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Scale-up is generally defined as the process of increasing batch size. Scale-up
of a process can also be viewed as a procedure for applying the same process
to different output volumes. There is a subtle difference between these two
definitions: batch size enlargement does not always translate into a size
increase of the processing volume.
In mixing applications, scale-up is indeed concerned with increasing
the linear dimensions from the laboratory to the plant size. On the other
hand, processes exist (e.g., tableting) where the term ‘‘scale-up’’ simply
means enlarging the output by increasing the speed. To complete the picture,
one should point out special procedures (especially in biotechnology)
where an increase of the scale is counterproductive and ‘‘scale-down’’ is
required to improve the quality of the product.
In moving from research and development (R&D) to production scale, it
is sometimes essential to have an intermediate batch scale.This is achieved at the
so-called pilot scale, which is defined as the manufacturing of drug product by a
procedure fully representative of and simulating that used for full manufacturing
scale. This scale also makes it possible to produce enough product for clinical
testing and to manufacture samples for marketing. However, inserting an
intermediate step between R&D and production scales does not, in itself, guarantee
a smooth transition. A well-defined process may generate a perfect product
both in the laboratory and the pilot plant and then fail quality assurance
tests in production.
Imagine that you have successfully scaled up a mixing or a granulating
process from a 10-liter batch to a 75-liter and then to a 300-liter batch. What
exactly happened? You may say, ‘‘I got lucky.’’ Apart from luck, there had
to be some physical similarity in the processing of the batches. Once you
understand what makes these processes similar, you can eliminate many
scale-up problems. |
