Drug Establishment Registration

As per 21 CFR 207, it is the manufacturer’s obligation to register their establishments with USFDA before marketing the drugs in the USA. The drug manufacturers are also required to list all the drugs manufactured at their establishment and intended for marketing in the US.

Foreign facilities are required to appoint the US Agent for FDA drug establishment registration purposes. He will do all kinds of communications with the FDA for the NON-US firms.

The timelines for the renewal of the Drug Establishment are from 1st of October to 31st of December of every year.

The FDA drug establishment registration is applicable to bulk drugs, OTC drugs, and prescription drugs, generic drugs both for domestic and foreign import.

Who is required to register?

All the drug establishments – foreign and domestic must register their establishments and list all their drug products that are in commercial distribution in the USA.

Drug establishment registration and listing are required for the new/investigational drugs, generic/OTC/homeopathic drugs, facilities like drug testing, sterilization, etc.

Foreign establishments whose products are imported into the United States are required to appoint a US Agent. The US agent will physically be located in the US and will act as a liaison between the FDA and the firm.

Over-the-counter drugs (Non-prescription drugs) are categorized as “Generally Recognized as Safe and Effective (GRASE)” by the general public without seeking the advice of health professionals and they do not require FDA drug approvals such as NDA or ANDA. The structured Product Labelling (SPL) format needs to be followed to submit the drug establishment information for the registration. A coded data format (SPL), adopted by FDA is used for FDA drug establishment registration and drug listing. Drug Product Label & Drug Information in SPL format will have to be submitted in the process of OTC drug listing.

For each therapeutic class, an OTC drug monograph is developed and published by FDA.OTC monograph act as a “standard recipe’ which covers all the information like ingredients, dose, formulations, etc. Once an OTC monograph is implemented, manufacturers can make and market an OTC drug without FDA’s pre-approval.

Homeopathic drugs covered in Homeopathic Pharmacopeia of United States- HPUSP does not require FDA drug approval before they are marketed. Same regulations for Homeopathic drug products and OTC drugs will have to be followed.

Search FDA Drug Establishment Registration Database

https://www.accessdata.fda.gov/scripts/cder/drls/default.cfm

This FDA database contains details of currently registered establishments that manufacture FDA-approved drugs. 

If I am required to register my drug facility and list my drug products, how do I proceed?

Basically, 3 steps to be followed, and in each step, you will have to submit the periodic updates to maintain an accurate and current status: 

Step 1 – Establishment registration

Step 2 – Labeller code

Step 3 – Drug product listing(s)  

 FDA has picked up extensible mark-up language (XML) files in the SPL format for users to submit registration and listing data. Users may transmit the submission in the same format through FDA’s electronic submission gateway (ESG).

Registration Process

Create and submit an SPL document to register with FDA. 

The following has to be included for FDA Drug Establishment Registration:

Verification of the Name & DUN & Bradstreet, or Data Universal Numbering System (DUNS) number of the establishment 

Responsible person’s contact details for FDA communications  

All applicable business operations that the establishment performs

Name and DUNS of a U.S. agent and all importers required for foreign organizations 

Drug establishment current registration site-

https://www.accessdata.fda.gov/scripts/cder/drls/default.cfm

If you wish to look at the already registered organizations that can distribute the compound/drug in the US, you can visit the above link. The data is updated on each business day.

The database will keep updating based on the registration inactivation by FDA in case of non-compliance. For incomplete/expired/deregistered registrations as well the removal from the database is done. 

National Drug Code (NDC Code)

Drug establishments have to report all the drugs manufactured at their facility to FDA. Drugs are identified by a three-segment number called National Drug Code. National Drug Code serves as FDA’s universal product identifier for drugs.

 National Drug Code Directory is published by FDA which lists the NDC number and is updated daily. National Drug Code Directory contains information on drugs that are submitted to FDA in structured product labelling (SPL) electronic listing files by the manufacturer. National Drug Code Directory contains data for all drugs- prescription drugs and over-the-counter drugs. 

The first group of numbers (mentioned in the coloured font) identifies the labeller- drug manufacturer, repackager, or distributer- 12345-6789-0

The second group of numbers is the product code which identifies strength, dosage forms, or formulation- 12345-6789-0

The third group of numbers is the package code which identifies package sizes and types.12345-6789-0

 Two main configurations:

5-4-1 example: 12345-6789-0

5-3-2 example: 12345-678-90

Where can you find an NDC number?

The USFDA maintains a searchable database for National drug code search on their website. 

https://www.accessdata.fda.gov/scripts/cder/ndc/index.cfm

The NDC code can also be found in the package insert and/or on the packaging.