Overview of How a Drug Is Developed

[Guest guest]

Overview of How a Drug Is Developed

Beth Lorenzi, MPH, Research Associate, CMSC/NARCOMS Project, Yale

Multiple Sclerosis Research Center, Yale University School of Medicine

and VA Connecticut Healthcare System, West Haven, CT

MSQR - V20. N4. Winter 2001

In the USA, development of every new medicine takes an average of 12

years and costs the sponsoring company approximately $350 million. This

extensive and rigorous development process is regulated by the Food and

Drug Administration (FDA) to make sure that new products are safe and

effective.

New drugs begin in the laboratory with scientists, chemists, and

pharmacologists who identify cellular and genetic factors that play a

role in specific diseases. They search for chemical and biological

substances that target these biological markers and are likely to have

druglike effects. Compounds are then identified, which have various

interactions with drug targets that are helpful in treatment of a

particular disease. Often during this stage of development, initial

studies are conducted in animals (in vivo) and in human cells in the test

tube (in vitro) to compare various lead compounds and how they are

metabolized and affect the body. It is estimated that of 5,000 compounds

that undergo pre-clinical testing, only 5 make it to human testing—then

only 1 of these 5 tested in people is approved.

The stages of evaluation of potential new drugs are briefly described

below. Upon satisfactory completion of each stage, the drug sponsor meets

with the FDA to determine pertinent testing criteria to be used in the

next phase of study. Progress reports must be submitted to the FDA

annually throughout the clinical trial phases.

Pre-Clinical Studies

The process of developing a new drug begins with approximately 3 years of

laboratory and animal studies to determine safety and biological

activity; that is, obtaining information about side effects, the amount

of the drug taken up by the tissue being targeted, the amount of the drug

that stays in the body, and the drug’s therapeutic effect.

Investigational New Drug Application (IND)

Following pre-clinical studies, the sponsor asks the FDA for permission

to test the potential new drug in humans. This request involves filing an

IND containing information from the pre-clinical studies, details about

drug content and manufacture, how the drug will work in the body, and any

toxic effects determined in animal studies. This is accompanied by a

proposal detailing how the sponsor plans to study safety and dosage in

people.

Clinical Trials, Phase I: Safety

Phase I of the clinical trial program is to evaluate safety

(determination of acute adverse effects) in humans and establish a safe

dose range for future trials. This phase usually lasts about l year and

involves 20 to 80 healthy volunteers.

Clinical Trials, Phase II: Safety and Efficacy

Phase II studies are done to determine the safety and effectiveness of

the potential new drug on the medical condition for which it is intended

as a therapy. Thus, these are carried out on persons who have the

targeted medical condition. Phase II studies usually involve 100 to 300

individuals at several different medical facilities, for about 2 years.

(If it is thought a potential new drug could be an effective therapy for

more than one medical condition, then a separate Phase II clinical trial

must be conducted for each condition targeted.)

Clinical Trials, Phase III: Controlled Safety and Efficacy

Phase III studies are undertaken to verify safety, dosage, and

effectiveness of the drug in volunteer patients, including monitoring for

rare but significant adverse effects. These very large trials often

involve 1,000 to 3,000 participants at numerous clinics and hospitals,

and can last for 3 to 4 years.

New Drug Application (NDA)

When the sponsor company finishes collecting and analyzing data from the

clinical trials, if the data successfully demonstrate safety and

effectiveness, it submits an NDA to the FDA for marketing approval. This

lengthy application must include all data the sponsor has collected on

the potential new drug. NDAs typically run 100,000 pages or more. The FDA

is supposed to review an NDA in 6 months, but the average time is usually

more than 2 years.

FDA Approval and Phase IV: Post-Approval Monitoring

After the FDA has approved an NDA, physicians can prescribe the new

medicine. The sponsor company must continue to monitor for any adverse

effects and report these to the FDA. In addition, the FDA may require

sponsors to conduct post-approval studies (Phase IV) to evaluate the

long-term effects. FDA regulations governing biopharmaceuticals and drugs

require that manufacturing records be kept for every lot of the product

that is produced; manufacturing facilities are inspected by the FDA every

2 years.

http://www.epva.org/MSQR_Archive/Winter01_6.htm