Who Must Register a Drug Facility with FDA?
This guide explains exactly which establishment types must register, the difference between Drug Establishment Registration and Drug Listing, how NDC numbers work, the DRLM submission portal, exemptions, and what FDA Registration Assistance manages for drug companies worldwide.
Drug Establishment Types — Required vs. Exempt
Under 21 CFR Part 207, the registration requirement depends on the specific activities performed at the establishment — not just the company's commercial role. The table below shows which establishment types must register and which are exempt:
| Establishment Type | Registration Required? | Notes |
|---|---|---|
| Drug Manufacturer (finished dosage form) | Required | Manufactures prescription or OTC drugs for U.S. commercial distribution. Domestic and foreign. |
| API Manufacturer | Required | Manufactures active pharmaceutical ingredients for incorporation into drug products for the U.S. market. |
| Contract Manufacturer (CMO) | Required | Manufactures, processes, or packs drug products under contract for another company. Must register regardless of who holds the NDA. |
| Repackager / Relabeler | Required | Repackages or relabels drug products for U.S. commercial distribution. Considered a manufacturing operation under 21 CFR Part 207. |
| Salvager | Required | Reconditions drug products. Must register and list reconditioned products. |
| Outsourcing Facility (503B) | Special Registration | Human drug compounders voluntarily registering under Section 503B of the FDCA (added by DQSA 2013). Subject to CGMP and biennial inspections. Separate pathway from standard drug manufacturers. |
| Quality Control / Analytical Testing Lab (testing only) | May Be Exempt | Laboratories that only perform quality control testing without any manufacturing, packing, or labeling activities may be exempt. Regulatory review required to confirm. |
| Licensed Practitioner (professional practice) | Exempt | Physicians, pharmacists, and other licensed practitioners who prepare drugs solely in the course of professional practice for their own patients — not for sale — are exempt under 21 U.S.C. § 360(g). |
| Pharmacy (compounding per valid Rx) | Exempt (traditional Rx compounding) | State-licensed pharmacies compounding pursuant to valid patient-specific prescriptions under 503A are generally exempt from registration. Outsourcing facilities (503B) are not exempt. |
| Distributor (no manufacturing) | Not Required | Entities that only distribute finished drug products without performing any manufacturing operations do not register as manufacturers. Drug listing obligations may still apply depending on the role. |
Drug Establishment Registration vs. Drug Listing — What's the Difference?
The live page on the site conflates these two requirements. They are entirely separate obligations with different purposes, different submission formats, and different update triggers. Both are submitted through the DRLM portal but serve different regulatory functions:
Drug Establishment Registration
What it identifies: The facility — its legal name, address, establishment type, and U.S. Agent for foreign establishments.
Governing regulation: 21 CFR Part 207.21
Renewal: Annual — October 1 through December 31 every year.
Key output: FDA Establishment Registration Number (ERN). This number must appear on drug labeling for certain drug products.
Drug Listing
What it identifies: Each specific drug product — its NDC number, active and inactive ingredients, dosage form, route of administration, labeling, and marketing status.
Governing regulation: 21 CFR Part 207.49
Updates: During annual renewal AND within 30 days of any product change — new product, discontinuation, formulation change, labeling change.
Key output: NDC number on file in FDA's drug listing database. Required for commercial distribution.
Both registration and listing are submitted electronically in SPL (Structured Product Labeling) format through the DRLM (Drug Registration and Listing System) portal at access.fda.gov. SPL is an XML-based document standard. Non-SPL submissions are not accepted.
NDC Numbers — What They Are and Why They Matter
The National Drug Code (NDC) number is the unique product identifier for every drug product marketed in the United States. It is a 10-digit or 11-digit number divided into three segments: Labeler Code (assigned by FDA when the establishment registers), Product Code (assigned by the labeler for each product formulation), and Package Code (assigned by the labeler for each distinct package size or type).
Every distinct drug product — defined by its active ingredient(s), dosage form, route of administration, and labeling — must have its own NDC number registered in FDA's drug listing system. Products with the same formulation but different package sizes (e.g., 30-count and 90-count bottles) have different package codes but share the same product code.
Why NDC Numbers Matter for Import
Drug shipments entering the United States are screened against FDA's NDC database. A drug product arriving at a U.S. port without a registered NDC number — or with an NDC number that does not match the product's formulation and labeling on file — will be flagged for examination or refused admission. NDC accuracy in drug listing submissions is a critical compliance point for foreign drug manufacturers.
