La gestion des OOS au cœur de cette injonction....
1. Failure to adequately investigate and document out-of-specification results according to a procedure, and implement appropriate corrective actions.
Our investigator found that your firm repeatedly, and without justification, resampled and retested crude heparin batches when your quantitative polymerase chain reaction (Q-PCR) test for ruminant DNA exceeded your established specification limit of ≤ (b)(4) parts per million (ppm). As a result, your firm used crude heparin batches that potentially were out-of-specification (OOS) to manufacture heparin sodium API for the U.S. market.
For example, according to your Deviation Handling Sheet No.07-2015021, you resampled and tested crude heparin batch Y102-1504005 multiple times, with the following results.
Ruminant DNA Q-PCR test results for batch Y102-1504005
Specification (ppm)
|
Value (ppm)
|
Result
| |
Sample one
|
(b)(4)
|
47.4
|
OOS
|
Sample two
|
(b)(4)
|
343.0
|
OOS
|
Sample three
|
(b)(4)
|
2.3
|
batch released
|
You neither evaluated the initial sample OOS, nor conducted retesting of the initial original sample to confirm it. Instead, you resampled until you obtained a passing result.
Similarly, your initial test results for another crude heparin batch (Y102-1503008) were also OOS. Again, you resampled without justification, and accepted the batch when you obtained results within specification.
Disregarding the OOS results, and resampling and retesting without scientific justification, constitutes “testing into compliance.” This practice is unscientific and objectionable under CGMP.
Your response is inadequate because you did not adequately address how you would investigate OOS lab results prior to resampling.
Pour en savoir plus sur la gestion des OOS selon l'US FDA cliquer ici.
Pour en savoir plus sur cette warning letter.
