TABLE IV

Case Study: Potential Failure Mode, Causes, and Effects

Potential Failure ModePotential Cause(s)Potential Effect(s)
The extraction into methanol is started at the wrong pH (i.e., the pH is not within the 4.8–5.2 range).The operator made an error when reading the pH result before starting the extraction. After significant investigation, it was determined that the operator read the result for the solution temperature off the PLC screen and mistook it as the pH result.
The temperature was 5.1 °C when he started the extraction into methanol. (The real pH is unknown but it was clearly not within the required 4.8–5.2 range.)
On the equipment, it is noted that the temperature display on the PLC screen is right next to the pH display.		Performing the extraction at the wrong pH results in

  • A low yield extraction.

  • High levels of Impurity A being carried over into the methanol.

  • A potential out-of-specification API batch that will have to be rejected.

  • Potential hazards to the patient if the batch is released with high levels of Impurity A.