Scale-up in the 4th dimension in the field of granulation and drying or how to avoid classical scale-up

In the pharmaceutical industry, the production of granules is based on a batch concept. This concept offers many advantages, as a batch can be accepted or rejected. However, the scale-up of the batch size may lead to problems. The variety of the equipment involved does not facilitate the scale-up process and the capital invested in space and equipment is high. An alternative approach is the use of a continuous process. However, continuous processes have the disadvantage among others that the batch size is not well defined. Thus, a special quasi-continuous production concept was developed, taking into account the advantages of a batch type and a continuous process. This concept was developed in cooperation with the Institute of Pharmaceutical Technology of the University of Basel, Glatt CH-4133 Pratteln and F. Hoffmann-La Roche, CH-4070 Basel. The equipment allows to implement a “Just in Time Production Concept” as a large batch B consists of n subunit (SU) batches b, i.e. B=nb. The subunit batch b corresponds to, e.g. 7-kg material for the production of pharmaceutical granules for further processing such as tabletting. At the Roche production site, this novel process equipment was used to manufacture batch sizes B with n=10, n=100 and so far up to n=600 subunits. This leads to an optimal use of capital invested in GMP space and equipment. The difference to the classical scale-up is the following: with classical scale-up, the dimensions of the equipment x, y, z is enlarged and the process time is more or less kept constant. With this novel concept, the dimension x, y, z of the equipment is kept constant and the process is repeated in the 4th dimension “n times”. Thus, for the scale-up in the 4th dimension, i.e. in the time, the equipment needs to show a “self-cleaning” property and appropriate formulations. The novel concept is of special interest, as the quality of the product is not changed during scale-up.