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.

Pharmaceutical establishments based in the U.S. and outside the U.S. that are involved in manufacturing, relabeling, repackaging, distributing, or importing OTC drugs for commercial use in the United States are required to register and list their products. FDA drug establishment registration includes submitting establishment information in the Structured Product Labeling (SPL) format. SPL is a coded data format adopted by the FDA for drug establishment registration and drug listing. OTC drug listing also requires submitting drug product labels and drug information in SPL format.