The FDA Drug Approval Process

Introduction

Q6.1 The US Food and Drug Administration (FDA) is the federal agency charged with regulating all of our foods, human and veterinary drugs, medical devices, biologics, and cosmetics. Although the general public assumes that physicians know a great deal about the FDA, in fact physicians actually receive little education about the FDA in medical school, residency, or other postgraduate training. This may be partly because most FDA activities deal largely with legal issues or social policy. However, science and medical research information is fundamental to carrying out the FDA’s missions, and the agency’s policies have a tremendous impact on public health and on the practice of medicine. The FDA regulatory jurisdiction (direct and indirect control) is estimated to encompass an enormous 20 cents of every dollar Americans spend on products, or 2 cents per day for every American. The FDA is part of the Health and Human Services Department, which is in the executive branch of the federal government. Thus, the FDA Commissioner is appointed by the President, with advice from and the consent of Congress. Q6.2 Until the 1992 imposition of ‘user fees,’ the FDA budget for the drug approval process was almost totally derived from Congress, which also has oversight responsibility for the FDA. The FDA now spends about US$1.4 billion on approving, labeling, and monitoring drugs, with more than 4000 people throughout the agency involved in this process. This amount compares favorably with the US$47 million spent in 1992, before the prescription drug user fees were instituted. In addition to user fees for prescription drugs, FDA now collects user fees for regulation of medical devices, animal drugs, animal generic drugs, and biosimilars. Overall, the FDA budget for the 2017 fiscal year was US$5.1 billion (over half, US$2.7 billion, coming from user fees) with approximately 17,000 employees. Clearly the FDA budget is too small, with too few employees to actively make or supervise all of the decisions affecting 20% of the US product spending. The system therefore depends on a great deal of voluntary self-regulation from the pharmaceutical industry and other regulated industries. This chapter focuses primarily on the approval process for prescription drugs, although much of the information is also applicable to biologics and devices.

Federal Legislation for Drug Safety and Efficacy

Phase I to IV Testing

For every 5000 pharmaceutical compounds evaluated or screened, five reach the stage of clinical trials, and only about one of these five actually reaches the market after FDA approval (see Table 6.2 ). Of those compounds reaching clinical trials, 70% pass phase I, 33% pass phase II, 33% pass phase III, and 25% to 30% receive an approved New Drug Application (NDA). The sponsors conduct and pay for those studies needed to prove safety and efficacy. The FDA evaluates and judges the test results, but rarely does drug testing. However, the FDA is involved in the sponsor’s test plans, especially those concerning human testing. As potential new drugs have not been proved safe and effective, they may not be given as therapy. The sponsor may give the investigational drug to patients for evaluation (testing) only after submitting an Investigative New Drug (IND) exemption.