Biomedical Engineering Reference
In-Depth Information
Sources and upstream processing
5.1 Introduction
The manufacture of pharmaceutical substances is one of the most highly regulated and rigorously
controlled of manufacturing processes. In order to gain a manufacturing licence, the producer must
prove to the regulatory authorities that not only is the product itself safe and effective, but that all as-
pects of the proposed manufacturing process comply with the highest safety and quality standards.
This chapter aims to overview the manufacturing process of therapeutic proteins. It concerns
itself with two major themes: (1) sources of biopharmaceuticals and (2) upstream processing. The
additional elements of biopharmaceutical manufacturing, i.e. downstream processing and product
analysis, are discussed in Chapters 6 and 7 respectively.
5.2 Sources of biopharmaceuticals
The bulk of biopharmaceuticals currently on the market are produced by genetic engineering using
various recombinant expression systems. Although a wide range of potential protein production
systems are available (Table 5.1), most of the recombinant proteins that have gained marketing ap-
proval to date are produced either in recombinant
E. coli
or in recombinant mammalian cell lines
(Table 5.2). Such recombinant systems are invariably constructed by the introduction of a gene or
cDNA coding for the protein of interest into a well-characterized strain of the chosen producer cell
(Chapter 3). Examples include
E. coli
K12 and CHO strain K1 (CHO-K1). Each recombinant pro-
duction system displays its own unique set of advantages and disadvantages, as described below.
5.2.1
Escherichia coli
as a source of recombinant, therapeutic proteins
Many microorganisms represent attractive potential production systems for therapeutic proteins.
They can usually be cultured in large quantities, inexpensively and in a short time, by standard
Search WWH ::
Custom Search