Inside the FDA

IN THIS SUMMARY
The United States Food and Drug Administration (FDA) has significant reach in the American economy, ranging from medicines and medical devices to items on the grocery store shelves. Since its inception in 1906, the agency has faced a variety of technical and political challenges. Looking ahead, the FDA faces many new demands that could enlarge the agency’s already expansive mandate. New responsibilities may include the cost of medicine, consumers’ pursuit of perfection through drugs, consumer lifestyles, tobacco, and counterterrorism. As the nature of public health changes over time, it is inevitable that the FDA’s scope and responsibilities will change as well. In Inside the FDA, Fran Hawthorne explains the history of the FDA, how its processes work, and what the future may hold for this government agency.

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2. INSIDE THE FDA
The Business and Politics Behind the Drugs
We Take and the Food We Eat
AUTHOR: Fran Hawthorne
PUBLISHER: John Wiley & Sons, Inc.
DATE OF PUBLICATION: 2005
338 pages

3. Inside the FDA by Fran Hawthorne
FEATURES OF THE BOOK
Inside the FDA is a comprehensive review of the agency’s history,
responsibilities, stakeholders, and future.

4. Inside the FDA by Fran Hawthorne
THE BIG IDEA
In Inside the FDA, Fran Hawthorne explains how the
agency’s processes work, as well as how the agency
interacts with different stakeholders.

5. Inside the FDA by Fran Hawthorne
INTRODUCTION
The United States Food and Drug Administration (FDA) has
significant reach in the American economy. Medicines and medical
devices cannot be sold unless this organization deems that they are
safe and effective. In addition, packaged foods cannot make health
claims without approval from the FDA. Since its inception in 1906,
the agency has faced a variety of technical and political challenges.
In Inside the FDA, Fran Hawthorne explores the history of the FDA,
how its processes work, and what the future may hold for the
agency.

6. Inside the FDA by Fran Hawthorne
THE HISTORY OF THE FDA
During the 1800s, no regulations existed for medicine or food. In
1862, Abraham Lincoln created the Department of Agriculture.
Within this Department, Dr. Harvey W. Wiley headed the Bureau
of Chemistry and championed the cause for food and drug safety.
This Bureau was later reorganized and called the Food and Drug
Administration. After publication of The Jungle by Upton Sinclair,
Congress passed the Food and Drug Act of 1906—the first
national legislation on food and medical safety.

7. Inside the FDA by Fran Hawthorne
THE HISTORY OF THE FDA
Despite this law, poisonous medicines and unsafe food products
continued to be sold. After 107 people were killed from an
antibiotic, the Food, Drug, and Cosmetic Act of 1938 was
implemented. This act created the framework for today’s FDA,
requiring manufacturers to show scientific proof that their products
are safe before they can be sold.

8. Inside the FDA by Fran Hawthorne
THE HISTORY OF THE FDA
Today’s Food and Drug Administration is comprised of five
branches:
3.The Center for Biologics Evaluation and Research (CBER)
4.The Center for Drug Evaluation and Research (CDER)
5.The Center for Food Safety and Applied Nutrition (CFSAN)
6.The Center for Veterinary Medicine (CVM)
7.The Center for Devices and Radiological Health (CDRH).

9. Inside the FDA by Fran Hawthorne
BRINGING A DRUG TO MARKET
There are five basic steps a firm must take to move a drug from
the laboratory to the marketplace in the United States:
Preclinical trials. These consist of tests on animals.
Investigational new drug application (IND). This document
describes the animal test results and the manufacturing process. It
also explains the human testing plans in detail. Drug companies
often schedule a pre-IND meeting with the FDA. The goal of this
meeting is to discuss the specifics of the human testing plans. If
companies can find out what the FDA wants in an IND, it is easier
to write an application that will be approved.

10. Inside the FDA by Fran Hawthorne
BRINGING A DRUG TO MARKET
Phase I clinical trials. Through testing on a small group of
healthy volunteers, the company ensures the drug is safe.
Phase II and III clinical trials. These are two progressively larger
trials on humans who suffer from the target disease. The goal is to
test both safety and effectiveness.
Applications to sell the drug. After the Phase III clinical trials,
companies must file either a biologics license application (BLA) or
a new drug application (NDA). BLAs are used for drugs made from
living materials (biologics) and NDAs are used for chemical-based
drugs.

