The Unapproved-Drugs Initiative Is Coming to an End

Reversion to Pre-2006 Regulatory Status 

With the Unapproved Drugs Initiative ending, the policy will revert to the pre-2006 regulatory status. The FDA will still be permitted to take enforcement action against misbranded and adulterated drugs that pose a risk to the public, as described in an FAQ published by HHS.⁵ The Notice does not apply to drugs that are the subject of existing Investigational New Drug Applications or existing approved New Drug Applications.

According to Vizient, a corporation that serves more than 5,000 not-for-profit health system members to improve the delivery of high-value care, 18 drugs could still be approved through the program, which would add an estimated $7.52 billion to U.S. healthcare costs.⁶ Existing market exclusivity for the five most expensive drugs approved through the Unapproved Drug Initiative would be expected to add a further $19.07 billion in costs through the life of their exclusivity. 

The FDA has estimated that 2% of all drug products marketed in the U.S. are unapproved; however, no complete list exists. To address this, in the Notice, HHS asks for input from the healthcare community. The agency specifically asks for help to: 1) identify the list of drugs first marketed prior to June 25, 1938, that are currently available on the market, and 2) determine whether these drugs have regulatory approvals in other countries or any published clinical studies or literature reviews pertaining to their use.

In 2019, Carico and colleagues published the most complete list of unapproved drugs to date.⁷ To identify unapproved drugs, they analyzed all products with National Drug Codes (NDCs) purchased by the Veterans Health Administration in fiscal year 2016 and cross-referenced that list with the FDA’s Electronic Drug Registration and Listing System. The team identified 600 NDCs comprising 130 active pharmaceutical ingredients and route pairs. This list includes many drugs used in the care of rheumatology patients, including salsalate tablets, hyaluronate injections, sodium fluoride dental, sodium chloride inhalation, ethyl chloride topical, urea topical, fluorescein ophthalmic and more.

HHS seeks to avoid legal challenges to withdrawal of the Unapproved Drug Initiative by preempting claims of reliance interest as seen in the Notice. HHS also claims the initial program was initiated through a guidance document rather than notice-and-comment rulemaking, which the agency states may not have been legally permissible.

Jason Melehani, MD, PhD, is a physician-scientist training in rheumatology and pulmonary medicine at Stanford University, Palo Alto, Calif. His research interest is in immune-mediated lung diseases. He is also interested in drug development and the role of the U.S. Food & Drug Administration in promoting development of innovative therapies.