This document discusses critical process parameters (CPPs) for aseptic processing and HVAC systems. It provides a process for establishing CPPs which involves assembling subject matter experts, listing process keywords, and defining enablers, parameters, attributes, impact assessments, and risks for each keyword. Several potential CPPs for aseptic processes and HVAC systems are defined, such as sterility, clean zones, sampling areas, and temperature, humidity, and particle levels. The document explains how to determine if a parameter is general or critical based on its impact on quality attributes. It also discusses qualification and commissioning approaches for CPPs.
This document discusses critical process parameters (CPPs) for aseptic processing and HVAC systems. It provides a process for establishing CPPs which involves assembling subject matter experts, listing process keywords, and defining enablers, parameters, attributes, impact assessments, and risks for each keyword. Several potential CPPs for aseptic processes and HVAC systems are defined, such as sterility, clean zones, sampling areas, and temperature, humidity, and particle levels. The document explains how to determine if a parameter is general or critical based on its impact on quality attributes. It also discusses qualification and commissioning approaches for CPPs.
This document discusses critical process parameters (CPPs) for aseptic processing and HVAC systems. It provides a process for establishing CPPs which involves assembling subject matter experts, listing process keywords, and defining enablers, parameters, attributes, impact assessments, and risks for each keyword. Several potential CPPs for aseptic processes and HVAC systems are defined, such as sterility, clean zones, sampling areas, and temperature, humidity, and particle levels. The document explains how to determine if a parameter is general or critical based on its impact on quality attributes. It also discusses qualification and commissioning approaches for CPPs.
This document discusses critical process parameters (CPPs) for aseptic processing and HVAC systems. It provides a process for establishing CPPs which involves assembling subject matter experts, listing process keywords, and defining enablers, parameters, attributes, impact assessments, and risks for each keyword. Several potential CPPs for aseptic processes and HVAC systems are defined, such as sterility, clean zones, sampling areas, and temperature, humidity, and particle levels. The document explains how to determine if a parameter is general or critical based on its impact on quality attributes. It also discusses qualification and commissioning approaches for CPPs.
HVAC AND ASEPTIC PROCESSING All products and their supporting processes and utilities must be supported by appropriate complete validation.
REMEMBER SO WHAT ? A good way to start QbD for a new project for an Aseptic process is to start from scratch …….
The recipe is as follows …..
1) Make a group of subject matter experts.
2) List the keywords of your process. 3) For each keyword, implement : 1) Enablers. 2) Parameters. 3) Attributes. 4) Make an assessment : « Direct impact VS Non direct impact » 5) Make a risk assessment. 6) Write a Validation Master Plan Critical Parameters Process
•Action limits •Bio burden
•Air changes. •Cleanroom •Alert limits. •Clean zone •As built. •Contact. •Aseptic filling. •Contaminant •Aseptic process •Critical processing •Air flow •Dosage •At rest •Efficiency Critical Parameters Process
•Filter •Risk based approach
•Gowning •Room Monitoring system •HEPA •Sterile drug substance •Isolator •Supplier •In operation •ULPA •Particle. •Viable particle •Pre filter •Sterility •Core process •RABs KEYWORD DEFINITION CPP DIRECT IMPACT
STERILITY MUST COMPLY C.F.U YES
WITH TEST FOR STERILITY. NO VIABLE PARTICLE DETECTABLE;
CLEAN ZONE FIVE DIFFERENT PRESSURE YES FOR
ZONES A TO E VELOCITY PREPARATION, DEPENDING ON HEPA ASEPTIC FILLING, THE DESIGN, AIR RH CRIMPING, OPEN FLOW, PRESSURE TEMPERATURE CONTAINER DIFFERNCE, AND TRANSFERS FILTRATION PREPARATION OF CELL BANKS Critical Parameters Zones
•Sampling area •Receiving raw materials •Dispatching •General labs •Storage •Microbiological •Cool store labs •Tank farm Production Zones
•Corridors •Sampling area
•Airlocks •Preparation area •To E •Production of master •To D cell bank •To C •Inoculum •To B preparation area. •Et.c •Final purification •Dispensing area steps area •Sterile filtration area •Sampling for IPC •Cell harvesting Production Zones
PERFORMED IN GRADE B AREAS WHICH TEMPERATURE MINIMIZE THE RH RISK OF …. CONTAMINATION HOW DO WE MAKE THE LINK BETWEEN CPP AND URS ? KEYWORD DEFINITION URS RISK
SAMPLING MUST BE PROVIDE : CONTAMINATION
PERFORMED IN •PROTECTION FALSE POSITIVES AREAS WHICH AGAINST MINIMIZE THE CONTAMINATION RISK OF •LOGICAL AND CONTAMINATION DIRECT FLOW •GOOD STAGING •GOOD ACCESS •NO POSSIBLE CONFUSIONS •NO MIX UPS •MINIMIZE DISTANCES •MINIMIZE HANDLING STEPS AND FOR THE PERSONNEL ? KEYWORD DEFINITION URS RISK
PERSONNEL MUST BE SEGREGATION CONTAMINATION
DESIGNED TO GOWNING FALSE POSITIVES PROTECT THE DEGAOWNING PRODUCT FROM PROTECTION CONTAMINATION SECURITY PROTECT THE ENVIRONMENT PROTECT THE PERSONNEL ENSURE SECURITY H.V.A.C PROCESS EXAMPLE URS RISK CRITERIA CRITICAL ROOM TEMPERATURE PARAMETERS
CONTAMINATION POLLUTED FLOOR LIST SOURCES OF EVALUATE
CONTAMINATION : CONDITIONS IN •EXTERNAL AIR CASE OF •BAD FILTRATION EQUIPMENT •DAMAGED FAILURE FILTERS RECOVERING TIME •BAD AIR FLOW INTERLOCKS •HVAC FAILURE FAIL SAFE MODES. •PERSONNEL …. •CONSTRUCTION MATERIALS •DRAINS •SPRINKLERS •MIX UP NOT AFFECTED CLOSED SYSTEMS H.V.A.C
ARE YOUR FAMILIAR
WITH FAIL SAFE ? CAMERA JACK
FILLING GOODS MACHINE
BADS
A CAMERA INSPECTION STATION DETECTS BAD VIALS AND SENDS A SIGNAL
TO AN EJECTION STATION CAMERA JACK
FILLING GOODS MACHINE
BADS
THE BAD VIAL IS SENT TO A REJECTED CONTAINER
SO HOW CAN I BE FAIL SAFE FOR HVAC ? IT IS SOMETIMES POSSIBLE :
1. LOCKERS : SIGNAL TO HVAC
2. COOLING BATTERIES 3. ETC IT IS SOMETIMES NOT POSSIBLE :
1. OPERATOR ACTION IN CASE OF FAILURE IN DESIGNING THE CRITERIA AND THE CPP CONSIDERATION MUST FOCUS ON RISK AND OPERATING RANGE.
