A Reference Listed Drugs (RLDs) refers to a marketed drug product approved by the FDA. The difference between the RLD and the generic drug lies in the purity of raw materials, the addition of other ingredients, and the manufacturing process. In Alfa Chemistry's consistency evaluation services, RLD is used to determine the bioequivalence of a product to an approved product. When our clients submit an ANDA, our experts refer to FDA-assigned RLDs in their applications that describe the full characteristics of the manufactured generic drug.
Purpose of RLD Research
The purpose of RLD research is to ensure that generic drugs meet the following general principles:
- Same safety and efficacy
- Same function (performance) and indications (intended use)
- Pharmaceutical equivalence
- Bioequivalence (BE)
Selection of the RLDs
When the selected RLD is no longer available (eg, discontinued for reasons other than safety and efficacy), the reference drug is a product approved through the ANDA pathway and designated as the Orange Book reference standard. Our experts help you select the correct RLD and Reference Preparations(RS) by using the guideline issued by the FDA, thereby alleviating from any confusion arising due to the use of RLD and RS while referencing the listed products in a generic ANDA application. Alfa Chemistry provides services of accurate identification of RLDs and RS during the pre-development phase of generic drugs.
| Types of Your Generic Drug | RLD | RS |
| Generic drug that is a duplicate of its RLD | The RLD is a listed drug approved for safety and efficacy under Section 505(c) of the FD&C Act and identified in the Orange Book as an RLD | If the RLD is marketed, it is also the RS
The applicants should check the Orange Book to confirm that the FDA has selected as the RS for that drug product |
| Generic drug for which a suitability application has been approved | The RLD is a listed drug with approved safety and efficacy as determined in the approved application for suitability | The listed drug identified in the approved suitability application is the RS |
| Generic drug that is the same as a drug product approved in a petitioned ANDA | The drug approved in the first petitioned ANDA is usually the RS
The applicants should check the Orange Book to confirm that the FDA has selected as the RS for that drug product |
Product Information Research
Our experts select RLDs based on available drugs that contain the same active pharmaceutical ingredient (API). Furthermore, the level of similarity between the product and the RLD largely determines the number of studies to be performed by comparing labels to determine the most appropriate RLD (e.g., in terms of route of administration or formulation).
- Whether legal raw materials are available
- Clinical data, adverse reaction data
- Product instructions
- Specifications of domestic and imported preparations
- Product quality standards (RLD standards, pharmacopoeia standards)
- Original prescription composition and process research data
- Drug stability information
- Patent status: Protection period of the reference product
- Production registration status (RLD product manufacturers, number of domestic production declaration manufacturers)
- Source of reference preparation
- Strengths and dosage forms
- API Form
- Dissolution profile
- Labelling
- Chemistry, manufacturing, and control: Inactive ingredients, scoring and conditions of use, bioequivalence and clinical deficiencies
