FDA eDRLS is the Electronic Drug Registration and Listing System — the electronic platform used to submit drug establishment registrations and drug product listings to FDA. It is mandated under Section 510 of the Federal Food, Drug, and Cosmetic Act and implemented through 21 CFR Part 207. eDRLS replaced paper-based drug registration. All drug establishment registrations and drug product listings must be submitted and maintained electronically through eDRLS. Submissions are formatted in SPL (Structured Product Labeling), an XML-based standard, and transmitted through FDA's Electronic Submissions Gateway (ESG).

How quickly can FDA Registration Assistance complete an eDRLS filing?

Timeline depends on the complexity of the establishment and product portfolio and the completeness of the documentation provided. Initial drug establishment registration through eDRLS is typically processed by FDA within a few business days of a correctly formatted submission. Drug product listing preparation in SPL format requires more time — typically one to two weeks depending on the number of products and completeness of ingredient and labeling data. Annual renewal submissions, when all information is current, are processed quickly. FDA Registration Assistance provides specific timeline expectations during the intake process.

Do API manufacturers need eDRLS registration separate from finished drug manufacturers?

Yes. Active Pharmaceutical Ingredient (API) manufacturers that manufacture APIs for drug products distributed in the United States must register their establishments through eDRLS under 21 CFR Part 207 separately from any finished drug product manufacturer that uses their APIs. API manufacturer registration and listing in eDRLS has become a more active compliance area as FDA has increased scrutiny of the global API supply chain. Foreign API manufacturers are subject to the same eDRLS registration requirements and must designate a U.S. Agent.

Can a drug company manage eDRLS internally without FDA Registration Assistance?

Technically yes — the eDRLS system is accessible to drug companies directly. However, most companies find that the technical complexity of SPL file preparation, the specific data requirements for drug product listings, the ESG submission technical requirements, and the ongoing maintenance obligations make internal management resource-intensive and error-prone. Rejection of SPL submissions due to formatting or data errors is common for first-time filers. FDA Registration Assistance provides done-for-you management that removes the internal resource burden and submission risk.

What are the consequences of eDRLS non-compliance for drug companies?

eDRLS non-compliance consequences include: Import Alert 89-06 for foreign drug establishments — every drug shipment automatically detained at U.S. ports; FDA Warning Letters citing failure to register under 21 U.S.C. 331 and 21 CFR Part 207 (non-compliance is a prohibited act); import refusal of drug shipments; seizure of drug products; and injunctive action. For domestic drug establishments: manufacturing, importing, or distributing an unregistered drug establishment's product is a prohibited act. These consequences can halt U.S. market access indefinitely.

Drug Registration & Listing

Last updated: February 2026

FDA eDRLS Compliance for Drug Companies

Q: Who must register through FDA eDRLS?

Under 21 CFR Part 207, the following drug establishment types must register through eDRLS: manufacturers of finished drug products (prescription and OTC); manufacturers of active pharmaceutical ingredients (APIs); contract manufacturers producing drugs for other companies; repackers who repackage drug products into different container/closure systems; relabelers who change or add labeling to drug products without opening the immediate container; private label distributors who distribute drug products under their own label; and salvagers who recover drug products from damaged containers. Foreign establishments meeting any of these descriptions that manufacture drugs imported into the United States must also register and designate a U.S. Agent.

Q: What is SPL and why is it required for drug product listings?

SPL stands for Structured Product Labeling — an HL7 standard XML-based format required by FDA for electronic drug product listings submitted through eDRLS. Drug product listings must be submitted in SPL format and must include: the drug product name; active ingredient(s) with strength and quantity; inactive ingredients; labeling content in SPL format; product category (prescription, OTC, homeopathic, biologic, etc.); and the National Drug Code (NDC) associated with the product. SPL files are transmitted through FDA's Electronic Submissions Gateway (ESG). Incorrectly structured or incomplete SPL files result in submission rejection.

Q: What is an NDC number and how is it obtained?