11. Inside the FDA by Fran Hawthorne
CLINICAL TRIALS AND NEW DRUG APPLICATIONS
In recent years, several aspects of clinical trials have been debated:
The use of placebos. Typical scientific practice provides only half
of the test subjects with the drug being studied and the other half
receives a placebo. However, placebos cannot be used if patients
have life-threatening conditions. In the early 2000s, experts
suggested that only a direct comparison of drugs can demonstrate
that a newer and more expensive medication is better than an
existing, more affordable version.

12. Inside the FDA by Fran Hawthorne
CLINICAL TRIALS AND NEW DRUG APPLICATIONS
Drug dosages. The FDA encourages companies to experiment with
a variety of drug dosages during clinical trials. However, if this
introduces too much complexity, the agency may not insist. As a
result, only high doses are usually tested because they are more
likely to show strong results.
Demographic groups. Until 1993, it was FDA policy to exclude
women aged 14 to 50 from clinical trials, yet the individuals taking
drugs are not all healthy men. In 1989, the FDA published guidelines
for studying drugs in elderly populations and in 1993 issued similar
guidelines for studies using both men and women.

13. Inside the FDA by Fran Hawthorne
NEW DRUG APPLICATIONS
A new drug application is a company’s formal
application for selling a drug. Every NDA contains
every piece of information collected on every trial
participant. It is common for an application to have
between 100,000 and 200,000 pages, bound in
several hundred volumes.
An NDA is typically divided among several people at
the FDA: a chemist, pharmacologist, statistician,
toxicologist, perhaps a microbiologist, and the lead
reviewer who is a medical doctor specializing in that
type of drug. The reviewers are looking for two
patterns in the application: (1) the side effects,
deaths, and dropouts that point to safety, and (2) the
progress of improvement in conditions that point to
effectiveness.

14. Inside the FDA by Fran Hawthorne
NEW DRUG APPLICATIONS
The FDA approves approximately 75 percent of NDAs. The
other 25 percent meet three possible outcomes. In unusual
cases, the FDA will not consider an application at all and will
issue a “refusal to file” letter. Alternatively, the agency may
reject an application based on Class 1 (minor problems) or
Class 2 (major problems). The most common explanations for
rejection are trials that were not conducted based on the
protocol that had been planned with the FDA, unclear trial
results, or trial results that show only a small improvement in
patients. All drugs that are rejected can apply again, assuming
that new tests produce better data.

15. Inside the FDA by Fran Hawthorne
THE FDA APPROVAL PROCESS
The FDA changes the rules. The different divisions
within the agency have reputations for being tougher
or easier to deal with. The CDER is efficient, rule
abiding, and consistently meets its user fee
deadlines. The CBER is more academic, staffed by
research scientists. The CDRH has the most lenient
approval requirements, the smallest trials, and the
quickest reviews.
The agency does not understand the real world.
Although most agree that the FDA employees are
smart and dedicated, companies feel the staff does
not understand business issues and the cost of
developing a successful drug.

16. Inside the FDA by Fran Hawthorne
THE POWER OF THE PHARMACEUTICAL AND
FOOD INDUSTRIES
Both the pharmaceutical and food industries are very
influential in Washington. Hawthorne writes that the
FDA’s record for resisting industry influence is mixed.
The agency has had better luck with pharmaceuticals
than with food, but in general their stance has been too
weak.
In the 1970s, in response to complaints of long
approval times, the FDA decided to communicate more
openly with pharmaceutical companies. The belief was
that more communication prior to applications being
filed could contribute to drugs that followed the best
procedures related to safety and efficiency. Once an
application has been filed, however, it is too late for
advice.

17. Inside the FDA by Fran Hawthorne
THE POWER OF THE PHARMACEUTICAL AND
FOOD INDUSTRIES
Another controversial interaction between the FDA and
the pharmaceutical industry is when retired FDA
employees go to work for pharmaceutical companies.
The potential for conflicts of interest may arise long
before retirement, as FDA reviewers consider taking a
job in the industry at some future date.
When it comes to influencing the FDA, larger
pharmaceutical companies seem to have a better
chance. Small biotech firms often have a hard time
getting through the approval process, while large
manufacturers that have submitted applications for
many years can afford large government affairs
departments.

