses and safety-related characteristics (refer to
ISO/TR 24971:2020 Medical devices — Guidance on the application of ISO
14971 Appendix A and Appendix H).
Hazard
Possible hazard
Issue Feature determination (source)
(source).
identification

A.2.1 The Herpes Simplex Virus -Ⅰ/Ⅱ IgM (HSV-Ⅰ/Ⅱ

What is the IgM) Assay Reagent Kit (CMIA) a

intended use and chemiluminescent microparticle immunoassay

Information hazards H1
how is the (CMIA) for the qualitative determination of herpes

medical device to simplex virus IgM (HSV-Ⅰ/Ⅱ IgM) antibodies in

be used? human serum and plasma.

The Herpes Simplex Virus -Ⅰ/Ⅱ IgM (HSV-Ⅰ/Ⅱ

A 2.1.1 IgM) Assay Reagent Kit (CMIA) a

What is the chemiluminescent microparticle immunoassay

Information hazards H2
medical device’s (CMIA) for the qualitative determination of herpes

role relative to: simplex virus IgM (HSV-Ⅰ/Ⅱ IgM) antibodies in

human serum and plasma.

A 2.1.2
The Herpes Simplex Virus -Ⅰ/Ⅱ IgM (HSV-Ⅰ/Ⅱ
What are the
IgM) Assay Reagent Kit (CMIA) a
indications for
chemiluminescent microparticle immunoassay
use (e.g. patient Information hazards H3
(CMIA) for the qualitative determination of herpes
population, user
simplex virus IgM (HSV-Ⅰ/Ⅱ IgM) antibodies in
profile, use
human serum and plasma.
environment)?

A 2.1.3

What are the Not applicable / /

contraindications

A 2.1.4

Does medical
Not applicable. / /
devices sustain

or support life?

A 2.1.5 The failure of the medical device is caused by Improper use by users H4

Is special Forgot to put in the pipette tip, the barcode fell off, leads to wrong results.

intervention the information was entered incorrectly, and the Using hazards (source)

7
necessary in the reagent expired etc.. User use it without look H5

case of failure of The analyzer will automatically check the relevant in IFU.

the medical information, and if the operation is incorrect, an Operation hazards

device? error reminder will pop up. (source)

At the same time, at the beginning of the

experiment, the operator is prompted to put in the

pipette tip.

A 2.1.6

Can the

performance of
Improper temperature
the medical
and humidity may
device be 1. Store the kit at 2-8°C, with a stable period of 18
influent the test quality.
impacted in the months.
Improper H6
event of a 2. The kit must be used immediately after removal
storage/transport
security breach from 2-8℃ storage or the device was opened.
environment hazard
(performance
(source)
degradation or

loss of

availability)?

A 2.1.7

Can

unauthorized Test results of this kit are for clinical reference

access, only. It is recommended that a comprehensive

unauthorized analysis of the disease be conducted based on Operational hazards H7

activities, or loss clinical manifestations of patients and other

of data affect the laboratory tests.

medical device

safety?

A.2.2

Is the medical
Not applicable. / /
device intended

to be implanted?

A.2.3
The user uses sampling accessories to take
Is the medical
samples. Chemical hazards H8
device intended

to be in contact

8
with the patient

or other persons?

A.2.4

What materials

or components

are utilized in the

The kit contains test device; product insert;
medical device / /
calibration solution (optimal).
or are used with,

or are in contact

with, the medical

device?

A.2.5

Is energy

delivered to or Not applicable. / /

extracted from

the patient?

A.2.6

Are substances

delivered to or Not applicable. / /

extracted from

the patient?

A.2.7

Are biological

materials

processed by the

medical device Not applicable. / /

for subsequent

reuse,transfusion

or

transplantation?

A.2.8

Is the medical

device supplied
Not applicable. / /
sterile or

intended to be

sterilized by the

9
user, or are other

microbiological

controls

applicable?

A.2.9

Is the medical

device intended

to be routinely Not applicable. / /

cleaned and

disinfected by

the user?

A.2.10

Does the medical

device modify Not applicable. / /

the patient

environment?

A.2.11

Are It is used for in vitro quantitative detection to

Operational hazard H9
measurements provide concentration value

taken?

A.2.12

Is the medical
Not applicable. / /
device

interpretative?

