OOS Investigation

Dear all,

I want to know probeble cause for failing in Water content (KF) during one month stability.

we have investigate about analytical error and it found ok.

due to some regulatory aspect i m not able to disclosed some details of formulation.

but in what way we step ahead for investigation ?

Please Read this;
1.Why is it necessary to carry out an OOS investigation if the rejection of a batch is based on an OOS result?
To determine if the result is associated with other batches of the same drug product or other products.

2.How do I carry out a meaningful OOS investigation?
A meaningful OOS investigation should be: thorough, timely, unbiased, well-documented, and scientifically defensible.

3.When do I need to conduct a complete failure investigation?
If the initial assessment indicates that no errors were made in the analytical process used to obtain the data, a complete failure investigation should follow.
4.Who is responsible for the first course of action?
The analyst.

In case the investigation does not reveal a laboratory error, a full-scale OOS investigation has to be carried out.
Here, the guidance makes among others the following statements on retests:
1.“It is often important for the predefined retesting plan to include retests performed by an analyst other that the one who performed the original test. A second analyst performing a retest should be at least as experienced and qualified in the method as the original analyst.” Obviously, the FDA has taken into account industry comments saying that retests cannot always be performed by a second analyst, even if the second analyst is still considered very important.

2.“The maximum number of retests to be performed on a sample should be specified in advance in a written standard operating procedure (SOP). The number may vary depending upon the variability of the particular test method employed, but should be based on scientifically sound principles. The number of retests should not be adjusted depending on the results obtained.”


dear sir thanks for the reply…

i want some information that if present limit is 6.0%w/w and u got 6.2%w/w in 1 m stability…means…OOS
is it right to broad the limit up to 9.0%w/w.
is there any scientific justification requied for that for regulatory aspects.?what justification we will praposed at present condition.?

furthere i would like to add that if all other test such as assay, rs,dt,disso were found o.k within one month stability.i already done investigation and found there is not any analytical error and packing problem.

You cannot broaden the limit overnight from 6%w/w to 9%w/w .You need to have some justification.
I think you have to review many aspects before you write a change.
Any change will go into Change control document.
First of all you must find why there is a deviation of 0.2% in your product stability over 1 month period.