Presentation on theme: "World Health Organization"— Presentation transcript:
1 World Health Organization 13 April, 2017Good Manufacturing PracticeHeating, Ventilation and Air-Conditioning (HVAC) Part 3: Commissioning, Qualification, and maintenance
2 World Health Organization 13 April, 2017HVACObjectivesTo understand key issues incommissioning,qualification andmaintenance of HVAC systems8.
3 World Health Organization 13 April, 2017HVACDocumentation requirements to assist in commissioning, qualification and maintenanceDescription of design, installation and functionsSpecifications, requirementsManualsOperating proceduresInstructions for performance control, monitoring and recordsMaintenance instructions and recordsTraining of personnelprogramme and records
4 World Health Organization 13 April, 2017HVACCommissioningPrecursor to qualificationIncludes setting up, balancing, adjustment and testing of entire HVAC system to ensure it meets requirements in URS and capacityAcceptable tolerances for parametersTraining of personnel8. Commissioning, qualification and maintenance8.1 Commissioning8.1.1 Commissioning should include the setting up, balancing, adjustmentand testing of the entire HVAC system, to ensure that it meets all therequirements, as specifi ed in the user requirement specifi cation (URS), andcapacities as specifi ed by the designer or developer.8.1.2 The installation records of the system should provide documentedevidence of all measured capacities of the system.8.1.3 The data should include items such as the design and measurementfi gures for airfl ows, water fl ows, system pressures and electrical amperages.These should be contained in the operating and maintenance manuals(O & M manuals).8.1.4 Acceptable tolerances for all system parameters should be specifi edprior to commencing the physical installation.8.1.5 Training should be provided to personnel after installation of thesystem, and should include operation and maintenance.8.1.1, 8.1.4, 8.1.5
5 World Health Organization 13 April, 2017HVACCommissioning (2)Records and data maintained include:Installation records – documented evidence of measure capacities of the systemData: Design and measurement for, e.g. airflow, system pressuresO&M manuals, schematic drawings, protocols, reports8.1.3 The data should include items such as the design and measurementfi gures for airfl ows, water fl ows, system pressures and electrical amperages.These should be contained in the operating and maintenance manuals(O & M manuals).8.1.4 Acceptable tolerances for all system parameters should be specifi edprior to commencing the physical installation.8.1.5 Training should be provided to personnel after installation of thesystem, and should include operation and maintenance.8.1.6 O & M manuals, schematic drawings, protocols and reports shouldbe maintained as reference documents for any future changes and upgradesto the system.8.1.2, 8.1.3, 8.1.6
6 World Health Organization 13 April, 2017HVACQualificationValidation is an extensive exerciseQualification of the HVAC system is one component in the overall approach that covers premises, systems/utilities, equipment, processes, etc.See also full guidelines on "Validation" in WHO TRS No 937, 2005, Annex 4.Risk-based approach for HVAC qualification8.2 Qualifi cation8.2.1 Validation is a many-faceted and extensive activity and is beyondthe scope of these guidelines. Qualifi cation and validation guidelines areincluded in: Expert Committee on Specifi cations for Pharmaceutical Preparations.Fortieth report. Geneva, World Health Organization, 2005 (WHOTechnical Report Series, No. 937), Annex 4 (see also Fig. 28).8.2.1
7 World Health Organization 13 April, 2017HVACQualification (2)Described in a Validation Master Plan (VMP)VMP to include the nature and extent of tests, and protocolsDQ, IQ, OQ, and PQRisk analysis to determine critical and non-critical parameters, components, subsystems and controls8.2.2 The qualifi cation of the HVAC system should be described in a validationmaster plan (VMP).8.2.3 It should defi ne the nature and extent of testing and the test proceduresand protocols to be followed.8.2.4 Stages of the qualifi cation of the HVAC system should include DQ,IQ, OQ and PQ.8.2.5 Critical and non-critical parameters should be determined by meansof a risk analysis for all HVAC installation components, subsystems andcontrols.
8 DQ (Design Qualification) Documented evidence that the premises, supporting systems, utilities, equipments and processes have been designed in accordance with the requirements of GMP.IQ (Installation Qualification)The performance of test to ensure that the installation (such as machine, premises, manufacturing area, etc) used in manufacturing process are appropriately selected and correctly installed and operate in accordance with establish specification.OQ (Operational Qualification)Documented verification that the system or subsystem performs as intended over all anticipated operating ranges.PQ (Performance Qualification)Documented verification that the equipment or system operates consistently and gives reproducibility within defined specifications and parameters for prolonged periods.
