23-12-2010 . 88148 284 , 155 62 : : 210 6507-335 e-mail: trials@eof.gr

.

:

- : . :1. 1316/1983 ... ( 3), , 2. .. 96/1973 ( 172), , 3. 3/89292/31-12-03 ( 1973), , 2001/20/ 4 2001 , , 4. 3/79602/25-1-07 ( 64) , 2005/28/ 8 2005 , . 3/89292/31.12.2003 (1973) 2001/20/ 4 2001 , , 5. 2010/C 82/01 - , , (CT1) - 9 , .8 2001/20,

:

1

, , :

,

(CT-1) (2010/C 82/01) - . 1. 1.1. 1. , 3/89292/31-12-03. 3/89292/31-12-03 , 2 ), .. , 2 1 3()/83657 ( 2001/83/). , . 2. , 2 9 3( )/83657. 3. 3/89292/31-12-03 () . 4. 3 3()/83657 3/89292/31-12-03 . 5. 3/89292/31-12-03 : - , in vitro, - , - , . 6. (.. /, / , / ), . 1.2. 7. 3/89292/31-12-03 , , . , : - (IMP) ( ).

2

- 13 . - ( ) , - . 8. , . ( ). ICH , .

2. 2.1. 2.1.1.

9. 8 1 2 3/89292/31-12-03 : ... . ... . ... .. , .... . 2.1.2. , , 10. . 11. 8 4 3/89292/31-12-03 , 60 . 12. 60 . . ... , . (1). (1) . 11 2001/20/: , . 13. , 8 4, 5 6 3/89292/31-12-03

3

, , . , . 2.1.3. 14. , , . (IMP) 2.1.4. : 2.1.4.1. 15. , 10 2.1.2. .

2.1.4.2. 16. , . : (. 2.1.4.1 ). , 8 4 3/89292/31-12-03 . . , . , / . , 8 4, 3/89292/31-12-03 . : 8 3, 3/89292/31-12-03. 2.1.4.3. 17. . . fax EudraCT . , , , fax . , , , .

4

18. , ( ) . EudraCT : , ... 2.1.5. 19. IMPs . , IMP (GMO) : .. 11642/1943 831/2-7-2002 ( 98/81/) 38693/2017 1334/21-9-2005 ( 2001/18/ 12 2001 90/220/ ). 2.1.6. 20. , CD ROM. 2.2. EudraCT 21. , EudraCT EudraCT . , , . EudraCT , 2.3. 22. . EudraCT ( ) . 23. , . 24. , , : , .. . .

(scientific advice) , IMP , . (PIP), , 3 () . 1901/2006 , 12 2006, . PIP, , (. 2.9).

25. , .

5

26. . 27. (SUSAR). 28. (. 2.1.4.3), . 2.4. 29. 3/89292/31-12-03, , 10 EudraLex The Rules Governing Medicinal Products in the European Union . 30. , , . 31. : . . .

SUSARs , .

32. XML XML CD-ROM. 33. , :

. EudraCT . EudraCT.

33. , EudraCT. 34. , EudraCT . EudraCT .

2.5.

6

35. 2 ) 3/89292/31-12-03 , , , , . 36. , , ( ), , . 37. , 6 Community guideline on Good Clinical Practice (CPMP/ICH/135/95) . , : . , . , . 38. . 39. ... , : 6 3 ) 3/89292/31-12-03 3 2 () 3/89292/31-12-03) [. 6 3() 3/89292/31-12-03] , [. 6 3 () 3/89292/31-12-03 , [. 6 3 () 3/89292/31-12-03. 40. 8 2001/20/. 41. , . , , . ATC ( 3-5) . 42. , : (. 15 1 3/89292/31-12-03) (. 15 2 3/89292/31-12-03).

7

43. , () IMP. 10 EudraLex The Rules Governing Medicinal Products in the European Union . 44. first-in-human , Guideline on strategies to identify and mitigate risks for first-in-human clinical trials with investigational medicinal . 45. . 46. : - (. ) , .

2.6. () 47. 2 ) 3/89292/31-12-03, (IB) , . 48. (IB) (IB) (. ). , , , / , . 49. , () 8 1 3/79602/25-1-07 , , (CPMP/ICH/135/95). IMP . 50. () (IB) (IMP) ICH . ICH, . , IMP . IMP , () . 51. , () . . 52. () (. )

8

. 2.7. (IMP D) 53. 2 ) 3/89292/31-12-03 (IMP) : (placebo) , ( ) , . 54. (IMPD) IMP (. ), IMP . , IMP , (IMPD). 2.7.1 ( , (GMP) 2.7.3 ( ).

2.7.1. (GMP) 55. (GMP), : IMP ICH, IMP , . 56. IMP ICH , : , 12 1 3/89292/31-12-03 (QP) .. (GMP) , (GMP) .. , . 57. , (GMP) , 3 /7567/6-8-2008 IMP , / , 12 1 3/89292/31-12-03 /. 2.7.2. (IMPs) 2.7.2.1. 58. , (IMPD) IMPD. IMPD 2.7.3. 59. (IMPD) .