A.2.13

Is the medical

device intended

for use in

conjunction with
Not applicable. / /
other medical

devices,

medicines or

other medical

technologies?

A.2.14
Not applicable. / /
Are there

10
unwanted

outputs of energy

or substances?

A.2.15

Is the medical 1. Store the kit at 2-8°C, with a stable period of 18

device months.
Information hazard H10
susceptible to 2. The kit must be used immediately after removal

environmental from 2-8℃ storage or the device was opened.

influences?

All samples in the test should be handled as

A.2.16
contaminated items and should be operated in
Does the medical
accordance with the Code of Practice for Biological hazard H11
device influence
Infectious Disease Laboratories with attention to
the environment?
biosafety practices.

A.2.17

Does the medical

Yes, it is necessary to use quality control and Hazards of functional
device require H12
calibration products regularly failure
consumables or

accessories?

A.2.18

Is maintenance Hazards of functional

Yes, periodic calibration of the system is required. H13
or calibration failure

necessary?

A.2.19

Does the medical

Not applicable. / /
device contain

software?

A.2.20

Does the medical

device allow Not applicable. / /

access to

information?

A.2.21

Does the medical

Not applicable. / /
device store data

critical to patient

11
care?

A.2.22

Does the medical

Store the kit at 2-8°C, with a stable period of 18 Hazards of functional
device have a H14
months. failure
restricted shelf

life?

A.2.23

Are there any

delayed or Not applicable. / /

long-term use

effects?

A.2.24

To what

mechanical
Not applicable. / /
forces will the

medical device

be subjected?

A.2.25
Formulations, raw materials, processes and
What determines Information Hazard and
transportation, storage conditions ensure that the
the lifetime of Hazards of functional H15
product achieving the basic conditions of design
the medical failure
life.
device?

A.2.26

Is the medical
The kit and accessories are all single-used. Operational hazards H16
device intended

for single use?

A.2.27

Is safe

decommissioning
Not applicable. / /
or disposal of the

medical device

necessary?

A.2.28

Does installation Yes. Read the product manual carefully before

Operational hazards H17
or use of the use.

medical device

12
require special

training or

special skills?

A.2.29

How will
Information for safety will be offered through the
information for Information Hazard H18
IFU.
safety be

provided?

A.2.30

Are new

manufacturing
Not applicable. / /
processes

established or

introduced?

A.2.31

Is successful

application of the

medical device Not applicable. / /

dependent on the

usability of the

user interface?

A.2.31

Can the user

interface design
Not applicable. / /
features

contribute to use

error?

A.2.31.2

Is the medical

device used in an

environment Not applicable. / /

where

distractions can

cause use error?

A.2.31.3
Not applicable. / /
Does the medical

13
device have

connecting parts

or accessories?

A.2.31.4

Does the medical

Not applicable. / /
device have a

control interface?

A.2.31.5

Does the medical

Yes, wrong result reading. Information Hazard H19
device display

information?

A.2.31

Is the medical
Not applicable. / /
device controlled

by a menu?

A.2.31.7
1.This kit is intended for professional use.
Is the successful
2.The kit contains test device; product insert;
use of the
calibration solution (optimal).
medical device Operational hazards H20
3.The user uses the biological bag to store the used
dependent on a Biological hazard H21
medical device and sampling accessories for
user’s
proper disposal to avoid environmental pollution.
knowledge, skills
4.The kit and accessories are all single-used.
and abilities?

A.2.31.8

Will the medical

device be used Not applicable. / /

by persons with

specific needs?

A.2.31.9

Can the user

interface be used
Not applicable. / /
to initiate

unauthorised

actions?

A.2.32
Not applicable. / /
Does the medical

14
device include an

alarm system?

A.2.33

In what ways

might the

medical device Not applicable. / /

be misused

(deliberately or

not)?

A.2.34

Is the medical

device intended Not applicable. / /

to be mobile or

portable?

A.2.35

Does the use of

the medical Yes, it depends on the stability and accuracy of Hazards of functional
H22
device depend on reagents. failure

essential

performance?

A.2.36

Does the medical

device have a Not applicable. / /

degree of

autonomy?

