In the Words of the FDA

[Guest guest]

Strange, isn't it, that these principles don't appear

to apply to breast implants!

Thanks Lana,

Rogene

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Remarks by:

Jane E. Henney, M.D.

Commissioner of Food and Drugs

U.S. Food and Drug Administration

ASSURING SAFETY IN A RISKY WORLD

Kansas State University

March 9, 2000

" This text contains Dr. Henney's prepared remarks. It

should be used with the understanding that some

material may have been added or deleted during actual

delivery. "

Good evening. Thank you for the opportunity to be here

tonight. I appreciate having a chance to return to the

midwest-and be among friends and colleagues. We have

forged a friendship that has lasted for years. We've

sweated through grant getting and celebrated success

as we watched many post docs and graduate students

participate in a multi-center project.

Dr. Terry -- " Wizard " --has done so many things

for this community. Watch him for what is coming. You

had your own Harry Potter before Harry Potter was

cool. Just watch out if he gets a Nimbus 2000 and

starts zooming the skies.

I was asked to share with you some of the challenges

facing the FDA today in the area of product safety. It

is FDA's fundamental responsibility to assure the

safety of the many products it regulates-everything

from drugs for humans; drugs and feed for

animals--those you consume or those that you adore;

biologics such as gene therapy, blood and vaccines;

medical devices from tongue blades to pacemakers; to

foods and food additives; cosmetics, diagnostics; and

some things you may not realize, like microwave ovens

and other radiation-emitting devices. In assuring the

safety of medical products, the agency is always in

the business of weighing their benefits against their

risks. And there are inherent risks associated with

nearly all of the products we regulate.

You probably go about your day-buying and preparing

food, undergoing medical diagnosis and treatment,

filling a drug prescription or checking out the latest

over-the-counter remedy for baldness, trying out a new

shade of lipstick, or using a laser pointer in your

latest lecture. Whether you are aware of it or not,

your day-to-day lack of worry regarding the safety of

products we regulate hopefully reflects confidence

that the FDA is doing its job on your behalf.

Throughout its nearly 100 year history, the FDA has

enjoyed a high level of trust by the American people,

which continues to the present. But trust is a fragile

thing and we do all we can and should to assure that

we have your vote of confidence in the future. For

trust once lost is difficult to regain, as our

counterpart regulatory bodies in Europe have

experienced in recent years.

Our uniquely American way of representative government

has society's expectations--for matters ranging from

national defense to public health and

safety--reflected in law. A regulatory body is then

expected to make these laws operative.

The benefits of a strong regulatory agency such as the

FDA are many. The most important benefits are enjoyed

by patients and consumers who need safe and effective

products. But benefits are also realized from an

economic standpoint, for a high-quality, science-based

regulatory agency attains credibility and respect on a

global scale, stimulating innovation, enhancing U.S.

competitiveness abroad, providing a predictable and

level playing field for industry, and encouraging

increased foreign investment in this country.

What are some of the challenges we face? First and

foremost are the tremendous advancements in science

and technology. Both government and the private sector

have invested enormous resources in biomedical

research and biotechnology. The result of this

investment is, and will continue to be, a wealth of

new products and technologies that will be presented

to the FDA for our review and approval before they are

introduced into the marketplace.

In order to make these judgements, it is essential

that the FDA have the scientific talent to adequately

assess the safety and effectiveness of these novel

products and technologies. Our scientists must be

current in their fields of expertise, quick learners

in new areas, and have the creativity and ability to

collaborate with other scientists in the FDA and

outside the agency. When Wayne Gretzky, of ice hockey

fame, was asked what made him a successful player, he

said, " I skate to where the puck will be. " FDA is in a

similar position. We must be able to anticipate and

access the cutting-edge science that will be needed to

regulate the products of future technology.

Our scientists help to establish standards for product

performance and potency, provide data to support

regulatory decisions on product safety and information

to consumers for the safe use of products, and provide

the basis for science-based regulatory policies. The

safety of vaccines, acceptable levels of mycotoxins

such as fumonisin B1 in corn products, more rapid

methods of detecting pathogens in food, better

understanding of the significance of antibiotic

resistance, are all examples of the products of

research from within FDA laboratories. A high quality

staff and robust regulatory research program are

critical for supporting, in a scientifically sound

fashion, the review and regulatory decisions we make

every day.

The interaction between our researchers and our

regulatory, review and enforcement scientists is

becoming increasingly critical given the rapid pace of

advancements in science and medicine.

