41 

Improving Public Health Through Human Drugs 

Center for Drug Evaluation and Research 2000

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 
42 

CDER 2000 Report to the Nation 

This report is available on the Internet in Adobe Acrobat Portable 

Document Format and in hypertext markup language. The charts and 

graphs are available as Microsoft PowerPoint slides. The locations are: 

 PDF: http://www.fda.gov/cder/reports/rtn2000/rtn2000.pdf

 HTML: http://www.fda.gov/cder/reports/rtn2000/rtn2000.htm

 Slides: http://www.fda.gov/cder/reports/rtn2000/rtn2000.ppt

Suggested citation: Food and Drug Administration. CDER 2000 Report to 

the Nation: Improving Public Health Through Human Drugs. Rockville, 

Maryland, 2001. 

MISSION

The Center for Drug Evaluation and Research promotes and protects public 

health by assuring that safe and effective drugs are available to Americans. 

The Food and Drug Administration Modernization Act of 1997 affirmed 

the center’s public health protection role, clarified the FDA’s mission and 

called for the FDA to: 

Promote the public health by promptly and efficiently reviewing 

clinical research and taking appropriate action on the marketing of 

human drugs in a timely manner. 

Protect the public health by ensuring that human drugs are safe and 

effective. 

Participate through appropriate processes with representatives of 

other countries to reduce the burden of regulation, harmonize 

regulatory requirements and achieve appropriate reciprocal 

arrangements. 

Carry out its mission in consultation with experts in science, 

medicine and public health and in cooperation with consumers, users, 

manufacturers, importers, packers, distributors and retailers of human 

drugs. 

1 

2 

3 

4 
43 

Improving Public Health Through Human Drugs 

CONTENTS

DIRECTOR’S MESSAGE .............................................................. iii 

INTRODUCTION ........................................................................... 1 

2000 HIGHLIGHTS ....................................................................... 3 

 Scientific Research ............................................................. 4 

1 DRUG REVIEW ........................................................................ 5 

 New Drug Review .............................................................. 6 

 New or Expanded Use Review ......................................... 10 

 Electronic Submissions ..................................................... 11 

 Over-the-Counter Drug Review ........................................ 12 

 Generic Drug Review ....................................................... 13 

 Manufacturing Supplement Review ................................. 15 

 Assessing Data Quality, Research Risks .......................... 17 

 Pediatric Exclusivity ......................................................... 18 

 Drug Review Team ........................................................... 19 

 User Fee Review Performance .......................................... 20 

2 DRUG SAFETY AND QUALITY .............................................. 24 

 Types of Risks from Medicines ........................................ 25 

 Drug Safety ....................................................................... 26 

 MedWatch ......................................................................... 27 

 Drug Promotion Review ................................................... 28 

 Drug Recalls and Withdrawals ......................................... 30 

 Drug Product Quality ........................................................ 32 

 Drug Product Quality Research ........................................ 34 

 Export Certificates ............................................................ 35 

3 INTERNATIONAL ACTIVITIES ............................................... 36 

4 COMMUNICATIONS ............................................................... 38 

 Where to Find More Information ...................................... 40 

i 
44 

CDER 2000 Report to the Nation 

Graphs and Charts 

Original NDA Actions ................................................................. 6 

New Drug Application Approvals ............................................... 7 

New Molecular Entity Approvals ................................................ 8 

Efficacy Supplement Actions .................................................... 10 

Efficacy Supplement Approvals ................................................ 10 

OTC New Approvals and New Uses ......................................... 12 

Generic Drug Approvals ............................................................ 13 

Generic Drug Electronic Submissions ....................................... 14 

NDA Manufacturing Supplement Actions ................................ 15 

NDA Manufacturing Supplement Approvals ............................ 15 

Generic Drug Manufacturing Supplements ............................... 16 

Inspections of Clinical Research ............................................... 17 

User Fee Review Performance 

 Original NDAs .................................................................. 20 

 Resubmissions of Original NDAs ..................................... 20 

 Efficacy Supplements ....................................................... 21 

 Manufacturing Supplements ............................................. 21 

 Refuse-to-File Actions ...................................................... 22 

 Clinical Holds of Commercial INDs ................................. 22 

 User Fee Performance: 1993-1997 ................................... 23 

Sources of Risk from Drug Products ......................................... 25 

Post-Marketing Adverse Event Reports .................................... 26 

Adverse Event Reporting Inspections ....................................... 27 

Drug Promotion Review ............................................................ 28 

Drug Recalls .............................................................................. 30 

Safety-Based NME Withdrawal Percentages ............................ 31 

Export Certificates Issued .......................................................... 35 

Modular Structure of Common Technical Document ............... 37 

Average Monthly Use of CDER Internet Site ........................... 39 

ii 
45 

Improving Public Health Through Human Drugs 

iii 

DIRECTOR’S MESSAGE

Last year, we at the Center for Drug Evaluation and Research continued our 

efforts to strike the right balance in our programs. We have worked hard to 

provide rapid access to new therapies while maintaining rigorous safety and 

effectiveness standards; to listen to the voices of consumers, patients and health 

care professionals as well as those of regulated industry; to match the effort in 

premarket evaluation with a vigorous postmarket monitoring program; and, of 

course, to make sure we support the people in CDER as well as serving the 

outside world. In that regard, a highlight of the year was winning the W. Edwards 

Deming award for our scientific training program. 

Many Americans are benefiting from last year’s approvals of new drugs and new 

uses for already approved drugs. As a result of the new pediatric program, our 

youngest citizens—children—are starting to use therapies that have scientifically 

proven dosing regimens. In the process, we are expanding our knowledge of drug 

metabolism in the youngest patients. 

We held a landmark public meeting last summer on over-the-counter drugs. We 

invited wide participation, and this will help us enormously as we evaluate 

policies for OTC drugs. 

Our workload in reviewing applications for generic drugs continues to grow. This 

is good news for consumers. It means a steady supply of more affordable drugs 

that meet our uniform and stringent standards for safety, effectiveness and quality. 

This decade will be known for a focus on drug safety. We have laid a strong 

foundation for the drug safety program of the future. We established the Office of 

Post-Marketing Risk Assessment, which utilizes a functioning Adverse Event 

Report System that is receiving direct electronic submissions. An enhanced 

medication errors program is in place. 

We have made strenuous efforts to streamline our regulatory oversight of drug 

manufacturing. We hope we are beginning to see the payoff for these efforts as a 

downturn in manufacturing changes requiring our approval before 

implementation. This represents a reduction in workload for industry while 

ensuring the highest quality drug products for American consumers. 

We are making strenuous efforts to come to grips with the reality of globalization 

in the marketplace. Cornerstones of our efforts are the International Conference on 

Harmonization, the Mutual Recognition Agreement with the European Union, and 

building relationships with the international regulatory community. We have 

begun work to promote harmonization within the Americas. 

An urgent priority for us is improving our communications. Information is a key 

element in the safe and effective use of drugs. We are collaborating and 

leveraging with a broad spectrum of groups to improve information for prescribers 

and consumers. A highlight this year was publication of a proposed rule for a new 

format for the prescription drug package insert that is designed to improve 
46 

CDER 2000 Report to the Nation 

iv 

usability. In addition, the Internet is a tool that continues to grow in importance 

for our communications efforts. 

This year, concerns have been raised about review times. Some groups contend 

they have slowed down, others claim they are too fast. Our data demonstrate that 

the time we take to review new drug applications is on target: neither too short nor 

too long. Much of this confusion is caused by analyzing the wrong groups of data. 

For example, concerning a potential review slowdown, when review times are 

analyzed based on the year in which applications were submitted, rather then 

when they were approved, they haven’t changed. This Report to the Nation

presents approvals based on the year in which the approval took place, regardless 

of when the application was submitted. As you can see from the graph on page 7 

of the Report, more applications were approved in 2000 in a shorter time frame 

than in 1999. The longer median approval time for 2000 shown in the graph on 

page 8 of the Report refers to new molecular entities, which are drugs never 

before marketed in the United States. This longer NME approval time for 2000 vs. 

1999 is a result of seven historically older applications approved in 2000, 

including several that received deficiency letters, which had a negative impact on 

the total approval time. 

The concern about drugs being reviewed too fast links the user fee review times to 

the occurrence of drug withdrawals. It is misleading to analyze drug withdrawals 

based on the year of withdrawal. A drug approved in 1990 and withdrawn in 1999 

does not reflect on the 1999 review process, because that drug would have been 

reviewed in the 1980s. When analyzed by year of approval, the evidence shows 

our withdrawal rates are remaining stable at about 3 percent. We also do not find a 

relationship between a withdrawal for safety reasons and time taken to review the 

original new drug application. Most of the drugs approved under the user fee 

program and subsequently withdrawn had longer than average review times. 

We have many projects planned for the year ahead. We will continue to build our 

drug safety program by linking to new data sources and creating new partnerships 

and collaborations. A pilot electronic drug registration and listing system will be 

implemented. Additional standardization of review documents will occur under 

the Good Review Practices initiative, and we expect to be receiving new drug 

applications in the format of the new Common Technical Document developed 

under ICH. 

As we look to the challenges ahead, we remain steadfast in our commitment to 

facilitate the availability of safe and effective drugs, keep unsafe or ineffective 

drugs off the market, improve the health of Americans and provide clear and 

easily understandable drug information for safe and effective use. 

Janet Woodcock, M.D. 

Director 

Center for Drug Evaluation and Research 
1 

Improving Public Health Through Human Drugs 

INTRODUCTION

Who we are 

The Center for Drug Evaluation and Research is America’s consumer 

watchdog for medicine. We are part of one of the nation’s oldest consumer 

protection agencies—the Food and Drug Administration. The FDA is an 

agency of the federal government’s Department of Health and Human 

Services. We are the largest of FDA’s five centers, with nearly 1,700 

employees. Approximately half of us are physicians or other kinds of 

scientists. Many of us have experience and education in such fields as 

computer science, legal affairs and regulatory matters. 

What we do 

Our best-known job is to evaluate new drugs for safety and effectiveness 

before they can be sold. Our evaluation, called a review, makes sure that 

the drugs we approve meet our tough standards for safety, effectiveness 

and quality. We also make sure that you and your doctor will have the 

information you need to use medicines wisely. Once drugs are on the 

market, we monitor them for problems.

Reviewing drugs before marketing. A drug company seeking to sell a drug 

in the United States must first test it. We monitor clinical research to 

ensure that people who volunteer for studies are protected and that the 

quality and integrity of scientific data are maintained. The company then 

sends us the evidence from these tests to prove the drug is safe and 

effective for its intended use. We assemble a team of physicians, 

statisticians, chemists, pharmacologists and other scientists to review the 

company’s data and proposed use for the drug. If the drug is effective and 

we are convinced its health benefits outweigh its risks, we approve it for 

sale. We don’t actually test the drug when we review the company’s data. 

By setting clear standards for the evidence we need to approve a drug, we 

help medical researchers bring new drugs to American consumers more 

rapidly. We also review drugs that you can buy over the counter without a 

prescription and generic versions of over-the-counter and prescription 

drugs.

Watching for drug problems. Once a drug is approved for sale in the 

United States, our consumer protection mission doesn’t stop. We monitor 

the use of marketed drugs for unexpected health risks. If new, 

unanticipated risks are detected after approval, we take steps to inform the 

public and change how a drug is used or even remove a drug from the 

market. We also monitor manufacturing changes to make sure they won’t 

adversely affect the safety or efficacy of the medicine. We evaluate reports 

about suspected problems from manufacturers, health care professionals 

What is a drug? 

We regulate drugs 

used to treat, prevent 

or diagnose illnesses. 

However, drugs 

include more than just 

medicines. 

For example, fluoride 

toothpaste, 

antiperspirants, 

dandruff shampoos 

and sunscreens are all 

considered “drugs.” 

You can buy some 

drugs in a store 

without a prescription, 

while others require a 

doctor’s prescription. 

Some are available in 

less-expensive generic 

versions. 

Prescription drugs 

Prescription medicines 

must be administered 

under a doctor’s 

supervision or require 

a doctor’s 

authorization for 

purchase. There are 

several reasons for 

requiring a medicine 

be sold by 

prescription: 

 The disease or 

condition may be 

serious and require a 

doctor’s management. 

 The medicine itself 

may cause side effects 

that a doctor needs to 

monitor. 

 The same symptoms 

may be caused by 

different diseases that 

only a doctor can 

diagnose. 

 The different causes 

may require different 

medicines. 

 Some medicines can 

be dangerous when 

used to treat the wrong 

disease. 
2 

CDER 2000 Report to the Nation 

and consumers. Sometimes, manufacturers run into production problems 

that might endanger the health of patients who depend on a drug. We try to 

make sure that an adequate supply of drugs is always available. 

