Do you repeat process validation after change of API manufacturer?

Do you repeat process validation after change of API manufacturer?
one batch or more?


You need to perform confirmation study with one batch.

Luqman Ikram

Yes (you will have to review the documentation). The new supplier may have a different manufacturing process or may have supplied you with a new form (crystals instead of flakes or vice versa).

The impact to validation would require a “change management board” decision. This should be done with a variety of people at the company. Based on the changes, assessment, small scale/lab batches, etc. you might feel that the API’s should operate the same. If during document review, chemical analsysis, purity review, manufacturer audit, etc. you might determine that there is more risk that things will change. This would require full revalidation.

Regardless, I need to refer you to stability requirements (not my forte). I believe stability guidelines are clear what changes require stability lots to be tested and how many stability lots are tested. For example flavorants might not require stability, while preservatives do require more stability testing. For API changes (what we have here) stability testing will definitely need to be done (how many? I can’t help you on this).

In my personal oppinion, stabily testing will test much more rigorously than validation testing. Typically validation testing happens at T=0 (right after a lot is made). Stability testing can happen at time points (T=9 months for example). So, I think stability lots have much more information than validation lots.

One possibility is to do one “confimration run” and do increased sampling at T=0. In the validation report you can reference the T=0 results, but also reference the eventual stability results.

I don’t think the new API lot can be released for commercial release until stability is complete - so the validation report can wait (until stability is ready) and not mess up commercial release.

Please plan ahead because obviously, this can take many months to process before commercial release happens - so it doesn’t happen overnight.


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FDA answers you as following;
If you propose to add additional sources of API for the same drug substance, you should provide the following CMC information:

  • Comparison and justification of comparability (by the applicant) of the physico-chemical properties and impurities of the drug substance from each source.
  • Appropriate stability data on three batches of drug product qualifying the first API source used in the bioequivalence (BE) studies as recommended by the FDA stability guidance.
  • A single pilot scale batch of the drug product bio-strength(s) manufactured using the second or each of the other proposed API source(s) used to support the ANDA application, along with comparative dissolution data
  • Appropriate stability data (accelerated and long-term for 6 months at the time of filing) on the strength(s) manufactured for each API source. Appropriate stability data may in some cases include intermediate condition stability data


Can you post the reference (webpage) for the FDA quote?

For sure you may find it at the following link;
Please take a look at Q12.
Hope it helps.

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