sources of risk from drug products
DESCRIPTION
Sources of Risk from Drug Products. Known side effects. Medication errors. Product quality defects. Unavoidable. Avoidable. Preventable adverse events. Remaining uncertainties Unexpected side effects Unstudied uses Unstudied populations. Injury or death. - PowerPoint PPT PresentationTRANSCRIPT
Source: CDER 2000 Report to the Nation
Original NDA Actions
41%44%39%
49% 51%45%
38%31%
0%
50%
100%
1993 1994 1995 1996 1997 1998 1999 2000
Calendar Year
Pe
rce
nta
ge
Percentage of Actions that Are Approvals
Source: CDER 2000 Report to the Nation
Original NDA Actions
31%38%
45%51%49%
39%44% 41%
223
161
216
269235
199
190
238
0%
50%
100%
1993 1994 1995 1996 1997 1998 1999 2000
Calendar Year
Pe
rce
nta
ge
0
150
300
Ac
tio
ns
Percentage of Actions that Are Approvals Number of Total Original NDA Actions
Source: CDER 2000 Report to the Nation
New Drug Application Approvals
11.2
14.4
12.0
15.4
12.0
24.1
19.0
16.5
10.9
14.815.8
20.8
11.812.2 12.0
15.3
0
12
24
1993 1994 1995 1996 1997 1998 1999 2000
Calendar Year
Mo
nth
s
Median Total Approval Time Median FDA Review Time
Source: CDER 2000 Report to the Nation
New Drug Application Approvals
11.2
14.4
12.0
15.4
12.0
24.1
19.0
16.5
10.9
14.815.8
20.8
11.812.2 12.0
15.398
83
90
121131
6270
82
0
12
24
1993 1994 1995 1996 1997 1998 1999 2000
Calendar Year
Mo
nth
s
0
70
140
Ap
pro
va
ls
Median Total Approval Time Median FDA Review Time
Number of Original NDAs Approved
Source: CDER 2000 Report to the Nation
New Molecular Entity Approvals
13.9
15.614.3
11.612.0
15.9
23
13.4
17.5
12.010.0
11.9
15.2
12.8
15.3
21
0
12
24
1993 1994 1995 1996 1997 1998 1999 2000
Calendar Year
Mo
nth
s
Median Total Approval Time Median FDA Review Time
Source: CDER 2000 Report to the Nation
New Molecular Entity Approvals
13.9
15.614.3
11.612.0
15.9
23
13.4
17.5
12.010.0
11.9
15.2
12.8
15.3
21
27
3530
28
25 22
53
39
0
12
24
1993 1994 1995 1996 1997 1998 1999 2000
Calendar Year
Mo
nth
s
0
30
60
Ap
pro
va
ls
Median Total Approval Time Median FDA Review Time Number of NMEs Approved
Source: CDER 2000 Report to the Nation
Efficacy Supplement Actions
39% 41% 37%
60% 57%72%
53%
65%
0%
50%
100%
1993 1994 1995 1996 1997 1998 1999 2000
Calendar Year
Pe
rce
nta
ge
Percentage of Actions that Are Approvals
Source: CDER 2000 Report to the Nation
Efficacy Supplement Actions
39% 41% 37%
60% 57%72%
53%
65%122
196189
173185
122
184205
0%
50%
100%
1993 1994 1995 1996 1997 1998 1999 2000
Calendar Year
Pe
rce
nta
ge
0
115
230
Ac
tio
ns
Percentage of Actions that Are Approvals Number of Efficacy Supplement Actions
Source: CDER 2000 Report to the Nation
Efficacy Supplement Approvals
12.0
16.0
14.213.9
11.9 11.8
10.4 10.0
19.018.3
11.9 11.7
10.2 10.0
12.311.2
0
12
24
1993 1994 1995 1996 1997 1998 1999 2000
Calendar Year
Mo
nth
s
Median Total Approval Time Median FDA Review Time
Source: CDER 2000 Report to the Nation
Efficacy Supplement Approvals
12.0
16.0
14.213.9
11.9 11.8
10.4 10.0
19.018.3
11.9 11.7
10.2 10.0
12.311.2
48
69
118
50
108124
97
134
0
12
24
1993 1994 1995 1996 1997 1998 1999 2000
Calendar Year
Mo
nth
s
0
70
140
Ap
pro
va
ls
Median Total Approval Time Median FDA Review Time
Number of Efficacy Supplements Approved
Source: CDER 2000 Report to the Nation
OTC New Approvals and New Uses
5
1 1
9 98
20
8
3 3
1
7
0
12
24
1995 1996 1997 1998 1999 2000
Calendar Year
Nu
mb
er
New Approvals or Rx-to-OTC Switches New Uses
Source: CDER 2000 Report to the Nation
Generic Drug Approvals
23.026.9
19.318.6
