Quality Control for the Pharmaceutical Industry; Stage 3, Continued Verification, in the Lifecycle of Analytical Procedures

QC laboratories perform a critical role in demonstrating pharmaceutical products are consistently manufactured, safe, potent, and pure. At the same time, the number of tests run by QC laboratories is increasing. QC laboratories need to ensure they are working efficiently and effectively. They have no resources to waste. The analytical control strategy, provided in the lifecycle approach, is a key tool to ensure the analytical procedures are working as expected; the laboratory is not wasting time monitoring variables that are not important; and sources of variability are adequately controlled.

 

Quality Control (QC) laboratories are responsible for Stage 3 in the lifecycle of analytical procedures, Continued Procedure Performance Verification. In the lifecycle approach, the QC laboratory receives an analytical procedure that has been designed and developed to be fit for use in stage 1, Procedure Design and Development. Procedure Performance Qualification, stage 2, ensures the analytical procedure performs as expected. An output of stages 1 and 2 is the analytical control strategy, which is the understanding and control of sources of variability.

 

Laboratory instruments, used for weighing and pipetting, and HPLC sample preparation, are included in the analytical procedure and the control strategy. The technique, such as HPLC, is selected during stage 1. Its required performance, such as system suitability, is designed in stage 1, confirmed in stage 2, and is continually verified in stage 3. The uncertainty contributed by the weighing step is estimated in stage 1 and confirmed in stage 2. If the uncertainty is significant, then an adequate control strategy is used, for example, the performance of the balance at a specific weight is confirmed and recorded before use.

 

The analytical procedure must be fit for its use. This includes meeting the target measurement uncertainty requirement, which is determined in stage 1. If a potential source of variability is a significant contributor to the measurement uncertainty, then a control strategy is needed. A control strategy could be using a system suitability, trending a performance characteristic by using a control chart, providing detailed training to the analyst, including detailed instructions in the operating procedure, or other control mechanisms.

 

The control strategy can also help the QC laboratory perform efficiently. When an analytical procedure is designed, developed, and qualified with fit for use providing the goal, then steps that do not need special control are also identified. For example, if the uncertainty introduced in a dilution step is not significant, then a less rigorous dilution scheme could be used, saving time and resources.

 

With the lifecycle approach, the QC laboratory can use an analytical procedure efficiently and effectively. Time and resources will not be wasted. The QC laboratory can confidently defend its performance to any regulatory agency. The test results will support manufacturing. Time will not be lost investigating out of specification results caused by a poorly understood analytical procedure. 

 

Learning Objectives: