Machine Translated by Google

Subject of workshop no. 4

Drug Z is intended for the treatment of a rare disease. There is no alternative for this drug on the market. The
drug is in pharmaceutical form - capsules.

When controlling the Y series according to the specification for the Content parameter, results were obtained that
deviated from the specification limit of 95.0 - 105.0% in the initial analysis. In phase Ia, no analytical error was
confirmed.

Reanalysis from the same sample in phase Ib confirmed the results obtained in the initial analysis. OOS results
were confirmed for some tested samples:

Results
Sample 1 100.1%
Sample 2 90.9%
Ib Analysis:
Sample 3 99.3%
Sample 4 92.2%
Sample 5 80.6%
Sample 6 91.8%
Sample 7 100.1%
Average all samples 93.6%

For this series, during the analysis, an OOS result was obtained for the parameter UDU (Uniformity of dosage
form) with AV > 15.0%.

1
Machine Translated by Google

For individual capsules, the values for the content of the active substance below the specifications were obtained
border:

Sample
Sample Name
result (%)

Sample 1 82,64
Sample 2 98,88
Sample 3 101,05
Sample 4 101,01
Sample 5 100,21
Sample 6 102,44
Sample 7 100,66
Sample 8 102,07
Sample 9 68,70
Sample 10 101,25
OF: 29,5
Sample 1 100,05
Sample 2 105,67
Sample 3 101,85
Sample 4 101,47
Sample 5 71,40
Sample 6 100,45
Sample 7 99,96
Sample 8 101,81
Sample 9 102,40
Sample 10 101,67
Sample 11 101,60
Sample 12 99,61
Sample 13 101,14
Sample 14 66,78
Sample 15 100,20
Sample 16 102,45
Sample 17 100,43
Sample 18 101,48
Sample 19 102,69
Sample 20 100,01
OF: 21,7

2
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What will be done next as part of the investigation?

How to proceed with the investigation in phase II?

What would be the elements of a Phase II investigation?

Would additional testing and sampling be done in Phase II?

Can the investigation be extended to phase III?

Will the series be released?

I.

If the capsule filling equipment has the possibility of dividing the batch into produced fractions that are also physically separated (in

barrels) and the investigation shows that the deviation (root cause) occurred only in one fraction, would that fraction be excluded from

the yield and given the status ‚‚DOES NOT FIT‚‚ and would the rest of the series be released?