Monitoring drug information and advertising. Accurate and complete 

information is vital to the safe use of drugs. Drug companies have 

historically promoted their products directly to physicians. More and more 

frequently now, they are advertising directly to consumers. While the 

Federal Trade Commission regulates advertising of over-the-counter drugs, 

we oversee the advertising of prescription drugs. Advertisements for a drug 

must contain a truthful summary of information about its effectiveness, 

side effects and circumstances when its use should be avoided. We are 

monitoring the industry’s voluntary program to provide consumers useful 

information about prescription drugs when they pick up their prescriptions. 

We are watching this program closely to see that it meets its goals for 

quantity and quality of information.

Protecting drug quality. In addition to setting standards for safety and 

effectiveness testing, we also set standards for drug quality and 

manufacturing processes. We work closely with manufacturers to see 

where streamlining can cut red tape without compromising drug quality. 

As the pharmaceutical industry has become increasingly global, we are 

involved in international negotiations with other nations to harmonize 

standards for drug quality and the data needed to approve a new drug. This 

harmonization will go a long way toward reducing the number of 

redundant tests manufacturers do and help ensure drug quality for 

consumers at home and abroad.

Conducting applied research. We conduct and collaborate on focused 

laboratory research and testing. Research maintains and strengthens the 

scientific base of our regulatory policy-making and decision-making. We 

focus on drug quality, safety and performance; improved technologies; 

new approaches to drug development and review; and regulatory standards 

and consistency.

Why we do it 

Our present and future mission remains constant: to ensure that drug 

products available to the public are safe and effective. Our yardstick for 

success will always be protecting and promoting the health of Americans.

Getting consumer input. Protecting consumers means listening to them. 

We routinely consult the American public when making decisions about 

the drugs that they use. We hold public meetings about once a week to get 

expert, patient and consumer input into our decisions. We also announce 

many of our proposals in advance. This gives members of the public, 

academic experts, industry, trade associations, consumer groups and 

professional societies the opportunity to comment and make suggestions 

before we make a final decision. In addition, we take part in a series of 

FDA-sponsored public meetings with consumer and patient groups, 

professional societies and pharmaceutical trade associations. These 

stakeholder meetings help us obtain enhanced public input into our 

planning and priority-setting practices. 

Over-the-counter 

drugs 

You can buy OTC 

drugs without a 

doctor’s prescription. 

You can successfully 

diagnose many 

common aliments and 

treat them yourself 

with readily available 

OTC products. 

These range from acne 

products to cold 

medications. 

As with prescription 

drugs, we closely 

regulate OTC drugs 

to ensure that they are 

safe, effective and 

properly labeled. 

Generic drugs 

A generic drug is a 

chemical copy of a 

brand-name drug. 

There are generic 

versions of both 

prescription and overthe-counter drugs. 

Generic drugs 

approved by the FDA 

have the same 

therapeutic effects as 

their brand-name 

counterparts. 

The biggest difference 

between a generic drug 

and its brand name 

counterpart is usually 

price. A generic drug 

may be priced 

anywhere between 20 

percent and 75 percent 

of the cost of the 

brand-name version. 
3 

Improving Public Health Through Human Drugs 

2000 HIGHLIGHTS

We are pleased to present our fifth performance report. Our work last year 

offered many Americans new or improved choices for protecting and 

maintaining their health or new ways to use existing products more safely. 

Drug review 

Children have especially benefited from our approvals in 2000. Also, 

people with HIV, AIDS, cancer, heart disease and other serious conditions 

all benefited. We met our obligations to Congress for prompt and thorough 

review of drug applications supported by user fees. Our reviews of generic 

drugs have been prompt and predictable . We approved 98 new drugs, 

including 27 new molecular entities. New molecular entities contain an 

active substance never before approved for marketing in any form in the 

United Sates. We also approved 134 new or expanded uses of already 

approved drugs, 11 new or expanded uses for over-the-counter drugs and 

244 generic drugs. 

Drug safety and quality 

All medicines have risks. With modern, state-of-the-art tools and 

techniques, we are able to detect rare and unexpected risks more rapidly 

and take corrective action more quickly. Last year, we processed and 

evaluated nearly a quarter million reports of adverse drug events. We 

issued more than 1,000 letters to help ensure that the promotion of drug 

products presents a fair balance of risks and benefits and isn’t false or 

misleading. We mandated that five drug products be dispensed with 

specific consumer information that will help ensure the products are used 

safely and effectively. We issued a proposed rule to revise prescription 

drug labeling to improve its accessibility and enhance safe and effective 

prescribing and use. Our reviews of the safety profile of three approved 

drug products resulted in their voluntary withdrawal. We issued a public 

health alert about a once widely used decongestant that may cause strokes. 

The alert resulted in its withdrawal from the market by manufacturers. 

International activities 

We worked closely with our colleagues in Japan and the European Union 

on finding ways to make the drug development process more efficient and 

uniform. We agreed to a final version of the Common Technical Document 

that can be used for seeking approval to market new drugs in the United 

States, the European Union and Japan. We began harmonization efforts 

among the countries of North and South America. We led the U.S. 

consultations with the European Union to allow for reciprocal reliance on 

manufacturing plant inspections. 

Communications 

We continued our 

efforts to include 

greater input into our 

planning and decision 

making from 

consumers, patients, 

health-care 

professionals, 

academia and 

industry. 

We met almost weekly 

with outside experts on 

difficult scientific and 

public health issues. 

We responded to more 

than 58,000 individual 

requests for 

information. 

Our Internet 

information site 

averaged more than 

406,000 visitors and 

about 6.7 million hits 

per month. We 

developed public 

education campaigns 

in areas such as risk 

management and 

buying prescription 

drugs over the 

Internet. 

Drug withdrawals 

influence benefitrisk assessment 

The recent market 

withdrawals of some 

drugs resulted, in part, 

from the U.S. health 

care system’s inability 

to manage known and 

preventable risks. 

These experiences have 

catalyzed an evolution 

in our thinking on risk 

management and the 

evaluation of new 

drugs for approval. 

Our risk assessment 

must evaluate both a 

drug’s intrinsic safety 

profile as well as the 

ability of the health 

care system to 

adequately manage 

known toxicities. 

Unless effective risk 

management strategies 

and methods are 

brought to bear, 

additional effective 

drugs are likely to be 

withdrawn, and some 

drugs may never 

become available in the 

first place. 
4 

CDER 2000 Report to the Nation 

Scientific Research 

We focus on advancing the scientific basis of regulatory policy by 

developing new scientific methods and regulatory testing paradigms and 

by providing scientific support for the development of regulatory policy. 

We have focused specifically on creating tighter linkage between 

nonclinical and clinical studies, enhancing the methodology for assuring 

product quality, building databases for improved drug development and 

review and providing regulatory support through laboratory testing. 

Linking nonclinical and clinical studies 

Key achievements in this area include: 

 Establishing that biological markers for heart damage, such as troponin, 

are useful both experimentally and clinically to predict the incidence 

and extent of heart damage from exposure to certain drugs. 

 Identifying unique biomarker proteins found in blood that cause heart 

damage and that are generated after treatment with certain drugs. 

 Elucidating the molecular mechanisms operating in alternative 

transgenic mice that are used to test the cancer-causing potential of 

drugs. This understanding will make these models more rapid and 

reliable assessment tools. 

 Developing an experimental model for detecting reactive metabolic 

products of drugs in cultured liver cells. This will facilitate mechanistic 

analysis of certain types of liver damage. 

Database building 

Our work included: 

 Developing and implementing an Internet-enabled pilot of FDA’s 

toxicology knowledge base. This database is linked to an expanded 

chemical substance dictionary that permits searches using unique 

chemical structures as well as structural similarities. 

 Developing and distributing new computational software that predicts 

birth defects from drugs in rodent laboratory models. This was done 

under a commercial research and development agreement. 

 Developing computational toxicology software to predict the human 

no-adverse-effect level for a substance based on its chemical structure 

and extrapolation of information about the maximum therapeutic dose. 

 Developing computational models that use the pharmaceutical 

properties and molecular structure of drugs to predict their 

bioavailability in humans when administered orally. 

Leveraging 

scientific 

resources 

The Product Quality 

Research Institute is a 

unique and innovative 

collaboration among 

our scientists and those 

from academia and 

industry. PQRI 

conducts research to 

establish better testing 

methods, standards 

and controls for 

assessing product 

quality and 

manufacturing and 

management processes 

(PQRI 2000 update, 

page 34).

The institute’s 

research will help us 

develop consistent and 

reasonable 

requirements for 

product quality 

information in 

regulatory filings. 

Leveraging scientific 

expertise in this way 

contributes to 

streamlining the drug 

development and 

approval processes for 

industry and ourselves 

while ensuring the 

highest level of product 

quality for American 

consumers. 

Deming Award 

recognizes our 

scientific training 

Our program of 

scientific training based 

on core competencies 

received the prestigious 

W. Edwards Deming 

Outstanding Training 

Award for 2000 

presented by the 

Graduate School of the 

Department of 

Agriculture. See 

page 19 for details.
5 

Improving Public Health Through Human Drugs 

1 

DRUG REVIEW

Many Americans benefited from last year’s timely reviews of new 

prescription medicines, over-the-counter medicines and their generic 

equivalents. We met or exceeded nearly all goals for reviews supported by 

manufacturer user fees. 

We approved 27 new medicines that have never been marketed before in 

this country and 244 generic versions of existing drugs. We authorized 

eight medicines to be sold over the counter without a prescription. 

We conducted 528 foreign and domestic inspections that help protect 

volunteers for clinical trials from research risks and validate the quality 

and integrity of data submitted to us. 

Highlights of new medication options for American consumers include: 

 Three new drugs to treat cancer. 

 A first protease inhibitor approved to treat HIV infection in children as 

young as 6 months. 

 Four drugs to treat heart disease and circulatory disorders. 

 Three drugs to treat disorders of the nervous system. 

 A malaria treatment effective in areas where the disease is resistant to 

other anti-malarial drugs. 

 The first anti-inflammatory corticosteroid that can be used in a 

nebulizer by very young children. 

 The first in a new class of antibiotics. 

 The first thyroid replacement drug to undergo a stringent FDA review. 

 Three new drugs and five new uses of existing drugs for “orphan” 

patient populations of 200,000 or fewer. 

 13 new pediatric uses for already approved adult drugs. 

Mission 

We promote 

the public health 

by promptly and 

efficiently reviewing 

clinical research 

and taking 

appropriate action 

on the marketing 

of human drugs 

in a timely manner. 

2000 drug review 

accomplishments 

98 new drugs 

27 new 

molecular entities 

134 new uses 

for already approved 

drugs 

8 over-the-counter 

drugs 

3 new uses for overthe-counter drugs 

244 generic equivalents 

for prescription 

and over-the counter 

drugs 

3 orphan drugs 

5 orphan new uses 
6 

CDER 2000 Report to the Nation 

New Drug Review 

We took 238 actions on original new drug applications, of which 98 were 

approvals. In 1999, we took 190 actions, of which 83 were approvals. 

Total original NDA approvals 

The median total approval time for new drugs in 2000 was 11.2 months, 

compared with 12.0 in 1999. Approval time represents our total review 

time plus industry response time to our requests for additional information. 

The 10.9-month median FDA review time—our time only—was 8 percent 

shorter in 2000 than the 11.8 months in 1999. Three of the NDAs were 

approved for “orphan” uses in patient populations of 200,000 or fewer. In 

1999, we approved 12 NDAs for orphan uses. 

Priority reviews 

The new drug approvals in 2000 included 20 priority reviews. We perform 

a six-month review on priority drugs because they represent an advance in 

medical treatment. The median total approval time and the median FDA 

review time for these priority reviews were both 6.0 months. In 1999, there 

were 28 priority reviews. 

New molecular entity approvals 

Twenty-seven of the original new drugs we approved in 2000 were new 

molecular entities. NMEs contain an active substance that has never before 

been approved for marketing in any form in the United States. Nine of 

these received priority approvals. 

The median total approval time for NMEs was 15.6 months, and the 

median FDA review time was 13.9 months. These times were longer than 

those for all NDAs. Last year the number of NDAs approved increased 

from the previous year, but the number of NMEs approved fell. Although 

user fee goals were met, the longer times for some drugs had a 

disproportionately larger effect on NME statistics. In 1999, there were 35 

NMEs approved. 

