i.
CIP:
Manual cleaning →Pre wash→ WFI-I
(5mins) →WFI-II (5mins) →WFI –III (5mins) → sampling
Tests:
§ pH : 5.0-7.0
§ Conductivity : 1.3µsemen/cm
§ TOC : NMT 500ppb
§ BET : NMT 0.125EU/ml
§ Bioburden : 10CFU/100ml
ii.
SIP:
Ø Sterilization
by steam passing at NLT121°c to NMT140°c for 20mins (filter with stand up to
130-140°c)
Ø After steam sterilization
follows Air purging for removal of moisture inside the vessel.
iii.
Autoclave:
Ø 5 inbuilt probes for
autoclave (2-right, 2-left, 1 drain)
Ø 4 pressure gauges
§
Sterilization gasket
§
Non-sterilization gasket
§
Chamber
§
Jacket
Ø
Check the parameters & load patterns
Ø
Sterilization for 30min (121°c -124°c) [>124°c is over shoot temp]
Ø
121.0°c is stop temp, 120.9°c is re-set temp.
Ø
Cycle process as follows
§
Pre-vacuum , Pre-pressure (alternatively) – 3pulses (3*10mins)
§
Heat up stages ( heat up-1, heat up-2, heat up-3)
§
Sterile hold for 30mins
§
Post vacuum, post pressure – 2 or 3 pulses (pulse Time depend on load)
iv.
Washing:
Check points:
Ø Washing machine recipe
Ø
Machine Speed
Ø
Pressure of Compressed air (0.2µ), re-circulated water (1.2µ), WFI (1.2µ).
Ø
Washing cycles:
§
Re-circulated water –in
§
Re-circulated water-out
§
Compressed air – in
§
WFI – in
§
WFI - in, out
§
Compressed air – in
§
Compressed air – in, out
v.
Tunnel:
Check points:
Ø Tunnel recipe
Ø
Conveyer Speed
Ø
Tunnel strip chart
Ø
Tunnel Temp (300-330°c)
Ø
Pressure of Tunnel zones of
§
In-let/dry zone (25-50°c) [100-250pa]
§
Heating zone (300-330°c) [150-300pa]
§
cool zone (18°c) [100-200pa]
Ø
Time retain in heating zone min of 3mins for De-Pyrogenation.
vi.
Filling:
Check points:
Ø
Filling Machine recipe
Ø
Machine speed
Ø
NVPC
Ø
Environmental monitoring
Ø
Assembling
Ø
Fill volume set-up
Ø
Filling, Stoppering
Ø
In-process checks i.e... Fill Wt, Area Temp, DP, RH
vii.
Sealing:
Check points:
Ø Sealing machine recipe
Ø
Machine speed
Ø
Sealing Process
Ø
In-process checks
Ø
Seal integrity
Ø
Visual inspection
viii.
Lyophilization:
Ø CIP, SIP, Lyophilizer
History data, Vacuum leak test data of Lyophilizer
Ø
Vial Loading shelf wise (from 1,2,3…Last)
Ø
Freezing
Ø
Primary drying – removal of 95% moisture
Ø
Secondary drying – removal of remaining 5% moisture (Total moisture
100% remove)
Ø
Un-loading (from Last ….3,2,1)
Steps:
Shelf Pre-cooling (8°c)
→Freezing (-55°c) →Condenser cooling (-70°c) →Chamber evacuation
↓
Pressure rinse Test ← Secondary
drying (35°c) ←Pressure rinse Test ← Primary Drying (25°c, 30°c)
↓
Vacuumed Break & Stoppering
(manually by hydraulic rods) →Shelf cooling →Cycle end.
ix.
Terminal Sterilization:
Ø 5 inbuilt probes for
autoclave (2-right, 2-left, 1 drain)
Ø 4 pressure gauges
§
loading gasket
§
Un-loading gasket
§
Chamber
§
Jacket
Ø
Check the Load parameters
Ø
Sterilization for 20min (121°c -124°c) [>124°c is over shoot temp]
Ø
121.0°c is stop temp, 120.9°c is re-set temp.
Ø
Final Sterilization for reducing Bioburden Level 0 CFU/100mL
Ø Cycle process as follows
§ Cycle start
§
Purified water in
§
Heat up
§
Sterile Hold time for 20 mins
§
Heat exchange exhaust
§
Cooling
§
Heat exchange Delay
§
Heat exchange drain
§
Cycle end
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