ICH Good Clinical Practice Guideline

ISBN : 974-8044-95-5

2

2

I

(Good Clinical Practice: GCP)

GCP

GCP

ICH (International Conference on Harmonization) ICH GCP

ICH GCP

ICH GCP

ICH

GCP ICH

2

1. ICH GCP

2. GCP

(Thai Guideline for Good Clinical Practice)

ICH GCP

ICH GCP

2543

II

3

3

ICH Good

Clinical Practice Guideline (ICH GCP)

2543

4

4

I

II

III

1. 2-9

2. ICH GCP 10

3. , 11-14

4. 15-23

5. 24-34

6. 35-38

7. 39-44

8. 45-53

1 ICH GCP

2 ICH Secretariat ICH GCP

3 ICH Secretariat ICH GCP

5

5

*

(Good Clinical Practice: GCP)

(Declaration of

Helsinki)

ICH GCP

: * ICH

6

6

1. (GLOSSARY)

1.1 (Adverse Drug Reaction: ADR)

�“ �”

[ �“ ICH :

�” (ICH Guideline for Clinical Safety Data Management:

Definitions and Standards for Expedited Reporting)

1.2 (Adverse Event: AE)

( )

( �“ ICH

: �”)

1.3 (Amendment)

�“ (Protocol Amendment)

1.4 (Applicable Regulatory Requirement(s))

(investigational products)

1.5 (Approval) ( : IRB)

IRB

IRB, , GCP,

1.6 (Audit)

,

(Standard Operating Procedures: SOPs) , GCP,

1.7 (Audit Certificate)

7

7

1.8 (Audit Report)

1.9 (Audit Trail)

1.10 (Blinding/Masking)

(Single-

blinding)

2 (Double-blinding)

1.11 (Case Report Form: CRF)

(optical)

1.12 (Clinical Trial/Study)

/

(pharmacodynamics) /

/ (metabolism)

/

(clinical trial) (clinical study)

1.13 (Clinical Trial/Study Report)

, , ( �“ ICH

�” (ICH Guideline for Structure and Content of Clinical Study

Reports)

1.14 (Comparator)

( ) (placebo)

1.15 ( ) (Compliance)

, GCP,

1.16 (Confidentiality)

8

8

1.17 (Contract)

2

1.18 (Coordinating Committee)

1.19 (Coordinating Investigator)

1.20 (Contract Research Organization: CRO)

( )

1.21 (Direct Access)

.

( ,

, )

1.22 (Documentation) (

)

/

1.23 (Essential Documents)

[ 8 �“

�” (Essential Documents for the Conduct of a Clinical Trial)]

1.24 (Good Clinical Practice: GCP)

(integrity)

1.25 (Independent Data-Monitoring Committee:

IDMC) (Data and Safety Monitoring Board, Monitoring Committee, Data Monitoring Committee)

, ,

9

9

1.26 (Impartial Witness)

1.27 (Independent Ethics Committee: IEC)

( )

/ , , ,

GCP

1.28 (Informed Consent)

(informed consent form)

1.29 (Inspection)

/

1.30 (Institution)

1.31 (Institutional Review Board: IRB)

, ,

1.32 (Inteim Clinical Trial/Study Report)

10

10

1.33 (Investigational Product)

1.34 (Investigator)

[

�“ �” (Subinvestigator)]

1.35 / (Investigator/Institution) /

1.36 (Investigator�’s Brochure)

(clinical) (nonclinical)

( 7 �“

�”)

1.37 (Legally Acceptable Representative)

1.38 (Monitoring)

, , GCP,

1.39 (Monitoring Repeot)

/

1.40 (Multicentre Trial)

1.41 (Nonclinical Study)

1.42 (Opinion in relation to IEC)

/

11

11

1.43 (Original Medical Record) �“ �”

(Source Documents)

1.44 (Protocol)

.

ICH GCP �“

�”

1.45 (Protocol Amendment)

1.46 (Quality Assurance: QA)

(generated)

GCP

1.47 (Quality Control)

1.48 (Randomization)

1.49 (Regulatory Authorities)

GCP �“

�”

( 1.29) (competent authorities)

1.50 (Serious Adverse Drug Reaction: Serious ADR)

- - -

- /

- /

( �“ ICH :

�”)

1.51 (Source Data)

(

12

12

1.52 (Source Documents)

(

)

1.53 (Sponsor)

/

1.54 (Sponsor-Investigator)

1.55 (Standard Operating Procedures: SOPs)

1.56 (Subinvestigator)

/ (

) �“ �”

1.57 (Subject/Trial Subject)

1.58 (Subject Identification Code)

/

1.59 (Trial Site)

1.60 (Unexpected Adverse Drug Reaction)

(

/

) ( �“ ICH

: �”)

13

13

1.61 (Vulnerable Subjects)

1.62 (Well-being of the trial subjects)

14

14

2. ICH GCP

2.1

GCP

2.2

2.3

2.4

2.5

2.6

/

2.7 ( )

2.8

2.9

2.10

2.11

2.12 (Good

Manufacturing Practice: GMP).

