FDA Drug Listing: How Foreign Manufacturers Submit Product Information Under 21 CFR Part 207

Drug listing is one of the two core FDA filing obligations for drug manufacturers — alongside drug establishment registration. Under 21 CFR Part 207, every person who owns or operates an establishment that manufactures, prepares, propagates, compounds, or processes a drug product must list each drug in commercial distribution with the FDA. For foreign manufacturers, drug listing is submitted electronically through the FDA's Drug Registration and Listing System using the Structured Product Labeling (SPL) format, and each product must be assigned a unique National Drug Code (NDC) before the listing can be completed. Drug listing is not a one-time filing — it must be updated when products are added, discontinued, or modified, and the FDA uses listing data to maintain the NDC Directory, which is the authoritative public database of all drugs marketed in the United States.

What information the drug listing must include

Each drug listing submission must include the NDC number assigned to the product, the proprietary (brand) name and established (generic) name of the drug, the dosage form (tablet, capsule, liquid, cream, ointment, etc.), the route of administration (oral, topical, ophthalmic, etc.), the active ingredient(s) and their strength, the inactive ingredients, the name of the labeler (the entity whose name appears on the label), the manufacturing establishment(s) and their FEI numbers, and a copy of the current product labeling including the Drug Facts panel for OTC drugs or the prescribing information for prescription drugs. All of this information must be submitted in SPL (Structured Product Labeling) format — an XML-based standard that the FDA uses for all electronic drug listing submissions.

The SPL format and submission process

SPL (Structured Product Labeling) is an XML document standard based on the HL7 Clinical Document Architecture (CDA). The SPL file contains structured data fields for every element of the drug listing — ingredients, dosage, indications, warnings, manufacturer information, and the NDC number — plus the full text of the product labeling in a machine-readable format. The FDA provides the SPL authoring tool (SPL Xforms) and documentation to help manufacturers create compliant SPL files, but the format is technically demanding, and most foreign manufacturers either use regulatory software or work with regulatory service providers who have experience with SPL submissions. The completed SPL file is submitted to the FDA through the FDA Electronic Submissions Gateway (ESG) and is processed into the NDC Directory and the DailyMed database.

Timing and update requirements

Initial drug listings must be submitted within the first 60 days after the establishment's first registration. After the initial listing, updates must be submitted in June and December of each year to report changes, additions, or discontinuations. If a new drug product is added between the semi-annual updates, the listing for that product must be submitted at the next regular update. If a product is discontinued, the discontinuation must be reported in the next semi-annual update. If a product's labeling changes (such as a warning addition or ingredient modification), the updated labeling must be submitted in SPL format at the next update. Failure to maintain current drug listings can result in the product being considered misbranded and subject to enforcement action.

NDC number assignment

Each drug product listing requires a unique NDC number. The NDC is a 10-digit, three-segment identifier in one of three formats: 4-4-2, 5-3-2, or 5-4-1 (where the segments represent the Labeler Code, the Product Code, and the Package Code respectively). The Labeler Code is assigned by the FDA when the company first registers or requests a Labeler Code. The Product Code and Package Code are assigned by the manufacturer and must be unique within the Labeler Code. The manufacturer is responsible for ensuring that each unique combination of product formulation, dosage form, and package configuration receives its own NDC number. The NDC must appear on the product label and is used throughout the US pharmaceutical supply chain for identification, reimbursement, and tracking.

Consequences of incomplete or inaccurate listings

Drug products that are not properly listed with the FDA are considered misbranded under Section 502 of the FD&C Act. For foreign manufacturers, an unlisted drug product will be refused entry at US ports, and the manufacturing establishment may face increased scrutiny for all future shipments. The FDA also uses drug listing data to identify products for inspection and sampling — an establishment with incomplete listings may be flagged for a compliance inspection. Additionally, US distributors, wholesalers, and pharmacies rely on the NDC Directory to verify that products are legitimately marketed, and a product that does not appear in the NDC Directory may be rejected by supply chain partners regardless of its actual compliance status.

How FDABridge handles drug listing

FDABridge manages the complete drug listing process for foreign manufacturers, including NDC assignment, SPL file preparation, electronic submission through FDA's ESG system, and semi-annual updates. Our team has experience with OTC drug listings across multiple therapeutic categories and can ensure your product information is accurately formatted and submitted. Visit fdabridge.com/drug to see our drug registration services or fdabridge.com/contact to discuss your drug listing needs.