Center for Drug Evaluation and Research

CDER 1997 Report to the Nation

Improving Public Health Through

Human Drugs

U.S. Department of Health and Human Services

Food and Drug Administration

Center for Drug Evaluation and Research

Index of Graphs............................................................................. iv

Letter from the Director................................................................ v

Introduction.................................................................................... 1

What Americans Expect ........................................................... 1

Application Review Program.................................................... 1

Post-Marketing Surveillance ................................................... 1

FDA Modernization Act ............................................................ 2

Application Approvals .................................................................... 3

1997 Performance and Workload............................................. 3

Total Original NDA Actions ............................................... 3

Total Original NDA Approvals........................................... 4

New Molecular Entity Approvals ....................................... 5

Efficacy Supplement Approvals .......................................... 7

Manufacturing Supplement Approvals .............................. 8

PDUFA Application Review Performance ................................... 10

PDUFA Reauthorization Goals.................................................... 13

Overdue Reduction ...................................................................... 14

Refusal to File an Application ..................................................... 15

Clinical Holds ............................................................................... 16

Post-Marketing Risk Assessment................................................ 17

Adverse Event Reporting ....................................................... 17

Drug Safety Issues ................................................................. 19

OTC Update and Significant Switches ....................................... 20

Generic Drugs .............................................................................. 22

Export Certificates....................................................................... 23

Drug Advertising and Promotion ................................................ 24

International Harmonization ...................................................... 26

Applied Research.......................................................................... 28

Communications .......................................................................... 29

Ombudsmans Activity............................................................ 30

Improving Policy Consistency ..................................................... 31

New and Proposed Rules ........................................................ 31

Guidances to Industry ............................................................ 32

MAPPs..................................................................................... 33

Organizational Changes .............................................................. 34

Organizational Chart................................................................... 35

Contents

iii
Calendar Year 1997 Actions and Approvals:

Original NDA Actions ............................................................... 3

Original NDA Approvals........................................................... 4

NME Approvals......................................................................... 5

Efficacy Supplement Actions.................................................... 7

Efficacy Supplement Approvals ............................................... 8

Manufacturing Supplement Actions ........................................ 9

Manufacturing Supplement Approvals.................................... 9

PDUFA On-Time Review Performance:

Original NDAs: ....................................................................... 10

Resubmissions of Original NDAs ........................................... 11

Efficacy Supplements ............................................................. 12

Manufacturing Supplements ................................................. 12

Refusal to File Actions ................................................................. 15

Clinical Holds ............................................................................... 16

Post-Marketing Adverse Event Reports ..................................... 17

PDUFA Submission Cohorts: Adverse Event Reports................ 18

Generic Drug Approvals .............................................................. 22

Export Certificates Issued ........................................................... 23

Regulatory Action and Launch Campaign Letters ..................... 24

iv

Graphs
Dear President/CEO:

I am pleased to send you the second annual report from the Center

for Drug Evaluation and Research, U.S. Food and Drug Administration. The report highlights CDERs performance during 1997. This

past calendar year has been both successful and eventful.

In our new drug review program, the Center approved 39 new molecular entities, the second highest total for these important new

medicines. We continued to reduce review times. The median total

time to approval for NMEs was 13.4 monthsthe most rapid ever. Moreover, American consumers

were the first in the world to have access to more than half these drugs. We met all our six-month

goals for priority drug reviews.

The many drug review achievements highlighted in this report validate the joint commitment made

by CDER to accountability, predictability and quality. This commitment was embodied in the 1992

Prescription Drug User Fee Act and reaffirmed in last years FDA Modernization Act and reauthorization of user fees. The United States now has one of the fastest, if not the fastest, drug review

systems in the world. This has been accomplished without sacrificing the FDAs high standards of

scientific rigor. Moreover, drugs approved in this country have the data needed for physicians and

patients to make informed decisions.

The Centers management and user fee initiatives were the major component leading to the Innovations in American Government Award presented to the FDA by the Ford Foundation and Harvard

Universitys John F. Kennedy School of Government. This prestigious award recognized the hard

work that cut approval times for new drugs nearly in half while doubling the number approved.

Americans now have access to new therapies faster, suffer less, recover more rapidly, live longer

lives or enjoy an improved quality of life.

Our streamlining efforts have paid off in over-the-counter and generic drug reviews as well. Expanding the choices of modern, effective and safe drugs for self-medication directly benefits American

consumers. Generic drug reviews represent a true success story. Despite a growing workload, a

shrinking staff and the absence of user fees, the generics program approved a remarkable 431

products last yeara record for the 1990s while reducing time to approval from 39.6 months to

19.3 months over the last five years.

May 1, 1998

Janet Woodcock, M.D.

Director

Center for Drug Evaluation and Research

iv
We cannot, however, rest on our laurels. Our successes in streamlining drug reviews have unmasked

other concerns Americans have with their medicines. As the number of drugs increase and development and review times shorten, safety issues grow increasingly complex and important in the

publics mind.

We are in the process of implementing a new Adverse Event Reporting System that will make use of

terminology agreed to under the International Conference on Harmonization. This state-of-the-art

system will provide enhanced signal detection and replace an overtaxed, manual system.

Manufacturers reports entered into this new system will represent the first implementation of

electronic submissions. We are moving to a completely electronic submission and review environment by the year 2002. Our international harmonization efforts laid the critical foundations for this

transformation. Last year, we reached landmark agreement on common medical terminology and

standards for secure transmission of information between the pharmaceutical industry and regulatory authorities of the United States, Japan and the European Union.

Harmonization efforts have been so successful that what once seemed only a dream is becoming a

reality more rapidly than any of us could have imagined. By the turn of the century, it is highly

likely that we will have reached agreement on having essentially the same new drug review document submitted to the regulatory authorities in all three regions.

We are expanding on the lessons learned through our cooperative experience with PDUFA. We are

spearheading new collaborative efforts with academia, industry, professional societies and health

organizations. These hold the promise of finding scientifically sound ways of expediting drug development and making it easier for manufacturers to take advantage of newer production technologies.

Finally, the FDA Modernization Act of 1997 and the reauthorization of PDUFA have presented the

Center and the Agency with a huge portfolio of tasks. The time for implementing some of these

changes is short. If you want input into the process, I urge you to contact the Agency leads identified

on FDA Modernization Act of 1997 Implementation Chart available on the World Wide Web at http:/

/www.fda.gov/po/modact97.html.

I look forward to reporting to you next year on what is promising to be a most challenging year. If

you have any questions about this report, please contact Murray Lumpkin, M.D., Roger Williams,

M.D., or me at (301) 594-5400.

