2015

2015320
20-21
21
For
1

Long Yang

-

-

AHWP
AHWP
AHWP1
13

CFDA
CFDACE
CEFDA
FDA

Hlongmed
CR
OFDA 510kQSR820



QSR21CFR820

ISO13485

IVDGMP

SFDAFDACE







100

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510
k

CE

ISO13485

QSR

FMEA

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-

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+
+

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2
1

ISO14971

5
1

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/
/
/

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!

.

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13

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1
2

ISO14971

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>

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SFDA

CAs

FDA

HC

MHLW

SFDA
,FDA

NBs

CDRH
3rd Party

HC
3rd Party

MHLW
3rd Party

, ,

IIb,
I, IIa,

III

I, II, III

I, II,VIII, I I, II,VIII, I

CE

510K
PMA

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(Electrical beds)

e.g. bed, ac-powered adj

ustable hospital, Code:F Class I
NL
MDD rule 12
Class:2
Regulation No. 880.5100

(Absorbable sutures)

e.g.suture, absorbable, s
ynthetic, polyglyco
Code:GAM
Class:2
Regulation No. 878.4493

Class III
MDD rule 7

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hip, knee and shoulder replacements

Class III

Class IIb
93/42/EEC

(2007.03)

(2010.09)

2005/50/EC

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(ISO 13485)

(ISO 14971)

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Q9: Quality RM
Risk-Based Approach to cGMP

ICH
FDA

ISO 14971:2007

ISO / IEC

IT

ISO/IEC 16085: RM software

ISO / IEC

AS/NZS HB 203:2004 Environmental

ISO 14121:RA - machinery

ISO 14798: RA - lifts, escalators

ISO

IEC 62198

IEC

ISO/IEC guide73:2002 RM - Vocabulary

ISO/IEC Guide 51:1999 Safety aspects

ISO / IEC

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1997.10

EN 1441:1994

1998.10

ISO 14971-1: 1998

2000.12

ISO 14971: 2000

ISO 14971: 2000A1:
2003

2007.03

ISO 14971: 2007

EN 14971:2009
EN 14971:2012

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2
1

ISO14971

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ISO14971
 ISO 14971:2007
2007-03-01


 ISO 13485:2003

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Structure of the ISO 14971




-
-
-
-
-
-

 10

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Annex A-J A-J

A
B
C
D
E
F
G
H
I
J

()
()
()
()
()
()
()
()
()
()

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1 Scope

IVD

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2 Terms and definitions

risk
combination of the Probability of occurrence of harm an
d the Severity of that harm.
R = f (P, S)

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2 Terms and definitions

harm
physical injury or damage to the health of people, or da
mage to property or the environment.

hazard
potential source of harm.

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2 Terms and definitions

hazardous situation

circumstance in which people, property, or the environm

ent are exposed to one or more hazards.

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2 Terms and definitions

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2 Terms and definitions

E.1

P1

P2

P1P2

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2 Terms and definitions

life-cycle

all phases in the life of a medical device, from the initial concept
ion to final decommissioning and disposal.

RM

post-production

part of the life-cycle of the product after the design has been co
mpleted and the medical device has been manufactured.

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2 Terms and definitions

risk analysis

systematic use of available information to identify hazards and to

estimate the risk

risk estimation

process used to assign values to the probability of occurrence of h

arm and the severity of that harm

risk evaluation

process of comparing the estimated risk against given risk criteria

to determine the acceptability of the risk

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2 Terms and definitions

risk assessment

overall process comprising a risk analysis and a risk evaluat

ion
risk control

process in which decisions are made and measures implem

ented by which risks are reduced to, or maintained within, s
pecified levels

residual risk

risk remaining after risk control measures have been taken

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3.1
3.2
3.3
3.4
3.5

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3.1

risk assessment

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3.1

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3.2

a)
b)
c)
d)

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3.3


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3.4

a)
b)
c)
d)
e)
f)

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3.4

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3.5

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3.5

RM
RM
(DFMEA)
(PFMEA)

CAPA

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4.1
4.2

4.3








 /



4.4

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4.1

4.2 (Annex C)
4.3 (E.2)
4.4 (E.4)

