Clean-in-place Operations for Thin-cake Filtration Technologies

INTRODUCTION In many chemical and pharmaceutical processes, solid-liquid separation, cake washing and drying steps directly impact the effectiveness of the production operation. Process engineers devote much of their time to analyzing these steps. The solid-liquid separation step can be by pressure, vacuum or centrifugation as well as in a batch or continuous mode. In this separation step, there is a further choice both of the type of filter media and the thickness of the cake or the cake depth during which the separation occurs. Cake washing generally follows and the choices are displacement or reslurry options. Finally, drying may be necessary and there are many possibilities including vacuum, convection, spray, steam and a combination of techniques. This article discusses the choice of thin-cake (2 – 25 mm) separation technologies and their benefits to optimizing the effectiveness of the production process. The paper continues with a discussion of clean-in-place operations to meet current Good Manufacturing Practices (cGMP) guidelines including riboflavin test and validations. ANSI/ISA S88 (and IEC 61512-1 in the international arena) batch process control system standards are also examined. Finally, factory and site acceptance testing is described. IMPORTANCE OF THIN-CAKE FILTRATION Thin-cake solid-liquid separation can be defined as the formation of a cake in the 2-25 mm thickness range. In this range, cake compressibility becomes less important in the cake building stage of a separation process. Compressible cakes or those cakes that have average or poor filtration characteristics can be better handled at thinner cake depths. For example, an amorphous crystal that does not centrifuge well can be filtered at 45 psig with a cake thickness of 2 – 3 mm. Thin-cakes also lend themselves to more effective washing and drying as there is less of a chance of channeling and the mechanism of “plug-flow” of liquids or gases is enhanced. THEORY OF THIN-CAKE FILTRATION Filtration During the initial mechanism of cake forming in the filtration step, the filter cloth acts just to initiate filtration by capturing the first particles. These first particles form bridges over the pores of the cloth (bridging). As soon as a first layer of particles has accumulated on the filter medium, this cake will then act as the actual filter medium. When plotting the amount of filtrate obtained at constant filtration pressure versus the filtration time, a filtration curve is developed, which represents a root function, VF = Constant * tF , as shown in Figure 1. . Filtrate Volume versus Filtration Time for a Batch, Automated Pressure Filter VF = 4.2534tF 0.4934