Sincerely,

Janet Woodcock, M.D.

Director

Center for Drug Evaluation and Research

v
What Americans Expect

American consumers rely on the U.S. Food and Drug Administrations

Center for Drug Evaluation and Research to:

n Facilitate the availability of safe and effective drugs.

n Keep unsafe or ineffective drugs off the market.

n Improve the health of Americans.

n Provide clear, easily understandable drug information for safe and

effective use.

Application Review Program

Before new drugs can be marketed in the United States, they must undergo

an independent review by scientists at the Center for Drug Evaluation and

Research. If the review establishes that a drugs benefits outweigh its known

risks, the Center approves it for marketing.

In addition to prescription drugs, CDER regulates over-the-counter drugs.

The Centers continuing evaluation of products that have been on the market

for a number of years and its review of new over-the-counter drugs and drugs

reclassified from prescription status, ensure these drugs contain acceptable

ingredients, doses, formulations and consumer labeling.

The Center regulates the generic counterparts of prescription and

over-the-counter drugs. Companies seeking approval for generic drugs

must demonstrate that their products are the same as the reference

drugs in terms of strength, dosage form, route of administration, intended

use, quality and performance.

Post-Marketing Surveillance

The practical size of pre-marketing clinical trials means that CDER and the

industry cannot learn everything about the safety profile of a drug before it

is approved. Americans have chosen to accept this risk in order to have drugs

developed within a reasonable time. The trade-off for accepting this risk is

the continued vigilance of the Center and industry to collect and assess data

during the post-marketing life of a drug.

Introduction

1
The Center monitors the quality of marketed drugs and their advertising

and promotion through product testing and surveillance. In addition it

develops policies, guidance and standards for drug labeling, current good

manufacturing practices, clinical and good laboratory practices, and industry

practices to demonstrate the safety and effectiveness of drugs.

FDA Modernization Act

On Nov. 21, the FDA Modernization Act of 1997 became law. The act contains

some of the most sweeping changes to the Food, Drug and Cosmetic Act in 35

years. The act codifiesand validatesmany of CDERs Reinventing

Government initiatives and other existing programs.

Of critical importance to CDER is the reauthorization of the Prescription

Drug User Fee Act (PDUFA). The Modernization Act extends PDUFA for

five more years, through fiscal year 2002. Under this program, the

pharmaceutical industry pays user fees that enhance the Centers

resources for certain drug review activities.

Getting beneficial drugs on the market quickly is just as much a part

of the Centers mission as is keeping unproven or dangerous drugs off

the market. The Modernization Act creates heightened expectations for

CDERs responsiveness in some new areas in the investigational new drug

(IND) development phase as well as in the review phase of CDERs drug

oversight activities.

In addition to renewing PDUFA, the Modernization Act contains a number

of provisions that will change the way the Agency works and the way the

Center performs drug reviews. Some provisions will make the process easier.

But others will increase the Centers workload, especially over the short

term, as the Center meets its mandate to develop new regulations and

guidance documents for the industry.

The Center is working actively to implement these and many other

provisions of the law in the time frames expected.

Introduction

2
1997 Performance and Workload

CDER achieved the fastest median approval times for new drug

applications (NDAs) and approved the second highest total of new molecular

entities (NMEs) in the calendar year 1997. NMEs represent products that

contain an active substance that has not been previously marketed as a

drug in the United States. Often these products represent new therapies

or improved therapies for various diseases. Most importantly, the Center

accomplished this without creating a backlog of applications.

Total Original NDA Actions

The Center took 235 actions on original new drug applications. PDUFA has

resulted in more applications that can be filed immediately, and reviewed

and approved more quickly. As a result, new products with the needed

scientific data get on the market faster. The proportion of total actions that

are approvals during the initial review cycle has risen steadily from under

one-third in 1993 to just over half in 1997. Both CDERs and industrys

Original NDA Actions

31 39 51 38 49

223 216 235

161

269

1993 1994 1995 1996 1997

Calendar Year

Percentage

0

50

100

150

200

250

300

Number

Percentage of Actions that Are Approvals

Number of Total Original NDA Actions

0

10

20

30

40

50

60

Application Approvals

3
performance, predictability and accountability have significantly improved

as a result of:

n Additional human and financial resources.

n Significant investment in improved information technology.

n The use of project management methodology to guide the review process

and monitor the increasing workload.

n The elimination of backlogs.

n The increased emphasis on timeliness as a performance measure.

Total Original NDA Approvals

Of these 235 actions, 121 were approvals of original NDAs. This represents a

75 percent increase in the annual number of NDAs approved over the Centers

performance level in 1993.

Application Approvals

4

Original NDA Approvals

19

16.5

14.4 15.8

12.2

15.4

24.1 months

15.3 14.8

20.8 months 121

131

82

70 62

0

5

10

15

20

25

1993 1994 1995 1996 1997

Calendar Year

Times in Months

0

20

40

60

80

100

120

140

Number of 

Approvals

Median Total Approval Time in Months

Median Total FDA Review Time in Months

Number of Original NDAs Approved
The median total FDA review time for these products was 12.2 months,

18 percent shorter than the year before. The median total FDA review time

for these applications has fallen 41 percent from the performance level at the

beginning of the PDUFA program.

In addition, the median total time to approval (total FDA review time plus

industry response time to agency approvable or not approvable letters)

was 14.4 months, 6 percent less than the 15.4 months for those products

approved in calendar year 1996. The median total time to approval has fallen

40 percent from the performance level at the beginning of PDUFA.

Note: The median time is a value that falls in the middle of all times. It

provides a truer picture of performance than average time, which can be

unduly influenced by a few extremely long or short times.

New Molecular Entity Approvals

Of the 121 NDAs approved in calendar year 1997, 39 were new molecular

entities. This represents a 56 percent increase in the annual number of NMEs

approved compared with the Centers performance level at the beginning of

NME Approvals

17.5

15.9

13.4

15.3

12.8

14.3

23 months

15.2

12

21 months

39

53

28

22 25

0

5

10

15

20

25

1993 1994 1995 1996 1997

Calendar Year

Times in Months

0

10

20

30

40

50

60

Number of 

Approvals

Median Total Approval Time in Months

Median Total FDA Review Time in Months

Number of NMEs Approved

Application Approvals

5
the PDUFA program. In the 1960s, the average number of NMEs approved

each year was 13.7. In the 1970s, that went up to 17.3. In the 1980s, the

average was 21.7. In the first half of the 1990s, it stood at 25.6.

