According to the U.S. Food and Drug Administration's (FDA) Drug Regulations, all establishments involved in the formulation, development, manufacturing, distribution, processing, or packaging of drugs marketed in the United States must register with the FDA. Additionally, all establishments involved in the formulation, development, manufacturing, processing, or packaging of drugs sold in the U.S. must list all their marketed products through the Electronic Drug Registration and Listing System (eDRLS).

This applies to all manufacturers, processors, packagers, and labelers of OTC (over-the-counter) drugs, APIs (active pharmaceutical ingredients), non-prescription drugs, homeopathic products, and prescription drugs, both domestic and foreign. For registration, companies located outside the United States must designate a U.S. agent to serve as the primary point of contact with the FDA on behalf of the foreign company.

Registered drug establishments are required to provide the FDA with an updated list of all drugs manufactured, prepared, propagated, compounded, or processed for commercial sale. Drugs are identified and reported using a unique 10-digit, three-segment number called the National Drug Code (NDC Labeler Code), which serves as the universal product identifier for drugs. The FDA publishes the NDC numbers listed in the NDC directory, along with the information submitted as part of the listing.

To obtain an NDC Labeler Code, drug manufacturers must submit an application in SPL (Structured Product Labeling) format through the FDA's Electronic Submissions Gateway (ESG). In order to successfully submit the SPL, drug manufacturers should work with their U.S. agent to ensure that the relevant information is updated.