A.2.37 There is no description

Does the medical of important

As interpret the results, the patient’s overall
device produce information in the
clinical situation, including symptoms, medical
an output that is IFU,resulting in H9
history and other related data, should be referred
used as an input incorrect use
to.
in determining Information Hazards

clinical action? (Source)

H.2.1 The Herpes Simplex Virus -Ⅰ/Ⅱ IgM (HSV-Ⅰ/Ⅱ

Intended use and IgM) Assay Reagent Kit (CMIA) a

Operational hazards H1
reasonably chemiluminescent microparticle immunoassay

foreseeable (CMIA) for the qualitative determination of herpes

15
misuse simplex virus IgM (HSV-Ⅰ/Ⅱ IgM) antibodies in

human serum and plasma.

This kit is intended for professional use.

The Herpes Simplex Virus -Ⅰ/Ⅱ IgM (HSV-Ⅰ/Ⅱ

IgM) Assay Reagent Kit (CMIA) a

H.2.1.1 chemiluminescent microparticle immunoassay

Analysis and (CMIA) for the qualitative determination of herpes Operational hazards H1

clinical use simplex virus IgM (HSV-Ⅰ/Ⅱ IgM) antibodies in

human serum and plasma.

This kit is intended for professional use.

H.2.1.2 Warnings or suggestive text are missing or not

Device prominent enough and the IFU for use are not Information Hazards H23

description detailed enough.

The Herpes Simplex Virus -Ⅰ/Ⅱ IgM (HSV-Ⅰ/Ⅱ

IgM) Assay Reagent Kit (CMIA) a

chemiluminescent microparticle immunoassay Improper use by users

H.2.1.3
(CMIA) for the qualitative determination of herpes leads to wrong results. H1
Analytical use
simplex virus IgM (HSV-Ⅰ/Ⅱ IgM) antibodies in Using hazards (source)

human serum and plasma.

This kit is intended for professional use.

The Herpes Simplex Virus -Ⅰ/Ⅱ IgM (HSV-Ⅰ/Ⅱ

IgM) Assay Reagent Kit (CMIA) a

chemiluminescent microparticle immunoassay Improper use by users

H.2.1.4
(CMIA) for the qualitative determination of herpes leads to wrong results. H1
Clinical use
simplex virus IgM (HSV-Ⅰ/Ⅱ IgM) antibodies in Using hazards (source)

human serum and plasma.

This kit is intended for professional use.

There is no description

of important
H.2.2 As interpret the results, the patient’s overall
nformation in the
Characteristics clinical situation, including symptoms, medical
IFU,resulting in H9
related to patient history and other related data, should be referred
incorrect use
safety to.
Information Hazards

(Source)

H.2.2.1
See below for details / /
General

16
considerations

1.The batch does not

meet the requirements;

2.The specificity does

H.2.2.2 This product is a quantitative testing product with
not meet the
Performance analytical sensitivity, analytical
requirements;
characteristics specificity,diagnostic sensitivity and diagnostic H10
3.The stability of the kit
related to patient specificity and other performance characteristics
does not meet the
safety related to patient safety.
requirements.

Operation hazards

(source)

1.The batch does not

meet the requirements;

2.The specificity does

H.2.2.3
not meet the
Reliability Reliability features associated with patient safety
requirements;
characteristics of this product Includes kit quality controls H10
3.The stability of the kit
related to patient Stability and system availability (avoiding errors).
does not meet the
safety
requirements.

Operation hazards

(source)

H.2.2.4

Digital

information

technology Not applicable / /

characteristics

related to patient

safety

H.2.3

Known and
See below for details / /
foreseeable risks

to patients

H2.3.1 As interpret the results, the patient’s overall There is no description

Hazard clinical situation, including symptoms, medical of important H9

identification history and other related data, should be referred nformation in the

17
a)Incorrect to. IFU,resulting in

examination incorrect use

result Information Hazards

b)Delayed (Source)

examination

result

c)Incorrect

information

accompanying

the result

1.The batch does not

meet the requirements;

2.The specificity does

not meet the

requirements;

3.The stability of the kit

does not meet the

requirements.

Inconsistencies (reagents or quality controls) Operation hazards

H2.3.2 H10
within or between batches; (source)
Identification of H7
Samples or reagents carry contaminants (e.g. 4.Improper
hazards from H9
brought in by pipettes); storage/transportage
fault conditions
Reagent failure(during transport, storage or use); condition hazard

(source)

5.There is no

description of

important nformation in

the IFU,resulting in

incorrect use

Information Hazards

(Source)

1.The batch does not

H2.3.3
Inherent false negative and false positive rates; meet the requirements;
Identification of H10
Effects of interference substances in samples; 2.The specificity does
hazards from H9
Methodological limitations not meet the
normal use
requirements;

18
 3.The stability of the kit

does not meet the

requirements.

