FDA Drug Listing & SPL for Foreign Manufacturers: NDC, eDRLS, and Updates (2026)
Updated: Sep 24
Every year a foreign pharmaceutical manufacturer ships its first lot to the United States and gets stopped at the port — not because of a quality problem, but because the company registered in the wrong FDA portal. Food facility registration, medical device establishment registration, and drug establishment registration and listing are three separate systems with three separate rules. Registering a tablet plant in the food facility system, or assuming a device registration covers an API site, produces exactly the same outcome: no valid drug registration or listing on file, an import hold, and a scramble.
This guide explains, in plain language, what FDA drug listing and Structured Product Labeling (SPL) are, when a foreign manufacturer needs a National Drug Code (NDC) and a labeler code, how the electronic filing works at a high level, and how a drug-listing U.S. Agent differs from a food-facility U.S. Agent. Every regulatory statement below is drawn from the FDA and eCFR pages listed at the end, opened on 17 September 2026.
What is FDA drug listing?
FDA drug listing is the electronic record of each drug a registered establishment manufactures, repacks, relabels, or salvages for commercial distribution in the United States, submitted to FDA in SPL format through the Electronic Drug Registration and Listing System (eDRLS).
Two things sit together here. First, establishment registration: FDA states that drug manufacturers are required to register their establishments with FDA. Second, drug listing: registrants are also required to list each drug manufactured at their establishments that is intended for commercial distribution. Registration identifies the site; listing identifies the products made there. You cannot list without a registered establishment, and a registration with no listed products tells FDA nothing about what you ship.
One sentence FDA puts on its own eDRLS page deserves repeating verbatim, because foreign firms and their distributors get it wrong constantly: "Registering an establishment and listing drugs with FDA does not indicate the products are approved or that FDA has verified the information provided." Listing is a disclosure obligation. It is not clearance, not certification, and not approval.
What is SPL (Structured Product Labeling)?
SPL is the FDA-mandated XML document standard in which drug establishment registration and drug listing information — and the product's labeling content — are submitted electronically to FDA.
FDA's registration and listing instructions state that all registration and listing submissions must use SPL in XML format and must comply with FDA validation rules. In practice that means the data (labeler, establishment, product, package, marketing category, label text) is entered into a structured file rather than a PDF or a form, and FDA's system validates it before accepting it.
FDA describes three routes for creating and sending SPL files: FDA Direct (formerly CDER Direct), the free SPL Xforms tool, and commercial or in-house submission tools, with the latter transmitted through the Electronic Submissions Gateway Next Generation (ESG NextGen). Which route is right depends on how many products you have and whether you maintain your own regulatory IT — but the output is the same validated SPL file either way. This article stays at that level; it is not a software tutorial.
What is an NDC, and what is a labeler code?
The National Drug Code (NDC) is the numeric code that uniquely identifies a listed drug's labeler, product, and package size and type; the labeler code is its first segment and is assigned by FDA to the firm that will appear as the labeler.
Under 21 CFR 207.33, each finished drug product or unfinished drug subject to listing must have a unique NDC. The labeler code — four, five, or six digits — is assigned by FDA. The firm then proposes the product and package segments when it first submits listing information, and FDA assigns the NDC if it conforms to the rules and is not already reserved or assigned to a different drug. FDA's instructions treat this as three distinct submissions: establishment registration, a labeler code request, and drug listing. FDA also notes a firm may reserve an NDC up to two years before launch.
A common misunderstanding: an NDC appearing in FDA's National Drug Code Directory is not evidence of approval. The Directory publishes parts of the data firms submitted through listing; inclusion means a listing was filed, nothing more. Any marketing claim that treats an NDC as an FDA "approval number" is inaccurate.
What foreign drug establishments must do
A foreign establishment must register with FDA before any drug it manufactures, repacks, relabels, or salvages is imported or offered for import into the United States, list those drugs, and identify a single U.S. Agent plus its known U.S. importers.
The sequencing comes from 21 CFR 207.21(b): registration must be in place before import or offer for import — not within five days of starting operations, which is the domestic rule. FDA's 2024 registration workshop slides put it the same way: domestic manufacturers register no later than five calendar days after manufacturing starts; foreign manufacturers register before importation begins.
Foreign registrants must also provide the name, address, telephone and email of their U.S. Agent and of each importer, along with information on persons who import or offer to import the drug.
Drug-listing U.S. Agent vs food-facility U.S. Agent — not the same appointment
Same phrase, two different regulations, two different portals — food facility registration under 21 CFR Part 1 and drug establishment registration under Part 207 are not interchangeable appointments. The full side-by-side (portals, duties, cadence, fee posture) is in Drug Listing U.S. Agent vs Food Facility U.S. Agent.
