Control of Critical Parameters

The graph in Fig. 10.12 shows that the purity decreases very quickly below acceptable levels as retention factor of the more retained enantiomer decreases. Flowever, with minor adjustment of the SMB internal flow rates, a variation of more than 10 % of the retention factor of the more retained enantiomer still meets required purity, productivity, and eluent consumption. Control of critical parameters such as retention factors can be made without modification of the feed and eluent flowrates. 

Models of the self-assembly process also will be important. Because self-assembled structures can be diverse, those models are likely to be highly complex. Sensitivity analysis can be an important approach to the identification and control of critical parameters. 

Principal product specifications are microbial limits and testing methods, particle size, viscosity, pH, and dissolution of components. Process validation requires control of critical parameters observed during compounding and scale-up. Product stability examination is based on chemical degradation of the active components and interac-... 

A modem quality and safety assurance system should prevent contamination through the monitoring, recording, and controlling of critical parameters such as tern-... 

The most critical issue to be investigated during the initial biofeasibility study is the determination of which metabolic mode—aerobic or anaerobic—is more appropriate for the specific contaminants. As shown in Table 14.5, the redox potential is closely related to the metabolic mode, and careful control of this parameter is required to maintain the optimum metabolic mode during bioremediation. A general rule is that the redox potential should be above 50 mV to maintain the activity of aerobic and facultative anaerobic microorganisms and below that value for strictly anaerobic m icroorganisms.12... 

Critical Process Control Parameters. The critical process control parameters are those contollable parameters that have impact on the final product quality. Parameter operating limits and the methods of assuring control of these parameters within these limits are discussed in this section. 

These processing parameters could have a significant impact on in vitro dissolution of drug product. They should be understood and controlled for critical parameters. 

There are several parameters which require critical consideration. Firstly, the colour reagent should be selective for the drug molecule itself, discriminating against degradation products, impurities, and formulation excipients likely to be present. Secondly, the effect and control of any parameters likely to affect the colour reaction should be established, i.e. 

Independent monitoring systems used to implement the key qnality assurance controls must be validated (whether they are complex Supervisory Control and Data Acqnisition (SCADA) systems, or simple chart recorders). For an independent system to be accepted as a validated alternative in the monitoring of critical parameters, the system must be able to manage key quality assurance functions. Such functions inclnde, but are not necessarily limited to ... 

Hydropohobic and hydrophilic membranes Control of operating parameters (critical flux)... 

A common drawback of glass slides as supports for chemical microarrays, as well as of cellulose or polypropylene sheets, is the protein compatibility of fheir respective surface chemistries. It is inherently difficult to render polypropylene or silanated glass resistant to unspecific protein adsorption and is even more challenging to control a critical parameter such as ligand density on fhese polymers. 

A successful implementation of a manufacturing recipe in the plant is dependent on these critical parameters, and corresponding control intervals are found in the pilot production experiments. Identification of critical parameters and their allowed intervals is often time-consuming. 

Process control implies measurement of critical parameters of raw materials and intermediates as they are converted to finished products, and monitoring and controlling the critical process parameters that may influence finished product quality. Process control is what parametric release is all about. In processes where the level of reliability in process control can be predicted to be high, there is a sound basis for eliminating the sterility test. Where process control is not so reliable, the sterility test should be considered as one part of the armory of process control, tests rather than as an overriding end-product test, in other words a Pass in the sterility test should never in these processes be allowed to overrule evident failure to meet all of the prescribed in-process test criteria. 

The recent analytical literature abounds with reports on the development of electrochemical, fiber optic, piezoelectric, and other sensors. Novel detection principles are frequently announced, and attainment of improved sensor quality in terms of selectivity, sensitivity, and lifetime are the goal of many established as well as newly formed research groups. The need for continuous monitoring of critical parameters in clinical chemistry, biotechnology, pharmaceutical, chemical, and nuclear industries, chemical warfare or environmental control is the driving force behind the sensor research. 

The basis of all process validation studies is the demonstration of control of critical process input parameters for reproducible operation of a commercial-scale production process [11, 32]. Critical parameters vary among processes so they must be separately assessed for each new process [10]. As a typical process has hundreds of variables, critical process input parameters must be identified first, and then the extended range and normal (target) operating range for each critical parameter must be determined during process development and/or using historical data [11,... 

---