Validation of utility system (water system)

Validation of utility system (water system)

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  VALIDATION OF UTILITY SYSTEM(WATER SYSTEM) SUBJECT :- PHARMACEUTICAL VALIDATION , MPH 103-T SUBMITTED TO :- DR. ASIF HUSSAIN SUBMITTED BY :- SHAMEER (MASTER OF PHARMACY - PHARMACEUTICAL ANALYSIS) SEMESTER/YEAR:- 1/1 SESSION :- 2020-2021
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  CONTENTS:- • VALIDATION • PHARMACEUTICALWATER SYSTEM • DESIGN QUALIFICATION • INSTILLATION QUALIFICATION • OPERATION QUALIFICATION • PERFORMANCE QUALIFICATION • REVALIDATION • SANITIZATION • ALERT AND ACTION LEVEL • OPERATION, MAINTENANCE AND CONTROL
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  VALIDATION VALIDATION IS THEPROCESS OF ESTABLISHING DOCUMENTARY EVIDENCE DEMONSTRATING THAT A PROCEDURE, PROCESS, OR ACTIVITY CARRIED OUT IN TESTING AND THEN PRODUCTION MAINTAINS THE DESIRED LEVEL OF COMPLIANCE AT ALL STAGES. IN THE PHARMACEUTICAL INDUSTRY, IT IS VERY IMPORTANT THAT IN ADDITION TO FINAL TESTING AND COMPLIANCE OF PRODUCTS, IT IS ALSO ASSURED THAT THE PROCESS WILL CONSISTENTLY PRODUCE THE EXPECTED RESULTS
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  SUBSECTION OF VALIDATIONINCLUDE:- • EQUIPMENT VALIDATION • FACILITIES VALIDATION • CLEANING VALIDATION • PROCESS VALIDATION • ANALYTICAL METHOD VALIDATION • COMPUTER SYSTEM VALIDATION
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  PHARMACEUTI CAL WATER • PHARMACEUTICALWATER IS, PERHAPS, THE MOST IMPORTANT OF ALL PHARMACEUTICAL UTILITIES. IT IS USED AS AN EXCIPIENT IN MANY PHARMACEUTICAL FORMULATIONS, AS A CLEANING AGENT, AND AS A SEPARATELY PACKAGED PRODUCT DILUENT. IN ADDITION TO NON-COMPENDIAL SYSTEMS, PHARMACEUTICAL FACILITIES TYPICALLY INCLUDE SYSTEMS FOR DELIVERING PHARMACOPOEIAL PURIFIED WATER (PW) WATER FOR INJECTIONS (WFI), AND HIGHLY PURIFIED WATER (HPW).
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  WATER SYSTEM VALIDATION LIFE CYCLE
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  DESIGN QUALIFICATION THE DESIGNOF THE EQUIPMENT FOR WATER SYSTEM SHOULD COME FIRST BECAUSE IT IS DIRECTLY RELATED TO THE TYPE OF WATER IN DEMAND. FOR KNOWING THE DESIGN OF THE EQUIPMENT ONE SHOULD KNOW:- • TOTAL VOLUME OF WATER NEEDED FOR DAY OR HOUR • AVERAGE CONSUMPTION • PEAK DEMAND REQUIREMENT • REVERS CAPACITY • MINIMUM CIRCULATION NEEDED • WEATHER THE ELEVATED TEMPERATURE STORAGE IS NECESSARY • WHAT TYPE OF WATER PURIFICATION PROCESS IS NEEDED OR WILL MATCH THE REQUIREMENT ETC. TO ACHIEVE A PERFECT DESIGN QUALIFICATION THERE SHOULD BE INVOLVEMENT OF ALL APPROPRIATE GROUPS LIKE:- ENGINEERING DESIGN, PRODUCTION OPERATION, QUALITY ASSURANCE, ANALYTICAL SERVICES ETC.