New drug 

statistics 

 98 new drugs 

 27 new molecular 

entities 

 3 orphan drugs 

 20 priority reviews 

 Median total 

approval time: 

11.2 months 

 Median FDA review 

time: 10.9 months 

Priority new drug 

approvals (N=NME)

Abacavir/lamivudine/

zidovudine (Trizivir) 

Alosetron 

(Lotronex) (N) 

Arsenic trioxide 

(Trisenox) (N) 

Atovaquone/proquanil 

(Malarone) 

Bexarotene (Targetin) 

Budesonide 

(Pulmicort) 

Didanosine 

(Videx EC) 

Gentuzumab 

ozogamicin (Mylotarg) 

(N) 

Levobetaxolol 

(Betaxon) 

Levofloxacin (Quixin) 

Linezolid (Zyvox) 

(3 NDAs approved, 

1 as NME) (N) 

Lopinavir/ritonavir 

(Kaletra) (2 NDAs 

approved, 1 as NME) 

(N) 

Mifepristone 

(Mifeprex) (N) 

Oseltamivir (Tamiflu) 

Skin Exposure 

Reduction Paste 

Against Chemical 

Warfare Agents (N) 

Unoprostone (Rescula) 

(N) 

Verteporfin (Visudyne) 

(N) 

Original NDA Actions

39% 44% 41%

49% 51% 45%

38%

31%

238

190

199

235 269

216

161

223

0%

50%

100%

1993 1994 1995 1996 1997 1998 1999 2000

Calendar Year

Percentage

0

150

300

Actions

Percentage of Actions that Are Approvals Number of Total Original NDA Actions
7 

Improving Public Health Through Human Drugs 

Notable 2000 new drug approvals 

Last year’s approvals benefited people with cancer, HIV, diabetes, heart 

disease and disorders of the circulatory and nervous systems. 

People with cancer 

Arsenic trioxide (Trisenox) treats acute promyelocytic leukemia, a cancer 

of white blood cells, in patients whose disease has recurred or who have 

failed to respond to standard therapy. Trisenox, a priority drug and an 

orphan drug, was approved in six months. The product’s total development 

time for this use was only three years. Gemtuzumab ozogamicin 

(Mylotarg), a monoclonal antibody, is a priority orphan drug for treating 

CD33 (an antigen on certain leukemia cells) positive acute myeloid 

leukemia in patients 60 years or older who have relapsed for the first time 

and are not suitable candidates for the standard but poorly tolerated 

cytotoxic therapy. Triptorelin pamoate (Trelstar Depot) is for the palliative 

treatment of advanced prostate cancer. It represents a new alternative for 

patients with prostate cancer in whom orchiectomy or estrogen 

administration is not indicated or is unacceptable. 

People with HIV and AIDS 

A combination of lopinavir and ritonavir (Kaletra) received accelerated 

approval as a protease inhibitor for the treatment of HIV infection in adults 

and children in combination with other antiretroviral agents. The product, 

indicated for twice daily dosing with a total of six capsules per day, is the 

only protease inhibitor approved for use in children as young as 6 months. 

People with heart and circulatory diseases 

Argatroban (Acova) is an anticoagulant for the prevention or treatment of 

thrombosis (abnormal blood clotting) associated with heparin-induced 

thrombocytopenia, a serious immune disorder caused by heparin, a 

common anticoagulant used to prevent blood clots. Bivalirudin (Angiomax)

is an anticoagulant for use in patients with unstable angina who are 

Alosetron (Lotronex) 

(withdrawn by 

manufacturer, page 30)

Argatroban (Acova) 

Arsenic Trioxide

(Trisenox) 

Articaine/epinephrine

(Septocaine) 

Balsalazide disodium`

(Colazal) 

Bivalirudin

(Angiomax) 

Cetrorelix acetate

(Cetrotide) 

Cevimeline (Evoxac) 

Colesevelam (Welchol) 

Docosanol (Abreva) 

Gemtuzumab 

ozogamicin

(Mylotarg) 

Insulin aspart 

recombinant

(NovoLog) 

Insulin glargine

(Lantus) 

Linezolid (Zyvox) 

Lopinavir/ritonavir

(Kaletra) 

Meloxicam (Mobic) 

Mifepristone

(Mifeprex) 

Nateglinide (Starlix) 

Oxcarbazepine

(Trileptal) 

Pantoprazole

New molecular 

entities in 2000 

New molecular 

entities in 2000

(continued) 

New Drug Application Approvals

16.5

19.0

24.1

12.0

15.4

12.0

14.4

11.2

15.3

12.2 12.0 11.8

20.8

15.8 14.8

10.9

98

82

70 62

131 121

90

83

0

12

24

1993 1994 1995 1996 1997 1998 1999 2000

Calendar Year

Months

0

70

140

Approvals

Median Total Approval Time Median FDA Review Time Number of Original NDAs Approved
8 

CDER 2000 Report to the Nation 

undergoing coronary angioplasty. It is to be used with aspirin. Colesevelam 

(WelChol) is used in conjunction with diet and exercise for the reduction of 

elevated LDL cholesterol in patients with primary hypercholesterolemia. 

The novel, non-absorbed, lipid-lowering agent is to be administered alone 

or in combination with an HMG-CoA reductase inhibitor (statin). 

Tinzaparin (Innohep), a low-molecular-weight heparin, is a once-daily 

treatment for deep vein thrombosis with or without pulmonary embolism 

when administered in conjunction with warfarin. 

People with diabetes 

Insulin aspart recombinant (NovoLog) is for the treatment of type 1 and 

type 2 diabetes. Insulin glargine (Lantus) is a long-acting recombinant 

human insulin for type 1 and type 2 diabetes. Nateglinide (Starlix), the first 

in a new class of drugs, is for the treatment of type 2 diabetes. 

People with gastrointestinal disorders 

Alosetron (Lotronex) was to treat irritable bowel syndrome in women 

whose predominant bowel symptom is diarrhea, but the drug was 

withdrawn by the manufacturer (page 30). Balsalazide disodium (Colazal)

is for the treatment of mild to moderately active ulcerative colitis, a 

chronic and debilitating inflammatory disease of the gastrointestinal tract. 

Pantoprazole (Protonix), a proton pump inhibitor, is a delayed-release 

tablet for the short-term (up to 16 weeks) treatment in the healing and 

symptomatic relief of erosive esophagitis. 

People with neurological disorders 

Oxcarbazepine (Trileptal) is for treatment of epileptic partial seizures as 

monotherapy in adults or as adjunctive therapy in adults and children as 

young as 4. Rivastigmine tartrate (Exelon), a cholinesterase inhibitor, 

treats mild to moderate Alzheimer’s disease. Zonisamide (Zonegran) is for 

adjunctive therapy in the treatment of partial seizures in adults with 

epilepsy. 

New molecular 

entity statistics 

 27 approvals 

 9 priority reviews 

 Median total 

approval time: 

15.6 months 

 Median FDA review 

time: 13.9 months 

Median time 

The median time is one 

that falls in the middle 

of the times in a group. 

It provides a truer 

picture of performance 

than average time, 

which can be unduly 

influenced by a few 

very long or short 

times. 

Average, or mean, 

approval times and 

other statistics are 

available on our Web 

site at http://www.fda. 

gov/cder/rdmt/default.

htm.

New Molecular Entity Approvals

13.9

17.5

13.4

23

15.9

12.0

11.6

14.3 15.6

21

15.3

12.8

15.2

11.9

10.0

12.0

39

53

25 22

28

30

35

27

0

12

24

1993 1994 1995 1996 1997 1998 1999 2000

Calendar Year

Months

0

30

60

Approvals

Median Total Approval Time Median FDA Review Time Number of NMEs Approved

New molecular 

entities in 2000

(continued)

(Protonix) 

Perfluoropolymethylisopropyl ether/

polytetrafluoroethylene (Skin 

Exposure Reduction 

Paste Against 

Chemical Warfare 

Agents) 

Rivastigmine Tartrate

(Exelon) 

Tinzaparin sodium

(Innohep) 

Triptorelin pamoate

(Trelstar Depot) 

Unoprostone isopropyl

(Rescula) 

Verteporfin

(Visudyne) 

Zonisamide

(Zonegran)
9 

Improving Public Health Through Human Drugs 

Infectious diseases 

Docosanol (Abreva) is an over-the-counter topical treatment for recurrent 

oral-facial herpes simplex infections, commonly known as cold sores or 

fever blisters. Linezolid (Zyvox) is the first antibiotic in a new class in 35 

years (the oxazolidinones) to treat infections caused by gram-positive 

bacteria. Gram-positive bacteria are regarded as one of the greatest 

challenges in hospitals. Oseltamivir (Tamiflu) oral suspension was 

approved for prevention of influenza virus in adults and adolescents aged 

13 years and older. Zanamivir (Relenza) treats uncomplicated influenza A 

and B in adults and children 7 years and older. 

People with thyroid disease 

Levothyroxine sodium (Unithroid), a thyroid replacement drug, is the first 

single-ingredient oral levothyroxine product approved for the treatment of 

hypothyroidism, a disease that causes mental and physical sluggishness, 

including stunted growth. Although oral levothyroxine drugs products have 

been marketed in the United States since the 1950s, this product meets 

FDA’s standards for safety and effectiveness as well as its standards for 

manufacturing processes, purity, potency and stability. 

People with eye disease 

Verteporfin for injection (Visudyne) is the first therapy to slow vision loss 

in people with the classic type of wet age-related macular degeneration, a 

disease that can cause blindness. Unoprostone isopropyl (Rescula) treats 

open-angle glaucoma or ocular hypertension. 

People with severe eczema 

Tacrolimus (Protopic) is an ointment for patients with moderate or severe 

eczema for whom standard eczema therapies present potential risks or who 

are not adequately treated by or do not tolerate standard eczema therapies. 

Children with asthma 

Budesonide inhalation suspension (Pulmicort Respules) is approved for 

children 1 to 8 years old with asthma. The product is the first antiinflammatory corticosteroid formulated for inhalation using a nebulizer in 

this age group. This is important because toddlers frequently cannot use 

metered-dose inhalers. 

Other NME approvals 

Articaine 4 percent and epinephrine hydrochloride (Septocaine) is a local 

anesthetic to be used for simple and complex dental and periodontal 

procedures. Cetrorelix acetate (Cetrotide) prevents premature ovulation in 

women undergoing controlled ovarian stimulation for assisted reproductive 

treatment. Meloxicam (Mobic) tablets are a once-daily treatment for the 

pain and stiffness associated with osteoarthritis. Mifepristone (Mifeprex) is 

to terminate pregnancies of 49 days or less from the beginning of a 

woman’s last menstrual period. Perfluoropolymethylisopropyl ether/

polytetrafluoroethylene (Skin Exposure Reduction Paste Against Chemical 

Warfare Agents), when used with Mission Oriented Protective Posture 

gear, reduces or delays the absorption of such agents through the skin 

when the paste is applied prior to exposure. 

Orphan drug 

approvals 

In 2000, we approved 

three “orphan” 

products to treat 

disorders with patient 

populations of 200,000 

or fewer: 

Arsenic trioxide 

(Trisenox) treats acute 

promyelocytic 

leukemia, a cancer of 

white blood cells, in 

patients whose disease 

has recurred or who 

have failed to respond 

to standard therapy. 

Somatropin, 

recombinant 

(Norditropin) is 

indicated for the longterm treatment of 

children who have 

growth failure due to 

inadequate secretion 

of endogenous growth 

hormone. 

Gemtuzumab 

ozogamicin (Mylotarg) 

treats CD33-positive 

acute myeloid 

leukemia in patients 

60 years or older who 

have relapsed for the 

first time and are not 

suitable candidates for 

the standard but 

poorly tolerated 

cytotoxic therapy. 

Malaria treatment 

A combination of 

atovaquone and 

proguanil (Malarone) is 

for the prevention and 

treatment of acute, 

uncomplicated 

malaria. It has been 

shown to be effective in 

regions where the 

disease has become 

resistant to other antimalarial drugs. 

PET drug initiative 

We approved F-18 

FDG, an injected 

radiopharmaceutical 

drug that localizes 

areas with abnormal 

glucose metabolism to 

assist in cancer 

assessments and in 

identifying reversible 

cardiac dysfunction. 

It was approved as 

part of an initiative 

under the FDA 

Modernization Act of 

1997, which included 

consultations with the 

public and an advisory 

committee, a review of 

literature and a 

Federal Register notice 

describing how the 

drug could be found to 

be safe and effective 

for certain indications. 
10 

CDER 2000 Report to the Nation 

Efficacy 

supplement 

statistics 

 134 approvals 

 18 priority reviews 

 5 orphan new uses 

 Median total 

approval time: 

10.0 months 

 Median FDA review 

time: 10.0 months 

New or Expanded Use Review 

Applications for a new or expanded use, often representing important new 

treatment options, are formally called “efficacy supplements” to the 

original new drug application. 

Last year we took action on 205 applications for new or expanded uses of 

already approved drugs. We approved 134, including 18 that were given 

priority reviews of six months or less. Five of the approvals were for 

orphan uses in patient populations of 200,000 or fewer. 

