ABSTRACT
Pharmaceutical biotechnology combines microbiology,
chemistry, traditional pharmaceutical technology, and
biochemical engineering with advances in genetic engin-
eering technology to prepare proteins and other biologic
products as therapeutic or diagnostic agents. These
biologics are produced in a suitable host cell by fermenta-
tion or cell culture processes. Cells from a qualified cell
bank are expanded in culture until sufficient numbers are
obtained for the desired production scale. During culture,
the product of interest may be either retained intracellu-
larly or secreted into the culture medium. If the product
remains inside the cell, then the cells must be harvested,
disrupted, and thedebris that is created removed to yield a
particulate-free extract for further purification. If the
product is secreted, the cells must be separated from the
conditioned culture medium prior to purification. These
process steps, shown schematically in Figure 1, include
initial product recovery followed by refolding
(if necessary), isolation, purification, viral inactivation (if
necessary), and finishing operations. Each of the process
stages shown in the figuremay be achievedusing a variety
of unit operations, aswill be discussed. The validation of a
biomanufacturingprocess encompasses validation of each
of these unit operations separately and in combination to
demonstrate that the process can reliably and reprodu-
cibly produce the desired product.