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  • INVOLVEMENT OF:- MATERIALSELECTION, EQUIPMENT STABILITY, OPERATIONAL CONTROL, CONSTRUCTION TECHNIQUES, CLEANING, SANITIZATION PROCESSES, COMPONENT COMP ABILITY PREVENTIVE MAINTENANCE STERILIZATION PROGRAM SAMPLING AND REGULATORY REQUIREMENT DESIGN QUALIFICATION GIVES THE LISTS OF THE ACTIVITY THAT ARE NECESSARY FOR THE CONSISTENT PRODUCTION OF THE STIPULATED GRADE WATER ,PROVIDES THE CALIBRATION OF CRITICAL INSTRUMENT THE DESIGN QUALIFICATION ALSO SETS THE MICROBIAL ACTION AND ALERTS LIMITS SPECIFIES SAMPLING PLANS AND PORTS OF CHEMICAL AND MICROBIAL TESTING , STIPULATED SANITIZATION METHODS AND DEFINES THE PROCEDURE FOR ANALYSIS AND PLOTTING OF DATA
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  WHAT SHOULD ABASIC DESIGN PACKAGE SHOULD INCLUDE :- • SCHEMATIC REPRESENTATION OF WATER SYSTEM SHOWING ALL THE INSTRUMENT , CONTROLS AND VALVES AND NUMBERING OF ALL THE VALVE TO BE DONE • A COMPLETE DESCRIPTION OF FUNCTION AND FEATURE OF THE SYSTEM. THIS PLAYS A CRITICAL ROLE FOR THE PRODUCTION AND QUALITY ASSURANCE PERSONNEL , • DETAIL SPECIFICATION CAN BE FOUND FOR PRETREATMENT AND TREATMENT OF WATER SYSTEM • DETAIL SPECIFICATION OF EACH AND EVERY COMPONENT/ELEMENT COMPRISING THE SYSTEM IS GIVEN SUCH AS STORAGE TANKS, PUMPS HEAT EXCHANGER VALVES PIPING COMPONENT ETC. • SPECIFICATION OF THE CONSTRUCTION TECHNIQUE IS TO BE GIVEN IN THE AREA WHERE QUALITY IS OF CRITICAL IMPORTANT • PROCEDURE FOR CLEANING THE SYSTEM IS TO BE GIVEN FOR BOTH ROUTINE AND AFTER CONSTRUCTION • SOPS FOR PROCEDURE SAMPLING STERILIZATION MAINTENANCE PROCEDURE INTEGRITY TESTING • PRELIMINARY PREVENTIVE MAINTENANCE PROCEDURE • PRELIMINARY SYSTEM CERTIFICATE
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  INSTILLATION QUALIFICATION IT CONSISTSOF SYSTEM DESCRIPTION FOLLOWING BY THE PROCEDURE SELECTION. • PROPER INSTILLATION ASSEMBLY OF THE VARIOUS ITEMS OF EQUIPMENT SHALL BE VERIFIED • THE CHECKING OF EACH RECEIVED ITEM IS DONE AND RECORDED FOR SIMILARITY (THE INSTILLATION OF EACH AND EVERY ELEMENT OF THE SYSTEM IS TO BE INSTALLED AS PER THE MENTIONED WAY OR THE SCHEMATIC DIAGRAM) CONTROL AND CALIBRATION OF ALL THE INSTRUMENT IN THE SYSTEM SHOULD BE ACCORDING / UNDER THE GUIDE LINE OF INTERNATIONAL STANDARDS AND NATIONAL STANDARD
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  OPERATIONAL QUALIFICATION (OQ) THECONSTRUCTION DEBRIS SHOULD BE REMOVED AND THEN THE SYSTEM IS SUBJECT TO CLEANING PROCESS AND THEN CHECKED, THIS IS DONE IN ORDER TO AVOID ANY CHANCES OF CONTAMINATION AND CORROSION. AFTER THE EQUIPMENT IS DONE WITH CLEANING THEN IT READY FOR OPERATION QUALIFICATION (STARTING, OPERATION, CLOSING) BY PERFORMING OQ ONE CAN FIND THE CAPABILITIES OF PROCESSING UNITS TO PERFORM SATISFACTORY RESULTS ARE THERE IN THE MACHINE OR NOT WHAT IT INCLUDES:- • FEED WATER QUALITY OF SYSTEM CAPACITY • TEMPERATURE CONTROL • STEAM PRESSURE HIGH /LOW • PRESSURE DIFFERENTIAL LIMIT SYSTEM SHOULD BE CHALLENGED WITH THE MAXIMUM AND MINIMUM CAPABILITY FOR OPERATION AND OUTPUT RESULTS. (RESULTS SHALL BE CHECKED AND IT SHOULD BE WITHIN THE ACCEPTANCE LIMITS ) NOW THE FINALIZATION OF THE SOPS (OPERATION CLEANING AND PREVENTIVE MAINTENANCE) TO DONE TRAINING OF THE TECHNICAL STAFF SHALL BE COVERED IN OQ