Efficacy Supplement Approvals

12.0

16.0

14.2

19.0

10.4 10.0

11.9 11.8 13.9

11.2 12.3

10.2 10.0

11.9 11.7

18.3

134

97

124

108

50

118

69

48

0

12

24

1993 1994 1995 1996 1997 1998 1999 2000

Calendar Year

Months

0

70

140

Approvals

Median Total Approval Time Median FDA Review Time Number of Efficacy Supplements Approved

Efficacy Supplement Actions

65%

53%

72% 60% 57%

39% 41% 37%

205 184

122

185

173 189 196

122

0%

50%

100%

1993 1994 1995 1996 1997 1998 1999 2000

Calendar Year

Percentage

0

115

230

Actions

Percentage of Actions that Are Approvals Number of Efficacy Supplement Actions
11 

Improving Public Health Through Human Drugs 

Electronic Submissions 

We have been receiving new drug application case report forms and case 

report tabulations in electronic format in place of paper since November 

1997. In February 1999, we started receiving the archival copy of the entire 

new drug application in electronic format in place of paper. 

The number of new drug electronic submissions has steadily increased. 

Last year, we received more than 500 electronic NDA submissions. 

Currently, we average more than 100 submissions per month. About 75 

percent of original new drug applications have some component in 

electronic format, and about 35 percent are entirely in electronic format. 

Since the program began, we have seen a 50 percent reduction in the 

average number of paper volumes for new drug applications. 

We have a pilot program for receiving post-marketing expedited safety 

reports in electronic format and have published a draft guidance for 

providing advertising and promotional material in electronic format. We 

also have a pilot program for receiving generic drug applications in 

electronic format (page 14). We are working on the ability to accept all of 

these submissions, along with investigational new drug applications and 

drug master files, in electronic format without paper in 2002. 

Priority efficacy 

supplement 

approvals 

Ciprofloxacin (Cipro) 

(5 supplements) 

Enoxaparin (Lovenox) 

Epoprostenol (Flolan) 

Irinotecan 

(Camptosar) 

Mitoxantrone 

(Novantrone) 

Nimodipine (Nimotop) 

Olopatadine (Patanol) 

Oseltamivir (Tamiflu) 

Paclitaxel (Taxol) 

Risedronate (Actonel) 

(2 supplements) 

Somatropin, 

recombinant 

(Genotropin) 

Tamoxifen (Nolvadex) 

Zanamivir (Relenza) 

Orphan efficacy 

supplement 

approvals 

Epoprostenol (Flolan) 

Follitropin alfa (GonalF) 

Fomepizole (Antizol) 

Mitoxantrone 

(Novantrone) 

Somatropin, 

recombinant 

(Genotropin) 

Notable 2000 new or expanded use approvals 

We added pediatric use to the labeling of 13 adult drugs including 

ibuprofen (Motrin and Advil), ranitidine (Zantac) for stomach acid reflux 

and cromolyn (Nasalcrom) for asthma and hay fever. 

Ciprofloxacin (Cipro), an antimicrobial product, was designed to reduce 

the incidence or progression of inhalational anthrax following exposure to 

Bacillus anthracis. Inhalational anthrax is an extremely rare disease, 

usually resulting from exposure to contaminated animal hides and hairs in 

an industrial setting, but the causative organism can be used as a biological 

weapon. 

Irinotecan (Camptosar) has a new use as a first-line therapy in 

combination with 5-fluorouracil and leucovorin (5-FU/LV) to treat 

metastatic colorectal cancer. The combination showed a clear survival 

advantage compared to 5-FU/LV alone. 

Tamoxifen (Nolvadex) was approved for use to reduce the risk of invasive 

breast cancer for women with preinvasive cancer of the ducts. 
12 

CDER 2000 Report to the Nation 

Over-the-Counter Drug Review 

In 2000, we approved eight new drugs and three new uses for over-thecounter marketing. 

New OTC medicines and new uses 

 Antacid and famotidine (Pepcid Complete Chewable Tablet) is the first 

antacid and H2 blocker combination product for heartburn. 

 Chlorhexidine gloconate (ChloraPrep) is a topical antimicrobial. 

 Clotrimazole (Trivagizole 3 Vaginal Cream) is an antifungal. 

 Docosanol (Abreva Cream) is a cold sore and fever blister treatment. 

 Ibuprofen (Advil Migraine Liqui-Gels) is for the treatment of migraine 

headache. 

 Ibuprofen (Infants’ Advil Concentrated Oral Drops) is now indicated 

for children ages 6 months to 23 months. 

 Ibuprofen (Motrin Migraine Pain) is for the pain of migraine headache. 

 Ibuprofen and pseudoephedrine (Children’s Motrin Cold Suspension) 

is a pain reliever, fever reducer and decongestant. 

 Loperamide and simethicone (Imodium Advanced Caplet) is for 

diarrhea and gas. 

 Piperonyl butoxide and pyrethrins (Rid Mousse) is a topical treatment 

for head and body lice and is the first OTC product approved as a new 

drug “deviation” to the pediculicide monograph. 

 Terbinafine hydrochloride (Lamisil AT Spray Pump and Solution 

Dropper) treats athlete’s foot, jock itch and ringworm. 

Over-the-counter 

drug statistics 

 8 new drug or 

Rx-to-OTC switch 

approvals 

 3 new use approvals 

Public meeting 

airs OTC drug 

issues 

We are open to the 

possibility of having 

more and different 

kinds of OTC 

medicines available to 

consumers. We 

explored these issues 

with more than 300 

stakeholders at a twoday public meeting. 

Discussions included 

how we determine 

which drugs should be 

available over the 

counter, who should 

initiate Rx-to-OTC 

switches and safety 

concerns about OTC 

availability of 

medicines for chronic 

conditions without 

symptoms. 

A brief report of the 

meeting is available at: 

http://www.fda.gov/

cder/pike/july2000.

htm#OTC. 

OTC New Approvals and New Uses

5

1 1

8

20

8 9 9

7

1

3 3

0

12

24

1995 1996 1997 1998 1999 2000

Calendar Year

Number

New Approvals or Rx-to-OTC Switches New Uses

How we regulate 

OTC drugs 

We publish 

monographs that 

establish acceptable 

ingredients, doses, 

formulations and 

consumer labeling for 

OTC drugs. 

Products that conform 

to a final monograph 

may be marketed 

without prior FDA 

clearance. 

Drugs can also be 

approved for OTC sale 

through the new drug 

review process. 

Improved labels 

for OTC medicines 

American consumers 

last year began to see 

new, easy-tounderstand labels on 

nonprescription drugs. 

Titled “Drug Facts,” 

the new labels are the 

result of a regulation 

we issued in 1999. 

These new labels will 

improve a consumer’s 

ability to use an OTC 

drug safely and 

properly and to find 

and understand its 

benefits and risks. 
13 

Improving Public Health Through Human Drugs 

2000 generic drug 

statistics 

 244 generic drug 

approvals 

 Median approval 

time: 18.2 months 

Generic Drug Review 

We received 365 submissions and approved 244 generic products in 2000, 

including 34 separate molecules in 52 products that represent the first time 

a generic drug was available for the brand-name product. The median 

approval time for generic drugs was 18.2 months. 

Initiatives to streamline the generic drug review process have resulted in an 

overall downward trend in approval times since 1994. We have also seen a 

drop in the number of review cycles needed to approve abbreviated 

applications for generic drugs. In 2000, the average application required 

2.8 cycles to reach approval. 

We also issued 61 tentative approvals last year. The only difference 

between a full approval and a tentative approval is that the final approval 

of these applications is delayed due to existing patent or exclusivity on the 

innovator’s drug product. 

Our approval of generic drugs last year could save the American people 

and the federal government hundreds of millions of dollars. 

Generic Drug Approvals

18.0 18.2

27.0

18.6 19.3

26.9 23.0

244

186

225

273

212

207

158

0

12

24

36

1994 1995 1996 1997 1998 1999 2000

Calendar Year

Months

0

100

200

300

Approvals

Median Approval Times Number of Generic Approvals

Generic drug 

submissions 

 2000: 365 

 1999: 296 

 1998: 345 

 1997: 330 

 1996: 307 

 1995: 283 

 1994: 199 

 1993: 215 

Notable 2000 

generic drug 

approvals 

Examples of first-time 

approvals include: 

 Doxazosin mesylate 

tablets, used in treating 

benign prostatic 

hyperplasia and 

hypertension. 

 Paclitaxel injection,

used in treating 

various ovarian and 

breast cancers. 

 Nifedipine extended 

release tablets, used in 

treating angina and 

hypertension. 
14 

CDER 2000 Report to the Nation 

Generic drug electronic submission initiative 

Last year, for original submissions, we received 85 electronic submissions 

for bioequivalence data and 79 electronic submissions for chemistry, 

manufacturing and controls data. In continued support of the electronic 

submissions initiative, we: 

 Enhanced our information technology infrastructure to support the electronic review process. 

 Promoted electronic submissions directly to industry and trade groups. 

 Held training sessions for industry. 

Generic Drug Electronic Submissions

44

85

10

32

44

79

55

0

0

50

100

1997 1998 1999 2000

Fiscal Year

Number

Bioequivalence data Chemistry, manufacturing, controls data

How we approve 

generic drugs 

Generics are not 

required to repeat the 

extensive clinical trials 

used in the 

development of the 

original, brand-name 

drug. Instead, they 

must show 

bioequivalence to the 

brand-name reference 

listed drug. 

Scientists measure the 

amount of the generic 

drug that reaches the 

bloodstream and how 

long it takes to get 

there. This rate and 

extent of absorption is 

called bioavailability. 

The bioavailability of 

the generic drug is 

then compared to that 

of the brand-name 

reference listed drug. 

The generic version 

must deliver the same 

amount of active 

ingredients into a 

patient’s bloodstream 

and in the same time as 

the brand-name 

reference listed drug. 

Brand-name drugs are 

subject to the same 

bioequivalency tests as 

generics when their 

manufacturers 

reformulate them. 

Quicker approvals 

without user fees 

We don’t receive user 

fees to review 

applications for 

marketing generic 

equivalents of 

prescription or overthe-counter drugs. 
15 

Improving Public Health Through Human Drugs 

Manufacturing Supplement Review 

We review many types of changes in the manufacturing of drugs and their 

packaging, including location, machinery, processes and suppliers of raw 

materials. We do this so that American consumers can trust the high 

quality of FDA-approved medicines. Manufacturers notify us in advance of 

certain manufacturing changes. These are known as “manufacturing 

supplements” to new drug or generic drug applications. In many cases, 

they represent the industry’s efforts to modernize plants and equipment or 

to make manufacturing more efficient. 

New drug 

manufacturing 

supplement 

statistics 

 1,345 approvals 

 Median FDA review 

time: 4.0 months 

NDA Manufacturing Supplement Actions

81% 84%

74%

67%

61%

80%

72%

83%

1,147 1,674 1,782 1,630 1,659 1,747 1,605 1,580

0%

50%

100%

1993 1994 1995 1996 1997 1998 1999 2000

Calendar Year

Percentage

0

1,000

2,000

Actions

Percentage of Actions that Are Approvals Number of NDA Manufacturing Supplement Actions

NDA Manufacturing Supplement Approvals

5.9

4.0 4.0

5.4 5.1

8.2

7.7 5.2

848

1,065 1,024

1,422

1,178

1,375 1,419 1,345

0

6

12

1993 1994 1995 1996 1997 1998 1999 2000

Calendar Year

Months

0

320

640

960

1280

1600

Approvals

Median Total Approval Time Number of NDA Manufacturing Supplements Approved
16 

CDER 2000 Report to the Nation 

Generic drug 

manufacturing 

supplement 

statistics for 2000 

 2,314 approvals 

 2,522 receipts 

Manufacturing supplements to generic drug applications 

In 2000, we approved 2,314 manufacturing supplements to generic drug 

applications. We received 2,522 manufacturing supplements during the 

year. 

Generic Drug Manufacturing Supplements

Receipts and Approvals

2,314

1,903 2,284 1,969

2,522

3,036

2,370

2,118

0

2,000

4,000

1997 1998 1999 2000

Calendar Year

Number

Number of Supplements Approved Number of Supplements Received
17 

Improving Public Health Through Human Drugs 

Assessing Data Quality, Research Risks 

To protect the rights and welfare of volunteers and verify the quality and 

integrity of data submitted for our review, we perform on-site inspections 

of clinical trial study sites, institutional review boards, sponsors, study 

monitors and contract research organizations. Our programs to protect 

volunteers are challenged by increases in the number of clinical trials; the 

types and complexity of products undergoing testing; and the increased 

number of trials performed in countries with less experience and limited or 

no standards for conducting clinical research. 

When obtaining data about the safety and effectiveness of drugs, sponsors 

rely on human volunteers to take part in clinical studies. Protecting 

volunteers from research risks is a critical responsibility for us and all 

involved in clinical trials, including manufacturers, institutional review 

boards, study sponsors, clinical investigators and their staffs, monitors, 

contract research organizations, hospitals and other institutions. 

