Possible Causes of Out of Specification (OOS) Results

OOS results occur when the test results fall outside the predefined acceptance criteria or specification limits. Causes can be grouped into three main categories:

1. Laboratory Errors

• Instrumental issues: Calibration errors, malfunction, or incorrect settings.

• Analytical method errors: Incorrect method execution, wrong parameters.

• Sample preparation errors: Wrong dilution, contamination during preparation.

• Data handling errors: Transcription mistakes, software/data integration errors.

• Environmental factors: Improper lab conditions (temperature, humidity) affecting results.

2. Manufacturing / Process-Related Causes

• Raw material issues: Non-conforming starting materials or APIs.

• Process deviations: Inaccurate mixing, incorrect temperature, time, or pressure.

• Inadequate cleaning: Cross-contamination between batches.

• Improper drying or blending: Leading to non-uniform product quality.

• Faulty packaging: Container-closure integrity failure affecting product stability.

3. Stability or Storage Issues

• Degradation of API or excipients due to temperature, humidity, or light.

• Expired materials: Use of components beyond their shelf life.

• Improper storage conditions during manufacturing, warehousing, or transport.

✅ Key Point:
During OOS investigation (per FDA Guidance & ICH Q7), the first step is laboratory error check. If lab error is ruled out, proceed to full-scale manufacturing investigation.