Reference Listed Drug
The originally approved drug product against which generics or biosimilars are compared for regulatory approval. The reference listed drug holds the original safety and efficacy data. Any biosimilar somatropin, for example, must demonstrate high similarity to a specific approved reference somatropin.
Technical Context
The RLD is identified in the FDA's Orange Book (Approved Drug Products with Therapeutic Equivalence Evaluations) for NDA products or the Purple Book (Lists of Licensed Biological Products with Reference Product Exclusivity and Biosimilarity or Interchangeability Evaluations) for BLA products. For ANDA applicants, the RLD determines: the active ingredient standard (must be identical), the dosage form and route of administration (must match), and the bioequivalence comparison standard (PK study comparing generic to RLD). For biosimilar applicants (351(k)), the reference product determines the analytical, functional, and clinical comparability standards. A single drug may have different RLDs in different markets (e.g. different somatropin products serve as reference in US vs EU). The RLD holder's data package provides the safety and efficacy foundation that generics and biosimilars rely upon.