Scale-down models

The adhesives were applied according to manufacturers directions to scaled down models of an application. Failure of the vulcanized, rubber to metal bond was detected by a loss of resistance resulting from the establishment of a leak path under the rubber. The samples were connected electrically to the zinc anode. The temperature, specific gravity, electrical conductivity and pH of the solutions were monitored during the test. 

Staled simplistically, capturing energy from nuclear fusion is like that of building immature suns on Earth, where temperatures and other physical parameters of dimensions that stretch the imagination are involved. Superbly durable materials are required and remain to be developed. Scaled-down models for experimental purposes are large and consequently costly to construct. Thus, it is dear that fusion power research is no abode for the short-term pragmatist, the irresolute, nr the impatient. ... 

Winkler, M. Use of generic studies and scale down models in process validation. IBC Process Validation for Biologicals. San Diego, CA, Feb. 14-15, 2000. 

One example of a miniaturized LC/MS strategy is the use of 96-well sample plates (Kaye et al., 1996) for extraction. This sample extraction procedure combines batch sample processing within a miniaturized format. Increased sensitivity and decreased volume advances have fostered a new wave of scale-down models. Experiments that were formerly performed at the bench are, instead, performed at the microliter scale in the batch mode. For example, synthetic process research was traditionally performed manually with apparatus at the milliliter level. This approach involves the testing of a range of synthetic conditions for optimum yield and minimum impurity production. Now, process research conditions are tested in microliter levels to produce information on purity and structure (Rourick et al., 1996). This strategy requires fewer reagents and accelerates the evaluation of a wider range of conditions in a shorter time. Another example includes the direct analysis of samples from cell culture experiments (Kerns et al., 1997). 

In addition to scale-up models, scale-down models are widely used to establish the oper-... 

Godavarti, R., Petrone, J., Robinson, J., Wright, R., and Kelley, B. D. (2005), Scale-down models for purification processes Approaches and applications, in Rathore, A. S., and Sofer, G. Eds., Process Validation in Manufacturing of Biopharmaceuticals Guidelines, Current Practices, and Industrial Case Studies, Taylor and Francis, Boca Raton, FL. 

Process validation involves the identification, monitoring, and control of sources of variation that can contribute to changes in the product. It starts with process characterization studies using scale-down models for optimization, operating range specification, extractables and leachables characterization, and clearance studies. Such work depends on validated assays and representative scale-down models. 

Normal operating range (NOR) limits are determined by run-to-rrm reproducibility with scale-down models and trending with control charts at production scale. NOR limits lie within MOR limits, which must allow for normal variability while maintaining acceptable operation. 

For the clearance of enveloped and non-enveloped viruses, today s requirements ask for an orthogonal combination of methods that are based on the different physical principles of removal and inactivation, and are complementary to each other [165]. Virus filtration and solvent/de-tergent treatment are state of the art for removal and inactivation [166, 167]. Partitioning steps are considered less robust, as they are somewhat influenced by the actual process conditions. In any case, scaled-down models must be designed... 

Statistical DOE used random combinations of selected control parameters at high/low values in scale-down model... 

Scale-down model to identify critical parameters... 

Validated scale-down model used to test robustness (via fractional factorial design), reuse and virus removal... 

Viral reduction during manufacture of Factor IX Scale-down models used to demonstrate log reduction. [86] (CSL)... 

There is increased regulatory concern over the accuracy of results obtained from small-scale models [52]. Consequently, the scale-down model must be validated to be consistent with full-scale manufacturing before validation studies begin. For chromatography steps, it is necessary to determine that product purity and yield are the same [52] or demonstrate comparable HETP, peak asymmetry, and retention time [5]. Any product streams tested should be representative of a commercial-scale process feed stream [52]. 

Meier SJ. (2005) Cell culture scale-up mixing, mass transfer, and use of appropriate scale-down models. Biochem. Eng. XIV. Harrison Hot Springs, Canada. 

The laboratory test should try to simulate actual service conditions. Occasionally, this may be accomplished simply by building a scaled-down model of a particular operation. If the service operation is not too large, actual parts of the system can be modified to a laboratory bench-top to permit a better simulation of the actual process. 

FIG. 1—Scaled-down model, circulating brine cooling/heating heat exchanger system. 

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