2 G
3 H
4 I

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4.1
G

Preliminary Hazard Analysis (PHA)Top to Down

Fault Tree Analysis (FTA)Top to Down
Failure Mode and Effects Analysis (FMEA)
For complex device system , FMEA is very useful in designing (DFME
A) and product controlling (PFMEA).Down to Top
Hazard and Operability Study (HAZOP)
Hazard Analysis and Critical Control Point (HACCP)

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4.1

4.24.34.4123

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4.2

1
2 C

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4.2

what is the device used for?

who uses the device?
medical staff, nursing staff, patient, cleaning staff etc.?
where is it used?
used?
hospital, at home, outside etc.?
when is it used?
time, how often etc.?
how is it used?
,

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4.2

C
(28C34
C.2.1
C.2.2
C.2.3
C.2.4

C.2.34

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4.3

1. EN 60601-2-X
2.
3.
4.
5.
6.
7.
8.
9.

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4.3
E E.1

-
-
-
-

-
-

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4.3
E E.2

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4.4

1 G
2 H 2.4.5E.4
3

P
P1

P2

P1P2

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4.4
E.4

(1)

( )

(1)

(2)

()

(1)

(2)

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4.4

a)
b)
c) (
)
d)
e)
f)
g)
h)

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PowerPoint

High permeability hemodialysis system

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPCD/cl
assification.cfm?start_search=1&Submission_Type_ID=&Dev
iceName=dialysis&ProductCode=&DeviceClass=&ThirdParty=
&Panel=&RegulationNumber=&Implant_Flag=&Life_Sustain_
Support_Flag=&PAGENUM=100

Device

dialyzer, high permeability with or without sealed

dialysate system

Regulation
Description

High permeability hemodialysis system.

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4.4

(
)

> 10

-3

10

-3

10

-4

10

-4

10

-5

10

-5

10

-6

< 10

-6

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4.4





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4.4

(
)

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4.4

5
(5
)

R1

R2

R5

R6

R4

R3

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 /



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5
(5
)

R1

R2

R5

R6

R4

R3

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5
(5
)

(ALARP)

R1

R2

R5

R6

R4

High Risk

R3

Medium Risk

Low Risk

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:
1) 6.2~6.6

2)

6.2~)
3)

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6.1
6.2

6.3




 /



6.4
6.5 /
6.6

6.7

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6.1
6.26.7

6.2: ()
6.3: ()
6.4: ()
6.5: /()
/
(
)
6.6: ()
6.7: ()

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6.2

a)
b)
c)

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6.2

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6.2

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6.3

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6.4

6.2

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6.4

R2

R5

R6

R1

R2
R4

R5

R6

R3

R1

R4

R3

R1,R5,R6

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6.4

D.8.4
:

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6.5 /

Benefit

Risk

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6.6

a)
b)

4.46.5

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6.7

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1 D.7

2 J

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8
,

[3.4
b]

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()

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C
FEMA

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<

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a)

b)

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2
1

ISO14971

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ISO
31010 -

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G.3 FTA

Top down
,

()
(
)

(deductive)
FMEA

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G.3 FTA
FTA

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(FTA)

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(FTA)

(=)
(,,,)

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(FTA)

:
,

:
,

:
mn,

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(FTA)

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G.3 FTA

()

FTA
FTA

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G.3 FTA

(System Block Diagram)

C
A

B
D

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G.3 FTA

Fa=0.1, Fb=0.2, Fc=0.2, Fd=0.3

C
A

B
D

Fe = Fc Fd= Fc x Fd = 0.2x0.3 = 0.06

Top

Ft = Fa U Fb U Fe
= 1- (1-Fa)x(1-Fb)x(1-Fe)
= 1- 0.9x0.8x0.94
= 0.3232

0.3232

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(FTA)

:


(FMEA)

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G.4 FMEA

(FMEA)

 FMEA
FMEA
FMEAFMEA

F
MEA FMECA

 FMEA

:FMEAIEC 60812

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G.4 FMEA
FMEA

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G.4 FMEA
FMEA

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G.4 FMEA
FMEA

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?
1.
2. :
,
:




,

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?
3. ,

3,4,5,610

: 1,2,3,4,
: 1,2,4,8
: 1,10,100,1000
: 1,3,7,10

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?
4.
5.
6.
7.

