Which are the CPPs? (Critical process parameters):
Temperature sensorOpen/close loop systemOpen jacket / limpet / dimpled jacket types2 Heat Exchangers – Dedicated PHEX for cooling & PIP for heatingCirculation pump with flow switchHeating & cooling utilities/ in built electrical heater
Acid and alkali dosing bottles
Acid & alkali dosing pump, in case of Bioreactor CO2 can be used.
All required Valves at appropriate positions.
Design for qualification / validation.
Dissolved Oxygen sensor
AIR , O2 supply
Mass Flow Controller
CASCADE mode with selection of aeration, agitation with VFD, O2, B/P.
Back Pressure control valve
Pressure sensor / transmitter
Back pressure control valve
Additive lines with aseptic transfer assembly.
Respective dosing bottles / integration with NDVs
Programmable dosing pumps
PURITY OF BATCH
Integrity of the system till sterile boundaries.
Individual sterilization of addition lines
Design with QRM
Sterile barrier on exhaust
Antifoam dosing bottle
Antifoam dosing pump
Mechanical Foam Breaker
Smart process automation for aeration & agitation.
WHY IT IS REQUIRED?
BAPS PROVIDES A SYSTEM WITH MULTIPLE PROCESS SEQUENCES
To ensure accurate communication & functioning of valves ON/OFF
PRESSURE HOLD TEST-PHT
To ensure the integrity of the Fermenter / Bioreactor with all sterile boundaries , prior to sterilization & a batch.
EMPTY VESSEL STERILIZATION-ESIP
To reduce the bioburden prior to charging a media it is imperative to sterilize the Fermenter / Bioreactor in empty condition, clean steam is directly introduced in vessel through spray balls, complete system along with all auxiliary lines/valves & sterile boundaries.
AIR INLET FILTERS STERILIZATION (SPARGER & OVERLAY/TOP AIR)
To sterilize air INLET filters along with the vessel or independent sterilization before media sterilization.
EXHAUST AIR FILTER STERILIZATION
To sterilize air EXHAUST filters along with the vessel or independent sterilization before media sterilization.
INDEPENDENT STERILIZATION OF TRANSFER IN /ADDETIVE LINES
All the isolation valves & lines for transfer IN line is sterilized in ESIP & FSIP. When any additive is to be transferred post media sterilization, respective reservoir is attached to respective addition port & in situ SIP is done , to ensure the closed operation & aseptic transfer.
CALIBRATION OF SENSORS
Before installing the sensors in Fermenter /Bioreactor, it has to be calibrated. Calibration of pH sensors for buffer 4 & 7, calibration of DO2 at 0% & 100% DO .
CALIBRATION OF DOSING PUMPS
For respective tube sizes, respective dosing pumps are calibrated for flow rate per min/hr. It helps during feeding a batch in programmed mode.
MECHANICAL SEAL /THERMOSYPHON POT STERILIZATION
In case of agitator with wet mechanical seal, it is required to sterilize the thermosyphon pot & inlet/outlets to mechanical seal.
Media is charged In Fermenter transferred from media preparation area in non-sterile condition. And in Bioreactor it is charged from media preparation area through sterile filter.
MEDIA STERILIZATION -FSIP
Transferred media in Fermenter is sterilized in situ by indirect heating by using plant steam in jacket. In Bioreactor, it is filter sterilized in closed operation with aseptic transfer through respective port. All the auxiliary lines & valves along with all sterile boundaries are sterilized in FSIP.
SEEDING / INNOCULATION
After media sterilization and cooling respective inoculum/seed is transferred aseptically to Fermenter/Bioreactor from bottle or seed fermenter depending on volume scale.
To run a system in specified controlled environment for specific time of incubation. Control of Temperature, pH, Dissolved oxygen, Agitator RPM , Foam, Back Pressure , AIR/Gas flow rate, Level & Nutrient dosing (in fed batch).
Aseptic sampling with SIP is mandatory for IPQC.
To sterilize FBV & harvest line for taking out a Fermentation broth in sterile condition or transfer to next unit operation of DSP.
CLEANING IN PLACE (CIP)
To avoid cross contamination of the product from batch to batch OR product to product, it is must to have proper cleaning of all the product contact parts along with all the auxiliary lines/valves till sterile boundaries. CIP with cleaning agents in recirculation and then it’s proof by conductivity.