NDC Numbers Are Not FDA Approval
Having an NDC number means the product is listed with FDA — not that FDA has approved it. For OTC monograph drugs, listing is sufficient for marketing; the NDC confirms the product is on FDA's radar. For prescription drugs, an NDC number must accompany an approved NDA or ANDA. Having an NDC without required approval does not make the drug legally marketable.
How Drug Establishment Registration Works — Step by Step
Determine Registration Obligation
Confirm the establishment's specific activities against the registration requirements of 21 CFR Part 207. Manufacturing, processing, packing, labeling, repacking, or relabeling drug products for U.S. commercial distribution all trigger registration. Testing-only labs and pure distributors should conduct a regulatory review to confirm their status. FDA Registration Assistance performs this assessment before any filings are made.
Obtain the Labeler Code
The first step in drug listing is obtaining a Labeler Code from FDA — the first segment of the NDC number. The Labeler Code is assigned by FDA when the establishment's drug listing information is first submitted through DRLM. The Labeler Code identifies the company responsible for placing the drug product into U.S. commerce. FDA Registration Assistance manages the Labeler Code assignment process.
Prepare SPL Submissions
Drug Establishment Registration and Drug Listing must be submitted in SPL (Structured Product Labeling) format — an XML-based standard. FDA does not accept paper submissions or non-SPL electronic formats for these filings. FDA Registration Assistance prepares all SPL submissions and handles the technical formatting requirements for DRLM submissions.
Designate a U.S. Agent (Foreign Facilities)
Foreign drug establishments must designate a U.S. Agent under 21 CFR Part 207.69 before registration is complete. The U.S. Agent must have a physical U.S. address, assist FDA with inspection scheduling and coordination, and serve as FDA's official domestic contact. The drug U.S. Agent has a specific inspection facilitation role under 21 U.S.C. § 360(b) — distinct from the food facility U.S. Agent. FDA Registration Assistance provides U.S. Agent services for foreign drug establishments.
Submit Through DRLM
Submit the Drug Establishment Registration and initial Drug Listings through the DRLM portal at access.fda.gov. Registration must be completed before commercial distribution begins. After submission, FDA processes the registration and assigns an Establishment Registration Number (ERN).
Annual Renewal — October 1 to December 31
Drug Establishment Registration must be renewed annually during October 1 through December 31. Drug listings must also be updated during this window — and within 30 days whenever any product information changes during the year. Missing the annual renewal results in inactive registration status and is a prohibited act under 21 U.S.C. § 331. FDA Registration Assistance manages annual renewals for all drug establishments it serves.
Special Requirements for Foreign Drug Establishments
Foreign drug manufacturers face all the same registration, listing, and renewal requirements as domestic establishments — plus additional requirements that apply specifically to foreign facilities:
U.S. Agent with Inspection Role
Under 21 CFR Part 207.69 and 21 U.S.C. § 360(b), the U.S. Agent for a foreign drug establishment must assist FDA with inspection scheduling and facilitation — a more active role than the food facility U.S. Agent. The U.S. Agent must be available to respond to FDA requests for records and assist with coordinating FDA inspectors' access to the foreign establishment.
CGMP Inspections
Foreign drug establishments are subject to FDA CGMP (Current Good Manufacturing Practice) inspections under 21 CFR Parts 210 and 211. FDA conducts foreign establishment inspections as part of its regular inspection program. Registration alone does not satisfy CGMP compliance — it is a separate concurrent requirement. The U.S. Agent plays a key role in inspection coordination.
Import Screening
Drug shipments from foreign establishments are screened against FDA's drug registration and listing database at U.S. ports of entry. Shipments from unregistered establishments, or shipments of unlisted drug products, can be detained or refused admission. NDC accuracy and active registration status are verified during import screening for every drug shipment.
FDA Registration Assistance serves foreign drug manufacturers in 135+ countries — managing Drug Establishment Registration, Drug Listing, Labeler Code assignment, NDC number structuring, U.S. Agent designation with inspection facilitation capability, and annual renewal management. Foreign drug companies do not need to navigate the DRLM portal or SPL format directly.
Register Your Drug Facility with FDA — Correctly, the First Time
FDA Registration Assistance manages the entire Drug Establishment Registration process — obligation assessment, SPL preparation, U.S. Agent designation, Labeler Code assignment, Drug Listing with NDC numbers, DRLM submission, and annual renewal. 1,000+ clients. 135+ countries. 15+ years of combined FDA regulatory experience.
Contact us at info@fdaregistrationassistance.com or call +1 (928) 275-8333.