Enhancing the agency's science base has been one of my

highest priorities since I became the Commissioner

almost one and a half years ago. We at the FDA

continue to work tirelessly to make this

happen-ensuring that the FDA has the strongest

possible scientific acumen-the most capable scientists

and the most current and reliable scientific

information to support our decisions. Clearly, having

a less than excellent scientific capability at the FDA

is not an option. Our scientific component includes

field investigators, laboratory researchers, reviewers

in all areas of FDA's product responsibilities, and

all other employees involved in scientific and policy

decision-making.

While we must be scientifically sound, consistent, and

predictable in our review of products and issues that

surround product approvals, it is equally vital to

maintaining credibility that our decision-making be

open and transparent to the lay public, health

professionals, the regulated industry, and any party

who depends on the outcome of FDA's decisions. All

should have access and the ability to provide input

and feedback to us.

Let's talk just for a moment about the judgements that

are rendered as we make decisions about which products

are safe and effective and ready to move to the market

place.

Calling a product " safe " does not mean that there is

no risk associated with its use. In reviewing drugs,

biologics, and devices, the FDA spends a considerable

part of the review weighing the benefits of a

particular product against its risks. There is a

continuum of uncertainty that is tolerated, depending

on the seriousness of the illness. For a drug that is

intended to treat a life-threatening illness, and for

which there is no other available treatment, more

uncertainty would be tolerated. As a medical

oncologist, I am well aware that patients faced with

grave diseases are willing to assume great risks.

On the other end of the spectrum, little or no

uncertainty would be tolerated for remedies for

alleviating minor symptoms of the common cold.

I want to assure you that uncertainties about risk do

not prevent us from making decisions. An increasing

number of drugs, biologics, and devices are being

approved every year, many of which are new molecular

entities and represent significant advances over those

that were available previously. The U.S. now leads the

world in terms of timeliness of review of new drugs

and biologics without compromising a very high

standard of safety. The average review time for drugs

is less than 12 months and for drugs for serious and

life-threatening conditions less than 6 months.

Cancer is an area where research is paying off in an

important way. Just this past year, eight drugs were

approved for the diagnosis or treatment of several

types of cancer, including early stage breast cancer,

relapsed anaplastic astrocytoma, and non-small lung

cancer that does not respond to cisplatin-based

chemotherapy. The FDA also approved a new biologic for

treatment of patients with advanced or recurrent

cutaneous T-cell lymphoma, and a new drug-device

combination for the treatment of certain precancerous

skin lesions.

We approved many treatments for non-cancerous

diseases, too, including treatment for HIV infections

in children and adults, a new drug for epilepsy, a

plasma-derived biologic for von Willebrand's disease-a

bleeding disorder, and an antibacterial drug to treat

infections associated with vancomycin-resistant

Enterococcus aecium. Also on our list of approvals

this past year is an immunosuppressant drug to prevent

acute organ rejection in patients receiving kidney

transplants, a new treatment for osteoarthritis,

menstrual pain, and other acute pain in adults, and a

new lipase inhibitor to treat obesity.

Other approvals include a variety of diagnostic test

kits, drugs for the flu, new products for managing

diabetes, new technologies for breast cancer

screening, new cardiac devices for treating aortic

aneurysms in the abdomen without major abdominal

surgery, and for removing blood clots from cardiac

arteries or bypass grafts prior to angioplasty.

New ophthalmic devices have also been approved in the

past year-implants to correct mild nearsightedness,

and an eye laser for correcting myopia in adults.

Every one of these newly approved products underwent

an extensive evaluation of its safety and

effectiveness, and the risks associated with its use.

But at the time of the review it is not feasible,

indeed, possible, for the agency to identify every

potential risk associated with the use-and abuse-of a

medical product. A key question is how extensively

drugs should be studied to uncover adverse reactions

before approval of a product. It should be obvious

that there is less certainty with a study of 500

people than one with 5,000 or 50,000 people. Still,

there are risks that we don't discover during clinical

trials because some adverse events are very rare or

may be only associated with a subset of the population

that is unusually sensitive compared to everyone else.

Determining the risk in a population does not

necessarily predict the risk for the next individual.

And from a practical standpoint, having to include

150,000 human subjects in a study would often be a

major obstacle to getting drugs on the market in a

timely fashion, especially for rare diseases.

A less obvious reason that risks unseen in clinical

trials appear when the drugs are used in the real

world is that in clinical trials, the drugs are only

studied for the condition for which the drug was

developed, and with all other factors carefully

controlled. Once the drug is on the market, it may be

prescribed for a condition other than that for which

it was approved, may be given using a different dosing

regimen, or it may be used in conjunction with a

variety of other drugs, foods or dietary supplements

that could interact with the drug. And the product

will be used in numbers of people much greater than

were used in the clinical trials, potentially

uncovering side effects not previously seen.