American consumers were the first in the world to have access to more than

half of these NMEs, according to data from the Pharmaceutical Research and

Manufacturers of America. In their report on the 39 NMEs approved in 1997,

they found:

n 17 were first marketed in the United States.

n Three had not yet been marketed elsewhere in 1997.

n Seven were first marketed in other countries before U.S. approval but

within 1997.

This is an improvement over 1996 when 17 of the 53 NMEs were first

marketed in the United States. An additional eight were first marketed in

other countries in the same year as U.S. approval.

The median total FDA review time for the NMEs approved in 1997 was

12.8 months, 38 percent faster than the Centers performance level for NME

review at the start of the PDUFA program.

In addition, the median total time to approval for these 39 NMEs was

13.4 months, 6 percent faster than in 1996 and 42 percent faster than the

performance level at the beginning of the PDUFA program.

Nine of the NMEs were priority drugs, which received an accelerated review

because they represent a major advance in medical treatment. Viracept

(nelfinavir mesylate), a new protease inhibitor for treatment of HIV

infection, was reviewed and approved in 2.6 months. Evista (raloxifene

hyrochloride), which is indicated for prevention of osteoporosis in

postmenopausal women, Rezulin (troglitazone) and Prandin (repaglinide), both

for treatment of patients with type II diabetes, were reviewed and approved in

six months or less.

Other important priority drugs approved last year were Rescriptor

(delavirdine mesylate), a combination therapy for HIV; Plavix (clopidogrel

bisulfate), for the prevention of second stroke in patients with hardening of

the arteries; Sclerosol (sterile talc powder), for the prevention of malignant

Application Approvals

6
secretions from the lung membrane; Agrylin (anagrelide hydrochloride), a

blood thinner for patients with thrombosis; and PYtest (urea C-14), a breath

test for the detection of Helicobacter pylori, a cause of stomach ulcers.

Noteworthy drug approvals in 1997 also included Tobi (tobramycin solution

for inhalation), the first inhaled antibiotic for patients with cystic fibrosis,

and Meridia (sibutramine hydrochloride), for the management of obesity.

Efficacy Supplement Approvals

The Center took action on 189 efficacy supplements, of which 108 actions

were approvals. Efficacy supplements are new uses for already approved

drugs and often represent important new treatment options for American

patients. The 1997 approvals represent a 125 percent increase in the annual

number of approved efficacy supplements over the Centers performance level

at the beginning of PDUFA. The annual average of 113 efficacy supplements

approved in 1996 and 1997 is more than double the annual average of 55.7

for the three years 1993 to 1995.

Efficacy Supplement Actions

39% 41% 37% 60% 57%

185

189

122

196

122

0

10

20

30

40

50

60

70

1993 1994 1995 1996 1997

Calendar Year

Percentage

0

50

100

150

200

Number

Percentage of Actions that Are Approvals

Number of Efficacy Supplement Actions

7

Application Approvals
The median total FDA review time for these applications fell 35 percent from

the Centers performance level at the start of the PDUFA program.

In addition, the median total time to approval fell 37 percent from the

performance level at the beginning of the PDUFA program.

Manufacturing Supplement Approvals

In fiscal year 1997 (from Oct. 1, 1996, to Sept. 30, 1997), the Center took

action on 1,647 manufacturing supplements, of which 1,178 were approvals.

Manufacturing supplements are only tracked on a fiscal year basis. In many

cases, manufacturing supplements represent the industrys efforts to

modernize plants and equipment or to make manufacturing of already

approved products more efficient. The approvals in 1997 are a 39 percent

increase in the annual number of approved manufacturing supplements

compared with the performance level at the beginning of PDUFA.

Efficacy Supplement Approvals

12

16

11.2 11.9

13.9

19 months

11.9

14.2

12.3

18.3 months 108

118

69

48 50

0

2

4

6

8

10

12

14

16

18

20

1993 1994 1995 1996 1997

Calendar Year

Times in Months

0

20

40

60

80

100

120

Number of 

Approvals

Median Total Approval Time in Months

Median Total FDA Review Time in Months

Number of Efficacy Supplements Approved

Application Approvals

8
The median total approval time for these applications fell 38 percent from the

Centers performance level at the start of the PDUFA program.

Manufacturing Supplement Approvals

7.7

5.9

5.4

8.2 months

5.1

1,422

1,065 1,024

848

1,178

0

1

2

3

4

5

6

7

8

9

1993 1994 1995 1996 1997

Fiscal Year

Times in 

Months

0

200

400

600

800

1000

1200

1400

1600

Number of 

Approvals

Median Total Approval Time in Months

Number of Manufacturing Supplements Approved

Manufacturing Supplement Actions

74% 67% 61% 80% 72%

1,674 1,630

1,580

1,782

1,147

0

10

20

30

40

50

60

70

80

1993 1994 1995 1996 1997

Calendar Year

Percentage

0

200

400

600

800

1,000

1,200

1,400

1,600

1,800

Number

Percentage of Actions that Are Approvals

Number of Manufacturing Supplement Actions

9

Application Approvals
The consistently high achievements of CDERs drug review program in recent

years reflect the importance of the managerial reforms and additional

resources provided under the Prescription Drug User Fee Act. Three unique

features made PDUFA work:

n Mutually agreed-upon, prospective performance goals for drug reviews.

These goals are time limits for a review based on submission cohorts,

identified by the fiscal year in which the application is submitted.

n A provision that user fees were to be collected only if taxpayer dollars

supporting the review program remained steady, making these truly

additive resources.

n A sunset provision to allow stakeholders to assess results before program

reauthorization.

By managing the review process to meet the PDUFA review performance

goals, CDER has transformed the new drug review program into one that is

Original NDAs

On-Time Review Performance

1996

10 9 reviews

100% on-time

1995

11 1 reviews

98 % on-time

1993

84 reviews

65% on-time

1994

92 reviews

95% on-time

0

20

40

60

80

100

Fiscal Year Submission Cohort

  PDUFA Goal (none in 1993)

Percentage

10

PDUFA Application Review Performance
Resubmissions of O riginal NDAs

On-Time Review Pe rformance

1996

89 reviews

99% on-time

1995

58 reviews

97% on-time

1993

2 reviews

100% on-time

(new category

in 1993)

1994

24 reviews

83% on-time

0

20

40

60

80

100

Fiscal Year Submission Cohort

 PDUFA G oal (none in 1993)

Percentage

not only thorough but also predictable and accountable. CDERs performance

has established shorter review times and shorter total times to approval

without sacrificing quality in the FDA application review process.

