As per FDA, A Reference Listed Drug (RLD) is an approved drug product to which new generic versions are compared to show that they are bioequivalent. A drug company seeking approval to market a generic equivalent must refer to the Reference Listed Drug in its Abbreviated New Drug Application (ANDA). The FDA assigns a single reference listed drug as the standard to which all generic versions must be shown to be bioequivalent; moreover, FDA hopes to avoid possible significant variations among generic drugs and their brand name counterparts. When the patent on a brand-name drug nears its expiration, drug companies that want to manufacture a generic drug can apply to the FDA to sell a generic version of the innovator brand drug.
The generic medicine is a copy of a brand-name drug that must have the same safety, same quality as the innovator brand medicine, and the same strength of active and inactive ingredients. The use of generic medicines eases the accessibility of patients to quality drugs at lower prices as compared to the price of an innovator brand drug.
The procedure of generic drug development
The FDA’s Drug Price Competition and Patent Term Restoration Act of 1984, also known as the Hatch-Waxman Act, amended the Federal Food, Drug, and Cosmetic Act to create an abbreviated pathway for approving new drugs therapeutically equivalent to a branded drug. According to this Act, a manufacturer needs to demonstrate the bioequivalence of a generic drug to a reference listed drug through an abbreviated new drug application (ANDA), rather than repeating the costly and time-consuming safety and efficacy studies required of innovative, new chemical entities. To get approval for a generic drug, an ANDA applicant is not required to provide independent evidence of the safety and effectiveness of the proposed generic drug. Instead, the applicant relies on FDA’s finding that a previously approved drug product, i.e., the RLD, is safe and effective and must demonstrate, among other things, that the proposed generic drug is the same as the RLD in certain ways.
The FDA regards a generic drug to be bioequivalent to the reference listed drug if the rate and extent of absorption of the generic drug do not show a significant difference from the rate and extent of absorption of the listed drug when administered at the same molar dose of the therapeutic ingredient under similar experimental conditions in either a single dose or multiple doses. Once the FDA approves the ANDA and the branded version is no longer protected by patent or market exclusivity, one can bring the generic product to market.
Statistics on Generic drug development
According to the FDA 2019 Annual Report of the Office of Generic Drugs (OGD) in the Center for Drug Evaluation and Research (CDER), FDA accomplished more than 1000 generic drug final and tentative approvals.