Pharmaceutical Manufacturing Dashboard 2017 Review

1. Case Study
Inadequate investigation of OOS result for
Tablet Content Uniformity
November 2017
US-FDA
Obaid Ali, RPh. M.Phil, Ph.D.
Civil Service Officer, Government of Pakistan

2. Invalidation of initial OOS result without assignable root cause ….
Knowingly that there is no laboratory error …. Release of batch on
testing of new sets of units … hypothesis is unproven and insufficient
to conclude investigation

3. OOS
Invalidation of initial OOS result without assignable root cause ….
Knowingly that there is no laboratory error …. Release of batch on
testing of new sets of units … hypothesis is unproven and insufficient
to conclude investigation

4. OOS 2 individual units and acceptance value for a batch
Invalidation of initial OOS result without assignable root cause ….
Knowingly that there is no laboratory error …. Release of batch on
testing of new sets of units … hypothesis is unproven and insufficient
to conclude investigation

5. OOS 2 individual units and acceptance value for a batch
No evidence of laboratory error
Invalidation of initial OOS result without assignable root cause ….
Knowingly that there is no laboratory error …. Release of batch on
testing of new sets of units … hypothesis is unproven and insufficient
to conclude investigation

6. OOS 2 individual units and acceptance value for a batch
No evidence of laboratory error Retest & re-sonicated sample-same OOS
Invalidation of initial OOS result without assignable root cause ….
Knowingly that there is no laboratory error …. Release of batch on
testing of new sets of units … hypothesis is unproven and insufficient
to conclude investigation

7. OOS 2 individual units and acceptance value for a batch
No evidence of laboratory error Retest & re-sonicated sample-same OOS
Improper solution & dilution error concluded
Invalidation of initial OOS result without assignable root cause ….
Knowingly that there is no laboratory error …. Release of batch on
testing of new sets of units … hypothesis is unproven and insufficient
to conclude investigation

8. OOS 2 individual units and acceptance value for a batch
No evidence of laboratory error Retest & re-sonicated sample-same OOS
Improper solution & dilution error concluded Uncertain conclusion
Invalidation of initial OOS result without assignable root cause ….
Knowingly that there is no laboratory error …. Release of batch on
testing of new sets of units … hypothesis is unproven and insufficient
to conclude investigation

9. OOS 2 individual units and acceptance value for a batch
No evidence of laboratory error Retest & re-sonicated sample-same OOS
Improper solution & dilution error concluded Uncertain conclusion
Invalidation of initial OOS result without assignable root cause ….
Knowingly that there is no laboratory error …. Release of batch on
testing of new sets of units … hypothesis is unproven and insufficient
to conclude investigation

10. OOS 2 individual units and acceptance value for a batch
No evidence of laboratory error Retest & re-sonicated sample-same OOS
Improper solution & dilution error concluded Uncertain conclusion
Invalidation of initial OOS result without assignable root cause ….
Knowingly that there is no laboratory error …. Release of batch on
testing of new sets of units … hypothesis is unproven and insufficient
to conclude investigation

11. OOS 2 individual units and acceptance value for a batch
No evidence of laboratory error Retest & re-sonicated sample-same OOS
Improper solution & dilution error concluded Uncertain conclusion
Invalidation of initial OOS result without assignable root cause ….
Knowingly that there is no laboratory error …. Release of batch on
testing of new sets of units … hypothesis is unproven and insufficient
to conclude investigation

12. OOS 2 individual units and acceptance value for a batch
No evidence of laboratory error Retest & re-sonicated sample-same OOS
Improper solution & dilution error concluded Uncertain conclusion
Invalidation of initial OOS result without assignable root cause ….
Knowingly that there is no laboratory error …. Release of batch on
testing of new sets of units … hypothesis is unproven and insufficient
to conclude investigation

13. 125%
75%
98%
102%

15. Characterize more extensively the
uniformity of the batch produced in hours
or in few shifts
Take Home Message
Set the Tone on Full Compliance Mode

16. Don’t miss the opportunity to investigate possible
manufacturing cause of inconsistency in content
uniformity if initial OOS is not laboratory error
It is not a choice, it is an obligation
Take Home Message
Set the Tone on Full Compliance Mode