What is OOS in pharma, how to Investigate Out of Speciation results. 

OOS is an abbreviation of term “out of specification” the specification means the standards of the quality attributes like assay, measure of content in the formulation, Colour standard, written visual description, identification, and purity etc.

When a product or a material falls out of the lower or upper limit, meaning the observed values, observation is not within the specified limit provided in specification, the product or material quality attributes are not meeting with the specification, it means that they are failing.

The other term for test results which are failing, and not passing through the specification limit, such failing result or observation is called as “out of specification”.

An out of speciation or OOS means the product is failing in to its test and specifications.

There are two possibilities that the product is really failing due to its poor quality, due to its material or faulty manufacturing procedures, act or its failing due to improper testing in the laboratory, analyst’s error, or improper sampling.

Failing product is a risk to pharma companies as it raises questions on its capabilities, and in event the OOS is observed in case of a batch already distributed for sale, then it is a direct risk to the patient’s life.

Out-of -specification results are required to be investigated and the root cause for OOS should be rectified, corrected and preventive action should have been implemented in the CAPA system by logging CAPA number in the CAPA log book. So that the laboratory error does not lead to OOS in future due to the same cause.

Why to investigate the OOS?

Investigation of OOS has a definite and exhaustive procedure where one is required to verify the, weighing of product, or material taken for analysis, accuracy of the weighing balances, proper transfer of the product or material in the test sample preparation, procedure of analysis is verified if it is followed, like sonication time, solubilisation time, filtration method etc., which are tricky, and are skills of analyst.

These are verified in the laboratory by a senior analyst and confirmed if there are any errors in the analysis.

If there is error in a particular step this is corrected through the process of training.

If there is no error in the analysis, further the investigation is done for raw material purity, dispensing, and manufacturing. And a correct root cause is required to be identified through the process of why why analysis, ishikawa fish bone analysis, or brainstorming sessions. After an investigation is completed a root cause is assigned which is logged in to CAPA for correction and prevention in future.

If this is not done there are chances that product or material may face OOS results frequently due to unaddressed causes, in first OOS.

How to handle an OOS?

Every OOS must be investigated as the results found are not confirming to the specifications which are must to comply.

OOS investigation is done in three phases.

Phase 1 investigation of OOS: It is done in the laboratory to verify the error in laboratory testing and analyst’s error.


Phase II investigation of OOS: In the event that it is confirmed that there is no error or root cause in phase I, phase two investigation is started focused on the dispensing and manufacturing process and storage etc.

Phase III Investigation of OOS. In event the phase two investigation does not yield any result, Phase Three investigation is started. Which again is focused on the manufacturing process, and resampling and retesting of the product is authorized by QA in phase three investigation.

In all of the above three phases of investigation, a written protocol approved by quality assurance is followed, and every head of the protocol is required to be followed meticulously, without any bias.

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