These factors must all be taken into account as we

work with sponsors of new products to make sure they

are safe and effective, and available to patients in a

timely manner...yet be alert to new findings after a

product is on the market.

The FDA monitors the adverse reactions of drugs for

both predictable and unexpected side effects. This

requires effort on the part of scientists and medical

officers in FDA; physicians and other healthcare

professionals in the community; drug manufacturers;

and the patients themselves to report any side

effects, particularly previously unknown side effects

associated with the use of a product.

The recent report from the Institute of Medicine

entitled " To Err is Human " has brought renewed

attention to the issue of risk management by all of us

in the health care delivery system. This IOM report

indicates that medical mistakes are responsible for

the deaths of about 98,000 people every year.

An important point made in the IOM report is that the

majority of injuries and deaths in the U.S. that are

attributable to medical products are from known side

effects, and not from unexpected ones.

The findings of this study confirmed what the FDA said

in its earlier report issued last May, " Managing the

Risks from Medical Product Use: Creating a Risk

Management Framework " .

Since most medical products have some inherent risks

associated with their use, some greater than others,

as these products enter or are in the market place it

remains our responsibility to identify the risks, and

communicate that information effectively to

physicians, nurses, pharmacists, patients, consumers,

and anyone else who may be affected by those risks or

their management. Risks involving specific

subpopulations of people, for example, children or

pregnant women, must be clearly conveyed.

FDA cannot and should not do this work along. The

entire health care delivery system must have adequate

safeguards in place. This begins with the development,

manufacture, and approval of a product, and continues

with physician prescribing practices, pharmacy

dispensing, and proper administration of the product

to patients in a hospital setting, or at home by the

patients themselves.

Communication, feedback and correction-throughout the

entire system--about the benefits and risks of a drug

or other product for a particular use, is critical to

the health care system's effort to reduce the

incidence of medical errors. Communication, feedback

and correction needs to take place between drug

companies and physicians, between physicians and

patients, between pharmacists and patients, on the

product label and package insert, and in any

advertisements promoting a particular product.

The agency is now committing considerably more

resources to post-market surveillance of FDA-regulated

products than it ever has in the past. Doctors,

pharmacists, and patients can report serious adverse

events to the FDA through our MEDWATCH system, or they

can report effects to the manufacturer who, in turn,

must report the incidents to the FDA. The agency

frequently sends " Dear Health Professional " letters to

inform doctors, pharmacists, and others of new safety

issues. Sometimes the new information warrants a

change in the product's labeling, or more rarely, the

product's withdrawal from the market.

In other words, products must be developed, tested,

manufactured, labeled, prescribed, dispensed, and used

in a way that maximizes benefit and minimizes risk.

Managing risks also extends to venues that never

existed before. We now have an issue of enormous

promise, but also substantial concern-the Internet. In

the health care area alone, the explosion of products

and services available to consumers with a few clicks

of a mouse and a credit card number is truly

mind-boggling.

The Internet presents unique challenges to state

license boards, health professional organizations, and

state and Federal law enforcement agencies.

The sale of drugs and other medical products over the

Internet is growing at an astonishing rate. Online

prescription drug sales by reputable pharmacists is

one area with clear benefits to consumers. Patients

can order new and refills of prescriptions, and obtain

information on how to use a medication properly, 24

hours a day. This is a real boon for those patients

who live in rural areas, those who are clearly

disabled or for whatever reason have found that a trip

to the corner drug store is not easy. This

convenience, access and privacy are very strong and

important attributes of this means of transaction.

But, not all Internet purveyors of medical products

and advice are as scrupulous as the reputable

pharmacist in your corner drug store, for the Internet

purchase can bypass all of the public health

safeguards set in place for you, the consumer.

This detour around the standard safeguards creates an

enormous potential for increased side effects, drug

interactions, exposure to impure or unknown

ingredients in unapproved drugs, and drugs that are

simply not efficacious.

It is not unusual to see web sites that offer drug

prescriptions on the basis of a questionnaire alone.

Lost are the doctor-patient interaction, the history

of the patient, and the physical examination, an

accurate diagnosis, and the joint decision-making

process to determine the best treatment for a

particular individual. Inherent in this is the risk

that a person will unknowingly buy a product that is

inappropriate for the condition, or is actually

contraindicated for that person because of a

misdiagnosis or an underlying condition. Hence, the

risk increases for serious side effects, drug

interactions, and failure to treat the disease.

