API source replacement

Hello everyone, I have a question for an API supplier replacement. The product is developed and registered (for other applicants) with an API (CEP) and for commercial reasons we have decided the replacement of the API supplier.
Is it possible for a new application to have CEP LoA only for the new API supplier without a LOA for the old one although the development and validation/ stability is based on the old one API ?
In the variation guideline BIII13 for replacement of a CEP API supplier no further validation studies are required, but this is the case for replacement of an API supplier to an approved dossier and not for a new application).
I would appreciate your assistance on that

Hi Zapia u are not going to use the old api supplier commercially so.i would concentrate on the pharmaceutical development and show equivalency there only. In other words in whatever market u are submitting the certificate is not going to be used to support manufacture

Hi Zampia,
In my opinion one has to differentiate here between the GMP-guided implementation of a new API source and the regulatory aspects. CEPs do not address “subtle” aspects like particle size distribution and routes of synthesis are usually different between manufacturers, so from GMP perspective at least some validation activities on finished-product level are needed. Depending on a case-by-case evaluation, also a new stability evalution might be appropriate.

In any case, you need a comprehensive comparison between the current and new API regarding all quality characteristics, e.g.: is their impurity profile similar (not only: does it comply with the EP limits)? How is their particle size distribution (especially if it matters for the drug product). Do the two APIs have a similar re-test period? How stable is the API?

From pure regulatory perspective, I see no direct obligation to include stability data of finished product batches with the new API in a new application for this product. However, one should shortly discuss the suitability of the stability data of batches with the old API for the “new” product. Also, if a new FP-stability study is done anyway (which I would recommend), one can commit this in module 3.2.p.8.2. in order to assure assessors that one is aware and has adequately addressed this topic. H

In my company we have much experience for exchanging/ introducing new API sources by post-approval variations and the above approach was generally excepted in EU. However, several non-EU countries may have national requirements in place to presend 6-12 months FP-stability data with a new API source.

Hope this helps - kind regards,