The National Drug Code (NDC) is a unique 10-digit identifier for each drug product — structured as three segments: labeler code (assigned by FDA), product code (assigned by the labeler), and package code (identifies the specific package size/type). The labeler code is assigned by FDA when the drug establishment registers through eDRLS. The NDC must appear on the drug product label and in the drug product listing in eDRLS. Foreign manufacturers must obtain their own FDA labeler code — they cannot use a U.S. importer's labeler code for their own products. FDA Registration Assistance coordinates NDC labeler code assignment as part of the eDRLS registration process.

Q: What is the annual renewal requirement for FDA drug establishment registration?

Drug establishment registration must be renewed annually — October 1 through December 31 of each year. This is different from FDA Food Facility Registration, which renews biennially (every two years). Missing the annual renewal window can result in FDA removing the establishment from the registration database, which triggers Import Alert 89-06 for foreign establishments (causing automatic detention of drug shipments) and constitutes a prohibited act under 21 U.S.C. 331. FDA Registration Assistance manages annual drug establishment registration renewal for all clients.

Q: What is Import Alert 89-06 and how does it affect drug companies?

Import Alert 89-06 is an FDA Import Alert that subjects drug shipments from foreign drug establishments with registration violations to Detention Without Physical Examination (DWPE) at U.S. ports. Foreign drug establishments placed on Import Alert 89-06 have every subsequent drug shipment automatically detained — without FDA needing to physically inspect each shipment. Common triggers: initial failure to register through eDRLS, missing annual renewal, inconsistencies in the registration data, or other eDRLS compliance violations. Removal from Import Alert 89-06 requires completing or correcting the eDRLS registration through FDA Registration Assistance or similar qualified support.

Q: What triggers a new drug listing or listing update in eDRLS?

A new drug listing or listing update in eDRLS is required when: a new drug product is introduced to the U.S. market; a drug product is discontinued; the product formulation changes (active or inactive ingredient changes); the drug product labeling changes; the NDC number changes; the labeler name or address changes; the product category changes; or the drug product's marketing status changes. Drug listings must be maintained to reflect current, accurate information. Outdated or incorrect drug listings in eDRLS can create regulatory inconsistencies that affect product importation and market compliance.

Q: What is the FDA Electronic Submissions Gateway (ESG) and how does it relate to eDRLS?

The FDA Electronic Submissions Gateway (ESG) is the secure electronic platform through which drug establishment registration and drug product listing submissions (formatted in SPL) are transmitted to FDA. eDRLS submissions — including initial registration, annual renewal, drug product listings, and updates — are transmitted through the ESG. The ESG requires specific account credentials and technical submission requirements. FDA Registration Assistance manages all ESG submissions on behalf of drug establishment clients, ensuring submissions are correctly formatted, transmitted, and confirmed.

Q: How does drug establishment registration differ from food facility registration?

Several key differences: (1) Governing regulation — drug establishments register under 21 CFR Part 207; food facilities register under 21 CFR Part 1 Subpart H. (2) Submission system — drug establishments use eDRLS; food facilities use FURLS (FDA Unified Registration and Listing System). (3) Renewal frequency — drug establishment registration renews annually (October 1–December 31 every year); food facility registration renews biennially (every 2 years). (4) Product listing — drug establishments must submit drug product listings in SPL format; food facilities have no equivalent drug-style product listing requirement. (5) U.S. Agent role — the drug U.S. Agent has an active inspection facilitation role (21 CFR 207.69) that is more demanding than the food U.S. Agent's role.

eDRLS — the Electronic Drug Registration and Listing System — is the mandatory FDA system for drug establishment registrations and drug product listings under Section 510 of the FD&C Act and 21 CFR Part 207. Drug establishment registration renews annually — October 1 through December 31 — every year (not biennially like food). Drug product listings must be submitted in SPL (Structured Product Labeling) XML format through FDA’s Electronic Submissions Gateway (ESG). Foreign drug establishments must designate a U.S. Agent under 21 CFR 207.69 — with an active inspection facilitation role more demanding than the food U.S. Agent. Missing the annual renewal triggers Import Alert 89-06 — automatic detention of every drug shipment.

This guide explains the eDRLS system, who must register, the SPL drug listing format, NDC codes, annual renewal requirements, the U.S. Agent obligation for foreign drug establishments, and what FDA Registration Assistance does to manage the entire eDRLS compliance lifecycle.

