Biology Reference
In-Depth Information
Release
Before the release of any rHuEPO lot, the final material is thoroughly tested to
ensure sterility, concentration, lack of endotoxin and bioburden, and product
integrity according to quality control requirements. Additionally, batch records
from the manufacturing run are reviewed to ensure that no deviation was made
during the production run. Finally, as each lot is released,the product is
shipped to wholesalers according to validated procedures.
Summary
An example of commercial production of rHuEPO is discussed in this chapter,
where the manufacture starts with a cell line that is engineered to produce
product in commercial quantities of required quality. The cell line is banked,
and the cell bank is used as the starting material for the manufacturing process.
In this example, recombinant HuEPO is secreted from genetically engineered
mammalian cells in a fermentation process and then recovered and purified as
rHuEPO bulk in a purification process, to achieve the desired product charac-
teristics specified by the manufacturer. The bulk rHuEPO is formulated to
achieve the required dosage forms and put into dosage forms that are used in
the clinic. The manufacturing process is performed in a cGMP facility and
monitored for consistent performance. Regulatory and other safety require-
ments are followed to produce a safe, efficacious product.
References
1 Center for Biologics Evaluation, Research (CBER), Center for Drug Evaluation, Research
(CDER) (1996)
Guidance for industry for the submission of chemistry, manufacturing, and con-
trols information for a therapeutic recombinant DNA-derived product or a monoclonal antibody
product for
in vivo
use
. www.fda.gov/cber/gd/ns/cmcblood.htm. Accessed 04-30-2003
2 Freshney RI (1983)
Culture of animal cells.
Alan R. Liss, Inc., New York
3 Ozturk SS (1996) Engineering challenges in high density culture systems.
Cytotechnology
22:
3-16
4Chu L, Robinson DK (2001) Industrial choices for protein production by large-scale cell culture.
Curr Opin Biotechnol
12: 180-187
5 Monroe RS, Huber BE (1994) The major form of murine asialoglycoprotein receptor - cDNA
sequence and expression in liver, testis and epididymus.
Gene
148: 237-244
6 Center for Drug Evaluation, Research (2001)
Q7A Good manufacturing practice guidance for
active pharmaceutical ingredients
. www.fda.gov/cder/guidance/4286fnl.htm. Accessed 04-30-
2003
