OOS (Out of Specification) As PER USFDA & MHRA

August 20, 2021March 10, 2024 Pharmaceutical Guidanace

OOS (Out of Specification)

Definition: It is defined as those results of the in-process or Finished which has been sed products testing, which falling out specified limit or acceptance Criteria which has been specified in the official Monograph or Product registered Specification.

OOS was found due to the following reasons:

Laboratory Related OOS

Process Related OOS

Sample Homogeneity OOS

1. Laboratory-Related OOS (Testing Error):

Method of Analysis

Non- Calibrated Instruments Used

Calculation Error

Analyst Error

Instruments Failure

2. Process-Related OOS (Manufacturing Error):

Operator Error

Equipment Error

Deviation from Validated Procedure

Quality of RM/Intermediates Used

In-process Control During Manufacturing

3. Sample Homogeneity OOS (Sampling Error & Handling):

Sampling Error

Handling of Sample

Pooling of Sample

Magnehelic Gauge

Investigation of OOS As Per USFDA

Phase I Investigation – Laboratory Investigation

Phage II Investigation – Full-Scale Investigation

Phase I Investigation – (Laboratory Investigation)

Assessment of Raw Data

Calculation

Instruments Calibration

Reference Standard/Chemical

Method Validation

Reexamination of Volumetric/glassware

Phage II Investigation – (Full-Scale Investigation)- It is divided into two parts

Phage II (A) –

Production Process Review

All Departments Involved In Production

Phage II (B) –

Additional Laboratory Testing

Retesting

Resampling

Investigation of OOS As Per MHRA

Phase I Investigation – Laboratory Investigation

Phage II Investigation – Manufacturing Investigation

Phage III Investigation – Extended Manufacturing Investigation

Phase I Investigation – Laboratory Investigation:

Phase I A: Primary Laboratory Investigation

Phase I B: Extended Laboratory Investigation

Phage II Investigation – Manufacturing Investigation:

Process Parameter

Drying Parameter

Input RM Quality

Training of Personnel

Cleaning of Equipment

Environmental Monitoring

Phage III Investigation – Extended Manufacturing Investigation:

Sampling Error

Authorized for Resampling

Re-analysis

If root cause found -Define the CAPA If not

Diverted to the Matter R&D, ADL, or PD Lab

Conclusion of All Team Members (QA, QC, Production, R&D, ADL, or PD Lab)

Decided the Fat of Batch by QA Head

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