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Who Must Register

Drug Establishment Types That Must Register Through eDRLS

Establishment Type	eDRLS Registration Required?	Drug Product Listing Required?	Notes
Finished drug product manufacturer (prescription or OTC)	Yes — 21 CFR Part 207	Yes — SPL format	Annual renewal October–December. NDC labeler code assigned at registration.
API (Active Pharmaceutical Ingredient) manufacturer	Yes — 21 CFR Part 207	Yes — API listing	Foreign API manufacturers increasingly scrutinized. U.S. Agent required for foreign API facilities.
Contract manufacturer (manufactures drugs for other companies)	Yes — as the manufacturing facility	Yes — as the contract manufacturer of record	Both the contract manufacturer and the finished drug product labeler typically have eDRLS obligations.
Repacker (repackages drug products into different containers)	Yes	Yes — for repackaged products	Must list repackaged products separately. Repacker name may appear on the label.
Relabeler (changes or adds labeling without opening immediate container)	Yes	Yes	Must register as a relabeler. New listing required for relabeled products.
Private label distributor (distributes under own label, does not manufacture)	Yes — commonly missed	Yes — under own labeler code	Own FDA labeler code and drug listing required even though drug is manufactured by a contract manufacturer.
Foreign drug establishment (any of the above, outside the U.S.)	Yes + U.S. Agent required	Yes — SPL format	Import Alert 89-06 for missing or non-compliant registration. U.S. Agent must facilitate inspections under 21 CFR 207.69.

The eDRLS Submission Process

How FDA Drug Establishment Registration and Listing Works Step by Step

Obtain DUNS NumberA DUNS (Data Universal Numbering System) Number is required before eDRLS registration. The DUNS identifies the business entity. It is used to obtain an FDA NDC labeler code. Foreign drug establishments must obtain a DUNS for their specific facility.

Designate U.S. Agent (Foreign Establishments Only)Under 21 CFR 207.69, foreign drug establishments must designate a U.S. Agent with a physical U.S. address. The drug U.S. Agent must actively assist FDA in scheduling and facilitating inspections — a more demanding role than the food U.S. Agent. The U.S. Agent’s information is part of the eDRLS registration submission.

Create FDA ESG Account and Submit Drug Establishment RegistrationDrug establishment registration is submitted through FDA’s Electronic Submissions Gateway (ESG) via eDRLS. The registration assigns an FEI (Facility Establishment Identifier) — the primary identifier FDA uses to track the establishment. The labeler code (first segment of the NDC) is assigned upon registration.

Prepare Drug Product Listings in SPL FormatDrug product listings must be submitted in SPL (Structured Product Labeling) — an HL7 XML-based standard. Each SPL listing must include: drug product name, active ingredients with strength, inactive ingredients, dosage form, route of administration, product labeling, NDC number(s), marketing category (Rx/OTC/homeopathic/biologic), and marketing start date. SPL file preparation is technically complex — submission errors cause rejections.

Submit Drug Product Listings Through ESGCompleted SPL files are transmitted through FDA’s Electronic Submissions Gateway. FDA processes the listings and the data becomes accessible in FDA’s DailyMed and other public drug databases. Rejected submissions must be corrected and resubmitted.

Renew Annually — October 1 through December 31Drug establishment registration must be renewed every year — October 1 through December 31. Missing the window results in lapsed registration. For foreign drug establishments, a lapsed registration triggers Import Alert 89-06 and automatic DWPE detention of every drug shipment. FDA Registration Assistance tracks and manages all annual renewals.

Update Listings for Any ChangesDrug listings must be updated whenever there is a change to the product formulation, labeling, NDC, marketing status, or facility details. Outdated or incorrect drug listings in eDRLS can create regulatory inconsistencies affecting importation and market compliance.

NDC and SPL — The Technical Core

National Drug Code (NDC) Structure and SPL Drug Listing Requirements

12345 ‑ 678 ‑ 90

Labeler Code (FDA-assigned)

Product Code (labeler-assigned)

Package Code (labeler-assigned)

The NDC must appear on the drug product label and in the eDRLS drug product listing. The labeler code is assigned by FDA upon eDRLS establishment registration.