27.0
18.0 18.2
0
12
24
36
1994 1995 1996 1997 1998 1999 2000
Calendar Year
Mo
nth
s
Median Approval Times
Source: CDER 2000 Report to the Nation
Generic Drug Approvals
23.026.9
19.318.6
27.0
18.0 18.2158
207
212
273
225
186
244
0
12
24
36
1994 1995 1996 1997 1998 1999 2000
Calendar Year
Mo
nth
s
0
100
200
300
Ap
pro
va
ls
Median Approval Times Number of Generic Approvals
Source: CDER 2000 Report to the Nation
Generic Drug Electronic Submissions
4444
32
10
85
0
55
79
0
50
100
1997 1998 1999 2000
Fiscal Year
Nu
mb
er
Bioequivalence data Chemistry, manufacturing, controls data
Source: CDER 2000 Report to the Nation
NDA Manufacturing Supplement Actions
83%
72%
80%
61%67%
74%81%
84%
0%
50%
100%
1993 1994 1995 1996 1997 1998 1999 2000
Calendar Year
Pe
rce
nta
ge
Percentage of Actions that Are Approvals
Source: CDER 2000 Report to the Nation
NDA Manufacturing Supplement Actions
83%
72%80%
61%67%
74%81% 84%
1,580 1,782 1,630 1,6591,6741,147 1,747 1,605
0%
50%
100%
1993 1994 1995 1996 1997 1998 1999 2000
Calendar Year
Pe
rce
nta
ge
0
1,000
2,000
Ac
tio
ns
Percentage of Actions that Are Approvals
Number of NDA Manufacturing Supplement Actions
Source: CDER 2000 Report to the Nation
NDA Manufacturing Supplement Approvals
8.27.7
5.9
5.1
4.0 4.0
5.45.2
0
6
12
1993 1994 1995 1996 1997 1998 1999 2000
Calendar Year
Mo
nth
s
Median Total Approval Time
Source: CDER 2000 Report to the Nation
NDA Manufacturing Supplement Approvals
5.9
4.0 4.0
5.27.7
8.2
5.4 5.1
1,3451,4191,375
1,178
1,422
1,0241,065848
0
6
12
1993 1994 1995 1996 1997 1998 1999 2000
Calendar Year
Mo
nth
s
0
320
640
960
1280
1600
Ap
pro
va
ls
Median Total Approval Time Number of NDA Manufacturing Supplements Approved
Source: CDER 2000 Report to the Nation
Generic Drug Manufacturing SupplementsApprovals
1,903
2,284
1,969
2,314
0
2,000
4,000
1997 1998 1999 2000
Calendar Year
Nu
mb
er
Number of Supplements Approved
Source: CDER 2000 Report to the Nation
Generic Drug Manufacturing SupplementsReceipts and Approvals
1,9692,2841,903
2,3142,118
2,370
3,036
2,522
0
2,000
4,000
1997 1998 1999 2000
Calendar Year
Nu
mb
er
Number of Supplements Approved Number of Supplements Received
Source: CDER 2000 Report to the Nation
Inspections of Clinical Research
312
42 49
143
184 191
4 7 1 4 1028
393
297 296293
246
6164
28 40
155158170
0
250
500
1995 1996 1997 1998 1999 2000
Calendar Year
Nu
mb
er
U.S. Clinical Investigators Foreign Clinical Investigators
Institutional Review Boards Sponsors, Monitors, CROs
Source: CDER 2000 Report to the Nation
Original NDAsFiscal Year Cohort Within Goal Review Performance
100% 100% 99%100% 100% 100%85%
66%
0%
20%
40%
60%
80%
100%
FY '98114 reviews12-mo: 84 6-mo: 30
FY '99126 reviews12-mo: 9510-mo: 63 6-mo: 31
FY '00121 filed* 12-mo: 9210-mo: 78 6-mo: 29
User Fee Goal*84 reviewed (1 overdue), 37 pending (none overdue) as of Feb. 28, 2001
Pe
rce
nta
ge
12-month review 10-month review 6-month review
Source: CDER 2000 Report to the Nation
Resubmissions of Original NDAsFiscal Year Cohort Within Goal Review Performance
100% 100% 100%
82%
100% 96%100% 100%98%
0%
20%
40%
60%
80%
100%
FY '9854 reviews
Class I (6-mo.): 22Class I (2-mo.): 18Class II (6 mo.): 32
FY '9964 reviews
Class I (4-mo.): 17Class I (2-mo.): 17Class II (6 mo.): 47
FY '0080 resubmitted* Class I (4-mo.): 25Class I (2-mo.): 24Class II (6 mo.): 55
User Fee Goal*75 reviewed (1 overdue), 5 pending (none overdue) as of Feb. 28, 2001
Pe
rce
nta
ge
Class I (6-mo.) Class I (4-mo.) Class I (2-mo.) Class II (6 mo.)