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  PERFORMANCE QUALIFICATION (PQ) THEPURPOSE OF PERFORMANCE QUALIFICATION IS TO PROVIDE RIGOROUS TESTING TO DEMONSTRATE THE EFFECTIVENESS AND REPRODUCIBILITY OF THE TOTAL INTEGRATED PROCESSES NOW TO MEET THE RELIABILITY AND ROBUSTNESS OF THE SYSTEM, THE THREE PHASE VALIDATION REGULATORY ADOPTED A. PHASE1 TEST PERIOD CONSISTS OF 2-4 WEEKS (14 DAYS MINIMUM ) FOR MONITORING THE SYSTEM INTENSIVELY DURING THIS TIME PERIOD THE SYSTEM SHOULD BE PERFORMING CONTINUOUSLY WITHOUT FAILURE OR PERFORMANCE DEVIATION THINGS THAT SHOULD BE TAKEN UNDER CONSIDERATION DURING THIS TIME SPAN INCLUDES:- • PERFORMING MICROBIAL AND CHEMICAL TESTS AS DEFINE • SAMPLING OF FEED WATER IS DONE ON REGULAR BASIS (IN PURIFICATION STEP TOO) • HAVE A LOOK OVER THE OPERATING RANGES IN ORDER TO DEVELOP/MENTION THEM • DEVELOP AND FINALIZE THE OPERATING, MAINTENANCE, CLEANING, AND SANITIZATION PROCEDURE
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  B. PHASE 2:- THIS WILL REQUIRE ABOUT 2-3 WEEKS (30 DAYS), THIS IS DONE IN ORDER TO PERFORM MORE INTENSIVE MONITORING IN THIS THE SAMPLING SCHEME IS KEPT SAME AS IN PHASE 1 APPROACH SHOULD BE IN SUCH A MANNER THAT IT WILL INCLUDE • DEMONSTRATION CONSISTING OPERATION WITHIN THE ESTABLISH RANGES • DEMONSTRATION CONSISTING PRODUCTION AND DELIVERY OF WATER TO THE REQUIRED QUALITY AND QUANTITY (WHEN THE SYSTEM IS OPERATED IN ACCORDANCE WITH SOP) C. PHASE 3:- THIS PHASE RUNS FOR 1 YEAR AFTER HAVING THE SATISFACTORY RESULT OBTAINED FROM PHASE 2. DURING THIS PROCESS THE MANUFACTURED WATER CAN BE USED THE OBJECTIVE AND FEATURE THAT IT SHOULD BE CONTAINING • MAKE SURE THE SEASONAL VARIATION ARE EVALUATED • DEMONSTRATE EXTENDED RELIABLE PERFORMANCE • THE SAMPLE LOCATIONS, SAMPLING FREQUENCIES AND TEST SHOULD BE REDUCED TO THE NORMAL ROUTINE PATTERN BASED ON ESTABLISHED PROCEDURES PROVEN DURING PHASE 1 AND PHASE 2 AFTER COMPLETION OF PHASE 3 OF THE QUALIFICATION PROGRAM OF WATER SYSTEM A ROUTINE PLAN SHOULD BE ESTABLISHED
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  REVALIDATION • REVALIDATION SHOULDBE PERFORMED ONLY WHEN THERE HAS BEEN A SIGNIFICANT • CHANGE TO THE SYSTEM OR TO THE OPERATIONAL PARAMETERS. ROUTINE • MONITORING AND INSPECTION WILL CONTINUE UNDER THE SAME CONDITION AS • THOSE THAT EXISTED DURING THE ORIGINAL VALIDATION. ROUTINE MAINTENANCE • OR REPLACEMENT OF PARTS SHOULD HAVE A SPECIFIC WRITTEN PROCEDURE, • WHICH MUST BE VALIDATED AT THE TIME OF ORIGINAL VALIDATION.