NDC — National Drug Code

The NDC is the unique 10-digit identifier for each drug product. Three segments: the labeler code (FDA-assigned based on the registrant’s DUNS and establishment registration); the product code (assigned by the labeler to identify the specific formulation); and the package code (identifies the specific package size and type). The NDC must appear on every drug product label and in the eDRLS drug listing. Foreign manufacturers must obtain their own FDA labeler code — they cannot use a U.S. importer’s labeler code.

SPL — Structured Product Labeling

SPL is the HL7 XML-based standard required for all drug product listings submitted through eDRLS. Each SPL file must include: drug product name; active ingredient(s) with strength per dosage unit; inactive ingredients; dosage form; route of administration; product labeling content in structured XML format; NDC number(s) for each package configuration; marketing category (Prescription/OTC/homeopathic); and marketing start date. Incorrectly structured SPL files are rejected by FDA’s submission processing system. SPL preparation is a technical discipline that FDA Registration Assistance manages on behalf of drug companies.

Import Alert 89-06

What Happens When Foreign Drug Establishments Miss eDRLS Compliance

⚠ Import Alert 89-06 — Automatic Detention of Drug Shipments from Non-Compliant Foreign Establishments. Foreign drug establishments with missing or non-compliant eDRLS registrations are placed on Import Alert 89-06 — causing every subsequent drug shipment from that establishment to be detained without physical examination (DWPE) at U.S. ports. There is no per-shipment review — DWPE is automatic until the establishment petitions for and obtains Import Alert removal through corrected eDRLS compliance.

Common Triggers for Import Alert 89-06

✗ Initial failure to register through eDRLS before first drug shipment to the U.S.

✗ Missing the annual October–December renewal — lapsed registration

✗ Inconsistencies in the eDRLS registration data (company name, address, establishment type)

✗ Missing or inactive U.S. Agent designation in the eDRLS registration

✗ Drug product listing not filed or incorrectly filed in eDRLS

How to Get Removed from Import Alert 89-06

Removal from Import Alert 89-06 requires demonstrating to FDA that the underlying eDRLS compliance issue has been corrected. For missing registration: submit and complete the eDRLS registration correctly with accurate establishment information and active U.S. Agent designation. For lapsed renewal: renew through eDRLS for the current registration period. For listing issues: correct and resubmit SPL files. FDA Registration Assistance manages Import Alert 89-06 removal by completing the corrective eDRLS filings.

Done-For-You eDRLS Compliance

FDA Registration Assistance Manages Your Entire eDRLS Compliance Lifecycle

FDA Registration Assistance provides complete, done-for-you eDRLS compliance: drug establishment registration including DUNS coordination and labeler code application; U.S. Agent services for foreign drug establishments; SPL drug product listing preparation and submission; annual renewal management (October–December every year); listing updates for formulation, labeling, or facility changes; and Import Alert 89-06 removal support. 1,000+ clients. 135+ countries. 15+ years of FDA regulatory experience.

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FAQ

Frequently Asked Questions — FDA eDRLS Compliance for Drug Companies

1. What is FDA eDRLS?

FDA eDRLS is the Electronic Drug Registration and Listing System — the mandatory electronic platform for drug establishment registrations and drug product listings under Section 510 of the FD&C Act and 21 CFR Part 207. All drug establishment registrations and drug product listings must be submitted and maintained electronically through eDRLS in SPL format via FDA’s Electronic Submissions Gateway (ESG).

2. Who must register through FDA eDRLS?

Under 21 CFR Part 207: finished drug product manufacturers (Rx and OTC); API manufacturers; contract manufacturers; repackers; relabelers; private label distributors (commonly missed); and salvagers. All foreign establishments meeting any of these descriptions that manufacture drugs imported into the United States must also register and designate a U.S. Agent.

3. What is SPL and why is it required for drug product listings?

SPL (Structured Product Labeling) is the HL7 XML-based standard required by FDA for all drug product listings submitted through eDRLS. Drug listings must include: drug product name; active ingredients with strength; inactive ingredients; dosage form; route of administration; product labeling in XML format; NDC number(s); marketing category; and marketing start date. Incorrectly structured SPL files are rejected.

