Feed batch approach

Fermentation follows for several days subsequent to inoculation with the production-scale starter culture (Figure 5.7). During this process, biomass (i.e. cell mass) accumulates. In most cases, product accumulates intracellularly and cells are harvested when maximum biomass yields are achieved. This feed batch approach is the one normally taken during biopharmaceutical manufacture, although reactors can also be operated on a continuous basis, where fresh nutrient media is continually added and a fraction of the media/biomass continually removed and processed. During... 

At a fixed temperature, a single, reversible reaction has no interior optimum with respect to reaction time. If the inlet product concentration is less than the equilibrium concentration, a very large flow reactor or a very long batch reaction is best since it will give a close approach to equilibrium. If the inlet product concentration is above the equilibrium concentration, no reaction is desired so the optimal time is zero. In contrast, there will always be an interior optimum with respect to reaction time at a fixed temperature when an intermediate product in a set of consecutive reactions is desired. (Ignore the trivial exception where the feed concentration of the desired product is already so high that any reaction would lower it.) For the normal case of bin i , a very small reactor forms no B and a very large reactor destroys whatever B is formed. Thus, there will be an interior optimum with respect to reaction time. 

The embedded model approach represented by problem (17) has been very successful in solving large process problems. Sargent and Sullivan (1979) optimized feed changeover policies for a sequence of distillation columns that included seven control profiles and 50 differential equations. More recently, Mujtaba and Macchietto (1988) used the SPEEDUP implementation of this method for optimal control of plate-to-plate batch distillation columns. 

There were two possible approaches to addressing the segregation issue. The first was to modify the blend (granulation, etc.). The second was to modify the blend feed system. The latter was chosen in an effort to prevent recurrence in other, similar formulations. After the modification of the tablet press overhead-feed system, all subsequent batches passed unifonnity testing and eventually a validation exercise. 

Figure 14.3. Representation of countercurrent extraction batteries, (a) A battery of mixers and settlers (or separators), (b) Schematic of a three-stage countercurrent battery, (c) Simulation of the performance of a three-stage continuous countercurrent extraction battery with a series of batch extractions in separatory funnels which are designated by circles on the sketch. The numbers in the circles are those of the stages. Constant amounts of feed F and solvent S are mixed at the indicated points. As the number of operations is increased horizontally, the terminal compositions Et and R3 approach asymptotically the values obtained in continuous countercurrent extraction (Treybal, 1963, p. 360).

Every quality control programme should include periodic laboratory analysis of ingredients and mixed feed. Care should be taken to insure that samples are representative, by taking samples from various points in the batch, mixing them and then drawing a subsample of 500-1000 g for analysis. For bagged material a common approach is to collect a sample with a probe from 10-15% of the bags in the batch. It is advisable to use only one-half of the sample for laboratory analysis and to retain one-half as a back-up in case of subsequent problems, discrepancies or disputes. 

Whereas the operation of batch reactors is intrinsically unsteady, the continuous reactors, as any open system, allow for at least one reacting steady-state. Thus, the control problem consists in approaching the design steady-state with a proper startup procedure and in maintaining it, irrespective of the unavoidable changes in the operating conditions (typically, flow rate and composition of the feed streams) and/or of the possible failures of the control devices. When the reaction scheme is complex enough, the continuous reactors behave as a nonlinear dynamic system and show a complex dynamic behavior. In particular, the steady-state operation can be hindered by limit cycles, which can result in a marked decrease of the reactor performance. The analysis of the above problem is outside the purpose of the present text ... 

For simplicity, we restrict ourselves to having a feed flowrate that starts at some value F0 and ramps down with a constant slope S. This practical approach to trajectory optimization is recommended by Smith and Choong6 for batch processes. We want to find the values of F0 and S that achieve the desired conversion and selectivity. There will be many pairs of values that will satisfy the two criteria. Each will have a different batch time and a different amount of C produced. 

Other common continuous mixers involve substantial modification of single and twin screw extruders, aimed at improving distributive mixing capability in particular, and leading to the development of continuous mixers such as the Transfermix (50) and the Buss Ko-Kneader (51). Another approach in continuous mixer development is to transform batch mixers into continuous ones. Thus, the roll-mill can be converted into a continuous mixer by feeding raw material on one side and continuously stripping product on the other side. In addition, the Banbury mixer was imaginatively transformed into the Farrel Continuous Mixer (FCM) by Ahlefeld et al. (52), and, later, two similar continuous mixers were developed by Okada et al. (53) at Japan Steel Works and by Inoue et al. (54) at Kobe Steel. 

Xie L, Wang DI (1997), Integrated approaches to the design of media and feeding strategies for fed-batch cultures of animal cells, Trends Biotechnol. 15 109-113. 

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