Drug Establishment Registration via EDRLS: Complete Guide

What Is EDRLS?

The Electronic Drug Registration and Listing System (EDRLS) is FDA's mandatory electronic portal for drug establishment registration and drug product listing. Since 2017, FDA has required all drug registration and listing submissions to be made electronically in Structured Product Labeling (SPL) format — paper submissions are no longer accepted.

EDRLS replaced the legacy paper-based registration process (FDA Forms 2656 and 2657) and is integrated with FDA's broader SPL submission infrastructure. The system is accessible through the FDA Electronic Submissions Gateway (ESG) or through FDA's SPL submission portal. For the official guidance, see FDA's EDRLS Instructions.

SPL Format Basics

Structured Product Labeling (SPL) is an XML-based document markup standard approved by Health Level Seven (HL7). All drug establishment registrations and drug product listings must be submitted as SPL documents. Key SPL concepts include:

• SPL document types: Establishment registration (type 26), drug listing (type 25), and other specialized types
• SPL authoring tools: FDA provides a free SPL authoring tool (FDA SPL Xforms), and third-party tools are available from commercial vendors
• Validation: SPL documents must pass FDA's validation checks before acceptance

Who Must Register Through EDRLS

Under 21 CFR Part 207, the following establishments must register with FDA:

• Manufacturers: Establishments that make finished drug products or active pharmaceutical ingredients (APIs)
• Repackers: Establishments that repackage drugs into different containers
• Relabelers: Establishments that replace or modify drug labeling
• Salvagers: Establishments that salvage drugs from damaged or returned shipments
• Foreign establishments: Any establishment outside the US that manufactures, repacks, relabels, or salvages drugs intended for US import

Important Exemptions

• Pharmacies that compound drugs for individual patients under state license
• Hospitals, clinics, and public health agencies that operate under local health jurisdiction
• Licensed practitioners who manufacture or compound drugs for their own patients
• Establishments solely engaged in distribution (not manufacturing) of drugs

Prerequisites for Registration

Before you can register through EDRLS, you need several identifiers and accounts:

1. DUNS Number

Every registering establishment needs a DUNS number from Dun & Bradstreet. This is the same identifier required for food facility registration. Request one at dnb.com — it's free and typically takes 1–2 business days.

2. NDC Labeler Code

Before listing drugs, you must obtain a National Drug Code (NDC) Labeler Code from FDA. The Labeler Code is the first segment of the NDC number and identifies the manufacturer, repacker, or distributor. Request a Labeler Code through the NDC Directory system.

3. FDA ESG Account or SPL Submission Account

To submit SPL documents electronically, you need an account with FDA's Electronic Submissions Gateway (ESG) or access to FDA's SPL submission web interface. The ESG is used for higher-volume automated submissions, while the web interface is suitable for individual submissions.

4. US Agent (Foreign Establishments)

Foreign establishments must designate a US Agent physically located in the United States. The US Agent's information is included in the SPL registration submission. Assurentry provides US Agent services for drug establishments.

EDRLS Registration Walkthrough

The registration process involves creating and submitting an SPL document of type "establishment registration" (SPL document type 26). Here is the step-by-step process:

Drug Listing Requirements

Drug listing is a separate but related requirement under 21 CFR Part 207. When you register your establishment, you must also list all drugs manufactured, repacked, relabeled, or salvaged at that establishment. Drug listing uses SPL document type 25.

What Information Is Required

• NDC number: The complete National Drug Code including labeler code, product code, and package code
• Drug name: Both proprietary (brand) and non-proprietary (generic) names
• Active ingredients: Each active ingredient with its strength
• Dosage form and route of administration: Tablet, capsule, injection, etc.
• Labeling: A copy of all labeling associated with the drug, including the package insert
• Establishment information: The FEI number of the establishment where the drug is manufactured

Listing Updates

Drug listings must be updated in June and December of each year, or within 5 business days of a change in the listing information (such as adding a new drug, discontinuing a drug, or modifying the formulation). For a deeper look at NDC number structure, see our NDC Number Complete Guide.

Annual Registration Renewal

Drug establishment registrations must be renewed annually between October 1 and December 31. Unlike food facility registrations (which are biennial), drug establishment registrations expire every year if not renewed.

Renewal Process

• Submit a new establishment registration SPL through EDRLS during the renewal window
• Review and update all establishment information, including activities, address, and US Agent
• Ensure all drug listings are current and accurate
• Foreign establishments must also pay the annual drug establishment fee under GDUFA or PDUFA (if applicable)

Annual Fees

Depending on the type of drugs manufactured, your establishment may be subject to annual user fees under the Prescription Drug User Fee Act (PDUFA) or the Generic Drug User Fee Amendments (GDUFA). These fees are separate from the registration process and are invoiced directly by FDA. Fee amounts are published annually in the Federal Register. For current fees, check FDA User Fee Programs.