Sponsors and clinical investigators protect volunteers by ensuring that: 

 Clinical trials are appropriately designed and conducted according to 

good clinical practices. 

 Research is reviewed and approved by an institutional review board. 

 Informed consent is obtained from participants. 

 Ongoing clinical trials are actively monitored. 

Special attention is given to protecting vulnerable populations, such as 

children, the mentally impaired or prisoners. 

We require sponsors to disclose financial interests of clinical investigators 

who conduct studies for them. This helps identify potential sources of bias 

in the design, conduct, reporting and analysis of clinical studies. 

International 

inspections 

We have conducted 

422 inspections in 45 

countries from 1980 to 

2000. 

We participate in 

international efforts to 

strengthen protections 

for human volunteers 

worldwide and 

encourage clinical 

investigators to 

conduct studies 

according to the 

highest ethical 

principles. 

These efforts include 

our work with the 

International 

Conference on 

Harmonization 

(page 36) and the 

Declaration of 

Helsinki. 

Top 5 deficiency 

categories for 

clinical 

investigator 

inspections 

 Failure to follow the 

protocol 

 Failure to keep 

adequate and accurate 

records 

 Failure to report 

adverse events 

 Failure to account 

for the disposition of 

study drugs 

 Problems with the 

informed consent form 

Inspections of 

clinical research in 

2000 

We conducted a total 

of 528 inspections last 

year. 

 296 U.S. clinical 

investigators 

 49 foreign clinical 

investigators 

 155 institutional 

review boards 

 28 sponsors, 

monitors or contract 

research organizations 

Inspections of Clinical Research

312

42 49

143

184 191

4 7 1 4 10 28

246

293 296 297

393

28 40

64 61

170 158 155

0

250

500

1995 1996 1997 1998 1999 2000

Calendar Year

Number

U.S. Clinical Investigators Foreign Clinical Investigators

Institutional Review Boards Sponsors, Monitors, CROs
18 

CDER 2000 Report to the Nation 

Pediatric 

exclusivity 

statistics 

 218 proposed 

pediatric study 

requests received 

 188 written requests 

issued 

Pediatric Exclusivity 

The 1997 FDA Modernization Act authorized us to grant six months of 

marketing exclusivity to manufacturers who conduct and file pediatric 

studies in response to our written requests. Pediatric exclusivity has helped 

us uncover important new information that will help pediatricians and 

other prescribers use drugs to treat children more safely and confidently. 

As of April 1, 2001, we had received 218 proposed pediatric study requests 

and had issued 188 written requests. These studies could potentially 

involve more than 20,000 children. In less than three years, more than 58 

pediatric studies have already been conducted. Reports from these studies 

have been submitted, and exclusivity granted to 28 drugs. 

Drugs that have or soon will have pediatric use information in their 

labeling are used to treat conditions such as: 

 Diabetes mellitus. 

 Gastroesophageal reflux disease. 

 Hypertension. 

 Juvenile rheumatoid arthritis. 

 Obsessive compulsive disorder. 

 Pain. 

 Depression. 

 HIV infection. 

 Seizures. 

 Anesthesia and sedation. 

A full report on our experiences with pediatric exclusivity is at http://www.

fda.gov/cder/pediatric/reportcong01.pdf. Our pediatric medicine page is at 

http://www.fda.gov/cder/pediatric/index.htm.

Pregnancy 

labeling 

We have reviewed the 

current system of 

labeling drugs for use 

by pregnant women 

and are developing an 

improved, more 

comprehensive and 

clinically meaningful 

approach. 

We are consulting with 

multiple government 

agencies, medical 

experts, consumer 

groups and the 

pharmaceutical 

industry to develop 

this new labeling 

format. 

Antimicrobial Resistance 

The emergence of drug-resistant bacteria is considered to be a major threat 

to the public health. 

We play an active role in the federal government’s efforts to address this 

growing problem and its effects on drug development and regulation. 

We are developing approaches to provide education and information on the 

appropriate use of antibiotics to health care professionals and consumers. 

Details of our efforts and other resources are at http://www.fda.gov/cder/

drug/antimicrobial/default.htm.
19 

Improving Public Health Through Human Drugs 

Drug Review Team 

We use project teams to perform drug reviews. Team members apply their 

individual special technical expertise to review applications: 

 Chemists focus on how the drug is manufactured. They make sure the 

manufacturing controls, quality control testing and packaging are 

adequate to preserve the drug product’s identity, strength, potency, 

purity and stability. 

 Pharmacologists and toxicologists evaluate the effects of the drug on 

laboratory animals in short-term and long-term studies, including the 

potential based on animal studies for drugs to induce birth defects or 

cancer in humans. 

 Physicians evaluate the results of the clinical trials, including the 

drug’s adverse and therapeutic effects, and determine if the product’s 

benefits outweigh its known risks at the doses proposed. 

 Project managers orchestrate and coordinate the drug review team’s 

interactions, efforts and reviews. They also serve as the review team’s 

primary contact for the drug industry. 

 Statisticians evaluate the designs and results for each important clinical 

study. 

 Microbiologists evaluate the effects of anti-infective drugs on germs. 

These medicines—antibiotics, antivirals and antifungals—differ from 

others because they are intended to affect the germs instead of patients. 

Another group of microbiologists evaluates the manufacturing 

processes and tests for sterile products, such as those used 

intravenously. 

 Biopharmaceutists evaluate the rate and extent to which a drug’s active 

ingredient is made available to the body and the way it is distributed, 

metabolized and eliminated. They also check for interactions with other 

drugs. 

 Clinical pharmacologists evaluate factors that influence the 

relationship between the body’s response and the drug dose. They 

assist physician members of the team in assessing the clinical 

significance of changes in the body’s response to drugs through the use 

of exposure-response relationships. 

Scientific training 

for reviewers 

Our systematic 

training program for 

reviewers in science, 

policy and job-related 

skills is based on core 

competencies, learning 

pathways and 

individual 

development plans. 

The program grew 

from seven courses 

offered in 1997 to more 

than 20 currently 

offered. Existing 

courses were also 

revised. 

Reviewer participants 

increased six-fold, 

from about 250 in 1997 

to 1,500 currently. 

Reviewer training 

hours quadrupled 

from 4,000 hours a 

year in 1997 to 16,000 

hours currently. 

Training costs were 

reduced through 

partnerships with 

pharmaceutical firms, 

associations, academic 

institutions and foreign 

governments. 
20 

CDER 2000 Report to the Nation 

User Fee Review Performance 

The timely performance of high-quality drug reviews in recent years 

reflects the importance of our managerial reforms and the additional 

resources provided us under the Prescription Drug User Fee Act. The law, 

first enacted in 1992, was renewed for an additional five years in the 1997 

FDA Modernization Act. Under the law, the drug industry pays user fees 

for new drug applications, efficacy supplements and some other activities. 

User fees helped us hire additional scientists to perform reviews. 

In 1992, we agreed to specific performance goals for the prompt review of 

four categories of submissions: original new drug applications, 

resubmissions of original NDAs, efficacy supplements to already approved 

Original NDAs 

Improved performance 

goals were a key 

element of the 

reauthorization of user 

fees: 

 Standard drugs 

began a phase-in to 10-

month reviews.

 Priority drugs have 

a performance goal of 

90 percent reviewed 

and acted upon within 

six months. 

 New molecular 

entities have the same 

review performance 

goals as standard and 

priority drugs. 

Resubmissions 

of original NDAs 

Resubmissions are 

divided into two 

classes: 

 Class I, involving 

minor changes, are 

phasing in two-month 

reviews. 

 Class II, involving 

changes not specifically 

identified in the user 

fee goals document, 

retain a six-month 

review. 

Original NDAs

Fiscal Year Cohort Within Goal Review Performance

100% 100% 100% 100% 100% 99%

66%

85%

0%

20%

40%

60%

80%

100%

FY '98

114 reviews

12-mo: 84

 6-mo: 30

FY '99

126 reviews

12-mo: 95

10-mo: 63

 6-mo: 31

FY '00

121 filed* 

12-mo: 92

10-mo: 78

 6-mo: 29

User Fee Goal

*84 reviewed (1 overdue), 37 pending (none overdue) as of Feb. 28, 2001

Percentage

12-month review 10-month review 6-month review

Resubmissions of Original NDAs

Fiscal Year Cohort Within Goal Review Performance

100% 100% 100%

82%

100% 100% 100% 96% 98%

0%

20%

40%

60%

80%

100%

FY '98

54 reviews

Class I (6-mo.): 22

Class I (2-mo.): 18

Class II (6 mo.): 32

FY '99

64 reviews

Class I (4-mo.): 17

Class I (2-mo.): 17

Class II (6 mo.): 47

FY '00

80 resubmitted* 

Class I (4-mo.): 25

Class I (2-mo.): 24

Class II (6 mo.): 55

User Fee Goal

*75 reviewed (1 overdue), 5 pending (none overdue) as of Feb. 28, 2001

Percentage

Class I (6-mo.) Class I (4-mo.) Class I (2-mo.) Class II (6 mo.)
21 

Improving Public Health Through Human Drugs 

marketing applications and manufacturing supplements to already 

approved new drug marketing applications. We have continued to meet or 

exceed nearly all the progressively more stringent user fee performance 

goals. 

With the reauthorization of user fees in 1997, we committed to goals that 

will help speed the time it takes for drugs to be appropriately tested and 

developed before submitting those results for our review. These goals 

include those related to meeting management, clinical holds, resolving 

major disputes and reaching agreement on certain protocols. There are 

expectations regarding electronic applications and submissions, 

simplification of action letters and expedited notification of deficiencies in 

applications. 

Efficacy 

supplements 

 Standard efficacy 

supplements began a 

phase-in to 10-month 

reviews. 

 Priority efficacy 

supplements have a 

six-month review goal. 

Manufacturing 

supplements 

 Manufacturing 

supplements to NDAs 

that require our prior 

approval before 

implementation have a 

phase-in to a fourmonth review. 

 The goal for those 

that don’t require our 

prior approval—

changes being 

effected—remains at 

90 percent reviewed 

and acted on within six 

months. 

Efficacy Supplements

Fiscal Year Cohort Within Goal Review Performance

99% 100% 100% 99%

85%

94%

80%

87%

0%

20%

40%

60%

80%

100%

FY '98

129 reviews

12-mo: 119

 6-mo: 10

FY '99

137 reviews

12-mo: 122

10-mo: 104

 6-mo: 15

FY '00

174 filed* 

12-mo: 156

10-mo: 146

 6-mo: 18

User Fee Goal

*114 reviewed (1 overdue), 60 pending (none overdue) as of Feb. 28, 2001

Percentage

12-month review 10-month review 6-month review

New Drug Manufacturing Supplements

Fiscal Year Cohort Within Goal Review Performance

99% 99% 98% 98% 97%

73% 75%

0%

20%

40%

60%

80%

100%

FY '98

1,442 reviews

Pr aprvl & CBE (6-mo.)

FY '99

1,458 reviews

Pr aprvl (6-mo.): 902

Pr aprvl (4-mo.): 660

 CBE (6-mo.): 557

FY '00

1,439 filed* 

Pr aprvl (6-mo.): 679

Pr 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

Percentage

Prior Approval (6-mo.) Prior Approval (4-mo.) Changes Being Effected (6-mo.)
22 

CDER 2000 Report to the Nation 

Notes: 

 When comparing the fiscal year user-fee performance charts with the 

calendar year performance charts, remember that work on one year’s 

submission cohort is often performed in the following year or years. 

 The first four charts in this section show a cumulative total and a 

subset. For example, the performance chart for NDAs shows 

performance on 12-month reviews and the subset of those that are 

10-month reviews. 

 This report tracks all applications, including those exempt from user 

fees, according to user fee goals. These numbers may differ slightly 

from numbers found in FDA’s official reports on applications that pay 

user fees. 

Refusal to file an application 

As a result of the user fee program, the 

quality of applications submitted by 

industry has improved. In addition we 

have exercised increased consistency in 

applying our authority to refuse to file 

an application. We refuse to file an 

application only when we determine 

there is a significant omission of 

needed information. 

Before 1993, we were refusing to file 

approximately 25 percent to 30 percent 

of submitted original new drug 

applications. The percentage of refuseto-file applications has dropped steadily 

to approximately 4 percent in recent 

years. 

Refuse-to-File Actions

Original NDAs

5% 4% 5% 3% 4%

26%

17%

2%

135 134

113

117 114 123

111

132

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)

Percentage

0

75

150

Number

Percentage Refused to File Number of Original NDAs Submitted

Clinical Holds of Commercial INDs

(as of Dec. 31, 2000)

10%

15%

9% 9%

13% 11%

8%

430 459

471

446

376 358 360

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)

Percentage on Hold

0

250

500

Number

Percentage of Commercial INDs Received on Hold

Number of Commercial INDs Received

Clinical holds 

By working with sponsors more 

closely, the percentage of commercial 

investigational new drug applications 

put on clinical hold has decreased 

dramatically. 

