Zoladex Flashcards
Zoladex Clean filtration Issues
Failure to get filter to pass integrity test
Extra settle plates were not put down/ Extra AAS not run to cover additional 4 hours after an issue with filter integrity.
Bioburden sample not taken
Catch pot valve not closed when starting filtration under pressure- loss of product (leaks out of vessel at speed). Acetic wash at end of batch then dilutes the remainder of batch.
Foreign matter found in API/ Copolymer/ Acetic acid- usually supplier caused but requires investigation/ batch assessment.
Zoladex Sterile filtration issues
Issues/ Delay at clean filtration causes knock on delay at sterile filtration. Extra settle plates were not put down/ Extra AAS not run to cover additional 4 hours.
Leaks found in dripper tubing assembly whilst pumping material from vessel up to drum freezer
Zoladex Drum Freezer issues
Frosting of drum freezer
Excessive drop off for tray A
Drum speed too fast/slow
Drum surface temperature too high / return coolant temperature too high
Gauntlet integrity failure/ hole in gauntlet
Zoladex Freeze Drier issues
Freeze drier step failure (sterilization, filter integrity test, leak rate) prior to batch
Category 1 alarms for cycle
Any catastrophic failure of freeze drier cycle
Zoladex Compaction issues
Equilibration conditions
Contaminated chutes
Particle excursions
Tamping rod touching particle point (aseptic concern)
Inadequate number of compactions
Catastrophic failure of compaction equipment with barrel + product in place
Zoladex Extrusion issues
Heat up and extrusion total time limit exceeded (aseptic limit)
Temperature probe(s) not in place correctly
Extrusion eurotherm chart cuts off final piston readings when force is dropped
Interventions required at extrusion are outside PST limit (no interventions routinely)
Zoladex Cutting issues
Surface particulate
Additional kit in shadow tray above qualified autoclave load
Particulate identified but dropped + not able to analyze
Depots remaining within LAF post line clearance activities
Smashed cylinder
Cracked cylinder
Zoladex Checkweigh issues
Incorrect actions taken in event of calibration (External cal/ autocal fails)
Depots weighed 3x (aseptic limit is two)
Depots remaining within LAF post line clearance activities
‘Rejects’ plural mentioned in comments but either only one or no reject depots present at time of action.
Describe the Zoladex manufacturing process and the Critical Processing Parameters.
Zoladex solution is preparation
CPPS – Quantity of Goserelin, Co-polymer charged, Contact time on product filter, Final Batch Weight
Filtered in to sterile area via sterilising filter (0.2micron)
Solution is then dripped on to a drum freezer to produce flake.
CPPS – Drum surface Temp, Tray Temp, Drum Speed,
Trays are placed in freeze dryer – to remove acetic acid
CPPS- Transfer time between drum freezer and freeze dryer, Pressure, Condensor Temp, shelf Temp, Cycle parameters,
Equilibration
CPP – relative humidity and Temp and Time
Compaction
CPP - relative humidity and Temp- max / min compactions
Extrusion
Heat up Time , Heat up Temp
Inspection Cut Check Weigh
Average subpart weight,
