The RLD / comparator is discontinued or not marketed — how do I source the reference product for my BE study?

Question

Accepted Answer

Older reference products are often withdrawn commercially — or were never launched in your country — so the comparator you need for the BE study cannot be bought locally. The reason for withdrawal matters: a product withdrawn for safety/efficacy blocks the generic; a commercial withdrawal does not. Steps: Confirm the correct comparator and its current status: FDA Orange Book (RLD / Reference Standard + the Discontinued list), the WHO list of international comparator products, and the EMA reference product for your molecule. Establish why it is discontinued. If withdrawn for safety or efficacy, a generic cannot rely on it — reassess the project. If commercial, you may proceed with a sourced comparator. Source the innovator batch from a recognised reference market (an ICH region — EU, US, Japan — or a WHO-listed comparator country) with full chain-of-custody: purchase invoice, batch number, expiry and Certificate of Analysis. If no comparator exists in any market, apply the WHO stepwise approach for selecting an alternative comparator (TRS 1003, Annex 6). Document the comparator justification, origin and status in the BE protocol and in Module 1 so the assessor accepts it up front.

The RLD / comparator is discontinued or not marketed — how do I source the reference product for my BE study?

Why this happens

What to do, step by step