A clinical hold temporarily halts the 

testing of a drug in humans because of 

concerns about safety. 

We have developed and published 

procedures that outline specific 

responsibilities and timelines for 

handling clinical holds imposed on 

investigational new drugs. 
23 

Improving Public Health Through Human Drugs 

User fee reforms benefit consumers 

As we continue to meet and exceed our 

application review performance 

commitments, more quality products are 

reaching American practitioners and 

consumers faster. 

The Prescription Drug User Fee Act has 

resulted in increasing numbers of applications 

filed, higher quality applications and quicker 

approvals for products with the requisite data. 

Our goals become more challenging each 

year. Nonetheless, application filings and 

quality remain high by historic standards and 

approval times continue to drop. 

Increasingly, American patients are receiving 

the benefits of important new drugs before 

they are available to citizens of other 

countries: 

 Of the new molecular entities approved in 

the United States from 1991 to 1995, 

primarily pre-PDUFA submissions, 43 

percent received their approvals within a 

year of their first introduction on the 

world market. 

 That percentage almost doubled to 80 

percent for NMEs approved in the United 

States from 1996 to 1998, primarily years 

of user-fee submissions. 

Source: Tufts University Center for the Study 

of Drug Development data in FDA’s fiscal 

year 2000 user fee performance report at 

http://www.fda.gov/ope/pdufa/report2000/.

User Fee Performance: 1993-1997 

Efficacy Supplements

0%

50%

100%

FY '93

92 reviews

41% on-time

FY '94

86 reviews

77% on-time

FY '95

77 reviews

95% on-time

FY '96

105 reviews

98% on-time

FY '97

146 reviews

99% on-time

User Fee Goal (none in 1993)

Resubmissions of Original NDAs

0%

50%

100%

FY '93

2 reviews

100% on-time

FY '94

24 reviews

83% on-time

FY '95

58 reviews

97% on-time

FY '96

89 reviews

99% on-time

FY '97

87 reviews

97% on-time

User Fee Goal (none in 1993)

Original NDAs

0%

50%

100%

FY '93

84 reviews

65% on-time

FY '94

92 reviews

95% on-time

FY '95

111 reviews 

98% on-time

FY '96

109 reviews 

100% on-time

FY '97

121 reviews 

100% on-time

User Fee Goal (none in 1993)

New Drug Manufacturing Supplements

0%

50%

100%

FY '93

1,045 reviews

50% on-time

FY '94

871 reviews

66% on-time

FY '95

1,249 reviews

90% on-time

FY '96

1,218 reviews

96% on-time

FY '97

1,262 reviews

98% on-time

User Fee Goal (none in 1993)
24 

CDER 2000 Report to the Nation 

2 

DRUG SAFETY

AND QUALITY

The practical size of premarketing clinical trials means that we cannot 

learn everything about the safety of a drug before we approve it. Therefore, 

a degree of uncertainty always exists about the risks of drugs. This 

uncertainty requires our continued vigilance, along with that of the 

industry, to collect and assess data during the post-marketing life of a drug. 

We monitor the quality of marketed drugs and their promotional materials 

through product testing and surveillance. As Americans are increasingly 

receiving the benefits of important new drugs before they are available to 

citizens of other countries, we must be especially vigilant in our 

surveillance. In addition, we develop 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. 

Highlights of drug safety and quality activities include: 

 Processed and evaluated 245,750 reports of adverse drug events, 

including 15,374 submitted directly from individuals. 

 Conducted 74 inspections to ensure adverse event reports submitted by 

manufacturers are accurate, timely and complete. 

 Issued 1,123 letters to help ensure that the promotion of drug products 

presents a fair balance of risks and benefits and isn’t false or 

misleading. 

 Mandated that five drug products be dispensed with specific consumer 

information to help make sure them the products are used safely and 

effectively. 

 Issued a proposed rule to revise prescription drug labeling to improve 

its accessibility and enhance safe and effective prescribing and use. 

 Conducted reviews of the safety profile of three approved drug 

products that resulted in their voluntary withdrawal from the market. 

 Issued a public health alert about a once widely used decongestant that 

has been withdrawn from the market by manufacturers. 

 Evaluated results of 1,144 preapproval inspections of new drugs, 1,085 

preapproval inspections of generic drugs and 1,436 postapproval 

inspections. 

 Issued 4,197 export certificates for U.S. drug products. 

Mission 

Protect the public 

health by ensuring that 

human drugs are safe 

and effective. 

Public meeting on 

safe drug use 

We held a two-day 

public meeting on the 

safe use of drug products to inform and obtain feedback from 

consumer and patient 

groups. 
25 

Improving Public Health Through Human Drugs 

Known side effects 

Unavoidable Avoidable 

Medication 

errors 

Product quality 

defects 

Preventable 

adverse 

events 

Injury 

or death 

Remaining 

uncertainties 

Unexpected side 

effects 

Unstudied uses 

Sources of Risk from Drug Products 

Types of Risks from Medicines 

Product quality defects. These are controlled through good manufacturing 

practices, monitoring and surveillance. 

Known side effects. Predictable adverse events are identified in the drug’s 

labeling. These cause the majority of injuries and deaths from using 

medicines. Some are avoidable, and others are unavoidable. 

 Avoidable. In many cases drug therapy requires an individualized 

treatment plan and careful monitoring. Other avoidable side effects are 

known drug-drug interactions. 

 Unavoidable. Some known side effects occur with the best medical 

practice even when the drug is used appropriately. Examples include 

nausea from antibiotics or bone marrow suppression from 

chemotherapy. 

Medication errors. The drug is administered incorrectly or the wrong drug 

or dose is administered. 

Remaining uncertainties. These include unexpected side effects, long-term 

effects and unstudied uses and populations. For example, a rare event 

occurring in fewer than 1 in 10,000 persons won’t be identified in normal 

premarket testing. 

Medication errors 

We help ensure the 

safe use of drugs we 

approve by identifying 

and avoiding brand 

names that contribute 

to problems in 

prescribing, dispensing 

or administration of 

the product. 

In 2000, we reviewed 

about 300 proprietary 

names and developed 

standard operating 

procedures on the 

review process. 

We developed a 

comprehensive Web 

site on medication 

errors at http://www.

fda.gov/cder/drug/

MedErrors/default.

htm.

U.S. risk 

management 

system fails to 

respond to new 

information about 

a drug’s risks 

We cosponsored a 

study of contraindicated use of 

cisapride. Our 1998 

regulatory action 

involving cisapride 

resulted in a blackboxed warning on the 

labeling and a “Dear 

Health Care 

Professional” letter 

from the manufacturer. 

The study indicated 

the percentage of 

patients inappropriately exposed to 

cisapride was 

unchanged after the 

warnings (http://jama.

ama-assn.org/issues/

v284n23/rfull/

joc00932.html).
26 

CDER 2000 Report to the Nation 

Drug Safety 

We evaluate the ongoing safety profiles of drugs available to American 

consumers using a variety of tools and disciplines. We maintain a system 

of postmarketing surveillance and risk assessment programs to identify 

adverse events that did not appear during the drug development process. 

We monitor adverse events such as adverse reactions, drug-drug 

interactions and poisonings. We use this information to update drug 

labeling and, on rare occasions, reevaluate the approval or marketing 

decision. 

As we discover new knowledge about a drug’s safety profile, we make 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. 

Information technology 

A powerful tool for detecting signals is the computerized spontaneous 

reporting evaluation system. We use a new, state-of-the-art system: the 

Adverse Event Reporting System. This system combines the voluntary 

adverse drug reaction reports from MedWatch and the required reports 

from manufacturers. These reports often form the basis of various 

“signals” that there may be a potential for serious, unrecognized, drugassociated events. After the signal is generated, further testing of the 

hypothesis is undertaken using various epidemiological and analytic 

databases, studies and other instruments and resources. The Adverse Event 

Reporting System offers paper and electronic submission options, 

international compatibility and pharmacovigilance screening. 

Adverse event 

reporting 

In 2000, we received 

245,750 reports of 

suspected drug-related 

adverse events: 

 87,160 

manufacturer 15-day 

(expedited) reports. 

 15,254 MedWatch 

reports directly from 

individuals. 

 143,336 

manufacturer periodic 

reports and other 

follow-up reports. 

Report types 

 15-day (expedited) 

reports. These report 

serious and unexpected 

adverse events to us as 

soon as possible within 

15 days of discovering 

the problem. 

 Direct reports from 

MedWatch. An 

individual, usually a 

health care 

practitioner, notifies us 

directly of a suspected 

serious adverse event. 

 Manufacturer 

periodic reports. These 

report all other 

adverse events, such as 

those that are less than 

serious or described in 

the labeling. This type 

of report is submitted 

quarterly for the first 

three years of 

marketing and 

annually after that. 

AERS on Internet 

You can learn more 

about the Adverse 

Event Reporting 

System at http://www.

fda.gov/cder/aers/

index.htm.

Post-Marketing Adverse Event Reports

262,334

246,822 245,750

228,611

189,073

143,597 154,558 136,836

117,718

83,517

83,310

0

100,000

200,000

300,000

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000

Calendar Year

Number

Manufacturer Periodic Reports Direct Reports (MedWatch) Manufacturer 15-Day (expedited) Reports
27 

Improving Public Health Through Human Drugs 

MedWatch drug 

safety Internet 

resources 

The latest medical 

product safety 

information can be 

found on the 

MedWatch Web site at 

http://www.fda.gov/

medwatch/.

You can sign up for 

immediate e-mail 

notification of 

MedWatch safety 

information at http://

www.fda.gov/

medwatch/new.htm.

Adverse event reporting enforcement 

We enforce regulations on postmarketing adverse event reporting to ensure 

that reports are accurate, timely and complete. During fiscal year 2000, we 

accomplished 74 inspections to ensure industry compliance. There were 52 

domestic and 22 foreign inspections. 

Drug safety research 

We sponsored research that identified the mechanisms for drug interactions 

between St. John’s Wort, an unregulated dietary supplement, and 

prescription drugs. 

Adverse Event Reporting Inspections

17

50

74

51

33

0

45

90

1996 1997 1998 1999 2000

Fiscal Year

Number

Inspections

Postmarketing 

adverse drug 

event reporting 

inspections in 

fiscal year 2000: 

 52 U.S. inspections 

 22 foreign 

inspections 

MedWatch Outreach and Reporting 

We administer the MedWatch program that helps promote the safe use of 

drugs by: 

 Rapidly disseminating new safety information on the Internet and by 

providing e-mail notification to health professionals, institutions, the 

public and our MedWatch partners consisting of professional societies, 

health agencies and patient and consumer groups. 

 Providing a mechanism for health professionals and the public to 

voluntarily report serious adverse events and problems with all FDAregulated medical products. Reports can be filed by mail, fax, 

telephone or the Internet. 

 Educating health professionals and consumers about the importance of 

recognizing and reporting serious adverse events and product problems, 

including medication errors. Our education program includes Internet 

outreach, speeches, articles and exhibits. 

Currently, we have 8,000 subscribers to our e-mail notification service and 

190 MedWatch partners. 

Drug-induced liver 

injury 

Drug-induced liver 

injury is the most 

common cause for 

removing approved 

drugs from the market, 

limiting a drug to 

second-line use or 

requiring special 

monitoring or 

restricted use. 

We have been working 

with manufacturers to 

address clinical studies 

in patients with 

impaired liver 

function. Data from 

these studies will 

provide information on 

dose adjustment and 

help prevent druginduced liver injury. 
28 

CDER 2000 Report to the Nation 

Drug Promotion Review 

The information about a drug available to physicians and consumers is just 

as important to its safe use as drug quality. We promote and protect the 

health of Americans by ensuring that drug advertisements and other 

promotional materials are truthful and balanced. We operate a 

comprehensive program of education, surveillance and enforcement about 

drug advertising and promotion. 

Launches and advisories 

When requested, we review advertisements and other promotional 

materials before drug companies launch marketing campaigns that 

introduce new drugs or campaigns that introduce new indications or 

dosages for approved drugs. In fiscal year 2000, we issued 276 advisory 

letters to companies regarding their promotional materials for launch 

campaigns. 

We also issued 306 other advisory letters to the industry regarding 

proposed promotional pieces, both professional and consumer directed. In 

addition, we issued 209 other types of correspondence to the 

pharmaceutical industry, such as letters of inquiry, closure letters or 

acknowledgement letters. 

Regulatory actions 

We issued 117 regulatory action letters to companies for prescription drug 

promotions determined to be false, misleading, lacking in fair balance of 

risks and benefits or that promoted a product or indication before approval. 

These were either “untitled” letters for violations or “warning” letters for 

more serious or repeat violations. Examples of specific types of violative 

promotions include “homemade” promotional pieces (seven letters), 

Internet Web sites (six letters), promotional exhibit hall displays (three 

letters), oral representations (two letters), plus traditional materials such as 

journal advertisements and sales brochures. 

