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5
COMPOUNDS
ONE FDAAPPROVED
DRUG
3 – 6 YEARS
PHASE 1
PHASE 2
PHASE 3
NUMBER OF VOLUNTEERS
20–100
100–500 1,000–5,000 6 – 7 YEARS
0.5 – 2 YEARS
Sources: Drug Discovery and Development: Understanding the R&D Process, www.innovation.org; CBO, Research and Development in the Pharmaceutical Industry, 2006.
INDEFINITE
“
”
“
”
“
”
“
”
• – –
• –I – II – III – IV
20 30 100 300 2000
• • • • •
•
Adverse Drug Reaction
–
–
•
Adverse Event :
• • • •
• AE – – – –
• –
• •
• – – –
• – • • •
• • • • • •
•
•
–
–
–
–
–
–
•
•
•
•
–
• • •
OHRP: Guidance on Reviewing and Reporting Unanticipated Problems Involving Risks to Subjects or
Others and Adverse Events
---NCI
•
Common Terminology Criteria --CTC
for Adverse Events
---AE
NCI-CTC AE
• Category ( ) • Adverse Event term ( • Grading ( )
)
Category ( )
Adverse Event Term ( )
Grading ( )
+
+
+
+
-
+
+
+
+
-
+
+
-
+
-
+
+
-
-
Causality
• •
• • •
4-5 /
SAE
•
•
SAE
24
•
•
24
•
•
No time to wait
SAE
•
• • • •
AE/SAE
• •
– – – –
SAE/AE
SAE
AEs
28
28
AEs
6
SAEs
28
28
SAEs
• • • • •
• • • ICH-GCP
•
•
–
–
–
–
–
–
• • • •
Drug (discovery) invention:
--longest time from concept to product (10-15 yrs) ----most regulated, most expensive ($1-2 Billion)
AE
SAE SUSAR
ADR
AE/SAE / /
/
•
–
• FDA
– 21 CFR 312.32 IND safety reporting and 312.64 Investigator reports
• EMEA
– EU Directive 2001/20/EC
•
–
–
• –
• –
• –
• • • • •
Drug Discovery
Preclinical
Clinical Trials
FDA Review Scale-Up to Mfg.
Post-Approval Surveillance
PRE-DISCOVERY
IND SUBMITTED NDA SUBMITTED
~ 5,000 – 10,000
250
• • • • • • •
AE
• WHO AE
• NCI CTC AE Version 3.0, Revised March 31, 2003
• NCI CTC AE Version 4.0, Revised May 28, 2009
– 26
1-5
– MedDRA
National Cancer Institute
–
•
•
•
•
•
• DSMC/DSMB
(DSMC Data and Safety Monitoring Committee)
•
•
•
•
•
•
•
•Leabharlann Baidu
• •
Tel 87343826 caoye@mail.sysu.edu.cn