Operation hazards

(source)

4.There is no

description of

important nformation in

the IFU,resulting in

incorrect use

Information Hazards

(Source)

Improper use by users

leads to wrong results.

H.2. 3.4 An unexpected activity by an user,such as a
Using hazards (source)
Identification of procedure that simplifies, attempts to optimize, H1
User do not use it
hazards from use improve, or omits the expected activity described H2
without look in IFU.
errors by the manufacturer in the IFU.
Operation hazards

(source)

Improper use by users

H.2.3.5
leads to wrong results.
Identify hazards Users without carefully reading the IFU or ignore
Using hazards (source)
resulting from the warnings, IFU,or other safety information in H1
User do not use it
reasonably the IFU; H2
without look in IFU.
foreseeable Incorrect storage of reagents;
Operation hazards
misuse
(source)

Improper use by users

False negative results may result in the leads to wrong results.

H.2.4 deterioration of preventable or treatable diseases Using hazards (source)

H1
Identify potential or loss or delay in treatment benefits, and false User do not use it
H2
hazards positive results may result in unnecessary medical without look in IFU.

interventions or loss or delay in treatment benefits Operation hazards

(source)

Hazard arising in Many factors in the procurement,processing and Hazard from H11

the procurement, production process have certain impact on the production errors 1

19
processing and quality of the kit, such as the reagent preparation (source) H12

production process did not follow the operating procedures, Hazard caused by

resulting in product failure; Products substandard

failure,comtamination,mixing in the sub-package purification of water H13

process, due to not following the operation (source)

procedure; Due to the packaging error, the model Hazard caused by

specifications of the product in use are not substandard production H14

correct. environment (source)

Hazards caused by H15

uncalibrated metering H16

instruments (source) H17

procurement Hazard H18

(Source)1

Production hazards

(source) H19

Hazards caused by

nonconforming

products not being H20

identified or recalled in

time (source)

Quantity shipped does

not match the quantity

ordered(source)

20
 Appendix 2 Hazard (Source) Analysis, including a foreseeable sequence of
events, hazardous situations and an analysis of possible harm and initial risk
control measures
Hazard
Hazard Foreseeable sequence Consequences or Initial risk control
(source) Hazard situation
(source) of events Harms measures
identification

Fail to clearly
Inappropriate
Information indicate the use of Standardize the content of
H1 representation of User misuse
hazards the product in the the IFU.
intended use
IFU.

The user
1. Procurement control.
accidentally eats
2. Carry out necessary
The user may have and touches
Reagents, samples biological safety tests on
direct contact with allergic
Chemical and other substances raw materials.
H2 potentially infectious substances
hazards have not been tested 3. Users are reminded to
samples, reagents or causing skin
for safety. pay attention to personal
other substances. allergies and
protection when operarting
even health
in the instructions.
threats.

Operated by Strictly follow the

Operational The wrong operation
H3 unskilled or Wrong Result instructions in IFU when
hazard performed by operator.
untrained personnel. perform the test.

Storage conditions

Information and expiry date are Information missing in Standardize the content of
H4 User misuse.
hazard not clearly indicated the IFU. the IFU.

in the IFU.

The IFU should indicate

After use, samples
Biological Environmental Environmental that the laboratory waste
H5 and reagents discard
hazards pollution. pollution should be treated as
at will.
infectious materials.

Hazards of Quality control is not Quality control should be

The system is Cause wrong test
functional H6 performed with strictly performed in
unconfirmed. results.
failure quality control. accordance with IFU.

Hazards of Calibration is not The system is not Calibration should be

Cause wrong test
functional H7 performed with confirmed through strictly performed in
results.
failure calibrator. calibrator. accordance with IFU.

21
 Wrong results Clarify the expiry date of
Hazards of Lead to wrong results
Product use beyond lead the doctor the product and indicate
functional H8 or failure to obtain
the expiry date. make the wrong the expiry date of the
failure results.
medical decision. product on the label.

