EQUIPMENT/PROCESS CONVERSANCY AIDE MEMOIRE – LVP LAGARDE AUTOCLAVES (Version 24 May 20019)

Sterilization medium: Super-heated water Application: Terminal sterilization of LVP infusion/irrigation solutions in final flexible bag pack form
Basic operation overview
Filling and Heating Plateau Cycle Cooling at the end of the Sterilization Plateau
The chamber is filled with water to a pre-determined level sufficient to flood Temperature and pressure are maintained for the pre-set sterilizing temperature and period Controlled cooling is required during this cooling phase. Rapid cooling could damage the bag or the over pouch.
the inlet of the circulating pump. Once this level is attained, the vent valve according to the selected program. The cooling water controller is programmed to reduce its set point at a required pre-determined rate by modulating the
closes, industrial steam is introduced into the autoclave and the circulating Sterilizing is achieved by superheated water sprayed into the chamber and then cascaded with even cooling water valve.
pump switches on, initiating continuous cascade of progressively heated distribution across the product load. Cooling of the water in the autoclave is via a heat exchanger and cooling tower.
water through the load via spray manifold – nozzles - shower trays mounted The internal pressure in the containers increases with temperature increase but this is countered by The water that is used during the sterilization cycle is used for the cooling and is therefore sterile.
in the upper sections of the chamber. the chamber overpressure setting being maintained. The chamber pressure is controlled throughout the cooling period until the temperature reaches a pre-set value, at which time
Steam and pressure is controlled to follow a pre-determined ramp up If the temperature of the clave drops below a pre-determined value during a cycle the timer will the water circulation pump is stopped, the drain valve is opened and after a predetermined time the vent valve opens. When
according to the program selected with pressure specifically selected to automatically pause and the cycle will auto extend until the temperature is above this set point again. the predetermined level, is reached, the end of the cycle is indicated.
counteract internal container pressure/expansion aspects developed as the It is only possible to open the autoclave doors when the pressure inside the autoclave reaches 0 kPa and the water level is less
contents heat up. At the end of the ramp up, the cycle enters the plateau than 5%.
cycle.
CRITICAL KEY PROCESS GATES (KPG)/ CRITICAL CONTROL POINTS (CCP) - EQUIPMENT/PROCESS CONTROL ELEMENTS THAT IF NOT CORRECTLY
PRODUCT UNDERTAKEN CAN IMPACT ON CQA ATTAINMENT/MAINTENANCE
QUALITY (M = MONTHLY, W = WEEKLY, D = DAILY, B = BEFORE EACH CYCLE, P = PHARMACIST, PA = PHARMACIST ASSSISTANT, PL = PRODUCTION PROCESS
ATTRIBUTES LEADER, O = OPERATOR) CONTROL,
(CQA'S) OF KPGS /CCPS/LEADING UP TO AND AFTER CONTROL -CHECK ACTIVITIES EXAMPLES CHECK INTERVAL - POTENTIAL IMPACT DISPLAY AND
THE FINISHED THE PROCESS RESPONSIBLE PERSON – ASPECTS IF CONTROL – KNOWN SYSTEM / REPORTING
PRODUCT O = OPERATOR CHECK ACTIVITIES NOT PROCESS MECHANISMS
DIRECTLY EQUIPMENT /PROCESS PHARM. TECH/ ASSISTANT = PROPERLY UNDERTAKEN OPERATING THAT
IMPACTED / DESIGN FEATURES THAT PT/PA KEY CRITERIA VULNERABILITY & CONTRIBUTE
INFLUENCED PROMOTE/ PHARMACIST = P /APPLICABLE CRITICAL ASSOCIATED TO/
BY THIS PROVIDE CQA IMMEDIATE PRODUCTION LEADER =PL PROCESS PARAMETERS MITITGATING CONSTITUTE
PROCESSING KEY EQUIPMENT - SYSTEM MAINTENANCE SYSTEM INPUT COMPLIANCE OFFICER =CO (CPP) KEY REFERENCES FACTORS CPV MEASURES
STAGE COMPONENTS / ELEMENTS/UTILITIES- VARIABLES
Sterility Autoclave itself  HMI with pre-  Competing  autoclave spray shower spray Over pouching operations O:- Daily basis  Impaired General set points: Clave operating SOP; Competing Steam
 Purpose built autoclave chamber, programmable password Steam supply check Checks to include: P - PA - PL: Minimum sterilization Temp and pressure BMR supply Autoclave cycle
Container trays and loading trolley controlled Recipe system  Human  visual cleanliness of bags weekly  Product Stability ramp up, plateau temp, QA Risk Assessments printout
Integrity  Water recirculation pump that locks autoclave reliance  shower tray check – Verification  Adequate vacuum draw basis impact pressure and hold-time, Clave PQ Reliance on human