CDERs top priority has been to exceed the application review on-time

performance goals established under PDUFA. For the first four years of

PDUFA, an on-time review meant that the Center would completely review

and act on original NDAs and efficacy supplements, priority and standard,

within one year of submission. Manufacturing supplements and

resubmissions of original NDAs would be completely reviewed and acted

upon within six months of their submission to the FDA. In addition, CDER

agreed to review and act on priority applications, both NDAs and efficacy

supplements, in six months or less for the fiscal year 1997 submission cohort.

A priority drug is one that appears to represent a major advance in therapy.

A standard drug appears to have therapeutic qualities similar to those of an

already marketed drug.

The review performance goals were predicated on the understanding that,

over the five years of the program, CDER would increase the human

resources available to perform reviews and install new management

techniques for the review process. Therefore, it was agreed to phase in the

percentage of applications that were expected to be reviewed on-time.

Starting with a goal of 55 percent of the applications filed in fiscal year

1994 expected to be reviewed on time, the goal increased each year: 70

percent for fiscal year 1995, 80 percent for fiscal year 1996 and 90 percent

for fiscal year 1997.

PDUFA Application Review Performance

11
The on-time review performance charts show CDERs results far exceeded the

PDUFA review performance goals. When comparing the fiscal year on-time

performance charts with the calendar year totals, remember that many

applications in a fiscal year submission cohort are actually reviewed and acted

on in the subsequent calendar year. So the results for the PDUFA fiscal year

1996 submission cohort substantially reflect the work effort of CDER in

calendar year 1997.

Efficacy Supplements

On-Time Review Pe rforma nce

1996

106 reviews

97% on-time

1995

77 reviews

95% on-time

1993

92 reviews

41% on-time

1994

86 reviews

77% on-time

0

20

40

60

80

100

Fiscal Year Submission Cohort

 PDUFA Goal (none in 1993)

Percentage

12

Manufacturing Supplements

On-Time Review Performance

1994

871 reviews

66% on-time

1993

1,045 reviews

50% on-time

1995

1,249 reviews

90% on-time

1996

1,218 reviews

96% on-time

0

20

40

60

80

100

Fiscal Year Submission Cohort

 PDUFA Goal (none in 1993)

Percentage

PDUFA Application Review Performance
Recognizing PDUFAs major contributions to improving the drug review

process and accelerating the delivery of new drugs to Americans, Congress,

with the Centers and the industrys support, last fall further enhanced the

user fee program and extended it for another five years. The act contains

changes in how fees are assessed and collected. For example, fees are

waived for first applications for small businesses, orphan products and

pediatric supplements.

A phase-in to a 10-month review time by fiscal year 2002 for standard new

drug applications and efficacy supplements highlights the expanded list of

review performance goals. The Centers successes in meeting and exceeding

the performance goals agreed to in 1992 give confidence that it can rise to

these new challenges. Currently, CDER is reviewing more than 90 percent of

priority drug applications in six months and standard drug applications in 12

months. Performance goals for priority drugsthose that appear to represent

an advance over available therapywill remain at six months for the five

years of the reauthorization.

In addition to performance goals for standard and priority drug reviews, the

Center has committed to goals that it believes will help speed the time it

takes for drugs to be appropriately tested and developed before submitting

those results for FDA review. These new performance goals include those

related to meeting management, clinical holds, resolving major disputes and

reaching agreement on certain protocols. In addition there are added

expectations regarding electronic applications and submissions, simplification

of action letters and expedited notification of deficiencies in applications.

PDUFA Reauthorization Goals

13
A primary goal of the PDUFA program was to reduce the overdue

applications that existed in 1992 and to transform the CDER new drug

review program into one that stays current with a minimum of overdue

applications at any given time. On Dec. 31, 1997, the number of applications

on hand in the Center, including those submitted but not yet officially filed,

and the number overdue were:

n Original NDAs: 129 on hand, none overdue.

n Efficacy supplements: 103 on hand, five overdue.

n Manufacturing supplements: 575 on hand, five overdue.

While CDER endeavors to avoid having any applications overdue, having only

1.2 percent overdue out of 807 applications pending on Dec. 31 is a significant

improvement over the Centers performance prior to PDUFA.

Overdue Reduction

14
Two remarkable successes of the PDUFA program have been the increased

quality of applications submitted by industry and the Centers increased

consistency in applying its authority to refuse to file an application. The

Center refuses to file an application when it determines there is a significant

omission of needed information.

Before 1993, the Center was refusing to file approximately 25 percent to

30 percent of submitted original NDAs. The percentage of refused-to-file

applications has dropped steadily to a low of less than 2 percent of the

original NDAs submitted in fiscal year 1997.

This significant change ensures that CDERs review efforts are not

expended on incomplete or low-quality applications.

Refuse-to-File Actions

Original NDAs

26% 5% 4% 1.6% 17%

117

113 114

124

111

0

5

10

15

20

25

30

1993

(29)

1994

(19)

1995

(6)

1996

(5)

1997

(2)

Fiscal Year

(number refused)

Percentage

104

106

108

110

112

114

116

118

120

122

124

Number

Percentage Refused to File Number of Original NDAs Submitted

Refusal to File an Application

15
By working with sponsors more closely, the percentage of commercial INDs

put on clinical hold over the last five years has decreased by more than

50 percent. A clinical hold halts the testing of a drug in humans because of

concerns about safety. The Center has developed and published procedures that

outline specific responsibilities and time lines for handling clinical holds

imposed on investigational new drugs (INDs).

Clinical Holds of Commercial INDs

(as of Nov. 30, 1997)

15% 11% 7% 7%

376 446 358

360

0

2

4

6

8

10

12

14

16

1994

(54)

1995

(41)

1996

(26)

1997

(30)

Fiscal Year (Number of Holds)

Percentage

100

150

200

250

300

350

400

450

Number

Percentage of Commercial INDs Received on Hold

Number of Commercial INDs Received

0

50

Clinical Holds

16
Adverse Event Reporting

In the last fiscal year, the Center received 254,841 reports of suspected

drug-related adverse events: 12,453 reports direct from individuals;

31,522 15-day manufacturer reports; 178,132 periodic manufacturer

reports; and 30,737 follow-up reports.

The average number of reports received has jumped to more than 175,000

per year in the last five years from about 75,000 per year in the previous five

years. This steep climb is due in part to PDUFA and the FDAs MedWatch

program. The record number of 128 NMEs approved for the 1993 to 1996

PDUFA submission cohorts accounts for almost 10 percent of the adverse

event reports. MedWatch, launched in 1993, solicits reports from individual

health care practitioners and makes it easier to submit them.

CDER has begun using a state-of-the art information technology system for

receiving, storing and analyzing the more than a quarter million reports it

receives each year. It is the first system in the world to implement the

information technology and safety reporting requirements reached as part

of the International Conference on Harmonization.