This SPL post stays on listing, NDC and eDRLS mechanics for foreign manufacturers; use that comparison when you need the program-level contrast.
Registration and listing updates: the annual and twice-yearly cadence
Drug listing information is reviewed and updated each June and December; establishment registration is reviewed and updated each year between October 1 and December 31; and the single blanket "no changes" certification for unchanged listings is made during that October–December annual registration update, not in June.
Three separate clocks, and they are easy to conflate. The first is listing. Under 21 CFR 207.57(b), registrants review and update their drug listing information each June and December — adding newly marketed drugs, reporting discontinuations and resumptions, and submitting any material change to previously listed information. FDA's eDRLS page says the same: updated listing information goes to FDA twice each year, in June and December, if the information has changed.
The second is registration. Under 21 CFR 207.29(b)(1), registrants review and update establishment registration "during the period beginning on October 1 and ending December 31 of each calendar year." FDA's 2024 registration workshop slides describe the same October 1–December 31 window and list the consequences of missing it: deficiency letters, removal of the establishment from the public registration database (DECRS), misbranding exposure, and import problems.
The third is the "no changes" certification, and this is where firms slip. 21 CFR 207.57(b)(2) provides that, after initial electronic listing, a registrant may satisfy the listing update requirement for unchanged listings by making a single "no changes" certification during the annual registration update under 207.29(b) — that is, in the October 1–December 31 window. It is not a June event. For listings that have not changed, that October–December blanket certification is how the update requirement is met; the June and December reviews are where new products, discontinuations, and material changes get reported.
Note the contrast with food again: food facility registration renews every other year, October 1–December 31 of even-numbered years. A firm that holds both a food facility and a drug establishment has different calendars to keep.
How Axentra Global Pharma Compliance supports foreign manufacturers
Axentra prepares and validates SPL registration and listing files, requests the labeler code, sequences the establishment registration ahead of first import, manages the June/December listing reviews and the October–December registration update (including the annual "no changes" certification), and acts as the U.S. Agent for drug establishments where that is in scope.
Drug listing work is quoted by product class and establishment count — a single-SKU OTC repacker and a multi-line API manufacturer are not the same file. Request a drug listing and SPL quote, or contact Axentra with your product list and establishment type.
Frequently asked questions
What is FDA drug listing and SPL?
FDA drug listing is the electronic record of each drug a registered establishment makes for commercial distribution in the U.S.; SPL (Structured Product Labeling) is the XML format in which FDA requires that listing, and the establishment registration, to be submitted. Listing is filed through FDA's eDRLS system, and FDA states that registering and listing does not indicate a product is approved.
When does a foreign drug manufacturer need drug listing and an NDC?
Before the drug is imported or offered for import into the United States. 21 CFR 207.21(b) requires the foreign establishment to be registered before import, and each drug in commercial distribution must be listed with a unique NDC under 21 CFR 207.33. The labeler code segment is assigned by FDA and is a separate request that precedes listing. An assigned NDC is an identifier, not an approval.
How do I submit SPL to FDA at a high level?
Register the establishment, obtain a labeler code, then build and validate an SPL XML file containing the listing data and labeling. FDA accepts SPL through FDA Direct, the SPL Xforms tool, or commercial and in-house tools submitted via the Electronic Submissions Gateway Next Generation. Foreign establishments also name a U.S. Agent and their U.S. importers in the registration. After that, listings are reviewed and updated each June and December (21 CFR 207.57), registration is reviewed and updated each October 1–December 31 (21 CFR 207.29), and a single "no changes" certification for unchanged listings is made during that October–December annual registration update.
Related reading
Sources (opened 17 September 2026)
FDA, Electronic Drug Registration and Listing System (eDRLS) — content current as of 02/05/2026 — https://www.fda.gov/drugs/guidance-compliance-regulatory-information/electronic-drug-registration-and-listing-system-edrls
FDA, Drug Registration and Listing Instructions — content current as of 08/03/2026 — https://www.fda.gov/drugs/electronic-drug-registration-and-listing-system-edrls/drug-registration-and-listing-instructions
FDA Guidance for Industry, Providing Regulatory Submissions in Electronic Format — Drug Establishment Registration and Drug Listing (May 2009) — https://www.fda.gov/media/71146/download
FDA CDER SBIA, "Complying with Establishment Registration Requirements" (12 Sep 2024) — https://www.fda.gov/media/184336/download
21 CFR 207.21, 207.29, 207.33, 207.57, 207.69 (eCFR, current) — https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-207
Axentra Global Pharma Compliance LLC provides regulatory consulting and U.S. Agent services. This article is general information, not legal advice, and does not imply FDA approval of any product.
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