4. What is an NDC number and how is it obtained?

The NDC (National Drug Code) is a unique 10-digit identifier structured in three segments: labeler code (FDA-assigned upon eDRLS registration, based on DUNS), product code (labeler-assigned), and package code (labeler-assigned for each package size/type). The NDC must appear on the drug product label and in the eDRLS drug listing. Foreign manufacturers must obtain their own FDA labeler code — they cannot use a U.S. importer’s labeler code.

5. What is the annual renewal requirement for FDA drug establishment registration?

Drug establishment registration must be renewed annually — October 1 through December 31 of every year. Unlike FDA Food Facility Registration (biennial, every 2 years), drug establishment registration renews every year without exception. Missing the window results in lapsed registration and Import Alert 89-06 for foreign establishments.

6. What is Import Alert 89-06 and how does it affect drug companies?

Import Alert 89-06 subjects drug shipments from foreign establishments with registration violations to automatic Detention Without Physical Examination (DWPE) at U.S. ports. Every subsequent drug shipment from a non-compliant foreign establishment is detained automatically. Resolution requires completing or correcting the eDRLS registration. FDA Registration Assistance manages Import Alert 89-06 removal.

7. What is the U.S. Agent requirement for foreign drug establishments?

Under 21 CFR 207.69, foreign drug establishments must designate a U.S. Agent with a physical U.S. address. The drug U.S. Agent must actively assist FDA in scheduling and facilitating inspections of the foreign facility — a more demanding role than the food U.S. Agent. The U.S. Agent’s information is included in the eDRLS registration submission. FDA Registration Assistance provides U.S. Agent services.

8. What triggers a new drug listing or listing update in eDRLS?

A new or updated drug listing is required when: a new drug product is introduced to the U.S. market; a product is discontinued; the formulation changes (active or inactive ingredients); the labeling changes; the NDC changes; the labeler name or address changes; or the product’s marketing status changes.

9. What is FDA’s Electronic Submissions Gateway (ESG)?

The FDA ESG is the secure electronic platform through which eDRLS submissions — drug establishment registration, annual renewal, drug product listings, and updates — are transmitted to FDA. ESG requires specific account credentials and technical submission requirements. FDA Registration Assistance manages all ESG submissions on behalf of drug establishment clients.

10. How does drug establishment registration differ from food facility registration?

Key differences: drug establishments use eDRLS (21 CFR Part 207); food facilities use FURLS (21 CFR Part 1 Subpart H). Drug registration renews annually (October 1–December 31 every year); food renews biennially. Drug establishments must submit SPL drug product listings; food facilities have no equivalent product listing requirement. Drug U.S. Agents have active inspection facilitation obligations under 21 CFR 207.69.

11. What are the most common eDRLS filing errors?

Most common: incorrect or missing DUNS Number; SPL file structure errors (wrong XML formatting, missing required elements); NDC format errors; missing or incorrect U.S. Agent information; incomplete ingredient data in the drug product listing; failing to update listings when formulations or labeling change; and missing the annual October–December renewal window.

12. Does FDA Registration Assistance handle both initial eDRLS filing and ongoing maintenance?

Yes. FDA Registration Assistance provides complete eDRLS lifecycle management: initial drug establishment registration (DUNS coordination, labeler code, U.S. Agent designation, ESG account setup); SPL drug product listing preparation and submission; annual renewal management; listing updates; and ongoing compliance consultation.

13. Do private label drug distributors need eDRLS registration?

Yes. Private label distributors — companies that distribute drug products under their own label without manufacturing — must register as drug establishments and submit drug product listings in eDRLS. Their name appears on the drug label as the labeler, requiring their own FDA labeler code. This is a commonly missed registration for companies sourcing finished drug products from contract manufacturers.

14. What is the FEI number?

The FEI (Facility Establishment Identifier) is the unique identifier FDA assigns to a drug establishment upon eDRLS registration. The FEI is the primary identifier FDA uses to track the establishment across registration, listing, inspection, and enforcement records. The FEI must be referenced in drug product listings and is associated with the U.S. Agent designation for foreign establishments.

15. What happens if my drug establishment’s annual renewal is missed?

Missing the October–December annual renewal results in lapsed registration. For foreign establishments: every subsequent drug shipment is automatically detained under Import Alert 89-06. For domestic establishments: lapsed registration is a prohibited act under 21 U.S.C. § 331 exposing the company to FDA enforcement. FDA Registration Assistance tracks and manages annual renewal for all drug establishment clients.