THIS WILL LEAD THE TIGHTNESS OF
CONTROL RANGE OF THESE PARAMETERS H.V.A.C IS TEMPERATURE A CRITICAL PARAMETER ?
YES IF THE CRITICAL QUALITY ATTRIBUTES LIKE
•QUALITY •STABILITY •EFFICIENCY
ARE AFFECTED
CRITICAL PARAMETER QUALIFICATION
H.V.A.C IS TEMPERATURE A CRITICAL PARAMETER ?
NO IF THE CRITICAL QUALITY ATTRIBUTES LIKE
•QUALITY •STABILITY •EFFICIENCY
ARE NOT AFFECTED
GENERAL PARAMETER COMMISSIONING
H.V.A.C – TEMPERATURE GRADE GENERAL CRITICAL PARAMETER PARAMETER A – ISO 5 18 – 26 °c MORE RESTRICTIVE B – ISO 7 IDEM MORE RESTRICTIVE C – ISO 8 IDEM MORE RESTRICTIVE D – ISO 8 17 – 27 MORE RESTRICTIVE E - NA 12 - 28 MORE RESTRICTIVE
COMMISSIONING QUALIFICATION SO WE CAN DO THE SAME FOR ALL THE CPP H.V.A.C – RELATIVE HUMIDITY RH GENERAL CRITICAL PARAMETER PARAMETER CONTACT WITH NO YES PRODUCT HUMIFIFIER MUST HAVE THE SAME CPP AS WATER USED IN THE PROCESS NO YES DESSICANT MUST BE EVALUATED AS CPP
COMMISSIONING QUALIFICATION H.V.A.C – PARTICLES PARTICLES GENERAL CRITICAL PARAMETER PARAMETER CONTACT WITH NA YES PRODUCT NA YES
COMMISSIONING QUALIFICATION H.V.A.C – MICRO ORGANISM MICRO ORGANISM GENERAL CRITICAL PARAMETER PARAMETER CONTACT WITH NA YES PRODUCT NA YES
COMMISSIONING QUALIFICATION H.V.A.C – ROOM AIR CHANGE RATES ACH/HR GENERAL CRITICAL PARAMETER PARAMETER CONTACT WITH NA YES PRODUCT NA YES
COMMISSIONING QUALIFICATION IMPACT ON COSTS :
-BATTERIES SIZES -AIR HANDLING UNITS SIZES -ENERGY CONSUMPTION -NUMBER OF FILTERS -…… H.V.A.C – RECIRCULATION ACH/HR GENERAL CRITICAL PARAMETER PARAMETER CONTACT WITH RISK ASSESSMENT RISK ASSESMENT PRODUCT
COMMISSIONING QUALIFICATION RISK OF CROSS CONTAMINATION
POTENT PRODUCTS
MULTI PRODUCTS H.V.A.C – RELATIVE PRESSURE DIFFERENCE - CASCADES DELTA P GENERAL CRITICAL PARAMETER PARAMETER CONTACT WITH RISK ASSESSMENT RISK ASSESMENT PRODUCT
COMMISSIONING QUALIFICATION EVALUATE : 1. OPEN OR CLOSED SYSTEMS 2. LOCAL EXHAUSTE : HOODS, DEDUSTERS 3. AIRFLOWS 4. POWDERS 5. REVERSAL FLOWS MONITORING PARAMETER CRITICAL MONITORING PARTICLES YES ON LINE CONTINUOUS MONITORING RECORDING DATA INTEGRITY
ROOM AIR SUPPLY YES DEFINE WHICH ROOMS CAN BE
SUPPLIED WITH FROM THE SAME AHU DEFINE RECIRCULATION AND % OF RECIRCULATION GEOMETRY YES ESTIMATE USER LOCATIONS ESTIMATE WORST LOCATION IN TERM OF AIRFLOW AND PARTICLES …. Start with the end in mind : start with the corrective actions
User requirements : H V A C :
1. Perform investigation for possible source of
contamination. 2. Perform air flow patterns. 3. Perform smoke tests. 4. Review aseptic technics of personnel. 5. Review gowning requirements. 6. Inspect incoming airfilters for leaks in filter. 7. Review air pressure differential across filter. Start with the end in mind : start with the corrective actions
User requirements : H V A C :
1. Review room desinfection/sanitation SOPs
2. Review sanitation intervals. 3. Review sanitation efficiency. 4. Check area pressure differential. 5. Evaluate equipment as source of contamination. 6. Evaluate integrity of the room (peeling paints, cracks ..) 7. Review risk to product. 8. Review maintenance and access ONCE YOU HAVE DONE ALL THAT.