2.13

15

15

3. (Institutional Review

Ethics Committee: IEC)

3.1

3.1.1 IRB/IEC

3.1.2 IRB/IEC

(curriculum vitae) /

IRB/IEC

- /

- /

- /

- / /

3.1.3 IRB/IEC

/ IRB/IEC

3.1.4 IRB/IEC

3.1.5 IRB/IEC 4.8.10

IRB/IEC /

3.1.6 (non-therapeutic trial)

( 4.8.12 4.8.14) IRB/IEC

/

3.1.7 ( 4.8.15) IRB/IEC

/

( )

16

16

3.1.8 IRB/IEC

3.1.9 IRB/IEC

3.2

3.2.1 IRB/IEC

IRB/IEC

. 5

. 1

. 1

IRB/IEC

3.2.2 IRB/IEC

GCP

3.2.3 IRB/IEC

3.2.4 IRB/IEC

/ /

3.2.5

/ IRB/IEC

3.2.6 IRB/IEC

3.3

IRB/IEC

3.3.1 ( )

17

17

3.3.2

3.3.3

3.3.4

3.3.5 /

3.3.6 IRB/IEC

/

3.3.7

/

IRB/IEC

(

) ( 4.5.2)

3.3.8 IRB/IEC

.

( 3.3.7, 4.5.2

4.5.4)

. /

( 4.10.2)

.

.

3.3.9 IRB/IEC /

. /

. /

. /

3.4

IRB/IEC (

/

) 3

18

18

IRB/IEC

19

19

4.

4.1

4.1.1

/ , IRB/IEC, /

4.1.2

4.1.3 GCP

4.1.4 /

4.1.5

4.2

4.2.1

( )

4.2.2

4.2.3

4.2.4

4.3

4.3.1 ( )

( )

20

20

4.3.2

/

/

4.3.3 (primary physician)

4.3.4

4.4 IRB/IEC

4.4.1 / /

IRB/IEC

( )

4.4.2 IRB/IEC /

/

IRB/IEC

4.4.3 /

IRB/IEC

4.5

4.5.1 /

/ IRB/IEC, ,

, /

4.5.2

/

IRB/IEC

( )

21

21

4.5.3

4.5.4

/

IRB/IEC

. IRB/IEC /

.

.

4.6

4.6.1 / -

(accountability)

4.6.2 / / /

-

/

4.5.3 / / /

,

,

(batch/serial numbers) ( )

,

4.5.4 (

5.13.2 5.14.3)

4.5.5

4.5.6 /

4.7

22

22

( )

.

(

)

4.8

4.8.1

GCP

/ IRB/IEC

4.8.2 .

/ IRB/IEC

4.8.3

4.8.4

4.8.5

/ IRB/IEC

4.8.6

( )

4.8.7

23

23

4.8.8

4.8.9

( )

4.8.10

.

. .

. (invasive)

.

.

.

.

.

. /

. ( )

. ( )

.

. IRB/IEC

/

24

24

. /

.

.

.

. /

.

.

4.8.11

.

4.8.12 ( )

( )

4.8.13 4.8.14 (

)

4.8.14

.

.

.

.

. IRB/IEC /

.

25

25

4.8.15

.

/ /

IRB/IRC

.

( 4.8.10)

4.9

4.9.1

4.9.2

4.9.3

( ) (

)

[ 5.18.4 ( )].

/

, , .

4.9.4 / �“

�” ( 8) /

4.9.5 ICH

2

ICH 2

.

/

( 5.5.12)

4.9.6

/

26

26

4.9.7 IRB/IEC

/

4.10

4.10.1 IRB/IEC

IRB/IEC

4.10.2

/ , IRB/IEC

( 3.3.8),

4.11

4.11.1

( )

, ,

/ .

IRB/IEC

4.11.2 /

4.11.3 IRB/IEC

( )

4.12

/

/

4.12.1 / IRB/IEC

27

27

4.12.2 ( 5.21)

/ IRB/IEC

4.12.3 IRB/IEC IRB/IEC /

( 3.1.2 3.3.9) /

4.13 (Final Report)

/

IRB/IEC

28

28

5.

