Reference Listed Drugs (RLDs) : Reference for the production of Generics

A Reference Listed Drug (RLD) is the original, innovative, branded product that has been approved by regulatory agencies such as the Food and Drug Administration (FDA) in the United States and European Medicinal Agency (EMA) in the European Union. The RLD Drug continues to remain as a standard or benchmark for the generic copies to obtain the licensing once the patent period from the RLD Drug is over.  The approval of the RLD Drugs undergoes several steps to obtain the approval. It begins with the submission of a New Drug Application (NDA) from a pharma company that develops a new drug.  Once this new drug is approved following all the safety and efficacy studies, the authorities assign the National Drug Code (NDC) to this innovative medicine as a special identifying number.

For a generic manufacturer, to manufacture the generic copies of the RLD Drug needs to undertake several steps:

1. Selection of the Reference Listed Drug (RLD): The first point is to choose the RLD Drug. To verify all patent related details and provision under the legal framework to develop a copy of the Reference Listed Drug when the product patent is valid in the country.
2. Development of formulation: Develop a   formulation that is qualitatively and quantitatively similar to the RLD Drugs in terms of its active ingredient, strength, dosage form, route of administration, and labelling.
3. Preclinical Trials: The preclinical studies (animal experiments) are usually exempted for the generic manufacturers. However, if required, on a case-to-case basis, it could be requested by the regulatory authorities.
4. Clinical trials – The generic drug needs to establish clinical equivalence to the RLD in terms of safety and efficacy. This is demonstrated by conducting comparative bioequivalence study with the Generic drug in healthy volunteers against the Reference Listed Drug (RLD).
5. Regulation submission: The generic drug manufacturer needs to submit an Abbreviated New Drug Application (ANDA) consisting of the pharmaceutical data, preclinical and the bioequivalence study reports to the authorities.
6. Evaluation and approval: After reviewing the ANDA, the regulatory authorities may ask for more details or clarifications, otherwise, if the submission meets the requirements, it will grant the licensee to manufacture and market the generic drug.
7. Post-marketing surveillance: Following the generic drug’s approval and placement on the market, the generics products will be monitored for therapeutic safety.

In conclusion, the Reference Listed Drug (RLD) is the original brand-name drug that is used to develop generic drugs. It is necessary to guarantee the high quality, safety, and efficacy of generic drugs similar to that of the Reference Listed Drug (RLD).