1.The outer box is

damaged in the
Information
course of production,
Hazards Users using the Strict control of the
transportation, Inappropriate
and product whose packaging process and
H9 handling and storage. packaging of the
Hazards of package is verification of the
2. The package is not product.
functional damaged. packaging.
strictly sealed.
failure
3. Inappropriate

packaging material.

The test card and Inadequate warnings

Operational accessories are not about the hazards of Standardize the content of
H10 User misuse.
hazards described in the IFU likely re-use of the IFU.

as singled-used. single-use products

The instructions are clearly

It is used by those who The product can’t
Operational Users can’t use the stated on how to use in the
H11 have some trouble with reach its intended
Hazard product correctly. IFU and read the IFU
reading. use.
carefully before use

1. Lack of detailed

information for use

Information Inadequate precautions Standardize the content of
H12 in the IFU. Users misuse.
Hazards in the IFU. the IFU.
2. Lack of necessary

warnings in the IFU.

Failure to obtain the Strictly follow the

Operational The wrong operation Cause wrong test
H13 results or get the instructions in IFU when
Hazards performed by operator. results.
wrong results. perform the test.

22
 The product cannot

achieve the proper The quality of the

Each batch of products are
analytical kit cannot be
Hazards of No enough verification tested for analytical
sensitivity,analytical guaranteed,
functional H14 of the product performance, confirming
specificity and/or which cause
failure performance. that only qualified products
diagnostic incorrect test
can be sold at the factory.
sensitivity,diagnostic results.

specificity.

1.Strict implementation of

the relevant provisions of

1.Raw materials are
Due to the shortage of Customer the Procurement Control
out of stock or
raw materials, complaints; Procedure.
suppliers are in stock.
Procument production could not No product 2.The procurement
H15 2.Peak logistics and
Hazard 1 proceed as planned, available and contract strictly agreed
transportation or
and products were in delays in clinical delivery time, in case of
customs acceptance
tight or out of stock. use. logistics and transportation
period.
peak consider in advance

of stocking.

1.The order details in 1.Delay the putting in

Customer 1.Strict implementation of
the purchase contract storage check,
complaints; raw materials procurement
do not match the affecting the normal
Procument No product procedure..
H16 arrival product production.
Hazard 2 available and 2.Test the raw materials
details. 2.Unqualified raw
delays in clinical according to the relevant
2.Raw materials exist materials affect
use. SOP.
quality problems. product quality.

Raw materials, 1.Use of unqualified 1.Product 1.Establish a standardized

primers, DNA raw materials during non-conformity material management

polymerase, production process, rate increased system, so that the flow of

nuclease-free water leads to risk to product lead to a large materials is clear,

have an impact on quality. number of waste traceable.

Production
H17 quality. 2.Unqualified and cost surge. 2.Unqualified products
Hazard 1
2.The failure of production 2.Non-conformin should be timely identified

ambient temperature environment is not g products flow and isolated.

and humidity to meet found in time, to the user side 3.For key process should

the standards has an production lines caused the establish a multi-person

impact on quality. continue to be exposed detection results review system to ensure

23
 3.The reagent to unqualified and real results of product quality, while

preparation production major errors, and strengthening the

operation error. environment. make the wrong supervision of the

3.Instrument operating medical decision. production process.

errors lead to an 4.Conduct the functional

increase in defective testing for key raw

rate. materials before the

production .

1.Lead to lots of

waste and cost 1.Before assembly, the

surge. assembly team leader

1.When assembled,
2.Wrong carefully check the
mix in the wrong
products flow to finished assembly list
semi-finished 1.Product
the market about the assembly items
product or quantity non-conformity rate
Production caused wrong test and quantities.
H18 does not match. increased
Hazard 2. results ,which 2.Carefully check the
2.After assembly, the 2.Wrong products are
leads to wrong project’s semi-finished
name of the lable put into the market.
diagnosis, products, IFU and
does not match the
treatment or qualities.
request.
monitoring of 3.After assembly,carefully

medical decision check the label.

for patients.

1.Regular stability It is stipulated that sample

inspection was kits should be inspected on

ignored, so that fail Unqualified a regular basis and reported

Hazards to find unqualified products caused in a timely manner.

caused by products in the wrong test Strengthen the training of

unqualified reserved samples Users continue to use results ,which QC users, strengthen their

products 2.QC inspection the products and trust leads to wrong ability to identify
H19
not being found unqualified the test results which diagnosis, non-conforming products,

identified reserved sample are already unreliable. treatment or and strengthen the

or recalled products, but not monitoring of supervision and monitoring

in time report in time. medical decision of the inspection process.

