Ординатура / Офтальмология / Английские материалы / Ophthalmic Medications and Pharmacology_Duvall, Kershner_2006

Appendix C

The Drug

Approval Process

The Drug Approval Process 125

How do drugs get through the regulatory process of the FDA? A complete description of this complicated, expensive, and time-consuming process is beyond the scope of this book; however, there are some general guidelines that can make sense of this sometimes bewildering and confusing process.

The FDA was established by the United States Congress to protect the health and welfare of the American public from the introduction of unproven or potentially dangerous drugs. The process of drug approval starts with an application to the FDA, usually from a drug developer or pharmaceutical manufacturing company. The overall process from application to drug approval generally takes 7 to 12 years and can cost the drug manufacturer hundreds of millions of dollars beyond the development costs of the drug. The company is obligated to obtain the clinical data necessary to prove efficacy, demonstrate safety, and discover any potential side effects or dangers. It begins with a clinical trial that has 4 phases (I-IV).

Clinical trials represent a pre-market testing ground for unapproved drugs. During these trials, a drug that is about to undergo investigation is administered to humans and is evaluated for its safety and effectiveness in treating, preventing, or diagnosing a specific disease or condition. The results of these trials will comprise the single most important factor in the approval or disapproval of a new drug, according to the FDA.

The FDA Center for Drug Evaluation and Research (CDER) is the branch of the FDA responsible for evaluating these studies. CDER is responsible for both prescription and OTC drugs and is the largest of the FDA's 5 centers, with a staff of about 1,800 people.

The goal of clinical trials is to maintain safety and effectiveness in data collection, the most important consideration being the safety of the patients involved in these trials. The clinical trials are strictly monitored for their design and conduct to ensure the safety of the individuals that participate and that they are not exposed to unnecessary risks. The process advances according to the following:

Investigational New Drug Application

A drug sponsor submits an investigational new drug application (IND) to the FDA. Drug companies, research institutions, and others in the drug development business must provide results of preclinical testing in laboratory animals and the studies in which they plan to conduct human testing. The FDA will then decide whether the company may move forward with testing the drug on humans.

Clinical Trials

After approval of the IND by the FDA, the study sponsors must approach the local institutional review board (IRB) at the institution in which the proposed studies will be conducted. This institution is usually a hospital, medical center, or academic environment. The IRB is a group of doctors, nurses, and nonmedical people (clergy, lawyers, administrators) who oversee clinical research within that institution.

The IRB approves the clinical trial protocols, which describe the type(s) of people who may participate in the clinical trial, the schedule of tests and procedures, the medications and dosages to be studied, the length of the study, and the study's objectives. The IRB makes sure the study is

126 Appendix C

acceptable to the institution, that participants have given consent and are fully informed of their risks, and that researchers take appropriate steps to protect patients from harm.

Phase 1 studies are usually conducted on healthy volunteers. This part of the study's goal is to determine the drug's most frequent side effects and how the drug is metabolized and excreted. The number of subjects typically ranges from 20 to 80. Safety is the end determinant of this phase.

Phase 2 studies begin if Phase 1 studies do not reveal unacceptable toxicity. While the emphasis in Phase 1 is on safety, the emphasis in Phase 2 is effectiveness. This phase determines whether the drug works in people who have a certain disease or condition. For controlled trials, patients receiving the drug are compared with similar patients receiving a different treatment—usually a placebo or a different drug. Typically, the number of subjects in Phase 2 studies ranges from a few dozen to about 300. Safety continues to be evaluated, and short-term side effects are studied.

Phase 3 studies begin if evidence of effectiveness is shown in Phase 2. These studies gather more information about safety and effectiveness, studying different populations and different dosages and using the drug in combination with other drugs. The number of subjects usually ranges from several hundred to about 3,000 people. At this stage, a drug manufacturer can make a new drug application to gain approval for marketing the drug.

Phase 4 studies occur after a drug is approved. These studies look at novel uses of the drug (other indications) or other populations. The long-term effects and how participants respond to different dosages are determined. Many times, a manufacturer can then apply for labeling, for other possible indications for the medication, or report to the FDA any unforeseen side-effects that were not determined in the initial clinical trials.

New Drug Application

This is the formal step required by a drug sponsor to have the FDA approve a new drug for marketing in the United States. A new drug application (NDA) includes all animal and human data on the drug as well as information about how the drug works, how a patient is administered the medication, and how the company will be manufacturing the compounds in the drug.

Bibliography

Drug applications. Center for Drug Evaluation and Research. Available at: http://www.fda.gov/cder/about/ smallbiz/clinical_investigator.htm. Accessed: May 21, 2005.

Index