BIOPROCESS

TECHNOLOGY-I

1. UNIT OPERATIONS IN BIOPROCESS

TECHNOLOGY
1. Introduction to sterilization in bioprocess
industry.
2. Equipment Sterilization
3. Monitoring of Sterilization
4. Validation of Sterilization.
5. Sterility audit and automation.
6. Introduction to the development of
inoculum for industrial processes.
7. Introduction to Response Surface
Methodology

Unit Operation
Unit Operation is a basic step in many chemical processes.
Bioprocesses such as production of penicillin or therapeutic
proteins can also be broken down into series of basic steps
called unit operations.
In penicillin production, besides fermentation, medium
sterilization, broth filtration, solvent extraction, centrifugation,
drying and distillation are some of the unit operations which
are connected to create the overall process. Similarly other
bioprocess may have many other unit operations to obtain the
desired product.
Treatment of the process in terms of individual unit operations
allows the process engineers to move away from product
specific operation to one which is general. Also the knowledge
gained in the treatment of one process can be used to a
completely new process.
In order to produce product of desired quality with the
maximum yield, each unit operation must be designed
correctly. Mathematical treatment of the process can lead to
prediction of conditions which will give the highest efficiency
for that unit operation.

1.2 EQUIPEMENT
STERILIZATION

VESSEL
AIR FILTERS
MEDIUM
VALVES AND PIPING

AIR FILTERS (already

Air inlet and vent ports
of sterile vessels.
discussed)

MEDIUM FILTERS (already

discussed)
Not hydrophobic.

VALVES & PIPING

Diaphragm valve. : commonly used as the actuating

mechanism is sealed from the process solution. Easy to clean
and sterilize.disadavantage : not crevice free
Steam
Uses
the
completely
drain
sampling
through
the
connection.
valve
to a
The
drain
boss
oriscondens
drilled
Assumes
that
the
dead legs
are not
more
than
6. un
Three
ways
toor
sterilize
valves:

The piping systems designed for steam sterilization should slope so that

1.3 MONITORING OF
STERILIZATION
Sterilization procedures should be
monitored through a combination
of
mechanical,
chemical, and
biological techniques
designed to evaluate the

MECHANICAL
Mechanical

CHEMICAL INDICATORS

internal and external, use sensitive chemicals to assess physical conditio

Indicator test results are shown immediately after the sterilization cycle

BIOLOGICAL INDICATORS
(BIS)
The most accepted means
of monitoring the sterilization process becaus

FREQUENCY OFBIOLOGICAL MONITORING (BI)

(SPORE TESTING)?

Correct functioning of sterilization cycles should be verified for each ster

In case of implantable device

Any
load
containing
implantable
devices should be monitored. Ideally,
implantable items should not be used
until the results of tests are known to
be negative.. A control BI (not
processed through the sterilizer) from
the same lot as the test indicator
should be incubated in the same
manner as the test BI. The control
biological
indicator
should
yield
positive results for bacterial growth.

In case of a positive
If the mechanical (e.g., time, temperature,
pressure) and chemical (internal or external)
indicators
suggest
that
the
sterilizer
is
functioning properly, a single positive spore test
result probably does not indicate sterilizer
malfunction. Items other than implantable items
do not necessarily need to be recalled; however,
sterilizer operators should repeat the spore test
immediately using the same cycle that produced
the positive BI. The sterilizer should be removed
from
service
and
sterilization
operating
procedures reviewed to determine whether
operator error could be responsible.
If the result of the repeat spore test is negative
and operating procedures were correct, then the
sterilizer can be returned to service. If the repeat
spore test result is positive, do not use the
sterilizer until it has been inspected or repaired