Critical equipment variables

For MR formulations the in vitro dissolution conditions, which achieve an optimal IVTVC, will be those which possess the discriminatory power to detect the effect of critical manufacturing variables on drug release. An investigation of the dependence of the formulation on pH and surfactants is recommended in media of various compositions. A dependence on dissolution equipment, and range of equipment settings should also be considered in the investigations. 

The equipment variables affecting the product quality shall be identified as critical for calibration. 

Manufacturing changes may involve the equipment used in the manufacturing process (critical manufacturing variable). If a manufacturer wishes to use manufacturing equipment that is not identical in every respect to the original manufacturing equipment used in the approved apphcation, appropriate validation studies... 

Critical variables may be characteristic of the materials and/or the process. Materials properties have already been discussed briefly and of course the equipment variables for the unit operations will depend upon differences in the raw materials. However, there are general relationships between the roller compaction process variables and the properties of the resulting ribbons and granules that can aid in process design. 

The design of a process monitoring and analysis system (note, from here on we will use the term PAT system to refer to such a system) is a step-wise procedure involving the selection of critical process variables, followed by the selection and placement of suitable monitoring and analysis equipments, and finally, the coupling of the monitoring and analysis tools to a control system to ensure that the selected critical process... 

The control of analytical variables, which includes analytical methodology, standardization and calibration procedures, documentation of analytical protocols and procedures, and the monitoring of critical equipment and materials. 

Instruments are used to monitor the pertinent process variables during plant operation. They may be part of automatic control loops or used for the manual monitoring of the process operation. Instruments that monitor critical process variables are fitted with automatic alarms to alert the operators to critical and hazardous situations. Miller [1] and Perry [2] provide details of process instruments and control equipment. 

The SIS in Figure 10.1 serves as an emergency backup system for the BPCS. The SIS starts automatically when a critical process variable exceeds specified alarm limits that define its allowable operating range. Its initiation results in a drastic action, such as starting or stopping a pump or shutting down a process unit. Consequently, it is used only as a last resort to prevent injury to people or equipment. The term Safety Interlock System was previously used, but the newer term Safety... 

Accurate and even application of test substance is absolutely critical to study success. If the application is highly variable or deviates significantly from the target application rate, the study results may be technically unusable and/or unacceptable to regulatory authorities. Accurate agrochemical application begins with careful calibration of the spray equipment. Hence Study Directors should be familiar with sprayer calibration techniques, even if they will not be personally making the applications. 

To address this situation, a data interpretation system was constructed to monitor and detect changes in the second stage that will significantly affect the product quality. It is here that critical properties are imparted to the process material. Intuitively, if the second stage can be monitored to anticipate shifts in normal process operation or to detect equipment failure, then corrective action can be taken to minimize these effects on the final product. One of the limitations of this approach is that disturbances that may affect the final product may not manifest themselves in the variables used to develop the reference model. The converse is also true—that disturbances in the monitored variables may not affect the final product. However, faced with few choices, the use of a reference model using the process data is a rational approach to monitor and to detect unusual process behavior, to improve process understanding, and to maintain continuous operation. 

Grain boundary defects are primarily responsible for the operation of zinc oxide (ZnO) varistors, a shortened form of variable resistor. The varistor behaves like an insulator or poor semiconductor at lower electrical field strengths, but at a critical breakdown voltage the resistance decreases enormously and the material behaves like an electrical conductor (Fig. 3.36). When a varistor is connected in parallel with electrical equipment, negligible power flows through it under normal low... 

---