OOS vs OOT vs OOE

For OOS, USFDA published a guidance in October-2006 and MHRA published OOS investigation guidance in August-2013.

As such there is no official guidance for OOT and OOE results.(ECA meeting will held on 23 and 24 October-2019 for OOT/OOE Results)  

But we can and we are investigating OOT and OOE results in the similar way as OOS investigation.

Now, how we can categorize the investigation in OOS/OOT/OOE.

For OOS: I think,there is no confusion to any one, as any generated result is not with in the Pre-defined specification limit is OOS result and the event should be investigated through OOS procedure.

Few examples;

For Assay, if Pre-defined limit is 98.0% to 102.0% and result is 97.9% ----it's OOS result.

For Dissolution, if Pre-defined limit is NLT 75%(Q) and result is 81(48-94) %---only one unit is failed-48%--Out from the S-3 stage criteria.

But for OOT and OOE there is no any written guidance till date to confirm that which result is OOT result and which one is OOE.

Many organizations have no separate SOP for OOE (Out of Expectation)  , they have Clubbed OOE concept with OOT .

So organization has made OOT/OOE -SOP and fix the criteria on basis of his own scientific knowledge and reasons. 

As per my recommendations OOT criteria should be as (Some one may have change of openion) --

For Assay: 

Fixed limit for release (if less than 30 batches data available) and for Stability--- +/-3.0% of labelled amount. If 30 or more batches data are available then based on statistical tools uses limit should be definede. g. LCL/UCL.

For Related Substances test;

For unknown impurity and known impurity (Non degradation impurity) :
For release: Fix limit is 50% of specification limit and if sufficient number of batches data available then define the limit based on statistical calculation.
For Stability:

If limit is less than 0.1% then no need to investigate. 

If limit is between 0.1 to 0.5% then 50% variation to be investigated. 

If limit is between 0.5 to 1.0% then 25% variation to be investigated. 

For more than 1.0% limit: 80% or more of the specification limit result to be investigated.
For Dissolution:
Any thing not complying in S1/L1/A1/B1 criteria.

OOE:
The results or neither OOS Nor OOT  but result looking questionable should be handle through OOE.
For example;
Dissolution result is complying S-1stage criteria - 83(80-86) %---Limit is NLT 75%Q.
Last 10 batches mean results are between 94% to 97%.
So this batch result is complying in S1 stage but out of Expactation.

For other test , you can ask my opinion.