Final Guidance Locks In FDA's Definitions For Suspect And Illegitimate Drug Product

By Holly Brevig, Ph.D.

In March 2023, the FDA issued guidance on definitions of suspect product and illegitimate product. Suspect product is defined in section 581(21) of the Food Drug & Cosmetic (FD&C) Act as a product for which there is reason to believe it:

• Is potentially counterfeit, diverted, or stolen.
• Is potentially intentionally adulterated such that the product would result in serious adverse health consequences or death to humans.
• Is potentially the subject of a fraudulent transaction.
• Appears otherwise unfit for distribution such that the product would result in serious adverse health consequences or death to humans. 

Illegitimate product is defined in section 581(8) of the FD&C Act as a product for which credible evidence confirms suspicions used to define a suspect product.  Although section 581 of the FD&C Act defines suspect and illegitimate product, the guidance is meant to provide FDA’s interpretation of the key terms used to define suspect and illegitimate product, including the terms counterfeit, diverted, stolen, fraudulent transaction, and unfit for distribution.  It’s important for trading partners including manufacturers, repackagers, wholesale distributors, and dispensers to understand these definitions so that they may appropriately identify a suspect product in their possession and to determine whether that suspect product is also illegitimate.  

Under section 582 of the FD&C Act (21 U.S.C. 360eee-1), as added by the Drug Supply Chain Security Act (DSCSA) (Title II of Public Law 113-54), a trading partner must notify FDA and immediate trading partners of illegitimate product in their possession or control.  Additionally, manufacturers are also required to notify FDA and immediate trading partners within 24 hours after determining there is a high risk that a product is illegitimate per section 582(b)(4)(B)(ii)(II) of the FD&C Act. 

The Final Guidance On Suspect And Illegitimate Product Is To Protect Patients

The FDA states that the DSCSA is meant to enhance its ability to help consumers avoid exposure to drugs that may be counterfeit, stolen, contaminated, or otherwise harmful and to improve detection and removal of potentially dangerous drugs from the drug supply chain to protect U.S. consumers.

By way of background, the FDA originally issued the draft guidance in March 2018.  Based on industry comments, FDA revised the draft guidance in June 2021 with updated definitions of diverted products, stolen products, fraudulent transactions, and products unfit for distribution. In the final guidance issued in March 2023, FDA expanded on the sections defining stolen products, fraudulent transactions, and products unfit for distribution.

The underlying theme of these revisions is that trading partners should not assume anything before conducting an investigation to confirm whether their:

• Unaccounted-for product is stolen or not.
• Transactional errors are fraudulent or not.
• Nonsaleable product (e.g., expired) is suspect or not.  

According to the final guidance, FDA recognizes that unaccounted-for product does not mean it was stolen.  However, the FDA recommends that trading partners with lost or missing product use current procedures to investigate the circumstances surrounding the lost or missing product to determine whether it has been stolen or is otherwise suspect or illegitimate product.  Although the FDA does not consider incorrect transaction data caused by errors or mistakes to be fraudulent, the FDA recommends that trading partners determine whether the clerical error or discrepancy can be resolved or whether the product is suspect or illegitimate.  

The FDA references its draft guidance for industry Enhanced Drug Distribution Security at the Package Level Under the Drug Supply Chain Security Act, which provides examples of potential clerical errors or discrepancies with product tracing information and recommendations to resolve the errors.  Regarding “unfit for distribution,” the FDA recommends that trading partners use current company policy and procedure to investigate the circumstances that determine whether the nonsaleable product (e.g., expired) rises to the level of suspect product.

Final Guidance Clarifies The Definition Of And Exceptions To Diverted Products

The FDA also clarified the definition of diverted products in the final guidance by revising the example of a product that left the U.S. pharmaceutical distribution supply chain and is reintroduced in the U.S. in a transaction with a trading partner.  The example now states “… this scenario would include when a trading partner reintroduces into the U.S. pharmaceutical distribution supply chain product after it was dispensed to a patient or otherwise removed from the U.S. pharmaceutical distribution supply chain” instead of “… this scenario would include product dispensed to a consumer or patient and then reintroduced into the U.S. supply chain to a trading partner.” 

The FDA added clarifying language making exceptions to what might otherwise be considered diverted product. The agency generally would not consider product suspect or illegitimate if trading partners obtain that product through:

• Surveillance activities including when the product is obtained by a trading partner from outside the U.S. supply chain or from a consumer who obtained the product from outside the U.S. supply chain. What the agency means by “surveillance” is not specified.
• Following regulatory action to address a drug shortage.
• Following emergency use authorization for that product under the FD&C.

The Agency Provides Other Resources To Help Companies Comply With DSCSA

Trading partners should review the final guidance as well as the other DSCSA guidance documents referenced.  In the final guidance, FDA references the final guidance for industry Drug Supply Chain Security Act Implementation: Identification of Suspect Product and Notification, which describes specific scenarios of how trading partners should identify, notify trading partners, and report to FDA suspect or illegitimate products in their possession or control. 

In addition, trading partners should ensure they have policies and procedures to investigate lost or missing product, transactional errors, and nonsaleable product to confirm whether these products are suspect or illegitimate or not.

About the Author:

Holly Brevig, Ph.D., is a medical device and biologics regulatory professional.  Most recently, she worked as a regulatory expert for Hyman, Phelps & McNamara, LLC. Previously, she worked for the Food and Drug Administration where she started in CDRH’s Division of Chemistry and Toxicology Devices in the Office of In-Vitro Diagnostics and Radiological Health. She moved from the medical device space to biologics with CBER’s Division of Manufacturing and Product Quality (DMPQ) in the Office of Compliance and Biologics Quality (OCBQ). Prior to the FDA, Dr. Brevig was a research analyst for the Center for Naval Analyses where she evaluated the implementation of healthcare related programs and policies, and provided recommendations on funding science and technology programs for the Navy and Marine Corps.