Definition
Reference Listed Drug (RLD) is the FDA-approved drug product identified by FDA as the standard to which all generic versions (ANDAs) or 505(b)(2) applications must show bioequivalence. The RLD provides the safety and efficacy foundation for abbreviated approval pathways.
How RLD Works
FDA designates RLDs in the Orange Book. Generic and 505(b)(2) applicants must conduct bioequivalence studies comparing their product to the RLD under similar conditions.
RLD Requirements
| Requirement | Description |
|---|---|
| Bioequivalence Testing | Must use RLD as comparator product |
| Same Strength | Match RLD strength(s) |
| Same Dosage Form | Match RLD dosage form |
| Same Route | Match RLD route of administration |
RLD Designation
FDA considers several factors when designating RLD:
- First approved drug product
- Suitability for comparative testing
- Availability for purchase
- Active ingredient and formulation stability
Why BD Teams Track RLD
For business development professionals, RLD affects development strategy:
- Deal Implication: RLD selection affects BE study design and 505(b)(2) strategy
- Due Diligence Focus: Verify RLD availability and any formulation changes
- Opportunity Signal: Products with complex RLD situations may need specialized partners