Frequently Asked Questions — FDA Drug Establishment Registration
1. Who must register a drug facility with FDA?
Any establishment that manufactures, prepares, propagates, compounds, processes, repacks, or relabels a drug product for commercial distribution in the United States must register under 21 U.S.C. § 360 and 21 CFR Part 207. This applies to domestic and foreign manufacturers, CMOs, repackagers, relabelers, API producers, and outsourcing facilities.
2. What is the governing regulation for FDA Drug Establishment Registration?
Drug Establishment Registration is governed by Section 510 of the FDCA (21 U.S.C. § 360) and implemented by 21 CFR Part 207. The 2016 final rule under Part 207 introduced mandatory SPL format for all submissions through the DRLM portal at access.fda.gov.
3. Do contract manufacturers (CMOs) need to register with FDA?
Yes. CMOs that manufacture, process, pack, or label drug products for U.S. distribution must register as drug establishments under 21 CFR Part 207 and list all drug products manufactured. The CMO's registration obligation is independent of — and in addition to — any NDA or ANDA held by the contract sponsor.
4. Do repackagers and relabelers need FDA drug establishment registration?
Yes. Repacking and relabeling are drug manufacturing operations under 21 CFR Part 207. Establishments that repack or relabel prescription or OTC drugs for U.S. commercial distribution must register and list the drug products they handle.
5. What is Drug Listing and how is it different from Establishment Registration?
Drug Establishment Registration identifies the facility under 21 CFR Part 207.21. Drug Listing identifies each specific drug product under 21 CFR Part 207.49 — including its NDC number, active and inactive ingredients, dosage form, route of administration, and labeling. Both are submitted through the DRLM portal in SPL format. An establishment can be registered before any products are listed, but drug products cannot be marketed without both active registration and current listing.
6. What is an NDC number and when is it required?
An NDC (National Drug Code) number is the unique product identifier for each drug product in the U.S. market. It consists of three segments: Labeler Code (assigned by FDA), Product Code (assigned by the labeler), and Package Code (assigned by the labeler per package size). Every distinct drug product must have its own NDC number registered in FDA's drug listing system before commercial distribution. Import shipments are screened against the NDC database at U.S. ports of entry.
7. How often must Drug Establishment Registration be renewed?
Drug Establishment Registration must be renewed annually — October 1 through December 31 every year under 21 CFR Part 207.29. Missing the window results in inactive registration status. Unlike FDA Food Facility Registration (biennial), drug establishment registration requires action every single year. FDA Registration Assistance manages all annual renewals.
8. What is the DRLM portal and how is it used?
DRLM (Drug Registration and Listing System) is FDA's electronic submission portal at access.fda.gov. All drug establishment registrations, drug listings, annual renewals, and updates must be submitted electronically through DRLM in SPL (Structured Product Labeling) XML format. FDA does not accept non-SPL submissions.
9. What types of drug establishments must register with FDA?
Under 21 CFR Part 207: drug manufacturers (finished dosage form); API manufacturers; contract manufacturers (CMOs); repackagers and relabelers; salvagers; and outsourcing facilities (Section 503B/DQSA). Analytical testing labs that only perform QC testing without manufacturing may be exempt — a regulatory review confirms this.
10. Are there exemptions from FDA Drug Establishment Registration?
Yes, under 21 U.S.C. § 360(g) and 21 CFR Part 207.13. Exempt categories include: licensed practitioners preparing drugs in professional practice for their own patients (not for sale); pharmacies compounding pursuant to valid patient-specific prescriptions under Section 503A; and blood banks under certain conditions. Drug manufacturers, CMOs, repackagers, and relabelers for commercial distribution are not exempt.
11. What are outsourcing facilities and how do they register?
Outsourcing facilities are human drug compounders voluntarily registered under Section 503B of the FDCA, added by the Drug Quality and Security Act (DQSA) of 2013. They can distribute compounded drugs without patient-specific prescriptions but are subject to CGMP requirements, biennial FDA inspections, and drug listing under 21 CFR Part 207. Outsourcing facility registration follows a separate pathway from standard drug manufacturer registration.
12. Do foreign drug manufacturers need to register with FDA?
Yes. Foreign establishments manufacturing drug products for U.S. distribution must register under 21 U.S.C. § 360 and 21 CFR Part 207, and must designate a U.S. Agent under 21 CFR Part 207.69 with a physical U.S. address.
13. What does the U.S. Agent do for a foreign drug establishment?
Under 21 CFR Part 207.69 and 21 U.S.C. § 360(b), the U.S. Agent for a foreign drug establishment must assist FDA with inspection scheduling and facilitation, help the establishment respond to FDA records requests, and serve as FDA's official domestic contact. This inspection facilitation role is more active than the food facility U.S. Agent obligation.