5.1

5.1.1

GCP

5.1.2

( 1.21), /

,

5.1.3

5.1.4 /

5.2 (CRO)

5.2.1 CRO

. CRO

5.2.2 CRO

5.2.3

CRO

5.2.4 CRO

CRO

5.3

5.4

5.4.1 (

)

29

29

5.4.2 : �“

�” [Clinical Trial Protocol and Protocol Amendment(s)] ( 6), �“ ICH

�”, ICH

, ,

5.5

5.5.1 ,

, ,

5.5.2

(critical

efficacy endpolints)

,

5.5.3 /

(remote electronic trial data systems)

.

[ (validation)

.

. [ ,

(data trail), (edit trail) ]

. . (

4.1.5 4.9.3

.

. ( )

)

5.5.1 (transformed)

5.5.2 ( 1.58)

5.5.3

( 8 �“ �”)

5.5.4

/

30

30

5.5.5 (

, , )

2

5.5.6

/

5.5.7

5.5.8

ICH 2

ICH 2

5.5.9 /

/

5.6

5.6.1 /

(

4.1 4.2)

/

5.6.2 /

/

5.6.3 /

. GCP (

4.1.3)

/ IRB/IEC ( 4.5.1)

. /

. (

4.1.4)

.

( 4.9.4 5.5.12)

/

5.7

31

31

5.8

5.8.1

( ) /

(malpractice) / (negligence)

5.8.2

5.8.3

5.9

/

5.10 /

(

)

/ (

) /

5.11 IRB/IEC

5.11.1 /

. IRB/IEC /

. IRB/IEC IRB/IEC GCP

. / IRB/IEC

/

IRB/IEC /

5.11.2 IRB/IEC /

(modification) ,

, /

/

/ IRB/IEC

32

32

5.11.3 /

IRB/IEC /

5.12

5.12.1

/

(route)

5.12.2 ( 7 �“ �”)

5.13

5.13.1 (characterized)

( )

/ ( ).

5.13.2

( )

( ).

( )

5.13.3

5.13.4

5.13.5

(

)

5.14

5.14.1 /

5.14.2 /

( / IRB/IEC

)

33

33

5.14.3

/

.

(

)

5.14.4 .

.

( 8 �“ �”)

. (

)

.

5.14.5 .

.

(specifications) ( )

.

5.15

5.15.1

/ /

IRB/IEC

5.15.2

IRB/IEC

5.16

5.16.1

5.16.2 /

/ IRB/IEC

34

34

5.17 / IRB(s)/IEC(s)

5.17.2

�“ ICH :

�”

5.17.3 (safety updates)

5.18

5.18.1 (purpose)

.

.

. /

GCP

5.18.2

.

.

/

. ,

, , ,

GCP,

5.18.3

,

(extensive written guidance)

GCP .

5.18.4

.

. ( 4.1,

4.2, 5.6)

35

35

. (1)

(2)

(3)

(4)

(5)

.

( )

.

.

.

.

/

.

. , , ,

.

(applications and submissions)

.

.

(1).

(2). /

(3). , ,

(4).

36

36

(5). (drop out)

.

(

)

.

.

GCP, , IRB/IEC, ,

. ( 8 �“

�”)

. ,

, GCP,

8.18.5

5.18.6

.

.

. (summary)

/ ,

, ,

, /

.

5.19

5.19.1

, , GCP,

5.19.2

37

37

. /

.

.

5.19.3

.

.

,

, , ,

.

.

.

GCP

.

5.20

5.20.1 , , GCP, /

/

5.20.2 /

/ /

/

5.21

/

. IRB/IEC /

38

38

5.22

�“ ICH

�” ( : �“ ICH �”

)

5.23

5.23.1

/

IRB/IEC

5.23.2 .

5.23.3

5.23.4 .

,

5.23.5

39

39

6.

6.1

6.1.1

6.1.2 ( )

6.1.3

6.1.4 (

)

6.1.5

6.1.6 (

) ( )

( )

6.1.7 /

/

6.2

6.2.1 6.2.2

6.2.3 ( )

6.2.4 (dosage

regimen)

6.2.5 , GCP,

6.2.6 6.2.7

6.3

40

40

6.4 (scientific integrity)

6.4.1 ( )

6.4.2 / [

, (placebo-controlled),

(parallel design)

6.4.3

.

. 6.4.4

(dosage form)

6.4.5

( )

6.4.6 (stopping rules) (discontinuation

criteria)

6.4.7 -

( )

6.4.8 (trial treatment randomization codes)

6.4.9 (

)

6.5

6.5.1 6.5.2 6.5.3 (

)

.

