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Inside FDA:
The Center for Drug Evaluation and Research

This is one in a series of articles on FDA activities and concerns.

The Food and Drug Administration's approval of the new AIDS drug Crixivan (indinavir) in just 42 days made news nationwide. While the evaluation of new drugs is the best known responsibility of the agency's Center for Drug Evaluation and Research (CDER), the center also promotes the public health by regulating the manufacture, labeling and advertising of drug products.

CDER is the largest of FDA's five centers, with a staff of about 1,800. It has responsibility for both prescription and over-the-counter drugs. Other centers have responsibility for medical and radiological devices, food, cosmetics, biologics, and veterinary drugs.

High-Quality Reviews

The center's job is to ensure that drugs are safe and effective. (See "Benefit Vs. Risk: How FDA Approves New Drugs" in the December 1987-January 1988 FDA Consumer.) CDER doesn't test drugs, although the center's Office of Testing and Research does conduct limited research in the areas of drug quality, safety and effectiveness.

It is the responsibility of the company seeking to market a drug to test it and submit evidence that it's safe and effective. (See "Testing Drugs in People" in the July-August 1994 FDA Consumer.) A team of CDER physicians, statisticians, chemists, pharmacologists, and other scientists reviews the sponsor's new drug application (NDA) containing the data and proposed labeling.

The 13 NDA reviewing divisions in CDER are grouped into five Offices of Drug Evaluation. Each office oversees drugs for certain medical conditions. The Office of Drug Evaluation I, for example, is responsible for neuropharmacological (relating to the nervous system), oncologic (involving tumors), and cardiorenal (relating to the heart or kidneys) drug products. Over-the-counter drugs are reviewed by the Office of Drug Evaluation V. The review divisions work side by side with reviewers in the Office of New Drug Chemistry, the Office of Clinical Pharmacology and Biopharmaceutics, and the Office of Epidemiology and Biostatistics to evaluate a drug's safety and effectiveness. In some cases, FDA seeks the recommendations of advisory committees made up of outside experts. (See "Getting Outside Advice for 'Close Calls'" in the December 1987-January 1988 FDA Consumer.)

Murray M. Lumpkin, M.D., CDER's deputy director for review management, is in charge of the review process (except for the review of generic drugs) and the 900 reviewers who make up about half the center's work force. A good drug review process must be predictable and thorough, according to Lumpkin. Predictability means timeliness, he says. "It used to be that people would ask, 'Do you want it right, or do you want it on time?' To get it right, reviewers often had to ignore the clock."

To get reviews done both right and on time, FDA needed additional financial resources. To meet this need, Congress passed the Prescription Drug User Fee Act of 1992, which requires drug companies to pay fees when submitting NDAs to the agency and in some other instances provides FDA funds to hire more reviewers. (See "User Fees to Fund Faster Reviews" in the October 1993 FDA Consumer.)

Consumers, Congress, and government and industry experts agreed on time frames for FDA's completion of reviews of drug applications covered by user fees. CDER's top priority, according to center director Janet Woodcock, M.D., is to exceed these user fee time frames while maintaining the high quality of reviews. (See "The CDER Director.") In 1994, CDER reviewed 96 percent of new drug applications within the 12-month performance goals, far surpassing the agency's 1994 goal of 55 percent.

User fees do not apply to generic copies of brand-name drugs because generics involve the review of different kinds of data. Once CDER approves a brand-name drug and any patent for that drug expires, CDER's Office of Generic Drugs can approve another product as a generic copy if it's shown to be equivalent to the brand-name drug. (See "FDA Ensures Equivalence of Generic Drugs" in the September 1992 FDA Consumer.)

