Some Practical Aspects - Freeze-drying of Pharmaceuticals and Biopharmaceuticals - page 124

Table 1 A typical scale-up and ICH manufacture programme
Safety issues
Evaluation of operator safety
Evaluation of waste disposal
Evaluation of cleaning process
Packaging issues
Selection and evaluation of vial, stopper and overseals
Formal studies of extractable components of the packaging
Development and qualification of stopper cleaning and sterilisation
Development and qualification of vial cleaning, depyrogenation
and sterilisation
Line tests of vials and stoppers
Optimisation of stopper siliconisation (where required)
Purchase of necessary change parts to lines
Fitting and qualification of change parts
Container closure integrity (dye leakage)
Vial headspace gas analysis (leak check)
Pilot-scale (1000 vials) development
Cleaning verification
Documentation for compounding and freeze-drying
Tech transfer of compounding methods
Transfer and qualification of compound-specific chemical analyti-
cal methods
Agreement on bioburden, sterility and standard analytical methods
Analytical methods transfer
Process refinement: three batches at pilot scale
Transfer to full-scale sterile development batches
Condenser water challenge
Full-scale water batch (dummy runs to checkout everything)
Cleaning verification and validation
Media fills (confirmation of sterile manufacture)
Finalisation of extractable volume and fill volume
Preparation of documentation (filling and manufacturing works
orders)
Full-scale development batches (2, 3)
Helium leak rate test
Manufacture of ICH stability lots
Preparation of documentation (filling and manufacturing works
orders)
Manufacture of three ICH stability test lots