FDA Proposes Updated Guidance On Verification Systems Under The DSCSA For Certain Prescription Drugs

On March 10, 2022, the FDA’s Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), and Office of Regulatory Affairs (ORA) announced the establishment of FDA-2018-D-3462 to solicit comments on the FDA's proposed update to Verification Systems Under the Drug Supply Chain Security Act for Certain Prescription Drugs guidance document. The FDA is proposing to amend the original guidance issued in October 2018 to describe the FDA’s interpretation of the requirements for verification systems.

This guidance provides recommendations for a robust verification system for the determination, quarantine, and investigation of suspect and illegitimate products; addresses the fashion in which FDA recommends that trading partners submit cleared product notifications; and addresses the statutory requirements for verification, including verification of saleable returns, at the package level for product identifiers on packages, and cases intended to be placed on the market.

Section 582 of the Federal Food, Drug, and Cosmetic Act (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), established requirements to facilitate the tracing and verification of certain prescription drug products (biological products and human cell- or tissue-based products (HCT/P) regulated as a drug) through the U.S. pharmaceutical distribution supply chain.

The FDA requires manufacturers, wholesale distributors, dispensers, and repackagers (all referred to as “trading partners”) to have a supply chain verification system in place to respond to requests for verification from other trading partners and verify certain information before further distribution of returned products to ensure the authenticity of drug products to prevent suspect, counterfeit, or fraudulent products from being placed on the market.

When a trading partner suspects counterfeit or fraudulent products, or receives a request for verification from the FDA, trading partners are required to quarantine the product and to investigate to determine whether it is an illegitimate product. Trading partners are required to establish and maintain systems to enable the quarantine and investigation of suspect, counterfeit, or fraudulent products.

The quarantine of suspect, counterfeit, or fraudulent products can be accomplished physically and/or administratively to prevent placing it on the market. The FDA recommends the quality control unit for manufacturers or repackagers, the facility manager for wholesale distributors, and the pharmacist-in-charge for a dispenser to maintain the authority for release of the product for further distribution.

The FDA requires trading partners to perform robust investigations pertaining to suspect products. Investigations should include a review of the transaction history, communication and coordination with trading partners as required, appropriate laboratory testing, an analysis of how the product came to be in its possession or control, and how to help prevent similar occurrences in the future.

The FDA requires the manufacturer to confirm that the National Drug Code (NDC) and lot number reported in the manufacturer’s internal records for the transaction information made at the time of the transaction corresponds to the information assigned to the suspect product and verify that the NDC, serial number, lot number, and expiration date of the product identifier imprinted on the suspect product correspond to the information originally assigned to the product by the manufacturer.

Repackagers are required by the FDA to confirm that the NDC and lot number reported in the repackager’s internal records for the transaction information made at the time of the transaction correspond to the information assigned to the suspect product and verify the NDC, serial number, lot number, and expiration date of the product identifier correspond to the information originally assigned to the product by the repackager.

The FDA requires wholesale distributors to confirm the NDC and lot number in the wholesale distributor’s internal records for the transaction information that corresponds to the information assigned to the product the wholesale distributor received from the manufacturer, repackager, or other wholesale distributor and verify with the respective manufacturer or repackager that the NDC, serial number, lot number, and expiration date of the product identifier correspond to the information assigned to the product by the respective manufacturer or repackager.

Dispensers are required by the FDA to confirm that the NDC and lot number in the dispenser’s internal records for the transaction information correspond to the information assigned to the product. Dispensers must also verify with the respective manufacturer or repackager that the NDC, serial number, lot number and expiration date of the product identifier imprinted correspond with the product identifier assigned to the product by the respective manufacturer or repackager.

The verification requirement for dispensers differs from that of other trading partners, as dispensers are required to verify the product identifier for at least three packages or 10 percent of such suspect product, whichever is greater, or all packages if there are fewer than three. Dispensers are also required to verify that the lot number corresponds with the lot number assigned to the product by the respective manufacturer or repackager.

The FDA encourages trading partners to periodically evaluate their investigation systems to identify opportunities for improvement and ensure the systems are compliant with the applicable verification requirements.

Trading partners are expected to inform the FDA about cleared product only if the suspect product is the subject of an FDA request for verification.  Trading partners are advised that once a product has been cleared, they must ensure compliance with applicable regulatory requirements before distributing the product.

When a trading partner determines the product is not an illegitimate product, the trading partner is required to promptly submit a cleared product notification to the FDA at drugnotifications@fda.hhs.gov. The FDA requires cleared product notifications to include the identity of the product, proprietary or established name, strength and dosage form, NDC, lot number, expiration date, serial number(s), container size, number of containers, date of FDA request for verification, name of the FDA office and/or employee making the request, reason why the product was determined to be suspect, a summary of the investigation, date the product was cleared, and the name and position of the individual clearing the suspect product. Records are required to be maintained for a period of at least six years after the conclusion of the investigation and cleared product notifications.

When a trading partner determines a product is an illegitimate product, physical and electronic quarantine should be utilized to prevent further distribution and it must notify other trading partners who may have in their possession product having the same product information.

The FDA requires trading partners to establish and maintain procedures detailing systems and processes for the disposition of illegitimate product, including the affected products at other trading partners. Disposition records are required to be maintained for a minimum of six years. Trading partners are also required to retain samples of the illegitimate product for further physical examination or analysis by the manufacturer or FDA. The sample must be representative of the illegitimate product, in a sufficient quantity for laboratory examination, appropriately stored according to required conditions, and appropriately labeled.

Trading partners are required to establish and maintain systems for notifying the FDA and immediate trading partners of an illegitimate product and, for manufacturers of products with a high risk of illegitimacy, respond to requests for verification from an authorized trading partner and allow them to process saleable return products intended for further distribution.

Make sure you are heard; submit written comments before May 9, 2022, to the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852 or electronic comments to https://www.regulations.gov. Please reference docket number FDA-2018-D-3462 with all comments. For questions, please contact the Center for Drug Evaluation and Research (CDER) Office of Compliance at 301-796-3130 or drugtrackandtrace@fda.hhs.gov.

About The Author:

Mark Allen Durivage has worked as a practitioner, educator, consultant, and author. He is managing principal consultant at Quality Systems Compliance LLC, an ASQ Fellow and an SRE Fellow. Durivage primarily works with companies in the FDA regulated industries (medical devices, human tissue, animal tissue, and pharmaceuticals) focusing on quality management system implementation, integration, updates, and training. Additionally, he assists companies by providing internal and external audit support as well as FDA 483 and warning letter response and remediation services. He earned a BAS in computer aided machining from Siena Heights University and an MS in quality management from Eastern Michigan University. He holds several certifications, including CRE, CQE, CQA, CSSBB, RAC (Global), and CTBS. He has written several books available through ASQ Quality Press, published articles in Quality Progress, and is a frequent contributor to Life Science Connect. You can reach him at mark.durivage@qscompliance.com with any questions or comments.