Post-Marketing Adverse Event Reports

Calendar Year

(except fiscal year 1997)

51,188 62,691 77,207 22,269

107,560

131,995 148,370164,551

193,336

254,841

0

50,000

100,000

150,000

200,000

250,000

300,000

1988 1989 1990 1991 1992 1993 1994 1995 1996 1997

Number

Direct Reports Manufacturer 15-Day Reports

Manufacturer Periodic Reports Follow-up Reports

Post-Marketing Risk Assessment

17
Reports of suspected drug-related adverse events are:

n Direct reports. An individual, usually a health care practitioner, notifies

the FDA directly of a suspected adverse event.

n Manufacturer 15-day reports. Drug manufacturers report serious and

unexpected adverse events to the FDA as soon as possible and within

15 days of discovering the problem.

PDUFA Submission Cohorts

Adverse Event Reports 

31,692

16,121

23,891

11,793

0

5,000

10,000

15,000

20,000

25,000

30,000

35,000

1993 1994 1995 1996

Fiscal Year Submission Cohort

Number

n Manufacturer periodic reports. Drug manufacturers periodically report all

other adverse events, for example, those that are less than serious or

described in the drugs labeling. Reports are submitted quarterly for the

first three years of marketing and annually thereafter.

n Follow-up reports. When additional information is required, a follow-up

report is submitted.

Post-Marketing Risk Assessment

18
Drug Safety Issues

As the Center discovers new knowledge about a drugs safety profile, it

makes risk assessments and decisions about the most appropriate way to

manage any new risk or new perspective on a previously known risk. Risk

management methods include new labeling, Dear Health Care Practitioner

letters, restricted distribution programs or product marketing termination.

Highlights of the Centers drug risk assessment program in 1997 were:

n Heart disease associated with diet drugs. The Centers risk assessors

participated in the initial review of adverse event reports of valvular heart

disease in people treated with the appetite-suppressant drugs fenfluramine

and dexfenfluramine. Using these reports, the Center then conducted an

epidemiologic study in partnership with five investigators across the

United States. The study uncovered a 30 percent rate of valvular disease,

much higher than expected. The manufacturer voluntarily withdrew the

products from the market.

n Diabetes associated with protease inhibitors. From reviewing MedWatch

reports, Center risk assessors identified high blood sugar levels and

diabetes as potentially serious adverse events associated with protease

inhibitors used to treat HIV infection. This work formed the basis for a

Dear Health Care Practitioner letter and an FDA Public Health Advisory.

n Potentially fatal heart condition associated with an antihistamine. Reports

of irregular heartbeats associated with the use of the antihistamine

terfenanadine and the availability of a similar drug without the risk led to

the Centers decision that products with terfenanadine should be removed

from the U.S. market.

Post-Marketing Risk Assessment

19
In January 1997, the Center consolidated administrative responsibility for

over-the-counter drugs marketed under the authority of approved NDAs in

the Division of OTC Drug Products. The responsibilities include postapproval

regulatory oversight, such as the evaluation of postmarketing safety reports

and the review of data submitted to provide for most changes to the approved

NDA. Approximately 235 approved over-the-counter NDAs were involved in

the transfer from the previous review divisions.

The Center approved eight new drugs or new indications for an existing drug

for OTC marketing, including:

n A nasal spray to treat allergy symptoms.

n New drugs to treat heartburn.

n A new toothpaste for gingivitis.

n An antifungal for one-day treatment of vaginal infections.

n A hair growth treatment for hereditary pattern baldness in men.

n A product for dandruff control.

In addition, more than 50 labeling reviews of OTC drugs were performed.

CDER published 14 monograph and rulemaking documents related to

over-the-counter drug products in the Federal Register, including:

n A proposed rule to increase the legibility and clarity of OTC labels in order

to improve consumers ability to understand important warnings and

directions for use.

n A proposal to include a warning to heavy alcohol users about the risk of

OTC internal analgesics.

n A proposal to remove the laxative ingredient phenolphthalein from

the OTC market.

n New labeling for drug products containing the antihistamine

diphenhydramine.

OTC Update and Significant Switches

20
Numerous OTC drug topics were discussed in public meetings. The

Nonprescription Drugs Advisory Committee (NDAC), jointly with other

FDA advisory committees and the Dental Panel, convened for a total of 12

days of meetings. The NDAC addressed a range of issues including the

prescription drugs switches to OTC marketing and new indications for

already marketed OTC products. In addition, the Dental Panel, previously a

subcommittee of the Devices Advisory Committee, became a subcommittee

of NDAC in the spring and continues to deliberate about remaining dental

products for the OTC Review.

Other important public meetings were held between FDA, industry and

interested professional and consumer groups. These meetings discussed

new safety or efficacy issues concerning products that have long been

marketed under OTC drug review procedures but are not yet covered

under a final monograph.

OTC Update and Significant Switches

21
The 431 generic drug approvals in 1997 represents a substantial increase over

302 approved in 1995 and 351 in 1996. This increase occurred despite a

continuing growth in workload over the past three years. From 1991 to 1994,

submissions remained relatively stable at approximately 323 applications

each year. In each of the three years since, there has been an increase in

submissions: 411 in 1995, 453 in 1996 and 464 in 1997.

Streamlining initiatives: CDER has undertaken several initiatives to make

the generic drug review process more efficient, including:

n Faxing deficiency letters to applicants.

n Increasing communications with firms receiving major deficiency letters to

help minimize review cycles.

n Making acceptable bioequivalence study protocols publicly available.

n Resolving simple refuse-to-file issues by telephone.

n Providing copies of currently approved labeling to applicants, thereby

eliminating the lengthy delay in obtaining this information through the

Freedom of Information process.

In addition, several other initiatives to streamline the review processsuch

as accepting the electronic submissions of bioequivalence data as well as

chemistry, manufacturing and controls dataare being implemented or

nearing implementation.

Generic Drugs

Generic Drug Approvals

39.6

26.9 27

23 19.3 249

219

302

351

431

0

5

10

15

20

25

30

35

40

1993 1994 1995 1996 1997

Calendar Year

Times in Months

0

50

100

150

200

250

300

350

400

450

Number

Median Approval Times in Months

Number of Generic Approvals

22
Export Certificates Issued

1,747

4,499 4,378

1,290

0

1,000

2,000

3,000

4,000

5,000

1994 1995 1996 1997

Fiscal Year

Number

Export Certificates Issued

Export Certificates

In 1997, the demand for certificates by foreign governments remained high

due to expanding world trade, ongoing international harmonization

initiatives and international development agreements. The demand was

met by the allocation of additional resources to the program, and CDER

currently has no overdue requests for certificates.

