Introduction - Bioprocess Engineering: Kinetics, Biosystems, Sustainability and Reactor Design - page 17

that enter human clinical trials receive approval. Recent FDA reforms have decreased the
time to obtain approval for life-saving drugs in treatment of diseases such as cancer and
AIDS, but the overall process is still lengthy.
This process greatly affects a bioprocess engineer. FDA approval is for the product and the
process together. There have been tragic examples where a small process change has allowed
a toxic trace compound to form or become incorporated in the final product, resulting in
severe side effects, including death. Thus, process changes may require new clinical trials
to test the safety of the resulting product. Since clinical trials are very expensive, process
improvements are made under a limited set of circumstances. Even during clinical trials it
is difficult to make major process changes.
Drugs sold on the market or used in clinical trials must come from facilities that are certi-
fied as GMP or cGMP and must follow the appropriate Code of Federal Regulations. GMP
stands for (current) good manufacturing practice. GMP concerns the actual manufacturing
facility design and layout, the equipment and procedures, training of production personnel,
control of process inputs (e.g. raw materials and cultures), and handling of product. The
plant layout and design must prevent contamination of the product and dictate the flow of
material, personnel, and air. Equipment and procedures must be validated. Procedures
include not only operation of a piece of equipment but also cleaning and sterilization.
Computer software used to monitor and control the process must be validated. Off-line
assays done in laboratories must satisfy good laboratory practice. Procedures are documented
by standard operating procedures.
The GMP guidelines stress the need for documented procedures to validate performance.
“Process validation is establishing documented evidence which provides a high degree of
assurance that a specific process will consistently produce a product meeting its predeter-
mined specifications and quality characteristics” and “There shall be written procedures
for production and process control to assure that products have the identity, strength, quality,
and purity they purport or are represented to possess.”
The actual process of validation is often complex, particularly when a whole facility design
is considered. The FDA provides extensive information and guidelines that are updated
regularly. If students become involved in biomanufacturing for pharmaceuticals, they will
need to consult these sources. However, certain key concepts do not change. These concepts
are written documentation, consistency of procedures, consistency of product, and demon-
strable measures of product quality, particularly purity and safety. These tasks are
demanding and require careful attention to detail. Bioprocess engineers will often find that
much of their effort will be to satisfy these regulatory requirements. The key point is that
process changes cannot be made without considering their considerable regulatory impact.
1.9. THE PILLARS OF BIOPROCESS KINETICS AND SYSTEMS
ENGINEERING
As a profession, Bioprocess Engineers must be well versed in thermodynamics, transport
phenomena, colloids, bioseparations, microbiology, bioprocess kinetics and systems engi-
neering, and process simulation and design. This text deals with the core of bioprocess engi-
neering. Unlike earlier texts in this subject area, this text integrates bioprocess engineering