Source: CDER 2000 Report to the Nation
Efficacy SupplementsFiscal Year Cohort Within Goal Review Performance
99% 100% 100%99% 94%
85%87%
80%
0%
20%
40%
60%
80%
100%
FY '98129 reviews12-mo: 119 6-mo: 10
FY '99137 reviews12-mo: 12210-mo: 104 6-mo: 15
FY '00174 filed* 12-mo: 15610-mo: 146 6-mo: 18
User Fee Goal*114 reviewed (1 overdue), 60 pending (none overdue) as of Feb. 28, 2001
Per
cen
tag
e
12-month review 10-month review 6-month review
Source: CDER 2000 Report to the Nation
New Drug Manufacturing SupplementsFiscal Year Cohort Within Goal Review Performance
99% 99%97%98% 98%
75%73%
0%
20%
40%
60%
80%
100%
FY '981,442 reviews
Pr aprvl & CBE (6-mo.)
FY '991,458 reviews
Pr aprvl (6-mo.): 902Pr aprvl (4-mo.): 660 CBE (6-mo.): 557
FY '001,439 filed*
Pr aprvl (6-mo.): 679Pr aprvl (4-mo.): 509 CBE (6-mo.): 760
User Fee Goal*1,378 reviewed (24 overdue), 61 pending (11 overdue) as of Feb. 28, 2001
Pe
rce
nta
ge
Prior Approval (6-mo.) Prior Approval (4-mo.) Changes Being Effected (6-mo.)
Source: CDER 2000 Report to the Nation
Original NDAs
0%
50%
100%
FY '9384 reviews
65% on-time
FY '9492 reviews
95% on-time
FY '95111 reviews 98% on-time
FY '96109 reviews 100% on-time
FY '97121 reviews 100% on-time
User Fee Goal (none in 1993)
Source: CDER 2000 Report to the Nation
Resubmissions of Original NDAs
0%
50%
100%
FY '932 reviews
100% on-time
FY '9424 reviews
83% on-time
FY '9558 reviews
97% on-time
FY '9689 reviews
99% on-time
FY '9787 reviews
97% on-time
User Fee Goal (none in 1993)
Source: CDER 2000 Report to the Nation
Efficacy Supplements
0%
50%
100%
FY '9392 reviews
41% on-time
FY '9486 reviews
77% on-time
FY '9577 reviews
95% on-time
FY '96105 reviews98% on-time
FY '97146 reviews99% on-time
User Fee Goal (none in 1993)
Source: CDER 2000 Report to the Nation
New Drug Manufacturing Supplements
0%
50%
100%
FY '931,045 reviews50% on-time
FY '94871 reviews66% on-time
FY '951,249 reviews90% on-time
FY '961,218 reviews96% on-time
FY '971,262 reviews98% on-time
User Fee Goal (none in 1993)
Source: CDER 2000 Report to the Nation
Refuse-to-File ActionsOriginal NDAs
4%3%4%5% 5%
26%
17%
2%
0%
15%
30%
FY '93(29)
FY '94(19)
FY '95(6)
FY '96(5)
FY '97(2)
FY '98(7)
FY '99(4)
FY '00(6)
Fiscal Year (number refused)
Pe
rce
nta
ge
Percentage Refused to File
Source: CDER 2000 Report to the Nation
Refuse-to-File ActionsOriginal NDAs
4%
2%
17%
26%
5%5% 4% 3%
132
111
123114117
113
135 134
0%
15%
30%
FY '93(29)
FY '94(19)
FY '95(6)
FY '96(5)
FY '97(2)
FY '98(7)
FY '99(4)
FY '00(6)
Fiscal Year (number refused)
Pe
rce
nta
ge
0
75
150
Nu
mb
er
Percentage Refused to File Number of Original NDAs Submitted
Source: CDER 2000 Report to the Nation
Clinical Holds of Commercial INDs(as of Dec. 31, 2000)
8%
11%13%
9% 9%
15%
10%
0%
10%
20%
FY '94(55)
FY '95(45)
FY '96(32)
FY '97(38)
FY '98(46)
FY '99(48)
FY '00(35)
Fiscal Year (number of holds)
Pe
rce
nta
ge
on
Ho
ld
Percentage of Commercial INDs Received on Hold
Source: CDER 2000 Report to the Nation
Clinical Holds of Commercial INDs(as of Dec. 31, 2000)
8%
11%13%
9% 9%
15%
10%
360358 376
446
471430 459
0%
10%
20%
FY '94(55)
FY '95(45)
FY '96(32)
FY '97(38)
FY '98(46)
FY '99(48)
FY '00(35)
Fiscal Year (number of holds)
Pe
rce
nta
ge
on
Ho
ld
0
250
500
Nu
mb
er
Percentage of Commercial INDs Received on Hold Number of Commercial INDs Received