3.Company did not for patients. Strict implementation of

carry out recall unqualified product control

procedures for procedures, product recall

24
 unqualified product. management procedures.

1.Before delivery carefully

1.The shipper did not Users receive fewer or
Customer check the order quantity.
The carefully check the more products than
complaints result 2.Before delivery carefully
quantity order quantity expected, resulting in
in a loss of verify the quantity on the
shipped 2.Shipping users did out-of-stock or
reputation for the demand list and fill in the
does not H20 not carefully check dissatisfaction.
company. kit batch number.
match the the order product Users receive products
Losses caused by 3.After packaging
quantity category,delivered that not match their
delays in clinical according to the demand
ordered wrong products to needs, leads to the
examinations. list check the shipping
costumers. delay of diagnosis.
items and quantities.

25
 Appendix 3 Risk assessment, control analysis, residual risk assessment form
Whether new risks are
Pre-measures risk Post-measures risk
created (if so, assess new
assessment assessment
risks)
Hazards Initial risk control measure Control measures implementation remark
pro
Severi Level Severit probabili Level Seve probabi Level of
babi
ty of risk y ty of risk rity lity risk
lity

H1 S3 P3 U Standardize the content of the IFU. Refer to IFU S3 P2 A N N N

1. Procurement control.

2. Carry out necessary biological safety

tests on raw materials.

H2 S3 P2 A Refer to test report and IFU S3 P1 A N N N
3. Users are reminded to pay attention to

personal protection when operarting in the

instructions.

Strictly follow the instructions in IFU when

H3 S3 P3 U Refer to training records S3 P2 A N N N
perform the test.

26
H4 S3 P4 U Standardize the content of the IFU. Refer to IFU S3 P2 A N N N

The IFU should indicate that the laboratory

H5 S3 P3 U waste should be treated as infectious Refer to IFU S3 P2 A N N N

materials.

Quality control should be strictly performed

H6 S4 P2 U Refer to IFU and Quality Control records. S3 P1 A N N N
in accordance with IFU.

Calibration should be strictly performed in

H7 S3 P3 U Refer to IFU and Calibration records. S3 P2 A N N N
accordance with IFU.

Clarify the expiry date of the product and

H8 S3 P3 U indicate the expiry date of the product on Refer to the Labelling. S3 P2 A N N N

the label.

Strict control of the packaging process and Refer to the Packaging and Package
H9 S3 P4 U S3 P1 A N N N
verification of the packaging. verification.

H10 S3 P3 U Standardize the content of the IFU. Refer to IFU S3 P1 A N N N

The instructions are clearly stated on how to

H11 S3 P3 U Refer to IFU S3 P2 A N N N
use in the IFU and read the IFU carefully

27
 before use

H12 S3 P4 U Standardize the content of the IFU. Refer to IFU S3 P2 A N N N

Strictly follow the instructions in IFU when

H13 S3 P4 U Refer to IFU S3 P2 A N N N
perform the test.

Each batch of products are tested for

Refer to the stability study and analytical
H14 S2 P4 U analytical performance, confirming that only S2 P2 A N N N
performance assessment.
qualified products can be sold at the factory.

1.Strict implement the relevant provisions

1.Strict implementation of the relevant of the Procurement Control Procedures,

provisions of the Procurement Control the efficiency of the supplier recorded in

Procedure. the “supply performance evaluation

H15 S2 P3 A 2.The procurement contract strictly agreed form.” S2 P2 A N N N

delivery time, in case of logistics and 2.The procurement contract strictly

transportation peak consider in advance of appoint the delivery time, in case of

stocking. logistics and transportation peak consider

in advance of stock.

1.Strict implementation of raw materials 1.Strict implement the “procurement

procurement procedure.. control procedures” related provisions.

H16 S3 P4 U 2.Test the raw materials according to the 2.Timely submission for Inspection with S3 P2 A N N N

relevant SOP. “inspection application form.”

3.The quality department strictly follow

28
 the “inspection control procedures” and

“material quality standards” for incoming

inspection.

4.For non-conforming raw materials for

return or replacement, the supply quality

accident recorded in the “supply side

performance evaluation form.”

