Peddi,

You are imprecise in your question! If this peak is in the solvent front and it does not interfere with the API assay, why is it OOS? If this is an RS (related substances) chromatography and you have performed a documented investigation, you may have a 'new' RS. Which means you will have to revise the method (go gradient) under CAPA (corrective action and preventative action).

Yes, it is for RS and we are using gradient method only. Since, the one injection which is leading to OOS is not comparable to other injections of the sequence we could not disregard this peak. Bruce Neagle

The basis behind 'forced degradation' (acid, base, heat, light) is to identify all peaks that are derived from the API (an RS) and the excipients. If this ghost peak is not an RS but from an excipient then nobody should care. However, if it is an RS you will have to revise your method and set an upper specification limit (USL).

Peddi,

The 'regulatory authorities' will expect a full documented investigation which includes an LIR (laboratory investigation report, HPLC suitability?) and an OOS. Until this lot has a assignable cause for the OOS it cannot be released to the market!

Peddi,

Your in never, never land. That is a NO win solution.

1. Implicate the HPLC: When was it maintained and calibrated? What else did it analyse? Was system suitability met at all times?

2. Implicate the analyst: What else did they analyze? Were they properly trained?

3. Implicate the method: When and how was it developed and what else was incompetently developed? Does it meet ICH Q2(r1) standards? What is its performance characteristics?

After answering the above questions, then the BIG question is production related! Did somebody through a bottle of cyanide into the soup? Remember the 'Tylenol' investigation!