Source: CDER 2000 Report to the Nation
Sources of Risk from Drug Products
Known side effectsUnavoidable Avoidable
Medicationerrors
Product qualitydefects
Preventableadverseevents
Injuryor death
Remaininguncertainties
Unexpected side effectsUnstudied uses
Unstudied populations
Source: CDER 2000 Report to the Nation
Post-Marketing Adverse Event Reports
83,310
83,517
117,718
136,836143,597154,558
189,073
228,611
246,822 245,750262,334
0
100,000
200,000
300,000
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000
Calendar Year
Nu
mb
er
Manufacturer Periodic Reports Direct Reports (MedWatch)
Manufacturer 15-Day (expedited) Reports
Source: CDER 2000 Report to the Nation
Adverse Event Reporting Inspections
17
50
33
51
74
0
45
90
1996 1997 1998 1999 2000
Fiscal Year
Nu
mb
er
Inspections
Source: CDER 2000 Report to the Nation
Drug Promotion Review
235
417 399
773
515
242
129 117
171
237245220
539558
350
159
276221
247215
0
400
800
1993 1994 1995* 1996 1997 1998 1999 2000
Calendar Year(*Change from counting campaigns to letters in last quarter 1995)
Nu
mb
er*
Regulatory Actions Launch Campaigns Other Letters DTC Advertising Letters
Source: CDER 2000 Report to the Nation
Export Certificates Issued
1,290
1,747
4,499 4,378 4,3823,973 4,197
0
2,500
5,000
FY '94 FY '95 FY '96 FY '97 FY '98 FY '99 FY '00
Fiscal Year
Nu
mb
er
Export Certificates Issued
Source: CDER 2000 Report to the Nation
Drug Recalls
255
304
191
248
316
93 102
60 5334
88
156
352
177
226
72
0
200
400
1993 1994 1995 1996 1997 1998 1999 2000
Fiscal Year
Nu
mb
er
Prescription Drugs Over-the-Counter Drugs
Source: CDER 2000 Report to the Nation
Safety-Based NME Withdrawal PercentagesBased on Year of Approval
1.9%
2.3%
2.7%
3.3%
0.0%
2.5%
5.0%
1981-1985(4)
1986-1990(2)
1991-1995(3)
1996-2000(5)
5-Year Approval Cohorts (number withdrawn as of March 30, 2001)
Only includes withdrawals resulting from joint FDA-manufacturer decisions
Pe
rce
nta
ge
Percentage of Cohort Withdrawn
Source: CDER 2000 Report to the Nation
Safety-Based NME Withdrawal PercentagesBased on Year of Approval
1.9%
2.3%
2.7%
3.3%121
107
131
184
0.0%
2.5%
5.0%
1981-1985(4)
1986-1990(2)
1991-1995(3)
1996-2000(5)
5-Year Approval Cohorts (number withdrawn as of March 30, 2001)
Only includes withdrawals resulting from joint FDA-manufacturer decisions
Pe
rce
nta
ge
0
100
200
Nu
mb
er
Percentage of Cohort Withdrawn Number of NMEs Approved in Cohort
Source: CDER 2000 Report to the Nation
Modular Structure of Common Technical Document
Nonclinical written and tabulated
summaries
Module I Administrative
and prescribing information
(not harmonized)
Module II General introduction and overall summaries of quality, nonclinical
and clinical information
Clinical written and tabulated
summaries
Module IV Nonclinical
study reports
Module III Quality
data
Module V Clinical
study reports
Source: CDER 2000 Report to the Nation
Average Monthly Use of CDER Internet Site
32,000
72,000
156,000
406,000
226,000
0
250,000
500,000
1996 1997 1998 1999 2000
Calendar Year
Vis
ito
rs
Average Monthly Visitors
Source: CDER 2000 Report to the Nation
Average Monthly Use of CDER Internet Site
32,000
72,000
156,000
406,000
226,000
6.7
2.5
3.1
1.30.5
0
250,000
500,000
1996 1997 1998 1999 2000
Calendar Year
Vis
ito
rs
0
5
10
Hit
s (
mill
ion
s)
Average Monthly Visitors Average Monthly Hits (millions)