CDER processes nine different types of certificates to foreign governments.

These certificates enable the manufacturers to export their products to

foreign customers and foreign governments. The certificates attest that the

drug products are subject to inspection by the FDA and are manufactured in

compliance with current good manufacturing practices. In addition, they

verify that the drug products being exported:

n Were freely marketed in the United States.

n Were in compliance with U.S. laws and regulations.

n Were in compliance with the importing countrys requirements.

n Met certain national or international standards, such as quality standards.

n Were free of specific contaminants.

23
CDER promotes and protects the health of Americans by ensuring that drug

advertising and promotional materials are truthful and balanced. The Center

operates a comprehensive program of education, surveillance and enforcement

about drug advertising and promotion. Included in this program are:

n Drug launch campaign advisories. The Center reviews drug advertising and

promotional materials before drug companies launch marketing campaigns

that introduce new drugs or introduce new indications or dosages for

approved drugs. In fiscal year 1997, the Center issued 532 advisory letters

to companies regarding their promotional materials for launch campaigns.

n Regulatory actions. The Center issued 183 regulatory action letters to

pharmaceutical companies for prescription drug promotions determined to

be false, misleading or lacking in fair balance. These were either untitled

letters for routine violations or warning letters for serious or repeat

violations.

n Other actions. The Center also issued 555 other advisory, acknowledgment

or closure letters to the industry regarding prescription drug advertising

and promotion.

Drug Advertising and Promotion

Advertising and Promotion

Regulatory Actions and Launch Campaigns

Fiscal Year

(* 1996 CDER changed from counting campaigns to individual letters) 

251 212 163 139 183

608 532

118 185 306

0

100

200

300

400

500

600

700

800

1993 1994 1995 1996 1997

Number *

Regulatory Actions Launch Campaigns

24
n Direct-to-consumer advertising. CDER issued 240 letters in all

categories regarding direct-to-consumer advertising.

n Improved patient information for prescription drugs. The Center

continued its research, education and outreach activities in support

of the public-private plan to provide consumers with easy-to-read

information about their prescription drugs. CDER and other FDA

components have been working with industry, non-profit agencies

and academic groups to ensure that useful drug information reaches

75 percent of patients by the year 2000.

n Improved drug label testing. In February 1997, CDER proposed

standardized over-the-counter drug label formats and is developing

proposed regulations for the professional labeling that accompanies

prescription drugs. To support these efforts, the Center continues

to test label prototypes.

n Risk vs. benefit communications research. The Center is

conducting research to assess the publics ability to understand

risk vs. benefit information. The goal is to develop useful and

meaningful ways of presenting important information about a

drugs known risks and benefits.

Drug Advertising and Promotion

25
Harmonizationmaking the drug regulatory process more efficient and

uniformis an issue that is important not only to CDER, but to drug

regulatory agencies and pharmaceutical companies throughout the world.

During the last seven years, the International Conference on Harmonization

of Technical Requirements for Registration of Pharmaceuticals for Human

Use (ICH) has worked to bring together government regulators and drug

industry experts from innovator trade associations in the European Union,

Japan and the United States.

Although drug regulatory systems in all three regions share the same

fundamental concerns for the safety, efficacy and quality of drug products,

many time-consuming and expensive technical tests have had to be repeated

in all three regions. To reduce, minimize and even eliminate unnecessary

duplicate testing during the research and development of new drugs, the ICH

process results in documents that recommend ways to find consistency in the

implementation and application of technical guidances and requirements for

product registration. ICH has four areas of focus: efficacy (human clinical

trials), safety (animal pharmacology/toxicology), quality (manufacturing) and

regulatory communication.

Highlights from the fourth biennial meeting, ICH 4, held in July 1997 in

Brussels, Belgium, included finalization of 10 harmonized guidances and

announcement of the next phasethe start of work on a Common Technical

Document that can be used in all three ICH regions.

The results in Brussels mean that work on more than three-quarters of the

guidances has been completed. After having made so much progress during

this first phase, the ICH steering committee agreed to launch a second phase

that will maintain the existing documents and develop a Common Technical

Document. This represents a logical progression from a single, harmonized set

of guidances for collecting the technical data to a common technical

information package for presenting the data. The goal is to harmonize format

so that essentially the same core submission could be provided to the

regulatory authorities in all three regions.

ICH 4 also announced finalization of the Medical Dictionary for Regulatory

Activities, which will provide a common terminology to facilitate regulatory

communication. Also, the release for consultation of the consensus draft

guidance, Specifications for New Chemical Drug Substances and Products

(Q6A), represents a step toward the goal of having the same specifications

International Harmonization

26
International Harmonization

27

for a drug product wherever it is marketed. The draft guidance has been

developed in close collaboration with the pharmacopoeial authorities in

each region.

Additional information on ICH activities may be found on the World Wide

Web at http://www.ifpma.org/ich1.html. ICH guidances are available on

CDERs Web site at http://www.fda.gov/cder/guidance/index.htm.
Applied Research

28

In 1997, CDER continued to support, facilitate and improve the drug

development and review process through applied research. Research within

the Center advances the scientific basis for regulatory policy and ensures

that policy and decisions are based on the best available science. Some of the

results of CDERs 1997 research included:

n Development of artificial intelligence software that will help assess

the cancer causing potential of new drugs and aid in drug development

and review.

n Implementation of a guidance describing data needed on drug metabolism

and drug-drug interactions. This will help assure the safety of new drugs

and aid in drug development and review.

n Development of a guidance that allows a short-term study in genetically

altered mice in combination with a standard two-year rodent study to

assess a drugs cancer causing potential. Continuing research will evaluate

the potential of genetically altered mice to support other improvements in

the requirements for animal testing.

n Assessment of near-infrared spectroscopy and development of a document

for qualifying such equipment. This will provide FDA and industry with a

common base for accepting data from this new technology and will

eventually contribute to improved product quality.

n Development of additional guidances that allow manufacturers to make

certain changes in equipment and production without requiring prior

approval from the Center.

CDERs applied research was expanded in 1997 through development of

external collaborations with industry, academia, professional societies and

other government laboratories, including:

n The Product Quality Research Initiative (PQRI) to focus on research to

support improvements in the area of drug quality and production.

n The Collaboration for Drug Development Improvement (CDDI) to support

scientifically sound approaches for expediting drug development.

Additional information on research is available on CDERs Web site

at http://www.fda.gov/cder/otr/index.htm.
Communications

29

CDERs evolution into an open and accountable organization within the FDA

has relied heavily on improved communications.

Dissemination Activities

The Center has invested heavily in the technology to make information

about its activities widely available to individuals, the media and industry.

The Center has made extensive use of traditional methods of communication

as well as the World Wide Web.

n The Center Internet Web site, http://www.fda.gov/cder, has grown by

nearly 100 megabytes of information a week. Use has exploded from about

30,000 hits a month in late 1996 to nearly 2 million hits a month currently.

n CDERs Electronic Freedom of Information Reading Room provides Internet

users ready access to its most frequently requested documents.

n CDERs Drug Information Branch answered more than 36,000 telephone

inquiries and 17,500 written requests from pharmacists, doctors, nurses,

pharmaceutical and insurance companies, consumers, Federal agencies and

others. They were provided the most current drug information.

n CDER scientists and regulatory experts participated in the development

of 15 Department of Health and Human Services press releases and 26

FDA talk papers. They took part in numerous media interviews related to

these activities. In addition, more than 1,000 interviews were conducted

for specialized publications serving the pharmaceutical industry.

Consumer and Industry Outreach Efforts

The Center cooperates with consumer health organizations, professional

societies and industry associations to help their members better understand

CDERs policies and actions.

n The Center in cooperation with FDAs Office of External Affairs

implemented Hot Topic briefings for health associations to explain in

detail actions with a high degree of public health impact.

n CDER engaged in a partnership to co-sponsor a 21⁄2-hour live

satellite broadcast to industry about the Centers developments in

adverse event reporting.
Communications

30

n The Centers scientists and regulatory officials routinely make

presentations to and participate in association conferences and workshops.

n The International Conference on Harmonization product quality guidances

were subject of a day-long CDER-sponsored training session held for

industry representatives.

n CDERs exhibit and information program completed successful showings

at three national health care conferences.

n The Center conducted about 150 domestic and foreign videoconferences for

academia, industry and associations.

Public Participation

CDER has expanded its efforts to obtain outside expertise and opinion to help

formulate policies and procedures that affect the public and industry.

n Panels of outside experts confer with CDER about difficult scientific issues.

These advisory committees met about 50 times a year during the five years

of PDUFA, compared with about 30 times a year in the preceding five

years.

n The Center has expanded its use of open public meetings to obtain input

on important public health policy issues.

n In addition to analyzing required public comments on proposed new

rules, the Center sought and received comments on its non-binding

guidances to industry.

Ombudsmans Activity

In its second year of operation, the Center Ombudsmans office doubled its

activity to more than 200 interactions. The goal of the Ombudsman is to

provide a mechanism for people inside and outside the Center to seek solutions

to problematic interactions and to suggest better ways for CDER to do its

work. The ratio of external to internal cases rose from 2-to-1 in the first year

to 3-to-1 in the second.
Improving Policy Consistency

New and Proposed Rules

In 1997, CDER published five proposed rules and 11 final rules. Some

highlights are:

n Electronic Records; Electronic Signatures Final Rule (62FR13430, March 20,

1997). New regulations that provide criteria for FDA acceptance, under

certain circumstances, of electronic records, electronic signatures and

handwritten signatures executed to electronic records as equivalent to

paper records and handwritten signatures executed on paper.

n National Environmental Policy Act (NEPA) Final Rule (62FR40570, July 29,

1997). Amendment to regulations governing compliance with NEPA that

increase the efficiency of FDAs implementation of the act and reduce the

number of evaluations by providing for categorical exclusions for additional

classes of actions that do not individually or cumulatively have a significant

effect on the human environment and for which neither an environmental

impact statement nor environmental assessment is required.

n Specific Requirements on Content and Format of Labeling for Human

Prescription Drugs; Addition of Geriatric Use Subsection in the Labeling

Final Rule (62FR45313, Aug. 27, 1997). Amendment to regulations governing

the content and format of labeling for human prescription drug products to

include information pertinent to the appropriate use of drugs in the elderly

and to facilitate access to this information by establishing a Geriatric Use

subsection in the labeling.

n Expedited Safety Reporting Requirements for Human Drug and Biological

Products Final Rule (62FR52237, Oct. 7, 1997). Amendment to expedited safety

reporting regulations to provide consistency with FDAs MedWatch program

and with ICH guidances. The amendments include definition changes, for

example, what constitutes a serious adverse reaction to a medication, and

changes to reporting content, format and time frames. The final rule is the

first of several proposed and final rules that CDER expects to publish during

in the coming year to implement the ICH guidances and update the

information technology used to report and record adverse events.

n Over-the-Counter Human Drugs; Proposed Labeling Requirements (62FR9024,

Feb. 27, 1997). Proposed new regulations that standardize the format for OTC

drug labeling to enable consumers to read and understand better OTC drug

product labeling and to apply this information to the safe and effective use

of OTC drug products.

31
Guidances to Industry

During 1997, in accordance with the FDAs Good Guidance Practices

(62FR8961, Feb. 27, 1997), 40 guidances for industry were issued either as

draft or final documents. Of these, 22 were the result of ICH efforts.

Guidance documents published during the last two years are available on

the CDER Web site at http://www.fda.gov/cder/guidance/index.htm. The

Center has undertaken a project to make all Center guidances available

on its Internet site.

Among the documents completed this year are two of four guidances begun

under the administrations Reinventing Government initiative. These

guidances clarify how to make and document manufacturing scale-up

and post-approval changes for non-sterile semisolid dosage forms and

modified-release solid oral dosage forms. They were published in May and

September 1997, respectively. Other guidances for industry completed in

draft or final form in 1997 include:

n Providing Clinical Evidence of Effectiveness for Human Drug and

Biological Products. This draft document is intended to provide guidance

to applicants planning to file NDAs or efficacy supplements on what

evidence should be provided to demonstrate effectiveness.

n FDA Approval of New Cancer Treatment Uses for Marketed Drug and

Biological Products. This draft guidance considers the quality and

quantity of data that may be adequate to add a new use to the prescribing

information for a product used in the treatment of cancer.

n Post-Marketing Adverse Experience Reporting for Human Drug and

Licensed Biological Products: Clarification of What to Report. This

guidance clarified reporting requirements for adverse experiences.

n Archiving Submission in Electronic FormatNDAs. This is the first in

a series that will provide guidance on how to submit applications in

electronic format.

Improving Policy Consistency

32
MAPPs

During 1997, the Center continued its efforts to implement its Manual of

Policy and Procedures (MAPP). More than 32 individual MAPPs were issued

to CDER staff. MAPP development is part of a long-term Center effort to

update the old staff directives. Old directives are being reviewed, revised and

revoked when necessary. New MAPPs are being developed to help the Center

better achieve its mission and to facilitate Center operational changes. All

Center MAPPs are available on the CDER Web site under Regulatory Policy

at: http://www.fda.gov/cder.