1. in accordance with the “material control

procedures” to establish and implement

1.Establish a standardized material
the “material warehouse operating
management system, so that the flow of
procedures” for the material partition
materials is clear, traceable.
storage, the site identification is clear and
2.Unqualified products should be timely
legible.
identified and isolated.
2.”non-conforming product control
H17 S3 P4 U 3.For key process should establish a S3 P2 A N N N
procedures” has stipulated that the quality
multi-person review system to ensure
department is responsible for the
product quality, while strengthening the
identification of non-conforming
supervision of the production process.
products, identification records, isolation,
4.Conduct the functional testing for key raw
review and tracking of treatment
materials before the production .
measures.

3.In accordance with the Production

29
 Process Control Procedures established

and implemented the Production Process

Management Procedures, which stipulates

that at least two or more people in the

production process at the same time to

work mutual review.

1.In accordance with the “material control

procedures” to establish and implement

the “material warehouse operating

1.Establish a standardized material procedures” for the material partition

management system, so that the flow of storage, the site identification is clear and

materials is clear, traceable. legible.

2.Unqualified products should be timely 2. “Non-conforming product control

H18 S3 P4 U identified and isolated. procedures” has stipulated that the quality S3 P2 A N N N

3.For key process should establish a department is responsible for the

multi-person review system to ensure identification of non-conforming

product quality, while strengthening the products, identification records, isolation,

supervision of the production process. review and tracking of treatment

measures.

3.In accordance with the Production

Process Control Procedures established

30
 and implemented the Production Process

Management Procedures, which stipulates

that at least two or more people in the

production process at the same time to

work mutual review.

1.Before assembly, the assembly team 1.Provide training for the relevant users ,

leader carefully check the finished assembly clear their responsibilities.

list about the assembly items and quantities. 2.Production manager and QA strengthen
H19 S2 P3 A S2 P2 A N N N
2.Carefully check the project’s the supervision of daily work, require

semi-finished products, IFU and qualities. relevant users strictly implement their

3.After assembly,carefully check the label. responsibilities.

It is stipulated that sample kits should be 1.The Quality management department

inspected on a regular basis and reported in formulated and implemented the

a timely manner. Stipulation on the Management of

Strengthen the training of QC reserved sample of In vitro Diagnostic

users,strengthen their ability to identify Reagents Finished Products, which

H20 S3 P3 U S3 P2 A N N N
non-conforming products and strengthen the stipulates that the inspection period of is 6

supervision and monitoring of the inspection months and 13 months, respectively, and

process. completes the “Regular Inspection

Strict implementation of unqualified product Summary Form”.

control procedures, product recall 2.The Sales Department has formulated

31
management procedures. and implemented the Product Recall

Before delivery carefully check the order Management Procedure, which provides

quantity. for the timely implementation of the recall

Before delivery carefully verify the quantity process for non-conforming products

on the demand list and fill in the kit batch found internally, and the relevant

number. departments fill out the Recall Product

After packaging according to the demand List and Recall Product Records.

list check the shipping items and quantities.

32
Annex 4: Production and post-production risk analysis record sheet
Once on the market, you should continue to pay attention to post-production information,
collect, transmit, analyze and process it in accordance with the provisions of the Risk
Management Control Procedures and record the information in the table below.
information that Harm
Risk
Post-production The source of include hazard Hazard Hazard that
control
information the information (source)previously (source) situation may
measures
not identify occur

Changes in Competent

regulations, such Authority / / / / /

as standards Official Website

Competent
Adverse events
Authority / / / / /
(internal, external)
Official Website

Competent

Notice/Recall Authority / / / / /

Official Website

Flight inspection

of similar / / / / /
Review by the products
supervisory
Review by
authority
supervisory / / / / /

authority

Customer return Customer

(customer feedback/
/ / / / /
complaint) Complaint

information record

Design and

Design changes development / / / / /

documentation

Quality of Raw materials

Purchased procurement
/ / / / /
products records, product

entry inspection

33
 records, raw

material pass rate

analysis.

Quality users

on-site spot
Issue in the
checks and
Manufacturing
production users / / / / /
process
to take the

initiative to

report.

Analysis of Product

product inspection inspection,

results and Reserved sample / / / / /

reserved sampled inspection

products records

Product storage

monitoring
Monitoring results
records
of the product / / / / /
(temperature and
storage process
humidity

records)

34