ANS: When the result of the substances fall out the specification or acceptance criteria by the manufacturer than it is called out of specification (OOS).
Question-2 What is the purpose of OOS?
Ans: The purpose of an OOS investigation is to identify the root cause of the OOS results and to take appropriate corrective and preventive action.
The investigation should included review of laboratory testing, manufacturing process and sampling procedures.
Question -3 Explain an OOS with a suitable example?
Ans: The specification limit or acceptance criteria for assay test parameter of a particular batch is 95- 105% but obtained result of the assay test is 94.3% then this result is out of specification limit and it is called OOS.
Question -4 What are the reason for an OOS results?
Ans: 1) Related to the laboratory issue.
2) Related to the process of the material or product.
3) Related to sample homogeneity.
Question -5 What are the causes of laboratory related OOS?
Ans: 1) Method parameter of analysis
2) Non calibrated instrument used
3) Instrument failure
4) Used of wrong potency of the standard
5) Analyst error
6) Dilution error
7) Calculation
8) Power failure
9) Obvious error.
Question -6 What are the causes of process related OOS (Manufacturing error)?
Ans: a) equipment error.
b)Operator error.
c)If the processing method deviated from validate procedure.
d) Quality of the RM (Active & Excipients ) used
Question-7 what are the causes of sample homogeneity OOS?
Ans: a) Sampling error
b) Handling of sample
c) Pulling off sample
Question-8 What are the investigation phases of OOS as per USFDA?
Ans: a) Phase first investigation laboratory investigation.
b) Phase second investigation (Full scale investigation)
Phase Second (A)
1- Manufacturing process review
2- All department involve in production
Phase second (B)
Additional laboratory testing, testing and resampling.
Question-9 What are the investigation phases of OOS as per MHRA?
Ans: Phase I investigation ( Lab investigation): There are two phases
Phase I A : Primary lab investigation
Phase l B : Extended lab investigation
Phase ll investigation ( Process investigation): Process parameters, Equipment failure, API quality, Cleaning of equipment.
Phase lll investigation (Extended process investigation): Sampling error and reanalysis.
Question-10 What is valid OOS and invalid OOS?
Ans: Invalid OOS: An OOS considered invalid, when the investigation has determine the laboratory error or any error other than the manufacturing results for the obseseve failure results.
Valid OOS: An OOS considered valid , when the investigation outcome confirm the obseseved failure results.