There may be thousands of drug products being prescribed and dispensed to
patients in the United States that have never been reviewed by the Food and
Drug Administration (FDA) for safety and efficacy or approved for marketing.
The agency is now taking steps to address the potentially large problem.
In June 2006, the FDA released a guidance document, "Marketed
Unapproved Drugs—Compliance Policy Guide," to clarify the rules
regarding drugs on the market that have not been reviewed or approved by the
agency's normal process and the agency's plan to enforce them.
Many of these unapproved drugs are advertised and listed in reference books
such as the Physicians' Desk Reference, prescribed by physicians, and
dispensed or sold to patients, according to the FDA guidance document.
Physicians and pharmacists are usually not aware of the unapproved status of
these drugs, which can be distributed based on a 10-digit number known as the
National Drug Code (NDC). The NDC number is issued to all types of drug
products, including unapproved investigational drugs, and does not guarantee a
drug's approval status. These products' labeling information does not
distinguish their approval status, nor is the labeling necessarily reviewed by
the FDA for safety claims and indications.
The FDA says on its Web site that most of these products remain on the
market illegally for "a variety of historic reasons." Most became
available before the Federal Food, Drug, and Cosmetic Act was revised in the
1960s to require that a new drug be evaluated by the FDA for efficacy as well
as safety. Before these regulations, new drugs only needed to be shown as
safe, and drugs deemed the same or similar to approved drugs needed no
independent review and approval process by the agency. The labels of these
products may not conform to current regulatory standards and may carry
unapproved claims and indications. Although the FDA had contracted with the
National Academy of Sciences/National Research Council to evaluate the
effectiveness of thousands of products approved only for safety between 1938
and 1962, not all products have gone through the approval process.
Even the drug products deemed illegal have not all been forced off the
market. Other provisions in the regulations have allowed older drugs without
labeling updates to slip through the cracks.
It is unknown how many currently marketed drugs are unapproved, and the
agency does not maintain a complete list of these products. The guidance
estimated that "several thousand drug products are marketed illegally
without required FDA approval" today and admits that the agency is"
unable to take action immediately against all. . .illegally marketed
products" because of a lack of resources.
Since the release of the guidance last year, the FDA has been
systematically issuing sanctions against certain unapproved products by
demanding their withdrawal from the market or convincing some manufacturers to
go through the official process by filing a New Drug Application for the
agency's review in order to legalize their products and update the product
labeling. A short list of drugs and manufacturers against which enforcement
actions have already been taken is posted on the FDA's Web site.
The guidance document claims that the enforcement priorities are given to
drugs that have potential safety risks, lack evidence of effectiveness, are
fraudulently promoted and sold, "present direct challenges to the new
drug approval and [over-the-counter] drug monograph systems," or are
reformulated to evade FDA enforcement action. Priority is also given to
unapproved new drugs that violate the regulations in other ways.
In 2006, unapproved products containing quinine and carbinoxamine with
unapproved labeling were targets. This September, the agency announced that it
will take "enforcement action" against manufacturers of unapproved
hydrocodone-containing cough syrups, citing reports of medication errors due
to formulation changes in the unapproved products and confusion over their
brand names. The agency is also concerned that "no hydrocodone cough
suppressant has been established as safe and effective in children under 6
years of age, and some of these unapproved products carry labels with dosing
instructions for children as young as 2 years old," warned Steven
Galson, M.D., M.P.H., director of the FDA's Center for Drug Evaluation and
Research in a press release.
The FDA Web page lists selected drugs and companies that have been cited
for enforcement actions, but includes no psychiatric drugs. However, the FDA
has not released a complete list of all unapproved drug products on the
market. Psychiatrists may be treating patients who are taking, for example,
unapproved hydrocodone, levothyroxine, and quinine products (for restless legs
Additional information about unapproved drugs and FDA actions is
Guidance for FDA Staff and Industry: Marketed Unapproved
Drugs—Compliance Policy Guide" is posted at<www.fda.gov/cder/guidance/6911fnl.pdf>.▪