Bioequivalence and Bioavailability Forum • CMDh reminder

CMDh reminder [Regulatives / Guidelines]

posted by Ohlbe – France, 2012-09-28 01:15 (5019 d 20:44 ago) – Posting: # 9272
Views: 5,015

Dear ElMaestro,

❝ Let's say the CRO has stored the samples in a freezer. Ok they are now XYZ months old and their content of the API may due to stability issues and a ton of other factors no longer be exactly what they were when the samples were analysed for the study report, but they do have some content and they are still real samples.

Hopefully the CRO has kept some QC samples along with the study samples. This way they will be able to extend their long-term stability data.

❝ So let's say we take then out and re-analyse them. And then we re-analyse them again for ISR purposes. We do not try to make any inference re. the differences between the first analysis and the first re-analysis - we only deal with the difference between first re-analysis and second re-analysis. Would that be acceptable?

I would say no. Not without a comparison to the initial analysis.

❝ After all, ISR gives us info about reproducibility (week-to-week or month-to-month) in real samples rather than in spiked samples as those that are used in validation.

Not only that. A major concern is the back-conversion of unstable metabolites, such as acyl-glucuronides, N-oxides etc., back to parent during sample processing. You won't see anything with ISR if you have 100 % back-conversion during processing, of course. But if you have a partial back-conversion, it is likely to vary from run to run and to be detectable with ISR (at least that's the theory). But if your unstable metabolite has turned back to parent, or has dramatically decreased, during the 3 years your samples will have spent at -20°C, you are unlikely to detect anything if you only compare a first re-analysis to a second re-analysis.

Regards
Ohlbe

—
Regards
Ohlbe

Complete thread:

Deficiency response kamblpa2 2012-08-13 10:33
- Deficiency response Ohlbe 2012-08-14 00:17
- CMDh reminder Ohlbe 2012-09-25 19:01
  - CMDh reminder ElMaestro 2012-09-25 20:21
    - CMDh reminder Ohlbe 2012-09-25 22:06
      - CMDh reminder Dr_Dan 2012-09-26 11:35
        
        Long-term storage samples? Helmut 2012-09-26 14:48
        CMDh reminder ElMaestro 2012-09-26 17:30
        
        CMDh reminderOhlbe 2012-09-27 23:15
        
        CMDh reminder Dr_Dan 2012-09-28 15:32
        
        CMDh reminder ElMaestro 2012-09-28 17:04
        
        90%+ off-topic Helmut 2012-09-28 17:48
        
        90%+ off-topic ElMaestro 2012-09-29 09:30