Drug promotion 

review statistics 

for FY 2000 

We issued a total of 

1,123 drug promotion 

letters last year. 

 117 regulatory 

action letters 

 276 launch 

campaigns 

 515 advisory 

acknowledgement or 

closure letters 

 215 direct-toconsumer advertising 

advisory and 

regulatory action 

letters 

Drug Promotion Review

235

417 399

773

515

220 245 237

171

129 117

242 221

276

159

350

558 539

215

247

0

400

800

1993 1994 1995* 1996 1997 1998 1999 2000

Calendar Year

(*Change from counting campaigns to letters in last quarter 1995)

Number*

Regulatory Actions Launch Campaigns Other Letters DTC Advertising Letters
29 

Improving Public Health Through Human Drugs 

Direct-to-consumer promotion 

We issued 215 letters regarding direct-to-consumer promotion, including 

47 letters for launch campaigns, 147 for non-launch advisories, and 20 

regulatory letters. Of the regulatory letters, 13 were for advertisements 

broadcast on television or radio and 7 were for print advertisements. 

We posted on our Web site the results from a national telephone survey of 

patient attitudes and behaviors associated with direct-to-consumer 

advertisements and obtained funding for a follow-up survey of patients and 

a new survey of physicians. 

Improved patient information for prescription drugs 

We held a two-day public workshop to discuss the findings of an interim 

study of the degree to which useful written information about prescription 

drugs was given to patients in eight states. The study examined if the 

information was consistent with the criteria specified in a 1997 action plan 

agreed to by the government and the private sector.

The meeting presented the study methodology and results. It provided us 

feedback before we developed an assessment of the year 2000 goals 

specified in the action plan. More information is at http://www.fda.gov/

cder/calendar/meeting/rx2000.

We obtained funding for the assessment and used feedback from the public 

meeting and written comments from the public to further develop the 

assessment methodology. 

Medication Guides 

We may require specific written patient information for selected 

prescription drugs that pose a serious and significant public health concern. 

These are called Medication Guides. They must be distributed to patients 

with each prescription dispensed. We determine if a drug requires a 

Medication Guide because information is necessary for patients to use the 

product safely and effectively or to decide to use or continue to use the 

product. Last year we issued Medication Guides for five products.

Proposed rule to revise prescription drug labeling 

We published a proposed rule that would revise the content and format of 

prescription drug labeling. The main purpose of labeling is to communicate 

essential information about prescription drugs to health care providers. 

The proposal would add a highlights section of critical prescribing 

information and an index. It would reorganize and reorder labeling to make 

the information easier for practitioners to find, read and use. We expect the 

proposed changes to contribute to our risk communication efforts by 

improving the accessibility of labeling information and consequently 

enhancing the safe and effective use of prescription drugs. 

Medication Guides 

issued in 2000: 

 Abacavir 

(Ziagen) 

 Abacavir, 

lamivudine and 

zidovudine 

combination (Trizivir) 

 Alosetron 

(Lotronex) 

 Isotretinoin 

(Accutane) 

 Mifepristone 

(Mifeprex) 
30 

CDER 2000 Report to the Nation 

Top 10 reasons for 

drug recalls in 

fiscal year 2000: 

 Lack of assurance 

of sterility in 

production or testing 

of sterile drug 

products 

 Deviations from 

current good 

manufacturing 

practices 

 Subpotency 

 Microbial 

contamination of 

nonsterile products 

 Chemical 

contamination 

 Penicillin crosscontamination of other 

products 

 Failure of or 

inability to validate 

manufacturing 

processes 

 Drug product 

marketed without an 

approved new or 

generic application 

 Failure of drug to 

dissolve properly 

 Product found to 

exceed limits set for 

impurities or 

degradation 

Drug Recalls and Withdrawals 

We coordinate drug recall information and prepare health hazard 

evaluations to determine the risk to public health by products being 

recalled. We classify recall actions in accordance to the level of risk, and 

we participate in determining recall strategies based upon the hazard and 

other factors including distribution patterns and market availability. We 

determine the need for public warnings and assist the recalling firm with 

public notification. 

Voluntary recalls 

A voluntary recall is taken by a manufacturer or distributor to carry out 

their responsibilities to protect the public health when they need to remove 

or correct a marketed drug product that presents a significant risk to public 

health. A voluntary recall is more efficient and effective in assuring timely 

consumer protection than an FDA initiated court action or seizure. 

Safety-based withdrawals in 2000 

In some cases, drugs are withdrawn from the market. Based on reports that 

we reviewed in consultation with the manufacturers, these drugs were 

withdrawn from the U.S. market last year: 

 Alosetron (Lotrenox), a treatment for irritable bowel syndrome in 

women, was voluntarily withdrawn after analysis of adverse event 

reports (http://www.fda.gov/cder/drug/infopage/lotronex/lotronex.htm).

 Cisapride (Propulsid), a treatment for severe nighttime heartburn, is no 

longer marketed in the United States. We and the manufacturer 

determined that many preventable adverse events were occurring in 

patients who should never have been prescribed cisapride.

 Phenylpropanolamine, a decongestant ingredient used in many 

prescription and over-the-counter cough and cold medications, was 

Drug Recalls

255

304

191

248

316

93 102

60 53

34

88

156

226

177

352

72

0

200

400

1993 1994 1995 1996 1997 1998 1999 2000

Fiscal Year

Number

Prescription Drugs Over-the-Counter Drugs
31 

Improving Public Health Through Human Drugs 

voluntarily removed from the U.S. market by manufacturers after FDA 

issued a public health advisory that it might cause strokes and 

announced it was taking steps that might lead to its withdrawal. 

Phenylpropanolamine was never formally approved for safety and 

efficacy (http://www.fda.gov/cder/drug/infopage/ppa/default.htm).

 Troglitazone, (Rezulin), a treatment for type 2 diabetes, was voluntarily 

withdrawn by after review of safety data showed that the drug is more 

toxic to the liver than two other more recently approved drugs that offer 

a similar benefit. 

Record of safety-based market withdrawals 

During the period 1981 to 2000, we approved 543 new molecular entities. 

Fourteen of these, or 2.6 percent, were withdrawn for safety reasons after 

joint FDA-manufacturer review. The record of withdrawal of drugs 

approved in recent years is similar to previous periods when we were 

criticized for taking too long to review drug applications. Nonetheless, the 

increased number of drugs and the large number of patients taking multiple 

drugs have created the potential for more drug safety problems. 

Safety-Based NME Withdrawal Percentages

Based on Year of Approval

1.9%

2.3%

2.7%

3.3%

184

131

107 121

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

Percentage

0

100

200

Number

Percentage of Cohort Withdrawn Number of NMEs Approved in Cohort

Recent safetybased drug 

withdrawals 

Drug name 

(year approved/ 

year withdrawn)

 Fenfluramine

 (1973/1997) 

 Ticrinafen 

 (1979/1980) 

 Zomepirac 

 (1980/1983) 

 Benoxaprofen 

 (1982/1982) 

 Nomifensine 

 (1984/1986) 

 Suprofen 

 (1985/1987) 

 Terfenadine 

 (1985/1998) 

 Encainide 

 (1986/1991) 

 Astemizole 

 (1988/1999) 

 Flosequinan 

 (1992/1993) 

 Temafloxacin 

 (1992/1992) 

 Cisapride 

 (1993/2000) 

 Dexfenfluramine 

 (1996/1997) 

 (not an NME)

 Bromfenac 

 (1997/1998) 

 Grepafloxin 

 (1997/1999) 

 Mibefradil 

 (1997/1998) 

 Troglitazone 

 (1999/2000) 

 Rapacuronium 

 (1999/2001)

 (manufacturer only 

 decision) 

 Alosetron 

 (2000/2000) 

 Phenylpro- 

 panolamine 

 (—/2000) 

 (never approved 

 by FDA)

Recent safetybased drug 

withdrawals 

(cont.)

1981-2000 NME 

withdrawals 

resulting from 

joint FDAmanufacturer 

reanalysis of risks 

vs. benefits 

 543 NMEs 

approved 

 14 withdrawn 

 2.6 percent 

withdrawn 
32 

CDER 2000 Report to the Nation 

Drug Product Quality 

We provide comprehensive regulatory coverage of the production and 

distribution of drug products. We manage inspection programs designed to 

minimize consumer exposure to defective drug products. We have two 

basic strategies to meet this goal: 

 Evaluating the findings of factory inspections of the conditions and 

practices in plants under which drugs are manufactured, packed, tested 

and stored. 

 Monitoring the quality of finished drug products in distribution through 

sampling and analysis. 

We identify, evaluate and analyze inspection findings for trends in 

deficiencies. We develop guidances to assist drug manufacturers in gaining 

a better understanding of our regulations. We communicate the 

expectations of compliance through outreach programs. We review all 

international pharmaceutical inspection reports. We determine which 

foreign manufacturers are acceptable to supply active pharmaceutical 

ingredients or finished drug products to the U.S. market. 

Manufacturing plant inspections 

FDA field offices conduct inspections of domestic and foreign plants that 

manufacture, test, package and label drugs. Before a drug is approved, 

FDA investigators must determine if data submitted in the firm’s 

application are authentic and if the plant is in compliance with good 

manufacturing practices. After a drug is approved, FDA conducts an 

inspection to make sure a firm can consistently manufacture the product. 

Finally, routine inspections evaluate the firm’s entire operations. 

 Preapproval inspections. During fiscal year 2000, FDA evaluated 

1,144 domestic plants in support of new drug applications. One user fee 

goal was missed. Also, FDA evaluated 1,085 domestic firms in support 

of generic drug applications. 

 Good manufacturing practice inspections. There were 1,436 good 

manufacturing practice inspections in fiscal year 2000. Of the warning 

letters that resulted from these inspections, we reviewed 34 policy 

consistency. We also reviewed 48 field recommendations for 

regulatory action and approved 28. These included two injunctions, 14 

seizures and seven warning letters. We reviewed 248 foreign 

establishment inspection reports. These reviews resulted in 11 warning 

letters and two import alerts. Import alerts prevent violative foreign 

drug products from entering the United States. 

New drug 

preapproval plant 

evaluations 

 FY 2000: 1,144 

 FY 1999: 773 

Generic drug 

preapproval plant 

evaluations 

 FY 2000: 1,085 

 FY 1999: 1,775 

Good 

manufacturing 

practice 

inspections 

 FY 2000: 1,436 

 FY 1999: 1,844 
33 

Improving Public Health Through Human Drugs 

Reporting systems for drug quality problems 

Two important tools help us rapidly identify significant health hazards 

associated with the manufacturing and packaging of drugs: 

 Field Alert Reports. Firms are required to notify FDA promptly of 

significant problems they discover that may represent safety hazards 

for their marketed drug products. 

 Drug Quality Reporting System. We analyze voluntary reports on drug 

product quality problems submitted by health care practitioners through 

MedWatch and other systems. We maintain these reports in a central 

database to aid in detecting problem areas and identify trends requiring 

regulatory action. 

Surveillance sampling of drugs 

The Drug Quality Surveillance Sampling Program helps determine the 

quality of imported and domestic drugs distributed in the United States. 

Samples of drug products are tested for conformance with quality 

specifications to ensure that the nation’s drug supply is safe and effective 

and to provide rapid identification of emerging problems. We have 

intensified surveillance of imported drug products because of the increased 

number of imports. 

Sampling criteria 

We chose drugs for the sampling program based on the following criteria: 

 New molecular entities. 

 Drugs with dissolution issues. 

 Highly active drugs that have effects in low doses. 

 Drugs with a history of quality problems, field alerts or recalls. 

 Suspected counterfeit drugs. 

Unsubstantiated claims; fraudulent, hazardous products 

We encounter many products that are vitamins, minerals, amino acids and 

herbal preparations with labeled drug claims. These products may be 

labeled as dietary supplements but make claims that they are safe and 

effective for the prevention, treatment or cure of such diseases as AIDS or 

cancer. Because these claims are unsubstantiated, they could present a 

health hazard when consumers delay or avoid seeking effective medical 

care. 

 We take enforcement action when these products are likely to cause 

serious injury. 

 We identify fraudulent or hazardous drug products and assist in 

developing enforcement strategies involving counterfeit drugs. 
34 

CDER 2000 Report to the Nation 

Drug Product Quality Research 

We conduct scientific research on drug product quality issues. Last year 

our efforts included: 

 Developing in vitro, or test tube, methods for studying the impact of 

excipients and diluting agents on the absorption of orally administered 

drugs. Excipients are commonly known as “inactive ingredients.” 

 Identifying genetic markers that will authenticate cultivated St. John’s 

Wort and detect contamination by related species. 

