Before a new drug comes to market, it must go through a long process of approval by the U.S. Food and Drug Administration (FDA). Today, federal law requires prescription drugs to be shown to be both safe and effective under the Kefauver Harris Amendment to the Food, Drug, and Cosmetic Act, which was passed in 1962. During the approval process, the applicant (drug manufacturer) must demonstrate that its manufacturing process can reliably produce products with expected identity, strength, quality, and purity. Additionally, all labelling must provide necessary information for health care professionals to understand the product's risks and uses. However, these requirements were not always in place.

The original Food and Drugs Act of 1906 prohibited the sale of misbranded or adulterated drugs but did not require FDA approval. In 1938, manufacturers were required to prove that the new drug was safe, but they were not required to prove efficacy. Then, in 1962, Congress amended the law and required manufacturers to show that their drugs were both safe and effective.

Conversely, there are some drugs (mostly older products) that, due to a variety of historical reasons, have been marketed and used without FDA approval. These may include:

• drugs available prior to the amended law requiring safety and efficacy;
• a manufacturer combining two approved products into a combination product without obtaining approval;
• a manufacturer marketing a currently approved product without obtaining FDA approval.

Verifying drug status

The Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book), identifies FDA-approved drugs that have undergone the mandatory safety and efficacy requirements of the Federal Food, Drug, and Cosmetic Act. If a medication is not included in the Orange Book, it has not demonstrated the requirements in accordance with this Act. Those drugs that entered the market based solely on safety and/or drugs that were on the market prior to 1938 are not included in the Orange Book.

Many health care providers continue to unknowingly prescribe unapproved drugs, usually because they are unaware of the non-FDA-approved status of the drugs.

Effective January 1, 2016, AmeriHealth will no longer cover non-FDA-approved drugs. The table below lists examples of non-FDA-approved drugs, as well as some FDA-approved alternatives.

For more information

To learn more, read the following articles published on the FDA website:

• Unapproved Prescription Drugs: Drugs Marketed in the United States That Do Not Have Required FDA Approval
• What are unapproved drugs and why are they on the market?

You can send inquiries regarding FDA-approved and non-approved drugs to druginfo@fda.gov.