Background:
FDA
issued warning letter to the most of the drug substance and drug product
manufacturer. During the inspection, FDA find out the fault, the way
investigation of OOS had been carried out by the manufacturer. There is no
proper investigation of OOS outcome. FDA warning letters often found that the
procedure for handling of OOS is lacking or poorly scripted. It is very much
important to know that how to meet the current regulatory expectation for OOS
investigation. However, a specific and well drafted adequate OOS SOP is
important for through investigation procedure assure an ample
investigation.
What
is Out‑of-Specification (OOS):
When
analytical results that does not meets the pre-established acceptance criteria
of in-house test specification or official pharmacopeial monograph
specification range then it termed as Out‑of-Specification results. OOS results
may be observed during the analysis of packing materials, raw materials,
excipients, drug substance, in-process or final drug products testing and
stability study analysis. All ambiguous results which observed out of set
specification is named as OOS results.
Investigation
of Out‑of-Specification Results:
The
main aim of OOS investigation should be focus on the definite outcome of the
root cause for the OOS result. OOS SOP is very much important to conclude
appropriate investigation. The investigation must be on time and competent
enough to conclude it’s root cause identification, impact evaluation and
finding efficient corrective action and preventive action’s. Most of the organization have OOS SOP but either it may not appropriate or not followed
properly. There is no through investigation carried out and no root cause
investigations had been carried out for these OOS results.
When
OOS is observed then systematic investigation need to be done to check if there
is an appropriate root cause. Prior to proceeding for proper OOS investigation
need to cross check analytical error methodically and confirm the initial test
results by repeating the analysis with the original sample and solutions.
Following is the important steps for performing the OOS
investigations:
OOS
may be observed due to the following errors but not restricted to these
factors.
1.
Error
related to analytical laboratory:
2.
Analytical
instruments or equipment’s used for analysis is not in valid calibration state.
3.
Analytical
test procedure not followed properly.
4.
Analyst
Error,
5.
Error
while doing calculations,
6.
Error
due to the instrument failure.
7.
Test
sample is not uniform or homogenous:
8.
Sampling
error i.e. sample is not uniform or proper
9.
Pooling
of sample is not appropriate
10.
Error
at the time of sample handling
11.
Manufacturing
process related error:
12.
Quality
of used excipients, raw materials or intermediates,
13.
Operator
error,
14.
Validated
procedure not followed correctly or Deviation from the standard procedure,
15.
At
the time of manufacturing in-process check or control not done properly,
16.
Error
due to the equipment failure.
For more information visit https://veeprho.com/blog/what-is-out-of-specification-investigation-and-how-to-proceed-for-it/