9

60. IMPD . IMPD . , . 61. IMPs , , 3 EudraLex The Rules Governing Medicinal Products in the European Union . 2.7.2.2. 62. , Guideline on the requirements to the chemical and pharmaceutical quality documentation concerning investigational medicinal products in clinical trials. (placebos). 63. IMPs, Guideline on virus safety evaluation of biotechnological investigational medicinal products, as amended. 64. , ( ), . TSE. 2.7.2.3. 65. IMP . , . . , , . . 66. , 4 (CTD), (eCTD). 67. 3 EudraLex Note for guidance on non-clinical safety studies for the conduct of human clinical trials and marketing authorisation for pharmaceuticals, as amended (CPMP/ ICH/286/95). 68. , . 69. (GLP), . (GLP) . 70. . .

10

2.7.2.4. 71. , 5 , (eCTD). 72. IMPs. 73. (GCP). , : - GCP . - , , . , . 74. . . , (CPMP/ICH/291/95) . 2.7.2.5. - 75. , . , . . , 3 5 3/89292/31-12-03 . 76. , IMP , (AUC), (C max ), , . .

2.7.3. IMPD 77. IMPD 1. 2.7.3.1. IB 78. IMPD IB IMPD. , , , IMP . IB, IMPD.

11

2.7.3.2. IMPD . 79. ( ICH, ) IMPD IMP ICH. 1. 80. , IMPD . . , , . 1.

81.

1 IMPD

12

IMP - .. ICH : - - - (. ) IMP - ICH IMP . IMP - ICH : - IMP CTA 1 : - CTA - CTA -

P+

+ P+A

+ P+A +S+ P+A

[S: P: IMP : IMP 2., : )].

1

. 2 CHMP/QWP/185401/2004(http://ec.europa.eu/enterprise/sectors/pharmaceuticals/documents/eudr alex/vol-10/index_en.htm)

13

82. , IMPD , . 83. IMP ATC (. , 2.5), IMPD / ATC. , IMP . 2.7.4. IMPD ( placebo) 84. IMP (placebo), 2. 85. 2 IMPD ( placebo) IMPD IMP (placebo) P+A

IMP IMP, . IMP CTA .

[S: P: IMP, : ( 1 ) ]. ( 1 ) CHMP/QWP/185401/2004 (http://ec.europa.eu/enterprise/sectors/pharmaceuticals/documents/eudralex/vol-10/index_en. htm).

2.8. ( NIMPs) 86. (NIMPs). IMPs NIMPs Guidance on Investigational Medicinal Products (IMPs) and other medicinal products used in Clinical Trials. 87. NIMPs . , NIMPs . ,

14

NIMPs ICH ( MRA) . , . , NIMP . 88. NIMP, EudraLex - The Rules Governing Medicinal Products in the European Union, Volume 10. 2.9. , 89. , : 1) ... . 2) , - . 2.1.4.2. 3) PIP, PIP , . , (. 2.3). , 2.1.4.2. 4) annex 13 3. 3.1. 90. 9 ) 3/89292/31-12-03 : , . , , - ... 7 9 .. 91. , . 92. / . 3/89292/31-12-03 , . , (. 3.6). 3.2.

15

93. 9 ) 3/89292/31-12-03: - ( . 2.1.4.2) - ... ... 94. 9 ) 3/89292/31-12-03 . . 95. (ASR) 16 2 3/89292/31-12-03 . , . , . 96. (. ) , . , , , . 3.3. 97. : . 98. , . 99. . . , , . 100. , . , . 101. 8 3/79602/25-1-07 . , . , .

102.

16

, . 3.4. 103. , . . 3.4.1. . 104. , : ) ) ) ) / ) , ) (placebo) ) , , ) ) ) ) IMPs ) IMPs ) IMPs ) / .

17

105. , : ) (.. , ...) ) / / ) (< 10 % ) ) > 10 % , : (monitoring) ) , / ) , / ) (. case report form) data collection form) ) ) ) . 3.4.2. IMPD 106. IMPD, 8 . 3.4.3. IB 107. IB, : ) ) (ASR).

18

3.4.4. . 108. , : ) ) IMPs. 109. , : ) , , (CRAs) (CRO) ( ) ) (. 3.2 ) ) ) / ) ) .

19

3.5. ; 110. , ..., . 111. , . 112. , 3/89292/31-12-03 ... ... . 113. 8 2001/20/. 114. ..., . 115. . 3.6. 116. O . ., . . . , . 3.7. 117. : ) , : - EudraCT ( ) , . - - [ ]. -

20

- - , EudraCT (. ) ) , , 10 EudraLex The Rules Governing Medicinal Products in the European Union. ) : - (track changes), - , , . , . . . ) , : - - / - - ) , XML . . 118. IMP, /... EudraCT . , (. 3.7). 3.8. , 119. 9 ) 3/89292/31-12-03 :

21

.. .. 35 . , . ... , 35 , . , , . 120. , ... 35 . .., 10 35 . .

121. ... , ... . 122. , , . 123. . , . . 124. , . 3.9. 125. 9 ) 3/89292/31-12-03 : () , , , . .... 126. .. , , (. 3.10) . 127. . , .. , . , , , . .