14. Can a drug product be sold in the United States without FDA establishment registration?
No. Distributing drugs from an unregistered establishment is a prohibited act under 21 U.S.C. § 331. Importing drug products from unregistered foreign establishments can be refused at U.S. ports of entry. Registration, Drug Listing, and any required NDA/ANDA approval are all separate, concurrent requirements that must each be satisfied independently.
15. Does Drug Establishment Registration mean the drug is FDA-approved?
No. Registration means the facility is in FDA's system as required by law. Drug approval — through an NDA or ANDA — is a separate product-specific scientific review process. OTC drugs marketed under a final FDA OTC monograph do not require an NDA but do require establishment registration and drug listing.
16. What is SPL format and why is it required?
SPL (Structured Product Labeling) is an XML-based document standard required by FDA for all drug establishment registrations, drug listings, and labeling submissions through the DRLM portal since the 2016 21 CFR Part 207 final rule. FDA does not accept paper or non-SPL electronic submissions for drug establishment registrations or drug listings.
17. Do API manufacturers need to register with FDA?
Yes. Active Pharmaceutical Ingredient manufacturers that manufacture APIs for drug products distributed in the United States must register under 21 CFR Part 207 and list their APIs. This applies to foreign API manufacturers exporting to the U.S. regardless of who holds the NDA for the finished drug product.
18. What is the difference between drug registration for Rx vs. OTC drugs?
The Drug Establishment Registration and Drug Listing requirements under 21 CFR Part 207 apply identically to both Rx and OTC drugs. The difference is in the product pathway: Rx drugs (and some OTC drugs) require NDA or ANDA approval; OTC drugs under a final monograph do not require premarket approval but must comply with monograph requirements. In both cases, the manufacturer must be registered and each product must be listed with an NDC number.
19. Must drug listings be updated and how often?
Yes. Drug listings must be updated annually during the October 1 – December 31 renewal window, and additionally within 30 days whenever a product is newly marketed, discontinued, or has a change in formulation, labeling, NDC number, or marketing status under 21 CFR Part 207. Outdated drug listings create a compliance discrepancy between what is marketed and what is on file with FDA.
20. What happens if a drug establishment fails to renew its registration?
An establishment that misses the October 1 – December 31 annual renewal has its registration become inactive. Distributing drugs from an inactive establishment is a prohibited act under 21 U.S.C. § 331. Import shipments from foreign establishments with inactive registrations may be refused admission at U.S. ports of entry. Reactivation requires re-registration through the DRLM system.
21. What are CGMP requirements and do they apply to registered drug establishments?
Yes. Current Good Manufacturing Practice requirements under 21 CFR Parts 210 and 211 apply to registered drug manufacturers, repackagers, and relabelers. Registration is a separate, concurrent requirement — not a substitute for CGMP compliance. FDA conducts CGMP inspections of registered drug establishments. Non-CGMP compliance can result in Warning Letters, Import Alerts, and drug approval withdrawal.
22. What are the most common drug establishment registration mistakes?
Most common mistakes: distributing before registration is complete; missing the annual October–December renewal window; incorrect establishment type in the DRLM submission; drug listings missing correct NDC numbers or SPL formatting; not updating drug listings within 30 days of product changes; foreign establishments without a designated U.S. Agent; and treating registration as equivalent to FDA approval.
23. Can FDA Registration Assistance handle both Establishment Registration and Drug Listing?
Yes. FDA Registration Assistance manages the complete Drug Establishment Registration process — regulatory obligation assessment, SPL submission preparation, Labeler Code assignment, NDC number structuring, Drug Listing through DRLM, U.S. Agent designation for foreign establishments, and annual renewal management for all registered drug establishments.
24. How does Drug Establishment Registration compare to Food Facility Registration?
Both are FDA registration requirements, but they are entirely separate systems. Drug Establishment Registration is under 21 CFR Part 207 via the DRLM portal — annual renewal. FDA Food Facility Registration is under 21 CFR Part 1 via FURLS — biennial renewal. Facilities that manufacture both drug and food products must maintain both registrations independently.
25. How do I get started with FDA Drug Establishment Registration?
Contact FDA Registration Assistance at info@fdaregistrationassistance.com or call +1 (928) 275-8333. Provide your establishment's location, the drug products you manufacture or process, and your U.S. distribution plans. FDA Registration Assistance will evaluate your registration obligations, prepare all SPL submissions, and manage the entire process.