To achieve consistency in approval decisions, all reviewers receive in-depth training. A guidance called "Good Review Practices" is being developed by a number of FDA staff members under the leadership of Robert Temple, M.D., CDER's associate director for medical policy and director of the Office of Drug Evaluation I. This guidance will establish the proper methods of performing medical and statistical reviews. And to improve the coordination among all CDER offices, a new manual of policies and procedures is being developed under the leadership of Jane Axelrad, J.D., the center's associate director for policy. The manual will improve the center's efficiency by documenting all CDER processes in one organized location so they're accessible to FDA personnel and to the public.

To achieve consistency on a larger scale, the International Conference on Harmonization is bringing together pharmaceutical industry representatives and the drug regulating agencies of the European Union, Japan, and the United States to establish common procedures to speed up the availability of new medicines worldwide. Roger Williams, M.D., CDER's deputy director for pharmaceutical science, is the lead CDER representative. "I think there will be a big payoff," he says, "in terms of avoidance of duplication and resource savings to industry."

Postmarketing Responsibilities

Despite efficient, high-quality reviews, the public health cannot be safeguarded without procedures to monitor the quality of drugs once they are marketed. CDER's Office of Compliance, directed by Stephanie Gray, M.P.H., has a many-sided role in protecting the public health. In addition to monitoring preapproval research and working side by side with field investigators to inspect manufacturing plants, the office implements programs to make sure that manufacturers comply with the laws and regulations enforced by FDA. The Office of Compliance sees to it that drug manufacturers operate under current good manufacturing practices as spelled out in FDA's regulations.

Betty Jones is the deputy director of the office. "CDER is made up mostly of scientific and medical experts," she says. "Without the Office of Compliance, the agency wouldn't have the capability to deal with firms or individuals that violate the law." The office's tools for dealing with violations include recalls, warning letters, injunctions, seizures, and criminal prosecutions.

It's also important that patients have accurate and complete information. While advertising of OTC drugs is regulated by the Federal Trade Commission, FDA oversees advertising of prescription drugs. CDER's division of drug marketing, advertising, and communications monitors prescription drug advertising to ensure that it contains a truthful summary of information about effectiveness, side effects, and circumstances when use is not advisable.

Despite CDER's vigilant premarket review, active postmarketing surveillance of drug adverse effects is also essential. Because all possible side effects of a drug can't be anticipated based on preapproval studies involving only several hundred to several thousand patients, FDA has a system called medwatch through which health professionals and consumers can report serious adverse reactions. (See "MedWatch: On Lookout for Medical Product Problems" in the November 1993 FDA Consumer.) CDER's Office of Epidemiology and Biostatistics collects information from medwatch and the pharmaceutical industry and conducts statistical evaluations on drug usage, adverse reactions, poisonings, safety, and effectiveness. When necessary, information can be passed on to patients and medical professionals.

The consumer's well-being will always remain FDA's most important concern. CDER's new Office of Training and Communications (OTCOM), directed by Lucy Rose, was established to enhance communications with the public and within the center. In cooperation with other offices, it educates the public on CDER and FDA policies and activities and prepares responses to drug-related questions. For CDER information, contact:

Drug Information Branch (HFD-210)
Division of Communications Management/OTCOM
FDA/Center for Drug Evaluation and Research
5600 Fishers Lane
Rockville, MD 20857
(301) 594-1012
Fax: (301) 594-3302
E-mail:dib@cder.fda.gov

Tamar Nordenberg is a staff writer for FDA Consumer.

The CDER Director

Before becoming director of CDER, she worked in FDA's Center for Biologics Evaluation and Research (CBER). As director of CBER's Office of Therapeutics Research and Review, Woodcock oversaw the review and approval of the first biotechnology-based treatments for multiple sclerosis and cystic fibrosis. Before that, she spent four years with CBER's division of biological investigational new drugs, as group leader for vaccines and allergenics and as director of the division.

Woodcock strives for efficient regulation. "The time of major backlogs is over; it's unacceptable to perform that way," she says. Her reorganization of CDER was a first step toward better performance. One of the most significant structural changes--establishing 13 reviewing divisions where nine existed before--is expected to speed up CDER's work by authorizing additional managers to sign off on drug reviews.