The sale of illegal prescription drugs is not a new

phenomenon in this country by any means.

Unfortunately, though, the Internet offers an

alarmingly efficient medium for these illegal

practices.

What is the FDA doing about this problem?

First, we have expanded our public education efforts

to warn consumers about dangerous practices involving

Internet sales of drugs that are not FDA-approved, or

sites that offer prescription drugs with little or no

involvement or interaction with a health care

professional. It is critical that we get this message

out so that consumers become more " internet-savvy " and

less likely to be taken in by erroneous health

information-better able to evaluate the credibility of

the source, and learn to spot illegal or unethical

drug sales practices. Our FDA Home Page is an

important resource for the public to gain information

about online drug sales. [buying Medical Products

Online--Shop Smart!]

We are expanding our enforcement activities against

illegal online sales of drugs through collaboration

with other interested parties. We have developed

partnerships with the State Boards of Pharmacy, Boards

of Health, and State Attorneys General in order to

take swift action against the illegal sales of

prescription drugs in the U.S. The Attorneys General

in both Kansas and Missouri have been very active in

this area. But as you may know, state jurisdictions

end at the state line, opening up the opportunity for

illegal practices to be carried on across state lines.

So when the pharmacy is in one state, the pharmacist

in another, the doctor in a third, and the patient in

the fourth, a Federal presence, whose jurisdiction can

span these boundaries, can stop this illegal activity

wherever it occurs.

We are optimistic that with this dual approach of

using educational and enforcement tools, you will be

better protected from some of the dangers associated

with online prescription drug sales.

Let's leave the medical area for a moment and talk

about risk in the edible world. The FDA is also

responsible for ensuring that foods for humans and

animals are safe and truthfully labeled. In the case

of food additives, safety means that there is a

reasonable certainty, in the minds of competent

scientists, that the substance is not harmful under

the intended conditions of use. Our current laws

prohibit the use of food additives that are

carcinogenic in animals or humans.

Testing every chemical that may contact foods, for

example, in food wrap substances, for its potential to

cause cancer in humans or animals would be

prohibitive. Instead, risk assessment principles are

used to determine if animal carcinogenesis tests are

needed. For example, using a procedure known as the

" threshold of regulation " , a chemical whose use in

food contact articles results in a dietary

concentration of one half part per billion or less

would be exempt from the process for a food additive

petition approval. Under another procedure known as

the " constituents policy " , a carcinogenic contaminant

of a non-carcinogenic food additive is permitted if

the lifetime cancer risk is negligible.

Thus, the rule of " reasonable certainty of no harm "

assures the safety of food without unreasonably

restricting the use of chemical substances that may

contribute to the safety of foods.

The presence of microbiological organisms such as

Salmonella or E. coli 0157H7 in food has received

considerable attention in recent years. The FDA has a

major effort under way, working jointly with other

federal and state agencies, to improve our ability to

detect food-borne illnesses rapidly, and to track

contaminated foods to the source as fast as possible

to prevent further illness. The process for

determining safety and risk for chemical contaminants

also applies to microorganisms in products.

Considerable research is being done to determine the

concentration of pathogens in food or other products

that represents risk of infection to the consumer.

Finally, I would like to say a few words about dietary

supplements. The dietary supplement industry is

booming, and while there are likely benefits from some

of these products, the potential for exaggerated

claims, unpredictable composition, and toxicity are of

considerable concern to the agency. There is also a

real and growing concern about interactions between

dietary supplements and medications.

Dietary supplements represent just one more area where

the strongest possible science must be brought to bear

on our decisions.

I would like to conclude with a few final thoughts

about the importance of strengthening FDA science for

a safe and healthy world. It is important to keep the

agency's mission uppermost in our minds-allowing

consumers to have confidence in the safety, quality,

and effectiveness of the FDA-regulated products they

buy and use. It is our responsibility to safeguard the

health of Americans, recognizing that in today's

marketplace, a decision by the FDA truly has global

implications.

For each of the issues that I've mentioned tonight

that relate to product safety and risk

considerations-food, safe use of medical products,

predictiveness of clinical trials, the sale of drugs

over the Internet, dietary supplements and others that

I simply did not have time to cover--each represents

its own challenge but all must have the best science

brought to bear for decision-making.

We will do our best so that all of you can feel safe

in a risky world.

Thank you for the opportunity to speak to you tonight.

(Hypertext created by mn 2000-MAY-25)