Validation process equipment/tooling

Chapter 17 - Vapor-liquid equilibrium (VLE) data are important for designing and modeling of process equipments. Since it is not always possible to carry out experiments at all possible temperatures and pressures, generally thermodynamic models based on equations on state are used for estimation of VLE. In this paper, an alternate tool, i.e. the artificial neural network technique has been applied for estimation of VLE for the binary systems viz. tert-butanol+2-ethyl-l-hexanol and n-butanol+2-ethyl-l-hexanol. The temperature range in which these models are valid is 353.2-458.2K at atmospheric pressure. The average absolute deviation for the temperature output was in range 2-3.3% and for the activity coefficient was less than 0.009%. The results were then compared with experimental data. 

Narrowly focused, the tenets of 21 CFR 11 are indisputable that firms must establish and maintain the integrity of their electronic information. What has been lost is the clear indication of which electronic information the requirements apply to. In my opinion, data generated outside a computerized system, that are manipulated by that system and are ultimately available in hard copy should not be subject to this ruling. Validation of the computerized system should be more than sufficient to establish that the final documentation accurately reflects the input information. In that instance, the computerized system is little more than a tool whose functionality can be readily established, yet firms are endeavoring to assure 21 CFR 11 compliance for numerous systems in which the computer is little more than an adjunct to the cGMP activity and corresponding hard copy. Batch record preparation, SOP and test method archives, and many process equipment control systems are examples of systems in which requirements for 21 CFR 11 compliance appear excessive. A system that processes or communicates data or records and subsequently retains and stores hard copies should not be subject to the 21 CFR 11 requirements. Far too many systems are being unnecessarily held to the very restrictive portions of 21 CFR 11. Electronic record retention as defined in 21 CFR 11 has its place, but not necessarily in every computerized system used within the industry. 

Rapid quantification of products and substrates in a fermentation process is essential for process development and optimization. Most fermentation laboratories have access to HPLC equipment with possibilities to couple them to quite inexpensive diode-array-detectors, and this equipment could be used for quantitative monitoring of the process. Because HPLC can allow multi-component analyses, i.e., several analytes in the same sample can be determined virtually simultaneously, and since it is often necessary to monitor more than one substance at a time, this technique is an important tool for bioprocess monitoring. HPLC coupled to expensive MS does not represent standard equipment at fermentation laboratories. Even if mass spectrometers are available, DAD is often sufficient for quantification because product concentrations are relatively high, so the MS could be used for other issues. In paper II the goal was to develop and validate a method for analytical quantification of both the product and the substrate to enable the proper characterization of the kinetics of the process i.e., the determination of the values of substrate conversion and product formation. 

Small-scale process models are an essential and valuable tool for process validation and ongoing troubleshooting [32]. Scale-down factors ranging from 10- to 10,000-fold are employed [3] with the extent of scale-down de-pending on the actual production scale and smallest scale that can reliably reproduce the process [51]. Small-scale equipment is permissible only if the scalability of the unit operation is demonstrated [12]. The same technical principles for scale-down are used as for scale-up for the step of interest [3]. 

The development of specialist software for the analysis of electron micrographs has equipped researchers with a variety of computational tools to analyse different types of sample. These methods are all based on the premise that a micrograph is a simple projection of the object and therefore have much in common. The main steps include (i) pre-processing of images, (ii) restoration of images, (iii) enhancement of images, (iv) determination of orientations and (v) reconstmction of the three-dimensional distribution of density. The result obtained must then be validated and interpreted. 

The experimental tooling system is equipped with extensive instrumentation in order to provide insights into the process and validate the 3D simulations. An important aspect is that data from process measurements are available for a comparison throughout the mold filling and cooling phases. It is important not just to compare the key geometrical features of the final product with the simulation, having utilized machine set points to provide... 

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