16. Do API manufacturers need eDRLS registration separately?

Yes. API (Active Pharmaceutical Ingredient) manufacturers must register their establishments through eDRLS under 21 CFR Part 207 separately from any finished drug manufacturer using their APIs. Foreign API manufacturers are subject to the same eDRLS requirements and must designate a U.S. Agent.

17. What SPL data elements are required for a drug product listing?

Required SPL elements: product name and labeler name; marketing category (Rx/ANDA, Rx/NDA, OTC monograph, homeopathic OTC, biologic, etc.); active ingredient(s) with strength per dosage unit; inactive ingredients; dosage form; route of administration; labeling content in SPL XML format; NDC number(s) for each package; marketing start date; and the FEI number of the registering establishment.

18. How does the eDRLS process work for a foreign drug manufacturer new to the U.S. market?

Step sequence for foreign drug manufacturers: (1) Obtain DUNS Number; (2) Designate U.S. Agent under 21 CFR 207.69; (3) Create FDA ESG account and submit drug establishment registration to obtain FEI and labeler code; (4) Prepare drug product listings in SPL format; (5) Submit drug product listings through eDRLS; (6) Renew annually October–December. FDA Registration Assistance manages all steps.

19. Can a drug company manage eDRLS internally?

Technically yes — eDRLS is directly accessible. However, SPL file preparation, ESG technical submission requirements, and ongoing maintenance are complex and error-prone for first-time filers. SPL submission rejections are common without specialized expertise. FDA Registration Assistance provides done-for-you management that removes the internal resource burden and submission risk.

20. What is the difference between eDRLS and FURLS?

eDRLS (Electronic Drug Registration and Listing System) is for drug establishment registrations and drug product listings under 21 CFR Part 207. FURLS (FDA Unified Registration and Listing System) is for food facility registrations under 21 CFR Part 1 Subpart H, dietary supplement facilities, MoCRA cosmetics, and other categories. Drug companies use eDRLS; food manufacturers use FURLS. A company manufacturing both food and drug products must comply with both systems independently.

21. How does FDA Registration Assistance help foreign drug companies with eDRLS?

U.S. Agent designation and ongoing services (21 CFR 207.69); DUNS Number coordination; eDRLS drug establishment registration submission; SPL drug product listing preparation; annual renewal management; listing updates; and FDA inspection coordination through the U.S. Agent. 1,000+ clients. 135+ countries. 15+ years of FDA regulatory experience.

22. What are the consequences of eDRLS non-compliance?

Import Alert 89-06 for foreign establishments — every drug shipment automatically detained; FDA Warning Letters citing 21 U.S.C. § 331 and 21 CFR Part 207; import refusal of drug shipments; seizure of drug products; and injunctive action. eDRLS non-compliance can halt U.S. market access indefinitely.

23. What is eDRLS used for beyond initial registration?

eDRLS is used throughout the drug product lifecycle: initial establishment registration; drug product listing at market introduction; annual renewal of the establishment registration; listing updates for formulation, labeling, or marketing status changes; and product discontinuation filings. It is an ongoing compliance platform, not a one-time filing.

24. Is eDRLS the same for OTC and prescription drug companies?

The eDRLS registration and SPL listing process is the same platform for both OTC and prescription drug establishments. The difference lies in the marketing category selected in the SPL listing (OTC monograph, OTC NDA, Rx NDA, Rx ANDA, etc.) and the applicable FDA approval or monograph compliance requirements for the drug itself. eDRLS registration and listing obligations are the same regardless of whether the drug requires a prescription.

25. How do I get started with FDA eDRLS compliance support?

Contact FDA Registration Assistance at info@fdaregistrationassistance.com or call +1 (928) 275-8333. Provide your drug establishment name and address, establishment type, whether domestic or foreign, drug product information, and any existing FDA registration information. FDA Registration Assistance will assess your eDRLS obligations and begin the registration and listing process. See also: food facility registration for food companies and medical device services if your company also manufactures devices.

Reviewed By Hector Matos, Senior Regulatory Compliance Specialist · 15+ years FDA compliance experience · Published February 2026