9 World Health Organization 13 April, 2017HVACQualification (3)Direct impact components and critical parameters should be includedNon-critical systems and components are subjected to Good Engineering Practices (GEP)Acceptance criteria and limits defined in design stageDesign conditions, normal operating ranges, operating ranges, alert and action limits8.2.5 Critical and non-critical parameters should be determined by meansof a risk analysis for all HVAC installation components, subsystems andcontrols.8.2.6 Any parameter that may affect the quality of the pharmaceuticalproduct, or a direct impact component, should be considered a criticalparameter.8.2.7 All critical parameters should be included in the qualifi cation process.Note: A realistic approach to differentiating between critical and noncriticalparameters is required, to avoid making the validation processunnecessarily complex.Example:• The humidity of the room where the product is exposed should be considereda critical parameter when a humidity-sensitive product is beingmanufactured. The humidity sensors and the humidity monitoring systemshould, therefore, be qualifi ed. The heat transfer system, chemical drier orsteam humidifi er, which is producing the humidity controlled air, is furtherremoved from the product and may not require operational qualifi cation.Figure 28Qualifi cation is a part of validationEquip 1 Equip 2 Equip 3 Equip 4 Equip 5 Equip 6QUALIFICATIONVALIDATIONEquip 7System 2 System 1ProcessEquip, equipment.80Figure 29System operating ranges• A room cleanliness classifi cation is a critical parameter and, therefore,the room air change rates and HEPA fi lters should be critical parametersand require qualifi cation. Items such as the fan generating the airfl owand the primary and secondary fi lters are non-critical parameters, andmay not require operational qualifi cation.8.2.8 Non-critical systems and components should be subject to GEP andmay not necessarily require qualifi cation.8.2.9 A change control procedure should be followed when changes areplanned to the direct impact HVAC system, its components and controlsthat may affect critical parameters.Acceptance criteria and limits should be defi ned during the designstage.The manufacturer should defi ne design conditions, normal operatingranges, operating ranges, and alert and action limits.
10 HVACDesign conditions and normal operating ranges set to achievable limitsOOS results recorded–
11 World Health Organization 13 April, 2017HVACQualification – examples of aspects to considerDQ – Design of the system, URS(e.g. components, type of air treatment needed, materials of construction)IQ – Verify installatione.g. relevant components, ducting, filters, controls, monitors, sensors, etc.includes calibration where relevant
12 World Health Organization 13 April, 2017HVACQualification (4)Typical parameters to be included in qualification (based on risk assessment):TemperatureRelative humiditySupply, return and exhaust air quantitiesRoom air change ratesRoom pressures (pressure differentials)For a pharmaceutical facility, based on a risk assessment, some ofthe typical HVAC system parameters that should be qualifi ed may include:— temperature— relative humidity— supply air quantities for all diffusers— return air or exhaust air quantities— room air change rates— room pressures (pressure differentials)— room airfl ow patterns— unidirectional fl ow velocities— containment system velocities— HEPA fi lter penetration tests— room particle counts— room clean-up rates— microbiological air and surface counts where appropriate— operation of de-dusting— warning/alarm systems where applicable.8.2.17
13 World Health Organization 13 April, 2017HVACQualification (5)Typical parameters to be included in qualification (based on risk assessment) (2):Room clean-up rateParticulate matter, microbial matter (viable and non- viable)HEPA filter penetration testsContainment system velocityWarning/alarm systems
14 World Health Organization 13 April, 2017HVACQualification (6)Conduct of the tests:Time intervals and procedure to be defined by the manufacturerInfluenced by the type of facility and level of protectionSee also ISO for methods of testingRequalification, and change controlThe maximum time interval between tests should be defi ned by themanufacturer. The type of facility under test and the product level of protectionshould be considered.Note: Table 3 gives intervals for reference purposes only. The actual test periodsmay be more frequent or less frequent, depending on the product and process.Periodic requalifi cation of parameters should be done at regularintervals, e.g. annually.Requalifi cation should also be done when any change, which couldaffect system performance, takes place.– , 8.2.9
15 World Health Organization 13 April, 2017HVACQualification (7)Tests performed according to protocols and procedures for the testsResults recorded and presented in report (source data kept)Traceability, e.g. devices and standards used, calibration records; and conditions specified
16 World Health Organization 13 April, 2017HVACSchedule of tests to demonstrate continuing compliance*Test procedure* and key aspectsMaximum time intervalObjectiveTest ParameterParticle counter. Readings and positions6 months or 12 months depending on ClassVerifies cleanlinessParticle count testMeasure pressure difference12 monthsAbsence of cross- contaminationAir pressure differenceMeasure supply and return air, calculate air change rateVerify air change ratesAirflow volumeVelocity measurementVerify unidirectional airflow and or containment conditionAirflow velocity8. Table 3*Test procedure as per ISO 14644
17 World Health Organization HVACWorld Health Organization13 April, 2017Recommended optional strategic tests*Test procedure as per ISO 14644Test procedure* and key aspectsMaximum time intervalObjectiveTest ParameterFilter media and filter seal integrity12 monthsVerify filter integrityFilter leakageAirflow direction and pressure differentialVerify absence of cross-contaminationContainment leakageTime taken maximum 15 minutesVerify clean-up timeRecovery (time)Airflow direction, documented evidenceVerify required airflow patternsAirflow visualization8. Table 3*Test procedure as per ISO 14644
