By definition, the NDC is a standard format of 10 numerical digits with dashes separating the 3 segments in a 5-4-1, 4-4-2, or 5-3-2 configuration.

The first 4 or 5 digits represent the manufacturer and are assigned by the FDA. The next 3 or 4 digits represent the specific product (drug, strength, dose, dosage form) and are assigned by the manufacturer. The final 1 or 2 digits represent the package size and are also assigned by the manufacturer.

Since June 1, 2009. the FDA requires that firms register and list their drug products electronically, limiting NDCs to 10-digits, and invalidating other formats. However, confusion exists because of a proliferation of different NDC notations and variants (derivatives).

For example, the Centers for Medicare and Medicaid Services (CMS) created an 11-digit NDC derivative which pads the product code or package code segments of the NDC with a leading zero, thus resulting in a fixed length 5-4-2 configuration (but always written without dashes). This format was adopted by data standards selected pursuant to HIPAA regulation, so other government agencies may use and databases may contain the 11-digit derivative of the original NDC. The 11-digit format is the only one permitted in National Council of Prescription Drug Programs (NCPDP) messages, and HIPAA regulations mandate the 11-digit format for all HIPAA transactions. There are other derivatives as well.

All prescription and over the counter drugs are assigned NDCs.