The actual yield is much broader for these types of processes than you would find in a final
dosage-form manufacturing situation. You should have some idea of what the cell viability is and
what your yield should be, but there will be a much wider range available to you. You should also
have enough historical information to have an idea of what that range is and define some
parameters to assess the process quality.
This is typically something that the process development scientists need to work out during
product scale-up, that is the appropriate ways to control yields. It will be different for different
kinds of processes. In some cases, there’s a need to control the amount of protein coming from
the cells, and sometimes it’s control of the amount of protein in a certain volume, because it
depends upon how robust the purification process is. The goal is to be able to ferment
consistently so that you can purify consistently, but the way you actually control it will vary from
process to process, and that needs to be worked out during development and the manufacture of
clinical material.
For classical fermentation in most cases it is an economic issue. The yield generally is not a
problem other than economics, because you usually have a purification process that follows the
classic fermentation, and the kind of compounds that can occur are likely to be removed by the
processes that are used.
It is important, though, when you do this work, to distinguish clearly between controls that are
being imposed to control product quality by GMP, as opposed to controls that are being imposed
for economic reasons, which are not GMP matters, in general.
