Overall Calibration Strategies

Calibration procedures are often similar to those used in the initial operational qualification of each module of the HPLC system. While each company s procedure might differ in the details, most share these common strategies. 

An analyst, a metrologist, or a qualified contractor can perform the calibration, though all must follow the company s prescribed standard operating procedure (SOP) and acceptance criteria. The cost effectiveness of using outside contractors or an internal metrology department is dependent on company size and the number of HPLC systems in the laboratory. 

Most HPLC systems in pharmaceutical laboratories are calibrated every 6-12 months. Periods longer than 12 months are not recommended while periods shorter than 3 months are deemed unnecessary because each HPLC system is also subjected to a daily system suitability check to ensure sufficiency for the application. Ideally, the frequency of calibration should be dictated by the historical data of calibration failures and the manufacturer s recommendation. In practice, 6 months appears to be the norm adopted by most laboratories. Calibration is also required after annual preventive maintenance or major repairs though only the affected modules, and not the entire system, need to be recalibrated. 

Here is a list of common strategies in selecting calibration procedure and adopting acceptance criteria  

---

FIGURE I Schematic diagram showing the overall validation strategy, which includes calibration, system validation, and system suitability testing. Figure adopted with ideas from Reference I. 

The error of a measurement system depends on the nonideal characteristics of each of the elements in the system. It is possible to identify which of the elements show significant nonideal behavior using calibration experiments. Compensation strategies may then be devised for each of these elements so that significant reductions can be accomplished for the overall system error. Some of these compensation methods are briefly highlighted, especially for nonlinear and environmental effects. 

As reported in Chap. 2, all aftertreatment devices have to be described mathematically with high accuracy. Therefore, aU chemical reactions and heat transfer phenomena are represented in a chemical and physical form. Since computational time has to be kept short, global reactions and rate formulations based on Lang-muir-Hinshelwood type are considered. Moreover, the calibration of the models represents a major step in the modeling work, requiring time and costs and directly affects the accuracy of the simulation of exhaust aftertreatment systems. For the development of control strategies, it is necessary to consider all affected aspects of the powertrain in form of a virtual test bench. The overall simulation tool includes the catalytic parts but also devices like sensors and ECU functions, which interact... 

---