Improving Policy Consistency

33
During 1997, the Center continued to fine-tune its organizational structure

based on the major reorganization announced in November 1995. The new

structure and the refinements made in 1997 helped improve management

efficiency and processes, increase application review efficiency and

consistency, improve policy decisions and reduce duplicative work. The 1997

organizational changes are partly responsible for the successes highlighted in

this report and will play a role in enabling CDER to continue to exceed its

user fee review performance goals in the future.

The formation of the Office of Information Technology in 1997 will provide

a more focused approach to CDER-wide information technology support,

services, investment management and strategic planning. Promoting these

functions to office level will maximize CDERs efforts to comply with the

Information Technology Management and Reform Act of 1996 and to

implement an electronic regulatory submission and review environmenta

major step toward the goal of accepting and reviewing electronic regulatory

submissions by 2002. Elements of electronic regulatory submission and

review are part of CDERs compliance with the 1997 PDUFA reauthorization,

the National Partnership for Reinventing Government and the Government

Performance and Results Act.

As CDER has grown, new divisions have helped better focus oversight

responsibility and level workload. In 1997, the Division of Special Pathogens

and Immunologic Drug Products was formed in response to the growth

of both the Division of Anti-Viral Drug Products and the Division of

Anti-Infective Drug Products. The new division will oversee, for example,

products used to treat systemic fungal, mycobacterial or parasitic diseases;

vaginal antifungal products; certain immunologic products; and the

quinolones. It is the third division in the Office of Drug Evaluation IV.

Other initiatives included the reorganization of the Office of Testing and

Research in the Office of Pharmaceutical Science and the formation of the

Special Projects Staff located in the Immediate Office of the Director, Office

of Management. The Special Projects Staff will facilitate the Centers

strategic planning. (See CDERs organizational chart on the next page.)

Organizational Changes

34
Office of the Center Director (HFD-1)

Janet Woodcock, M.D.

594-5400

FAX 594-6197

Deputy Center Director for Review Management (HFD-2)

Murray Lumpkin, M.D.

594-5400

FAX 594-6197

Deputy Center Director for Pharmaceutical Science (HFD-3)

Roger Williams, M.D.

594-2847

FAX 827-3698

Office of Drug Evaluation II

(HFD-102)

James Bilstad, M.D.

827-5920

FAX 480-6644

Division of Metabolic and Endocrine

Drug Products

Division of Pulmonary Drug

Products

Office of Drug Evaluation IV

(HFD-104)

M. Dianne Murphy, M.D.

827-2350

FAX 827-2510

Division of Anti-Infective Drug Products

Division of Anti-Viral Drug Products Office of Training and

Communications (HFD-200)

Nancy Smith, Ph.D.

827-1651

FAX 827-3056

Freedom of Information Staff

Division of Training and Development

Division of Communications Management

Medical Library

Office of Compliance

(HFD-300)

Stephanie Gray

594-0054

FAX 594-2114

Division of Labeling and

Nonprescription Drug Compliance

Division of Prescription Drug Compliance

and Surveillance

Division of Manufacturing and Product

Quality

Division of Scientific Investigations

Office of Drug Evaluation I

(HFD-101)

Robert Temple, M.D.

594-6758

FAX 594-5298

Division of Neuropharmacological

Drug Products

Division of Oncology Drug

Products

Division of Cardio-Renal Drug

Products

Office of New Drug Chemistry

(HFD-800)

Eric Sheinin, Ph.D.

827-5918

FAX 594-0746

Division of New Drug Chemistry I

Division of New Drug Chemistry II

Office of Clinical

Pharmacology and

Biopharmaceutics (HFD-850)

Larry Lesko, Ph.D.

594-5690

FAX 594-2503

Office of Testing and

Research (HFD-900)

James MacGregor, Ph.D.

827-5917

FAX 827-3787

Laboratory of Clinical

Pharmacology

Division of Applied

Pharmacology Research

Division of Product Quality

Office of Drug Evaluation III Research

(HFD-103)

Paula Botstein, M.D. (Actg)

827-3144

FAX 480-3761

Division of Gastro-Intestinal and

Coagulation Drug Products

Division of Anesthetic, Critical

Care, and Addiction Drug

Products

Division of Medical Imaging and

Radiopharmaceutical Drug Products

Office of Management

(HFD-10)

Russell Abbott

594-6741

FAX 827-5491

Division of Planning Evaluation and

Resource Management

Division of Management Services

Microbiology Team

Division of New Drug Chemistry III

Pharmacometrics Staff

Division of Pharmaceutical

Evaluation I

Division of Pharmaceutical

Evaluation II

Division of Pharmaceutical

Evaluation III

Office of Generic Drugs

(HFD-600)

Douglas Sporn

827-5845

FAX 594-0183

Division of Chemistry I

Division of Chemistry II

Division of Bioequivalence

Division of Labeling and

Program Support

CENTER FOR DRUG EVALUATION AND RESEARCH

AS OF: 3/24/98

Division of Drug Marketing,

Advertising, and Communications

Office of Drug Evaluation V

(HFD-105)

Michael Weintraub, M.D.

827-2250

FAX 827-2317

Division of Anti-Inflammatory, Analgesic,

and Ophthalmologic Drug Products

Division of Dermatologic and Dental Drug

Products

Division of Over-The-Counter Drug

Products

Office of Epidemiology and

Biostatistics (HFD-700)

Robert O’Neill, Ph.D.

827-3195

FAX 480-2825

Quantitative Methods Research Staff

Division of Pharmacovigilance and

Epidemiology

Division of Biometrics I

Division of Biometrics II

Division of Biometrics III

Division of Biometrics IV

Associate Director for Policy

Jane Axelrad

Ombudsman

James Morrison

Associate Director for Medical Policy

Robert Temple, M.D.

Executive Operations Staff

Deborah Henderson

EEO Staff

Margaret Bell

Office of Review Management (HFD-20) Office of Pharmaceutical Science (HFD-350)

Division of Reproductive and

Urologic Drug Products

Regulatory Policy Staff

Jane Axelrad (Actg)

Division of Testing and Applied

Analytical Development

Office of Information

Technology (HFD-070)

David Isom (Actg)

827-6240

FAX 594-5493

Quality Assurance Staff

Technology Support Services Staff

Division of Applications Development Services

Division of Data Management and Services

Division of Infrastructure Management and Services

Division of Special Pathogen and

Immunologic Drug Products

Special Projects Staff

Regulatory Research

Analysis Staff
U.S. Department of Health and Human Services

Food and Drug Administration

Center for Drug Evaluation and Research