. .

.

41

41

6.6 6.6.1 /

6.6.2 / ( )

/

6.6.3

6.7 6.7.1 (efficacy parameters)

6.7.2

6.8 6.8.1 (safety parameters)

6.8.2

6.8.3

6.8.4

6.9 6.9.1

[(planned interim analysis(ses)]

6.9.2

(

) (power)

6.9.3

6.9.4 6.9.5 , ,

6.9.6 (

/

)

6.9.7 (

)

6.10

/

IRB/IEC

42

42

6.11

6.12

6.13

6.14

6.15

6.16

(

�“ ICH �”)

43

43

7. (Investigator�’s Brochure; IB)

7.1

/

.

. (objective)

.

. (

)

. GCP

IRB/IEC /

IRB/IEC.

.

7.2

7.2.1 , (

) .

1

44

44

7.2.2 /

IRB/IEC

7.3

7.3.1 2

7.3.2

( 2 )

7.3.3

(

) , ,

( ),

,

.

7.3.4

( /

)

.

7.3.5

.

( )

(dose interval)

45

45

(duration of dosing)

- - - -

- -

,

, .

( ).

/

1

.

(

) (

)

.

.

(local and systemic

bioavailability)

.

( )

( )

46

46

7.3.6

, , ,

, , , ,

.

( )

- (

)

- (

)

- ( )

- (

)

. (

) , , ,

(

/ ). (implications) .

.

( ) .

/

.

.

. (

).

/

/

7.3.7

47

47

.

.

7.4. 1

( )

:

:

: ( )

( )

- :

- :

- :

- :

7.5 2

( )

- ( )

- ( )

1. 2. 3.

4.

5.

5.1 5.2

5.3 6.

6.1 6.2

48

48

6.3 7.

: 1.

2.

( )

49

49

8.

8.1

GCP

. /

.

(validity)

(integrity)

3

1. 2.

3.

/ 2 .

/

/

8.2

50

50

/

8.2.1

8.2.2

( )

/

8.2.3 -

(

)

-

(

)

-

( )

8.2.4

/

8.2.5

( )

8.2.6

- /

- /

( )

-

51

51

- /

( )

8.2.7 /

/

-

- ( )

-

-

-

( )

- -

( )

-

/

8.2.8 IRB/IEC

IRB/IEC GCP ( )

8.2.9 / /

/ / ( ) ( )

( )

8.2.10

/ /

8.2.11 / /

/

/ /

8.2.12 /

/ - ( )

/

-

-

(accreditation)

-

52

52

/ -

-

(validation) ( )

8.2.13

-

8.2.14

(

)

8.2.15

-

- -

8.2.16

8.2.17

(

)

8.2.18

(master randomi- (

zation list) )

8.2.19

(

8.2.20)

8.2.20

(

8.2.19)

53

53

8.3

/

8.3.1

8.3.2

- /

-

-

-

( )

8.3.3 /

/

IRB/IEC IRB/IEC

/

/

-

-

(1) (2)

(3)

( )

-

/

-

( )

54

54

8.3.4 /

/ ( )

( )

-

8.3.5 ( 8.2.10)

/

8.3.6 / /

/

/ ( 8.2.11)

/

8.3.7

/ ( )

/ ( 8.2.12)

/

-

-

-

/ -

-

( )

8.3.8 - ( 8.2.15)

8.3.9 - ( 8.2.16)

(new batches)

8.3.10

8.3.11

,

- , ,

-

-

55

55

8.3.12

GCP

( 8.2.3)

8.3.13

,

, -

8.3.14

- ( ) ( )

8.3.15 /

- ( ) ( )

8.3.16 -

-

4.11

8.3.17 /

( )

/ IRB/IEC

( ) 5.17 4.11.1

IRB/IEC 5.16.2

8.3.18

5.16.2

8.3.19

( )

IRB/IEC IRB/IEC 4.10

5.17.3

8.3.20 -

(subject ( )

screening log)

8.3.21 /

(subject -

56

56

identification code list)

/

8.3.22 -

(subject

enrolment log)

8.3.23

-

8.3.24

(signature sheet) /

8.3.25

/ ( )

(assay)

8.3 8.2 8.3

/

8.4.1 -

-

,

, ,

8.4.2 - -

(

)

8.4.3 -

(completed subject)

identification code list)

8.4.4

( )

8.4.5

(final trial close-out

report)

57

57

8.4.6

(treatment

allocation)

(decoding

documentation)

8.4.7

IRB/IEC (

)

(

)

8.4.8

( )