 Developing and validating numerous methods for testing the quality of 

pharmaceutical products. For example, near-infrared spectroscopy can 

detect and quantify different hydrated forms of an active ingredient in 

commercial drug products. 

PQRI 2000 update 

The Product Quality Research Institute (page 4) marked its first year by 

initiating seven working groups to address: 

 Blend uniformity. 

 Oral biopharmaceutics. 

 Packaging changes. 

 Bulk drug post-approval changes. 

 Drug substance impurity testing. 

 Drug substance particle size analysis. 

PQRI is expected to make recommendations in 2001 aimed at ensuring 

thorough mixing of a drug within the blend and dosage unit. 
35 

Improving Public Health Through Human Drugs 

Export Certificates 

We promote goodwill and cooperation between the United States and 

foreign governments through the Export Certificate Program. These 

certificates enable American manufacturers to export their products to 

foreign customers and foreign governments. The demand for certificates by 

foreign governments remains high due to expanding world trade, ongoing 

international harmonization initiatives and international development 

agreements. 

The certificates attest that the drug products are subject to inspection by the 

FDA and are manufactured in compliance with current good 

manufacturing practices. Export certificates verify that drug products being 

exported: 

 Were freely marketed in the United States. 

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

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

 Were free of specific contaminants. 

Export certificates 

issued in FY 2000: 

 4,197 

Export Certificates Issued

4,197 3,973 4,499 4,378 4,382

1,747

1,290

0

2,500

5,000

FY '94 FY '95 FY '96 FY '97 FY '98 FY '99 FY '00

Fiscal Year

Number

Export Certificates Issued

Drug Shortages 

We work to help prevent or alleviate shortages of medically necessary drug 

products. Drug shortages occur for a variety of reasons including 

manufacturing difficulties, bulk supplier problems and corporate decisions 

to discontinue drugs. 

Because drug shortages can have significant public health consequences, 

we work with all parties involved to make sure all medically necessary 

products are available within the United States. 

Drug shortages on 

Internet 

We developed a Web 

site that lists current 

drug shortages, 

describes efforts to 

resolve them and 

explains how to report 

them. The site is at 

http://www.fda.gov/

cder/drug/shortages/.
36 

CDER 2000 Report to the Nation 

3 

INTERNATIONAL

ACTIVITIES

Highlights from 2000 include: 

 Finalization of the Common Technical Document that can be used for 

seeking approval to market new drugs in the United States, the 

European Union and Japan. 

 Initiation of harmonization efforts among the countries of North and 

South America. 

 Leadership of the U.S. consultations with the European Union to allow 

for reciprocal reliance on manufacturing plant inspections. 

International Conference on Harmonization 

Harmonization—making the drug regulatory processes more efficient and 

uniform—is an issue that is important not only to Americans, but to drug 

regulatory agencies and pharmaceutical companies throughout the world. 

The International Conference on Harmonization of Technical 

Requirements for Registration of Pharmaceuticals for Human Use has 

worked to bring together government regulators and drug industry experts 

from innovator trade associations in the European Union, Japan and the 

United States. 

We are leading the FDA’s collaboration with the ICH. This work will help 

make new drugs available with minimum delays not only to American 

consumers but also to patients in other parts of the world. 

The drug regulatory systems in all three regions share the same 

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

Before ICH, many time-consuming and expensive technical tests had to be 

repeated in all three regions. The ICH goal is to minimize unnecessary 

duplicate testing during the research and development of new drugs. The 

ICH process results in guidance documents that create consistency in the 

requirements for product registration. 

Second ICH phase launched 

ICH embarked on a second phase of activities and agreed to broaden 

representation to other parties. This effort will have implications for 

already marketed drugs, over-the-counter drugs and generic equivalents. 

Mission 

We participate 

through appropriate 

processes with 

representatives of 

other countries to 

reduce the burden of 

regulation, harmonize 

regulatory 

requirements and 

achieve appropriate 

reciprocal 

arrangements. 

Internet sources 

We have published 

ICH documents as 

guidances to industry. 

These are on our Web 

site at http://www.fda.

gov/cder/guidance/

index.htm. 

More information 

about ICH activities is 

at http://www.fda.gov/

cder/audiences/iact/

iachome.htm. 

PAHO information is 

at http://www.paho.org

Information on 

PANDRH is at http://

www.paho.org/english/

gov/cd/cd42_13-e.pdf.

The Mutual 

Recognition 

Agreement is at http://

www.iep.doc.gov/mra/

mra.htm and on the 

European Union’s 

Web site at http://dg3.

eudra.org/. 
37 

Improving Public Health Through Human Drugs 

Harmonization initiative in the Americas 

We are working with the Pan American Health Organization to promote 

regulatory harmonization within the Americas. PAHO is part of the United 

Nations system, serving as the World Health Organization’s regional office 

for the Americas. The initiative, called the Pan American Network for 

Drug Regulatory Harmonization or PANDRH, will search for common 

ground on various topics in a prioritized work plan. 

We are the lead for two topics of high priority—good manufacturing 

practices and bioavailability/bioequivalence. We are working with the 

countries of Latin America to provide training on these two important 

issues. Training to the same standards should help lead to harmonization. 

U.S.-European Union Mutual Recognition Agreement 

This agreement provides for reciprocal reliance on inspection systems in 

the United States and the 15 member nations of the European Union. The 

globalization of the pharmaceutical industry is outpacing our resources to 

inspect pharmaceutical manufacturing plants worldwide. Once fully 

implemented, the agreement will allow us to base our regulatory decisions 

on inspection data from “equivalent authorities” in the European Union. 

Equivalent authorities are those with regulatory systems for good 

manufacturing practices that we have assessed and determined will achieve 

a comparable level of public health protection. 

While the agreement will allow us to use an inspection report from one of 

our European counterparts as though it were our own, the actual regulatory 

decision will be up to us. Our experts in good manufacturing practices are 

leading the FDA team that is working with a team from the European 

Union to implement this agreement. 

Common 

Technical 

Document 

finalized 

The ICH partners 

reached agreement on 

an information 

package of technical 

data, in the same 

format and with the 

same content, that can 

be submitted to drug 

review authorities in 

all three ICH regions. 

We expect to be able to 

accept new drug 

applications 

conforming to the new 

format by mid-2001. 

Work on making the 

document suitable for 

electronic submission 

is nearing completion. 

MRA update 

Last year marked the 

second year of a threeyear transition to 

implementation. 

Implementation has 

not proceeded as 

smoothly as planned, 

but both parties 

remain optimistic and 

continue to strive 

toward a mutually 

beneficial outcome. 

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 
38 

CDER 2000 Report to the Nation 

4 

COMMUNICATIONS

Highlights from 2000 include: 

 Meeting almost weekly with outside experts on difficult scientific and 

public health issues. 

 Responding to more than 58,000 individual requests for information. 

 Receiving nearly 5 million visitors and about 80 million hits on our 

Internet information site, which has 30,000 pages and documents. 

Public participation 

We confer with panels of outside experts in science, medicine and public 

health in meetings open to the public. We assure that patient 

representatives are included on advisory committees considering medicines 

for HIV, AIDS, cancer and other serious disorders. We analyzed public 

comments on proposed new rules, and we sought and received comments 

on our guidances to industry. 

In special public meetings, we received valuable input from consumer and 

patient groups, professional and scientific societies, industry and trade 

associations about: 

 Ways to include consumer input in our evaluation of the usefulness of 

written information currently dispensed with prescription drugs. 

 Reexamining a number of issues about over-the-counter drugs 

including prescription-to-OTC switches and classes of drugs available 

over the counter. 

 Strengths and weaknesses of the Prescription Drug User Fee Act. 

We cosponsored two public workshops on how consumers can make sure 

they use drug products safely and understand their role in improving the 

drug quality control system. 

Consumer and industry outreach 

We use a number of modern communication methods to reach our 

stakeholders. Highlights include: 

 Responding to more than 1,680 telephone and e-mail requests from the 

specialized media that focus on the pharmaceutical industry. This 

compares with 1,250 in 1999 and about 1,000 in 1998. 

 Completing successful showings of our exhibit and information 

program at 19 national health care conferences and meetings, reaching 

an estimated audience of over 100,000 health care professionals. 

Stakeholders in 

drug review, drug 

quality and safety 

We work closely with 

many organizations on 

issues of public health 

and safety, including: 

 Consumers, 

patients and their 

organizations 

 Scientific and 

professional societies 

 Industry and trade 

associations 

 Universities, 

hospitals and health 

care professionals 

 Federal, state and 

local government 

agencies 

 Foreign 

governments 

Mission 

Carry out our mission 

in consultation with 

experts in science, 

medicine and public 

health and in 

cooperation with 

consumers, users, 

manufacturers, 

importers, packers, 

distributors and 

retailers of human 

drugs. 

Reorganization 

of information 

activities 

Our Office of Training 

and Communication 

created the Division of 

Drug Information and 

the Division of Public 

Affairs to improve 

information 

dissemination to our 

stakeholders and 

enhance consumer 

outreach and 

education. 

Internet updates 

We have 33,000 

subscribers to our 

service that provides 

daily and weekly 

e-mail updates of new 

content on our Web 

site. 

To subscribe, visit 

http://www.fda.gov/

cder/cdernew/listserv.

html.
39 

Improving Public Health Through Human Drugs 

 Conducting about 70 domestic and foreign videoconferences for 

academia, industry and associations. 

Educational campaigns 

In response to the expressed need for additional information from the 

public and health care professionals, we developed public education 

campaigns about: 

 Benefits vs. risks of medication use. 

 Buying prescription medical products over the Internet. 

 Aspirin therapy to reduce the risk of heart attacks and strokes. 

 Pharmacy compounding. 

 The new over-the-counter medicine labels. 

Dissemination activities 

 CDER Live! We conducted two satellite television broadcasts for 

industry in which our scientific and regulatory experts engaged in panel 

discussions about minimizing medical errors and direct-to-consumer 

advertising. About 5,000 industry executives, scientists and managers 

viewed the programs live, with additional viewers by webcast. 

 E-mail information requests. We responded to more than 16,400 e-mail 

requests from industry, consumers, patients and health care 

professionals. 

 Other communication. We answered more than 27,000 telephone 

inquiries, 4,000 faxes and nearly 7,000 written requests. We responded 

to more than 9,500 requests for documents and guidance publications. 

Average Monthly Use of CDER Internet Site

32,000

72,000

156,000

226,000

406,000

0.5

1.3

3.1

2.5

6.7

0

250,000

500,000

1996 1997 1998 1999 2000

Calendar Year

Visitors

0

5

10

Hits (millions)

Average Monthly Visitors Average Monthly Hits (millions)

Workshop on 

postapproval 

changes in 

analytical methods 

and packaging 

We cosponsored a 

workshop to discuss 

scientific issues related 

to changes in analytical 

methodologies and 

packaging for 

pharmaceuticals. 

Participants explored 

viable scientific 

approaches for 

predicting the potential 

impact of changes on 

drug substance and 

quality. 

Ombudsman’s 

activity 

In its fifth year of 

operation, our 

ombudsman helped 

settle issues between 

the Center and 

industry, health 

professionals and 

consumers. 

The ombudsman 

handled about 100 

complaints. He 

answered more than 

1,000 e-mails, 

approximately 1,000 

telephone calls and 20 

letters. 

In addition, the 

ombudsman held 

about 50 meetings with 

external parties. 

Packaging training 

We cosponsored a 

training session for 

members of the 

pharmaceutical 

industry to discuss and 

clarify our guidance on 

container closure 

systems.
40 

CDER 2000 Report to the Nation 

Where to Find More Information 

We support multiple ways to obtain information about drug products and 

the laws, regulations and guidances concerning them. 

Selected Internet sites 

 FDA Internet home page: http://www.fda.gov/

 CDER Internet home page: http://www.fda.gov/cder/

 CDER’s consumer drug information sheets for new medicines 

approved since January 1998: 

http://www.fda.gov/cder/consumerinfo/default.htm

 FDA Modernization Act of 1997 CDER-related documents: 

http://www.fda.gov/cder/fdama/default.htm

 From Test Tube to Patient: New Drug Development in the United 

States: http://www.fda.gov/fdac/special/newdrug/ndd_toc.html

 CDER Handbook: http:// www.fda.gov/cder/handbook/index.htm

 CDER organizational charts: http://www.fda.gov/cder/cderorg.htm

 CDER key officials: http://www.fda.gov/cder/directories/keyoffic.pdf

Telephone 

We respond to specific questions about prescription, over-the-counter and 

generic drugs for human use. You can telephone us toll free at 

1-888-INFO FDA or directly at 301-827-4573. 

E-mail 

We can be contacted at druginfo@cder.fda.gov.

Regular mail 

U.S. Food and Drug Administration 

Center for Drug Evaluation and Research 

Drug Information Division 

HFD-240, Room 12B-31 

5600 Fishers Lane 

Rockville, MD 20857