18. Inside the FDA by Fran Hawthorne
THE CONSUMERS AND THE FDA
As late as the early 1980s, the FDA did not view patients and
consumers as stakeholders that the agency needed to answer to.
However, the AIDS epidemic changed patient activism and
affected the FDA approval process. AIDS activists helped spur the
creation of treatment INDs and parallel track programs that
hastened access to life-saving drugs. Patients also took on a
greater role in the drug approval process, as patient or consumer
representatives were added to FDA advisory committees. The
goal was to get regulators to think about the human aspects of
issues like dosage, safety, effectiveness, and scientific validity.

19. Inside the FDA by Fran Hawthorne
POLITICAL PRESSURES FACING THE FDA
The FDA is undeniably subject to different political pressures.
The Commissioner must be confirmed by the Senate and the
agency’s funding must be approved each year by Congress.
Traditionally, certain behaviors have been taboo when it comes to
politics and the FDA. For instance, appointments to advisory
committees are supposed to be based solely on scientific
credentials. In addition, the FDA is not supposed to lobby
Congress.

20. Inside the FDA by Fran Hawthorne
THE FDA, BIOLOGICAL PRODUCTS, AND
RESEARCH
Unlike chemical drugs, products made from living substances like
human cells are more individualized and experience unexpected
variations during production. Prior to 1972, biological products
were regulated by the National Institutes of Health (NIH) until the
Bureau of Biologics was created within the FDA. This organization
eventually evolved into the Center for Biologics Evaluation and
Research, which was distinct from the Center for Drug Evaluation
and Research.

21. Inside the FDA by Fran Hawthorne
THE FDA, BIOLOGICAL PRODUCTS, AND
RESEARCH
In science, research can be divided into basic (or pure) research
and applied research. Basic research explores questions about
the fundamental mechanism of what is being studied, without a
specific goal in mind. Applied research, in contrast, focuses on a
practical result. At the FDA, employees engage in a regulatory
form of applied research at both CDER and CBER.
Drugs are becoming more complicated with the advent of genetic
engineering, the decoding of the human genome, and other
biotechnological techniques. As a result, many say it is essential
that the CBER employees maintain their tradition of research.

22. Inside the FDA by Fran Hawthorne
DRUG ADVERTISING
Each year, the pharmaceutical industry spends more than $3
billion on television and magazine ads. In May 1983, the first drug
advertisement on television was broadcast. In response, the FDA
asked pharmaceutical companies to comply with a temporary
moratorium while it decided what actions to take. The FDA issued
a ruling, stating that consumer ads for drugs had to follow similar
rules to those in professional medical journals. They had to list all
the side effects, instructions, conditions, and warnings that were in
the package insert. Alternatively, companies could issue “reminder
ads” that mentioned a drug by name, but did not say what the
product did. In this case, the list of side effects could be omitted in
a television ad.

23. Inside the FDA by Fran Hawthorne
THE FUTURE OF THE FDA
Looking ahead, the FDA faces many new demands
on its resources that could enlarge the agency’s
already expansive mandate:
The cost of medicine. Anything the FDA can do to
move generics to market faster or to certify biologic
generics would create a supply of less expensive
drugs. Approving applications faster will save the
industry time and money which should translate to
lower prices. The FDA may want to incorporate a
cost effectiveness analysis into the approval process.
Consumers’ pursuit of perfection. If humanity-
altering drugs are developed, the FDA may need to
regulate drugs based on cultural values and ethical
issues.

24. Inside the FDA by Fran Hawthorne
THE FUTURE OF THE FDA
Consumers’ lifestyles. The FDA has not traditionally regulated
how people live. However, the Center for Food Safety has
identified obesity as one of its key issues. For some drugs with
dangerous side effects, the FDA already dictates patient behavior
concerning their use with birth control.
Tobacco. The FDA has no authority over tobacco today, but
cigarettes are dangerous to America’s health. If the FDA’s job is to
protect and advance public health, the biggest single step it could
take would be to regulate the product that is the number one cause
of death in the U.S.

25. Inside the FDA by Fran Hawthorne
THE FUTURE OF THE FDA
Fighting terrorism. To spur development of vaccines against
bioterrorist agents, the FDA has eased up on the efficacy
requirement. These vaccines are approved as long as they are
safe in humans and effective in animals. The FDA is also looking
at the food supply for deliberate acts of terror.
As the nature of public health changes over time, it is inevitable
that the FDA’s scope and responsibilities will change as well.

26. Inside the FDA by Fran Hawthorne
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