A Short History

FDA Regulations and U.S. Drug Law

The present system of FDA regulation has evolved over the course of this century. Before 1906, there were no laws guaranteeing the quality of medicines and no regulations requiring a doctor's prescription for medications. So-called "patent" medicines, many containing dangerous ingredients, were advertised with outlandish health claims and widely marketed in the United States.

By the turn of the century, it was apparent that some form of regulation was necessary. The following major developments in U.S. drug laws and FDA regulations demonstrate how the federal power to regulate drugs, which began as a simple effort to identify fraudulent medicine, has evolved into a complex system dedicated to ensuring the health and safety of the public. They also suggest how the government has tried to balance public safety with the desire to widen access to promising drugs for life-threatening illnesses.

• Food and Drugs Act (1906): This law targeted false and fraudulent "patent" medicines and required that drugs meet standards of strength and purity. A few years later, this act was extended to cover not only a ban on false or misleading labeling pertaining to ingredients, but also to claims of effectiveness. The 1906 act lacked "teeth"—it was difficult to enforce and was very narrowly applied.
  
  
• Federal Food, Drug, and Cosmetic Act (1938): It was not until 1937, when 107 people died from a poison in the patent medicine marketed as "Elixir Sulfanilamide," that Congress passed a more stringent drug law. The so-called FDC Act required manufacturers to prove the safety of drugs, authorized factory inspections, and established penalties for fraudulent claims and misleading labels.
  
  
• Durham-Humphrey Amendment (1951): This was the first federal law requiring a physician’s prescription for drugs "unsafe for self-medication."
  
  
• Kefauver-Harris Drug Amendments (1962): In Western Europe, thousands of babies were born with birth defects because their mothers had taken the sedative thalidomide during pregnancy. A delayed review process prevented the drug from being marketed in the United States, where it was being studied in a large number of subjects.
  
  

  In response to this tragedy, the Kefauver-Harris amendment mandated that manufacturers prove their drugs were effective for specific medical purposes, as well as safe, through "adequate and well-controlled" studies. This law applied retroactively to all drugs introduced since the 1938 FDC Act. Firms were also required to report all adverse reactions to the FDA and to include complete information (about adverse effects as well as benefits) for physicians in advertisements. For the first time, informed consent was required from patients participating in studies of a new drug.
  
  

  • See the A Guide to Understanding Informed Consent for more information about the informed consent process.
    
  
  
  
• Orphan Drug Act (1983): Orphan drugs are intended to treat rare diseases and conditions for which adequate drugs have not yet been developed. In the past, manufacturers had been reluctant to produce such drugs: the complex process of research and marketing a drug for only a small group of potential users may bring little or no profit. This law provided manufacturers with tax benefits for portions of their research and development costs. Furthermore, if a company developed an orphan drug, it was granted exclusive marketing rights for seven years.
  
  
• Drug Price Competition and Patent Term Restoration Act (1984): This law made generics, often sold at lower prices than brand-name drugs, more easily available. It also allowed drug manufacturers to "restore" part of the time spent researching drugs before approval to the patent life of the drug.
  
  
• Revision of Regulations for New Drug Application Regulations (1985): Changes in requirements for manufacturers called for better organized applications, clearer data, more information on adverse reactions, quicker problem-solving, and in some instances provided for approval based on foreign studies.
  
  
• Treatment Use of Investigational Drugs (1987): New regulations allowed "expanded access" protocols for promising investigational drugs. In less-restricted studies, researchers could learn more about the drug while also providing treatment for people with no effective alternative. These regulations still required researchers to formally investigate the drugs in well-controlled studies and provide reasonable evidence of effectiveness.
  
  
• Accelerated Approval (1987): Before this rule, drugs could be judged only according to their effect on the illness or patients’ length of survival. This regulation allowed the FDA to approve drugs based on a reasonable "surrogate endpoint" -- that is, an effect of the drug on some physiological process associated with the disease (an example would be CD4 cell counts, which measure the strength of the immune system).
  
  

  The "surrogate" is used to predict whether a new drug will offer therapeutic benefit. The regulation offered a way of making an apparently promising drug available without having to wait until the end of the clinical trials process. Under these rules, the FDA approves the drug only on the condition that the sponsor confirm actual clinical benefit through well-controlled studies.
  
  

• Procedures for Subpart E Drugs (1988): These procedures were designed to encourage early cooperation among manufacturers, clinical researchers, and the FDA to get new drugs to patients with life-threatening or severely debilitating illnesses as quickly as possible. For example, manufacturers may request to meet with the FDA early in the drug development process to reach agreement on the design of preclinical and clinical studies. Similar meetings may also be called after phase I testing to discuss how to design phase II clinical trials, with the goal that the data from phase II trials will provide sufficient data on the drug's safety and effectiveness for a decision about approval of the drug.
  
  
• Parallel Track Mechanism (1992): This U.S. Public Health Service policy made promising investigational drugs for AIDS and other HIV-related diseases more widely available under "parallel track" protocols at the same time that controlled clinical trials continued. The system is designed to make the drugs available to patients who have no therapeutic alternatives and cannot participate in the controlled clinical trials.
  
  
• Generic Drug Enforcement Act (1992): This law imposed disbarment and criminal convictions for fraudulent and illegal activities in new drug applications for generic drugs.
  
  
• Prescription Drug User Fee Act (1992): Manufacturers were now required to pay fees for certain new drug applications. The funds generated have been used to add review staff at the FDA to accelerate new drug reviews. Review times for new drug applications were set at 12 months for standard applications and at six months for priority applications; in other words, the FDA had to take action on the application within that time frame. The order in which applications are looked at is determined with the aid of a classification system, which gives priority to drugs with the greatest potential benefit.
  
  

  For example, all AIDS drugs receive the highest priority, and all drugs that offer a significant medical advance over existing therapies for any disease are considered "priority drugs." The breast cancer drug Herceptin, approved in September 1998, was assigned to priority review.
  
  

• Food and Drug Administration Modernization Act (1997): Extended the User Fee Act another five years and lowered the review times for standard new drug applications to 10 months.