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  SANITIZATION BY SANITIZATION PRACTICETHE WATER SYSTEM IS KEPT UNDER MICROBIAL LIMIT CHEMICAL OR THERMAL MEANS CAN BE INCORPORATED IN ORDER TO SANITIZE THE SYSTEM UV LIGHT AT A WAVELENGTH OF 254NM CAN ALSO BE USED TO SANITIZE WATER IN CONTINUOUSLY OPERATION CHEMICAL METHODS, WHERE COMPATIBLE CAN BE USED ON A WIDER VARIETY OF CONSTRUCTION MATERIALS. THESE METHODS TYPICALLY EMPLOY OXIDIZING AGENTS SUCH AS HALOGENATED COMPOUNDS ARE EFFECTIVE SANITIZERS BUT ARE DIFFICULT TO FLUSH FROM THE SYSTEM AND THEN TO LEAVE BIOFILMS INTACT. (HALOGENATED COMPOUNDS HYDROGEN PEROXIDE, OZONE OR PERACETIC ACID OXIDIZE BACTERIA AND BIOFILMS BY FORMING REACTIVE PEROXIDES AND FREE RADICALS NOTABLY HYDROXYL RADICALS)
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  ALERT AND ACTIONLEVELS • ALERT LEVEL:- ARE LEVELS OR RANGES THAT, WHEN EXCEEDED, INDICATE THAT A PROCESS MAY HAVE DRIFTED FROM ITS NORMAL OPERATING CONDITION. ALERT LEVELS CONSTITUTE A WARNING AND DO NOT NECESSARILY REQUIRE A CORRECTIVE ACTION. • ACTION LEVEL:- ARE LEVELS OR RANGES THAT, WHEN EXCEEDED; INDICATE THAT A PROCESS HAS DRIFTED FROM ITS NORMAL OPERATING RANGE. EXCEEDING AN ACTION LEVEL INDICATES THAT CORRECTIVE ACTION SHOULD BE TAKEN TO BRING THE PROCESS BACK INTO ITS NORMAL OPERATING
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  OPERATION, MAINTENANCE ANDCONTROL • A PREVENTIVE MAINTENANCE PROGRAM SHOULD BE ESTABLISHED TO ENSURE THAT THE WATER SYSTEM REMAINS IN A STATE OF CONTROL. • OPERATING PROCEDURE :- PROCEDURES FOR OPERATING THE WATER SYSTEM AND PERFORMING ROUTINE MAINTENANCE AND CORRECTIVE ACTION SHOULD BE WRITTEN, AND THEY SHOULD ALSO DEFINE THE POINT WHEN ACTION IS REQUIRED. THE PROCEDURE SHOULD BE WELL DOCUMENTED, DETAIL THE FUNCTION OF EACH JOB, ASSIGN WHO IS RESPONSIBLE FOR PERFORMING THE WORK, AND DESCRIBE HOW THE JOB IS TO BE CONDUCTED. • PREVENTIVE MAINTENANCE :- A PREVENTIVE MAINTENANCE PROGRAM SHOULD BE IN EFFECT. THE PROGRAM SHOULD ESTABLISH WHAT PREVENTIVE MAINTENANCE IS TO BE
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  • SANITIZATION:- DEPENDINGON SYSTEM DESIGN AND THE SELECTED UNITS OF OPERATION, ROUTINE PERIODIC SANITIZATION MAY BE NECESSARY TO MAINTAIN THE SYSTEM IN A STATE OF MICROBIAL CONTROL. TECHNOLOGIES FOR SANITIZATION ARE DESCRIBED ABOVE. • MONITORING PROGRAM :- CRITICAL QUALITY ATTRIBUTES AND OPERATING PARAMETERS SHOULD BE DOCUMENTED AND MONITORED. THE PROGRAM MAY INCLUDE A COMBINATION OF IN-LINE SENSORS OR RECORDERS (E.G. A CONDUCTIVITY METER AND RECORDER), MANUAL DOCUMENTATION OF OPERATIONAL PARAMETERS (SUCH AS CARBON FILTER PRESSURE DROP) AND LABORATORY TESTS. • CHANGE CONTROL :-THE MECHANICAL CONFIGURATION AND OPERATING CONDITION MUST BE CONTROLLED. PROPOSED CHANGES SHOULD BE EVALUATED FOR THEIR IMPACT ON THE WHOLE SYSTEM. THE NEED TO REQUALIFY THE SYSTEM AFTER CHANGES ARE MADE SHOULD BE DETERMINED.