 Heat exchanger operational control &  Manual tray holes are open to allow for  Seal integrity CO: Minimum every  Jeopardy of cooling time and ramp documentation – element for Load Recorded
Product  Water spray system sterilization cycle stacking uniform distribution of Truck Tray appraisal second day basis Primary release down rate qualification preparation and Alarms on the
stability - manifold parameters  Tray condition superheated water across the  Identification and removal from the floor of any grossly control record – presentation printout
characteristic s - spray nozzles production load during the cycle damaged trucks any discrepancy Sterilization plateau See also column
(degradation - overhead perforated trays  Digital & Graphic display of  Identification of trucks that can be repaired in loco – O: With every cycle always with major set points (Temp – Aluminium trays HMI-
risk)  Guillotine doors with inflatable seals time pressure and allocation of corner straightening and repair task to P - PA – PL: Minimum GMP & Pressure – Time): easily damaged – instrumentation
HMI, Instrumentation and control panels temperature suitable personnel every second day basis productivity Standard 50 ml product risk of incorrect -Control panel
 Magelis HMI – SCADA (Primary  Over pouching operations  screening checks of packed trucks with damaged such CO: Weekly impact 121.1C, 180KPa, 30 min seating & impact on references
operator interface allowing program that expected uniform water cascade will not be realised Soda Bic 50 ml product downward cascade
selection – start up- all other access  Exportable record  Truck Tray review or in question 118.5 C, 270KPa, 35 min of superheated
aspects reserved to Technicians) Tray loading Standard 100 &200 ml water through the
 Tray loading of bags  Verification of uniform loading of trays to defined stacking product load
 Jumo Autoclave Controller (access  Self-diagnostic control & pattern O:- With every cycle 121.1C, 180KPa, 45 min
totally reserved to Technicians) alarming system  Chamber inspection  Load patterns match SF, P – PA Standard 500 & 1000ml Mitigating factors:
  Load items/packs are correctly orientated PL - Daily basis product  Load patterns
 Endress & Hauser Memograph –  21cfr compliant audit CO: Minimum every 121.1C, 180KPa, 35 min defined in the PQ
 Recipe/Cycle Selection and  Pack/wrapping is of required quality, intact, and
Primary data capture point (Access report record second day basis Balsol 1000m l product stage of the
execution effectively sealed
reserved to Technicians – Operator 118.5 C, 270KPa, 60 min qualification
Chamber inspection
 Operators e
can only input batch details)  Off load check Physical inspection - verification checks to include that:
 Automatic cycle extension  trained on,
 Review of completed cycle Chamber drain is clear and free from debris
 PC and printer - Stores, prints back up processing,
feature:  Temperature probes and cabling are intact and correctly
cycle data from the Memograph If the temperature of the O:- With every cycle preparation,
positioned
P/PA: With every cycle load
clave drops below a pre-  Clave trolley is free moving and will allow for controlled
Pl – CO : Weekly configuration,
 ABS Mechanical chart recorder determined value during a offload
((access reserved to Technicians - cycle the timer will autoclave
Recipe/Cycle Selection and execution
automatically pause and operation
Operator input only to lifting of pens  Correct Load selection is reflected in both HMI and BMR
for chart removal the cycle will auto extend  Follow up checks
Sterilization cycle review & sign off
Secondary data capture point but until the temperature is by responsible
System provides for fixed reporting format including alarm
currently primary cycle reference in above this set point again persons.
events P – PA - Pl – CO : Weekly
the BMR. Merit is that it allows for at Review to include confirmation of correct:
glance view of cycle profile as it steps  Cycle application
through but without same fine  Step sequence - realization of required control
resolution as the Memograph outcomes/sterilization values
 Advisement and reaction should the report reflect any
 Emergency stop button anomaly/alarm event
 Temperature probes Off Load
 Pressure sensors Check for bag rupture/damage
Utilities
 Domestic water - Compressed air -
Factory steam