(,)
,(,
<50)
,(,)

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(Severity)
FMEA

10

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(Occurrence)/

1/2

10

1/8

1/20

1/80

1/400

1/1500

1/10000

1/40000

1/100000

1/1000000

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(Detection)

10

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RPN: Risk Priority Number
(S)(O)(D)
RPN = (S) x (O) x (D)

FMEA 1-1000

RPN RPN
RPN
RPN
(9 10 ) RPN

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 (FMEA)-

PRN

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 (FMEA)-

PRN

120

112

126

63

40

27

45

:
RPN:= S P D

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(FMEA)-

PRN

PRN

120

48

112

56

126

84

63

42

40

40

27

27

45

45

RPN100
RPN:= S P D
5
;

(FTA)

(FMEA)

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(PHA)

(FTA)

(FMEA)

(DFMEA)
(PFMEA)

(HAZOP)

(HACCP)

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(-?)

(HACCP) (HAZOP)

(FMEC
A/FMECA)

(FT
A)

IS
O 9001

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GMP

FTA

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2
1

ISO14971

5
1

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1.
2.
3.
4.
5.
6. BOM

7.
8.
9.

10.
11.
PFMEA

12.
13.
14.
15. DMRDHF
16.
17.
18.

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ISO14971C

IVDH

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DFMEA Design Failure Mode and Effect Analysis

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PFMEA Process Failure Mode and Effect Analysis

RPNSX O

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FME
A

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()

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FMEA

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2
1

ISO14971

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Design Control
Design inputs come from RM activities
Development of appropriate test methods
Prevent failures as early as in the feasibility phase
Validation of Processes
Material, Equipment, Operations, Test Methods
What & How to validate Master Val Plan, protocol designs
Purchasing/Supplier Management
CAPA complaints, nonconformities, recalls, etc.
Failure mode missed?
Severity or Probability underestimated?

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Equipment Control
Calibration and PM requirements
Internal Auditing
What & How to audit
Auditing the RM Program itself
Training
One of the most critical manufacturing risk controls!
Product Traceability
Which product components require traceability?
Environmental Control
Where to monitor
Acceptable limits

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Design Step

Risk Management Activities

Design and develop

ment planning

Hazard identificationhelps determine type and extent of desig

n controls, regulatory requirements and plans
Risk management planningestablishes risk goals, ownership, r
esources, etc.

Hazards List

Design input

Risk estimationestablishes linkage between requirements and

hazards, ensures safety requirements are complete

Preliminary or initial hazar

ds analysis

Design

Risk estimation and risk evaluationsystems- and component-l

evel risk assessments

FTA
FMEA

Verification and vali

dation

Verification of risk controlsMaintaining linkage between haza

rds, requirements, risk reduction measures, and V&V results ens
ures validation in normal and fault modes and ensures risk reduc
tion measures are effective

V&V test results or traceab

ility matrix

Design reviews

Risk evaluationsreview risk acceptability and residual risks d

uring appropriate phases. Helps ensure risk and safety form the f
oundations for decisions regarding the safety of the product

Risk decisions and justific

ations for acceptability

Design transfer

Risk management reportFormal review, approval, and release

as part of DMR ensures knowledge of risk/safety is transferred

Risk management report

Design change contr

ol

Reassess existing and potential new hazards/risks

Updated risk documents

RM Output

Risk management plan

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CAPA

Complaint?

Action required?
Complaints entered
into
Complaint Handling
System

(1)

Such as Finished Goods Returned,

Credit restock

(2)

The relationship will depend upon the

output of the investigation. This process
can be iterative

Known
Problem?

Action required?

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FMEAFTA

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--










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FMEAFTA
ISO13485FDA

A-D-L-I

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ISO14971

A
D

FMEA
FTA

1.

2.

L
I

3.

ISO13485
FDA

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Thanks

CRO

FDA
510k
QSR820

Mobile: 13510985530
Email
yanglongoscar@gmail.com
http://www.linkedin.com/in/yanglong
QQ:
1795224421
142

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