22

128. : - (. ) - 15 9 .2 . . 3/89292/31-12-03 (. , 4.2.2) - 15 16 . . 3/89292/31-12-03. 3.10. 129. . 130. : - - 9 ) . . 3/89292/31-12-03. , , , 9 .2 . . 3/89292/31-12-03, 15 . 131. , . , ( , . 3.7) ( , . 3.9). 132. . 133. , 15 9 2 . . 3/89292/31-12-03 (. 4.2). 3.11. / 134. 11 1 . . 3/89292/31-12-03 : 2 9 , , . , , / , . , , .., , .

23

135. , (. , 4.2). 3.12. 136. 11 2 . . 3/89292/31-12-03 : , . .., . 137. . 138. . 139. , .. .

4. 4.1. 140. 9 .2 . . 3/89292/31-12-03 : 90 , , .., . , 15 . 141. 2001/20/. ( , . 2.5). , . 3.4.1. 4.2. 4.2.1. 142. / . (. 4.1).

24

143. 90 . , 10 EudraLex The Rules Governing Medicinal Products in the European Union. 144. , EudraCT. 4.2.2. 145. , , , . 146. , .. , 15 , , , . 4.3. 147. , . . , 2009/C28/01. , , , 2009/C28/01 2008/C168/02 . .. 47392/1-8-2005.

Competent Authority (CA) EMA EudraCT

EudraCT Number GMO

A regulatory agency in an EU Member State European Medicines Agency EudraCT (European Union Drug Regulating Authorities Clinical Trials) is the European Clinical Trials Database of all interventional clinical trials of medicinal products commencing in the European Union from 1 May 2004 onwards. The EudraCT database has been established in accordance with Directive 2001/20/EC When registered, each Clinical Trial is issued with a unique EudraCT number, which identifies the protocol and Clinical Trial throughout its lifespan A genetically modified organism (GMO) or genetically engineered organism (GEO) is an organism whose genetic

25

Gene therapy medical product GCP GLP GMP IMP

Interventional Clinical Trial IB IMPD Paediatric Investigation Plan (PIP )

Placebo Protocol

Somatic cell therapy medicinal product

Sponsor Sponsor protocol code number Summary of Product Characteristics (SmPC) SUSAR Tissue Engineered Product

material has been altered using genetic engineering techniques Product aimed at the transfer of a prophylactic, diagnostic or therapeutic gene to human and its subsequent expression in vivo Good Clinical Practice Good Laboratories Practice Good Manufacturing Practice Investigational Medicinal Product. A pharmaceutical form of an active substance or placebo being tested or used as a reference in a Clinical Trial, including products already with a marketing authorisation but used or assembled in a different way from the authorised form, or when used for an unauthorised indication, or when used to gain further information about the authorised form A Clinical Trial in which the assignment of the subject to a particular therapeutic strategy is decided in advance by a Clinical Trial protocol Investigator Brochure Investigational Medicinal Product Dossier Document upon which the development and authorisation of medicinal products for the paediatric population is based. It is presented by an applicant early during the development of a product to the EMA Paediatric Committee in order to agree a paediatric development plan A placebo is a control product that does not contain an active substance (a dummy treatment) that is given to people taking part in a Clinical Trial A document that describes the objective(s), design, methodology, statistical considerations and organisation of a Clinical Trial. The term protocol refers to the protocol, successive versions of the protocol and protocol amendments The use of autologous (emanating from the patient himself ), allogeneic (coming from another human being) or xenogeneic (coming from animals) somatic living cells, the biological characteristics of which have been substantially altered as a result of their manipulation to obtain a therapeutic, diagnostic or preventive effect An individual, company, institution, or organization that takes responsibility for the initiation, management, and/or financing of a Clinical Trial Unique Identifier number for the protocol assigned by the sponsor This is the product information document which is made available to all prescribing physicians in the EU for marketed products Suspected Unexpected Serious Adverse Reaction A product that contains or consists of engineered cells or tissues, is presented as having properties for, or is used in or administered to human beings with a view to regenerating, repairing or replacing a human tissue

26

(CD-ROM). , IMPD . CD-ROM XML . :

2.3(. http://www.eof.gr/web/guest/clinical/interventional) EudraCT ( ) http://www.eof.gr/web/guest/clinical/interventional ) , . , . ( ) 2.5( ) ( , , ) IB IB, 2.6 IMPD/ IMPD, 2.7 2.7.3 (GMP) IMPs , 2.7.1. IMPs 2.7.2.2. NIMP, 2.8 , 2.9

27

- :

) ) ) ) / ) , ( 3.4.1). ) (placebo) ) , , ) . ) ) ) IMPs ) IMPs ) IMPs ) / .

:

) 28

) IMPs. ) IMPD ) IMPs ) IMPs ) IMPs ) ) ) IMPs ) IMPs ) IMPs ) ( ) ) IMPs ) ) test procedures ) test procedures IMPs ) test procedures - IB: ) ) (ASR). /: ) )

29

30