Checklist for OOS Investigations in Pharmaceutical Industry

What is the OOS Investigation Checklist?

• cGMP regulations require a laboratory test to ensure that components, containers and closures, in-process materials, and finished products meet specifications, including stability testing specifications.
• According to the USFDA, in order to confirm the OOS root cause, the OOS must be thoroughly investigated, unbiasedly, and with sound scientific justification.
• Certain checklists must be verified in order to meet regulatory requirements and conduct a thorough investigation. Laboratory investigation, manufacturing investigation, and warehouse investigation should be used as checkpoints.

What is OOS in pharmaceuticals?

• A result that is out of specification (OOS) is one that does not conform or meet the manufacturer's or laboratory's predetermined limit or acceptance criteria.

What is out-of-specification (OOS)?

• A result that is out of specification (OOS) is one that does not conform to or meet the manufacturer's or laboratory's predetermined limit or acceptance criteria.

Checklist for OOS Investigations

Checklists of OOS investigations are divided into three parts,

1. Laboratory investigation
2. Manufacturing investigation
3. Warehouse investigation

ALSO READ: SOP for Handling Out of Specification (OOS)

1.  Laboratory Investigation Checklist:

Laboratory investigation checkpoints include:

1. Analyst errors
2. Instrument/Equipment errors
3. Laboratory System errors

Analyst Errors	Yes	No	NA
Weighing and measurement errors (sample weight & measurement
Calculation errors (and raw data completeness)
Analytical errors related to dilutions, mobile phases, filters, chromatography, conditions, and so forth.
Analyze the critical steps that were followed during the analysis
The reference/working standard used in the analysis is correct
Assay value and storage condition are determined correctly for the reference/working standard
Check the appearance, potency, expiry date, and LOD/water mentioned.
Whether the test solution(s) are properly prepared
During preparation, any loss of standard solution or test solution
Other analytical techniques were not properly applied during the test
If any unusual or unexpected effect is observed for standard or test preparation (e.g. If equipment is contaminated by a previous sample)
Whether any alternate validated method is used for the analysis
If the analyst is qualified
Is the analyst trained to carry out the test?
Whether the environmental conditions are suitable for the test
Cleaning of glassware and calibration status
Analyst Qualification

Instrument/Equipment Errors	Yes	No	NA
Analytical equipment (including glassware) that didn’t work or was not calibrated was used in the analysis.
Verify if the system meets the requirements for RSD, resolution factor, and / or other criteria.
Ensure that the chromatographic analysis does not include any out-of-limit parameters.
Column used is correct
This column has been used previously
Instrument/equipment calibration status
Instrument/Equipment preventive maintenance
Laboratory System Errors	Yes	No	NA
Confirm that the analyst understands the test method; discuss the test method with the analyst.
A trained analyst should be familiar with the instrument/ equipment and maintain the records
Schedule of calibrations
Solutions shelf life
Calibration procedure and test method
Working standard qualification
Efficiency of columns
Environmental conditions

Documentation	Yes	No	NA
Write/ transfer error
Calculation error
Carrying out	Yes	No	NA
Carrying out
Incorrect procedure
Standard	Yes	No	NA
Correct standard
Expiration date
Storage
Initial weight
Dilution
Sample	Yes	No	NA
Correct standard
Storage
Initial weight
Dilution

ALSO READ: Data Integrity Checklist for Pharmaceutical Industry

2.  Manufacturing Investigation Checklist

• Manufacturing investigation checklists include:

1. Equipment errors
2. Operator errors Production system errors

Equipment Errors	Yes	No	NA
Is the equipment specified and validated?
Is there any malfunctioning of the equipment?
Are there any power outages for extended periods during manufacturing?
Operators Errors	Yes	No	NA
Do operators trained on the equipment
Did the operator make any errors (wrong weight, wrong material, incorrect sequence of additions)?
Interview with the operator
Production System Errors	Yes	No	NA
Are there any deviations from cGMP/SOP?
Is the process validated?
Does the specified environmental condition apply?
Is the standard Master Formula followed?
Are correct sampling procedures followed?
Do batch production records have the correct entries and standard manufacturing procedures is followed?
Is there a change in the blend time or dry time?
During processing, was there any spillage of material?
Does the environment meet the specified conditions?
Are all steps of the manufacturing process carried out within the approved timeframe?
The manufacturing process aspects that may be responsible for the problem are listed here.
When storage containers are at different stages of manufacturing, whether they are stored appropriately in designated locations.
Describe how long the containers are stored at various stages.
Are yields in the previous and next batch within acceptable limits?
Make sure the yield is reconciled at each stage. In case the yield exceeds the standard, explain why.
Does documentation of the process is reviewed?
If you have any other observations, record them.

3.  Warehouse Investigation Checklist

Warehouse Investigation	Yes	No	NA
Did the material come from an approved vendor?
Do RM/PM stores maintain their storage conditions?
Do the dispensing operators are trained?
Are the materials used as described in the bill of materials?
Do physical stock and written quantity match for used material?
Have previous and next batches been dispensed with proper line-clearance procedures?
Are the materials dispensed within the validated time before manufacturing begins?

If these checklists of OOS Investigation are followed, there are high chances of getting the root cause of OOS.

Conclusion

In comparison to routine incident investigation, OOS investigation is a lengthy and time-consuming activity. It will save time and help us find the root cause of the OOS if we prepare and follow an OOS investigation checklist.

ALSO READ: Audit Checklist for Quality Control Department