Drixoral

The U.S. Food and Drug Administration (FDA) regulates over-the-counter (OTC) drugs, and prescription and generic drugs. As Americans continue to participate more actively in their own health care decisions, many of the medications they purchase will be OTC drugs. Contributing to this trend is the expanding availability of OTC drugs reclassified from prescription status. This availability offers consumers greater medication choices. OTC drugs carry indications for conditions that are generally self-limited or that can be recognized and successfully treated by lay consumers. They are drugs generally regarded as safe for the consumer to use by simply following the required label directions and warnings.

Prescription Drug Categories

The 1951 Durham-Humphrey amendments to the Federal Food, Drug and Cosmetic Act defined in law three categories of drugs limited to prescription sale: certain habit-forming drugs listed by name (i.e., barbiturates, chloral, cocaine, codeine, morphine, paraldehyde); drugs not safe for use except under the supervision of a licensed practitioner, and drugs limited to prescription under the status of a new drug application (NDA). The definition of a licensed practitioner is left up to the states.

These statutory definitions, along with the basic statutory language requiring adequate directions for use, are still the principal criteria for determining prescription versus OTC drug classification. The assessment of the overall margin of safety includes not only the considerations described in the statute (toxicity, potential for harmful effects, method of use and collateral measures necessary to use), but also the potential for abuse and misuse, and the benefit-to-risk ratio.

Labeling Critical to Success of OTC Products

Many drugs used to treat serious disease conditions may cause adverse effects. These drugs must be used carefully to achieve the appropriate level of effectiveness without endangering the patient's safety. They are therefore considered too toxic to be used for self-treatment and will continue to be classified as prescription drugs. However, because any drug can be misused with some toxic result, the possibility that a drug can be misused is not the sole basis for prescription classification. Because all drugs have both benefits and risks, some degree of risk must be tolerated for patients to receive the benefits. For example, antihistamine drugs may cause drowsiness. However, consumers can be informed of the risks through adequate directions in the product labeling.

Since 1952, hydrocortisone had been marketed in the United States as a prescription drug. In December 1979, an FDA OTC Advisory Review panel recommended to the agency that hydrocortisone could be considered safe and effective for OTC use at concentrations of 0.25 to 0.5 percent. Based on the panel's recommendations, the agency allowed OTC marketing of hydrocortisone.

Interest in the process of switching drugs to OTC status has been heightened not only by the OTC drug review process, but also by the fact that many drugs are available for OTC use worldwide that are currently marketed only by prescription in this country.

Currently, more than 100,000 OTC products are on the market. However, fewer than 1,000 active ingredients are used in all OTC products. Most of those ingredients were on the U.S. market before 1972, when the FDA initiated its review of the existing OTC market as part of the mandate of the 1962 amendments to the Federal Food, Drug and Cosmetic Act.

Because so many OTC drug products are marketed, the FDA is reviewing the active ingredients and labeling of more than 80 therapeutic classes of drugs, instead of individual drug products. For each category, the goal is to establish "OTC drug monographs" that identify active ingredients generally recognized as safe and effective for specified uses that may be marketed in OTC drug products. The monographs also specify doses, formulations and consumer labeling for "older" active ingredients. This drug review ensures an ingredient's safety and effectiveness, and helps consumers understand how to best use these products. The monographs are published in three phases: proposed, tentative-final and final.

After a final monograph is published, existing OTC drug products must be removed from the market if they contain any active ingredient or labeling claim that is not recognized as safe and effective. Some products can be reformulated or appropriately relabeled. New products that conform to a final monograph may be marketed without further FDA clearance, while those that do not conform to a final monograph must undergo separate review under an NDA. A manufacturer may also petition to amend a final monograph to include additional ingredients or to modify labeling. However, the firm may neither market the drug nor use the labeling claim until the NDA is approved or the final monograph is amended. At this time, all monographs have been published, at least in proposed form. The FDA expects to complete the OTC review by publishing final rules within the next few years.

The FDA reviews NDAs for both initial OTC marketing and prescription to OTC switches. The agency defines initial OTC marketing to be the OTC marketing of a product containing an ingredient not previously marketed under prescription-only regulations or the OTC marketing of a product that differs from the approved prescription product in strength, dose, population, indication, dosage form, route of administration or duration of use.

The FDA review team consists of medical specialists plus experts in project management, pharmacology and toxicology, chemistry, biometrics, biopharmaceutics, microbiology, promotion and epidemiology. Team members come from five separate areas within the FDA's Center for Drug Evaluation and Research: the medical review division responsible for drugs of the relevant therapeutic category; the Division of OTC Drug Products; the Office of Epidemiology and Biometrics; the Division of Drug, Marketing, Advertising and Communications, and the Office of New Drug Chemistry.

Requirements for OTC Approval

Approval of a drug for OTC use requires an acceptable safety margin, a low potential for misuse and abuse, the ability of an average consumer to self-diagnose, self-recognize and self-treat the condition, and labeling adequate to be understood by the lay consumer. There must have been sufficient marketing experience with the drug to characterize serious toxicities, special toxicities of the particular class, the margin of safety, and both observed and potential drug interactions. Safety information can come from the clinical trials done for the original prescription approval, from post-marketing studies of the prescription product, from new clinical trials and from other sources, such as the literature, the FDA Spontaneous Reporting System database and foreign marketing, both prescription and OTC.

In 1991, the FDA announced the establishment of the Nonprescription Drug Advisory Committee. The purpose of the FDA advisory committees is to provide independent, expert, scientific advice to the agency. The Nonprescription Drug Advisory Committee and the recently established Generic Drug Advisory Committee are unique among the Agency's drug advisory committees in that they are the only two advisory committees to cut across therapeutic categories. The Nonprescription Drug panel has a core of 10 members, including physicians, pharmacists and nurses--both researchers and clinicians--with experience in the use of OTC products.

The core members are supplemented by specialists from the long-established therapeutic category committee appropriate to the product under consideration. For example, if a topical preparation were being considered, several dermatologists could be included. The committee also includes a voting consumer representative and a nonvoting industry liaison person. The first meeting was held in December 1992.

The Nonprescription Drug Advisory Committee has played a major role in the proliferation of prescription to OTC switches. No drug switched from prescription to OTC status in recent years has been required to return to prescription status. Tables 1 and 2 show major prescription to OTC switches for the years 1984 through 1994, and 1995 and 1996, respectively.

COPYRIGHT 1997 American Academy of Family Physicians
COPYRIGHT 2004 Gale Group