18 Cleanroom monitoring program (1) World Health Organization13 April, 2017HVACCleanroom monitoring program (1)Routine monitoring program as part of quality assuranceAdditional monitoring and triggers, e.g.1. Shutdown2. Replacement of filter elements3. Maintenance of air-handling systems4. Exceeding of established limits
19 World Health Organization 13 April, 2017HVACCleanroom monitoring programme (2) Particles and Microbiological contaminantsNumber of points/locations for monitoring determined, specified, documented in procedure and or protocolSufficient time for exposure, and suitable sample sizeIdentification and marking of sampling pointsDefinition of transport, storage, and incubation conditionsResults to reflect the procedure/protocol followedDefine alert and action limits as a function of cleanliness zone/classSee also ISO 14644
20 World Health Organization 13 April, 2017HVACCleanroom monitoring program (3)Cleanrooms should be monitored for microorganisms and particlesairExample of a sampling point
21 Definition of Conditions World Health Organization13 April, 2017HVACDefinition of Conditionsairas builtat restin operation
22 World Health Organization 13 April, 2017HVACQualification – examples of aspects to consider in qualification (OQ, PQ)TestDifferential pressure on filtersTurbulent / mixed airflowDescriptionUni-directional airflow / LAFRoom differential pressureAirflow velocity / uniformityAirflow volume / rateParallelismAirflow pattern2N/A2, 3Optional31 := As built (ideally used to perform IQ)2 = At rest (ideally used to perform OQ)3 = Operational (ideally used to perform PQ)This slide shows a series of tests to be carried out during qualification.There are different tests for the turbulent and for the uni-directional air flows.The differential pressure on filters is an indication of the clogging of the filters: with the charging of dust on the filters, the differential pressure will increase.In order to keep the volume of air constant, the fan speed may increase, with the following consequences:Damage to filters, and passage of unfiltered airParticles and micro-organismes will be “pushed” through the filter units.(Inspectors should check whether pressure differential manometers are installed on the AHUs. Without this means of monitoring the filters, the system could go out of control causing contamination problems.)Airflow patterns are interesting to visualize (smoke tests), as zones without proper flushing can be easily identified.It is also important to monitor air flow velocities for each HEPA filter according to a program of established intervals because significant reductions in velocity can increase the possibility of contamination, and changes in velocity can affect the laminarity of the airflow.Airflow patterns should be tested for turbulence, as these can interfere with the flushing action of the air.
23 World Health Organization 13 April, 2017HVACQualification – examples of aspects to consider in qualification (OQ, PQ)TestTurbulent / mixed airflowDescriptionUni-directional airflow / LAFRecovery timeRoom classification (airborne particle)Temperature, humidityN/A22,31 := As built (ideally used to perform IQ)2 = At rest (ideally used to perform OQ)3 = Operational (ideally used to perform PQ)The recovery time (clean-up time) is also an important parameter to be determined. Once doors have been opened and people have been entering a room, the original conditions have been disturbed and, for a short while, before recovering, the room does not always correspond to the laid down parameters. It is important to know how long this period is. There are no regulations laid down as to how long this clean-up time should be. However, the generally accepted time to clean-up from one cleanroom classification to the next higher classification, should be less than 15 minutes.It should also be remembered that a room is to be qualified “in operation” when it has a certain number of people in it. After qualification, the number of people in that room, as challenged during qualification, cannot be exceeded.Temperature and humidity can also be important (comfort in clean areas, stability of effervescent products, etc.)
24 World Health Organization 13 April, 2017HVACMaintenanceProcedure, programme and records for planned, preventative maintenancee.g. cleaning of filters, calibration of devicesAppropriate training for personnelChange of HEPA filters by suitably trained personsImpact of maintenance on:Product qualityQualification8.3 Maintenance8.3.1 There should be a planned preventive maintenance programme,procedures and records for the HVAC system. Records should be kept.8.3.2 Maintenance personnel should receive appropriate training.828.3.3 HEPA fi lters should be changed either by a specialist or a trainedperson.8.3.4 Any maintenance activity should be assessed critically to determineany impact on product quality including possible contamination.8.3.5 Maintenance activities should normally be scheduled to take placeoutside production hours, and any system stoppage should be assessed witha view to the possible need for requalifi cation of an area as a result of aninterruption of the service.8.3.1 – 8.3.5
25 World Health Organization 13 April, 2017HVACInspecting the air-handling systemVerification of design documentation, includingdescription of installation and functionsspecification of the requirementsOperating proceduresMaintenance instructionsMaintenance recordsTraining logsEnvironmental recordsOn site verification (walking around the site)
26 World Health Organization 13 April, 2017HVACConclusionAir-handling systems:Play a major role in the quality of pharmaceuticals and other biological products.Should be designed properly, by professionals.Should be treated as a critical system.