Activation control, leveling process

Constraint control strategies can be classified as steady-state or dynamic. In the steady-state approach, the process dynamics are assumed to be much faster than the frequency with which the constraint control appHcation makes its control adjustments. The variables characterizing the proximity to the constraints, called the constraint variables, are usually monitored on a more frequent basis than actual control actions are made. A steady-state constraint appHcation increases (or decreases) a manipulated variable by a fixed amount, the value of which is determined to be safe based on an analysis of the proximity to relevant constraints. Once the appHcation has taken the control action toward or away from the constraint, it waits for the effect of the control action to work through the lower control levels and the process before taking another control step. Usually these steady-state constraint controls are implemented to move away from the active constraint at a faster rate than they do toward the constraint. The main advantage of the steady-state approach is that it is predictable and relatively straightforward to implement. Its major drawback is that, because it does not account for the dynamics of the constraint and manipulated variables, a conservative estimate must be taken in how close and how quickly the operation is moved toward the active constraints. 

Incorporation of downstream processing steps known to inactivate a wide variety of viral types provides further assurance that the final product is unlikely to harbour active virus. Heating and irradiation are amongst the two most popular such approaches. Heating the product to between 40 and 60°C for several hours inactivates a broad range of viruses. Many biopharmaceuticals can be heated to such temperatures without being denatured themselves. Such an approach has been used extensively to inactivate blood-borne viruses in blood products. Exposure of product to controlled levels of UV radiation can also be quite effective, while having no adverse effect on the product itself. 

In ophthalmological application, this characteristic of the PFCLs is not used yet. In general, the products used are air equilibrated with the consequence that the oxygen partial pressure in the eye is increased from 15 Torr to 160 Torr and the CO2 partial pressure drops down from 50 Torr to 3 Torr initially. These differences are equilibrated intra-ocularly by diffusion processes, but the initial difference to the physiological level of gas concentration activates the constriction of the retinal vessels, resulting in an increase of the blood flow. In rabbit eyes, a damage of the retina could be attributed to this mechanism [38,39], On the other hand, endotamponade media with controlled levels of dissolved gases could not only avoid such a scenario but should also be useable for a therapeutic manipulation of the retinal perfusion. 

Fig. 2.8. Factors controlling the production of free radicals in cells and tissues (Rice-Gvans, 1990a). Free radicals may be generated in cells and tissues through increased radical input mediated by the disruption of internal processes or by external influences, or as a consequence of decreased protective capacity. Increased radical input may arise through excessive leukocyte activation, disrupted mitochondrial electron transport or altered arachidonic acid metabolism. Delocalization or redistribution of transition metal ion complexes may also induce oxidative stress, for example, microbleeding in the brain, in the eye, in the rheumatoid joint. In addition, reduced activities or levels of protectant enzymes, destruction or suppressed production of nucleotide coenzymes, reduced levels of antioxidants, abnormal glutathione metabolism, or leakage of antioxidants through damaged membranes, can all contribute to oxidative stress.

The oxygen level in the milkfat may be limited by either active or passive actions. For passive control, processing procedures and plant design are established to minimize air exposure. Deaeration devices (74), vacreation (60), the use of antioxidants (72), effective destmction of lipases (75), and nitrogen spanning of container headspace are examples of active control of product quality. 

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