1、Disinfection Peter Jay:Bioscience,UR&DPSTrumbull,US 14-16th November 2006BackgroundlRecent years weaknesses in cleaning and disinfection have been the major cause of incidents.lRecognised that greater emphasis on adherence to best practice principles is required.lOn site validation of procedures is
2、a key area that needs to be improved.Incident Learnings-Disinfection(1)lWater/Dilute Product Residues Left in Plant.Plant NOT disinfected prior to uselMANY incidentslDisinfection procedure NOT validatedlOperators INADEQUATELY trained lOperator did NOT follow documented disinfection procedurelDisinfe
3、ction NOT performed when requiredINCIDENT LEARNING C&DTime Immediately post clean=30 bugs/mlGrowth occurs.24 Hours later=10 million bugs/mlAssume undrainable pump holds two litresof dilute product residues:After 24 hours 20,000,000,000 bugs will be present in the 2 litres of water!-Would you bath in
4、 this?-Would you drink this?-Would you make product with this?Undrainable pipe arrangement-Leaving Dilute Product residues=“BUG FOOD”Water/Dilute Product Residues Left in PlantUndrainableCleaningandDisinfectionRulesINCIDENT LEARNINGSEnsure Cleaning and Disinfection protocols are documented and opera
5、tors are trained in the procedures.Regular checks by local hygienist are required to ensure complianceWHENWHOHOWMUST BE DEFINEDAND DOCUMENTEDTRAINING is keyDISIPLINE IN IMPLEMENTATION is essentialCleaning and DisinfectionDisinfectionlDestruction of micro-organisms but NOT usually bacterial spores.lD
6、isinfection does NOT necessarily kill all micro-organisms but reduces them to a level acceptable for a defined purpose,e.g.to a level which is not harmful either to health or to the quality of the goods being processed.Cleaning and Disinfection-HACCPlCan be handled as a GMP or as defined CCPslPrefer
7、red route is as CCPslEspecially when starting on HACCPlConsider CIP system in HACCP studylConsider where need manual interventionWhy CleanlProcesslPurpose to remove product soils and residues to produce clean equipment surfaces that will not taint the subsequent production of a differing variant.lMi
8、crobiological lPreparation of the plant surfaces for disinfection.Residual product left in equipment can prevent effective disinfection:lDeactivate some chemical disinfectants.lPhysical barrier preventing the successful elimination of the micro-organisms by protecting them lRemaining product residue
9、s will also act as a food source for resident micro-organisms.Poor cleaning can increase the risk of contamination through the formation of dilute and hence more hospitable product residues(sub lethal preservative levels).Why DisinfectlWe do NOT operate sterile processeslTherefore some micro-organis
10、ms WILL enter the manufacturing plantlDisinfection strategies are required to prevent the build up of contamination in the plant to a level that will result in out of specification productlDisinfection should reduce the microbial load on a surface to a level that will NOT be capable of surviving or
11、growing in finished productDisinfection lEquipment must be clean to be effectively disinfected.lEquipment must be drained dry to remain disinfected for any period of time.lDisinfection only protects equipment for a limited time.How to DisinfectlTwo options:lHeat lChemicalsThermal DisinfectionlRecomm
12、ended method of disinfectionlTemperatures of 70 degrees for 10 minutes will effectively disinfect plant(coldest part of plant must reach these conditions)lTarget temperature MUST be attained at the coldest part of the plant/circuit being disinfected.l10 minute contact time shall NOT be started until
13、 all parts of the circuit have reached this temperature.l It may take in excess of 15 minutes for all parts of plant circuit(varies with configuration/equipment)to reach this temperature.lValidation time/temperature is CRITICALl Lower temperatures and contact times will NOT deliver disinfection.Ther
14、mal DisinfectionlHeat more effective than chemical disinfection in destroying biofilmslEquipment must be able to withstand high temperatures and be engineered correctly to avoid implosion of tanks.lSteam:Rarely used outside US Plants not designed(seals/instruments etc.)to handle steamlOnly effective
15、 against non spore forming micro-organismslProtection against scalding requiredlThermal Disinfection Guidelines for the Manufacture of HPC Liquids.This document is available on the Global Hygiene Security Group website under Technical Documents.Chemical DisinfectionlRelies on physical contact with m
16、icro organismslChemical disinfection difficult on unhygienic plantlMany commercial disinfectants available.Most are NOT validated against HPC contaminants(especially on surfaces).lRecommended chemical disinfectants for HPC plants:lPeracetic AcidlSodium HypochloriteRoutine Chemical Disinfection-Recom
17、mendationsMax.300ppm Sodium Hypochlorite for 20 minutes or400 ppm Peracetic Acid for 20 minutesDisinfection-Key PointsHigher numbers of organisms adhere to elastomers(Viton,EPDM)than to stainless steel.More survivors of disinfection occur on elastomersKey area for validationPseudomonas aeruginosa an
18、d Burkholderia cepacia proved to be most resistant Gram Negative bacteria to chemical disinfectants(Sodium Hypochlorite and Peracetic Acid).When to DisinfectlRequired to destroy micro-organisms which may be accumulating in a process plant.lWhenlPlant has been idle either for planned downtime(week en
19、d or holidays)or for maintenance.lAfter a contamination incidentlPart of a preventative disinfection regimelPrior to commissioning new equipment/plantlDetection of significant contamination on plant surfacesPreventative DisinfectionlFactory should have a planned preventative disinfection schedule to
20、 prevent the accumulation of microbial contamination in a process plant.lFrequency of disinfection is typically based on lSusceptibility of the product to contamination.lHigher the product risk generally the more frequent the disinfectionlDegree equipment complies to hygienic design principleslHisto
21、ry of incidentsDisinfection Frequency GuidelinePlant AreaProduct RiskFrequency DisinfectionMakingHighWeeklyStorageHighMonthlyFillingHighTwo WeeklyMakingMediumThree MonthlyStorageMediumThree MonthlyFillingMediumThree MonthlyThe information is provided for guidance based on current practices.For opera
22、tions with a history of problems a more frequent regime wouldbe appropriate.With validation using environmental mapping techniques disinfection periods may be slightly extended.Environmenmental mapping can be performed on individual plants by for example swabbing of key sitesScheduling Preventative
23、DisinfectionlBest practicelSchedule and monitor the implementation of disinfection events by building it into the plant control software.lColour code system can be used.For example if a storage tank is scheduled to be disinfected monthly:Green:Disinfected within 25 DaysAmber:Tank needs to be disinfe
24、cted within the next 5 daysRed:Tank must be disinfected when it is empty.Summary-When to Clean and DisinfectHolding Times Rules Finished ProductCONDITIONS FOR PRODUCT BEING HELD PRODUCT RISK LEVELSPeriod held between CleaningPeriod held between cleaning and disinfectionTime held after equipment is e
25、mptied of product before cleaning requiredTime held after equipment cleaning before disinfection required*Time held after disinfection before equipment must be used in production*Very High Risk(9-10)Never exceed 7 DaysAnd assess case by caseNever exceed 7 DaysAnd assess case by caseNever exceed 12 h
26、oursAnd assess case by caseNever exceed 8 hoursAnd assess case by caseNever exceed 4 hoursAnd assess case by caseHigh Risk(6-8)Never exceed:7 days in Mixer30 days in Storage14 in days FillerNever exceed:7 days in Mixer30 days in Storage14 in days FillerNever exceed 12 hoursNever exceed 8 hoursNever
27、exceed 8 hoursMedium Risk(3-5)30 Days verified40-90 Days verifiedNever Exceed 3 DaysNever exceed 24 hoursNever Exceed 16 hours*Best Practice is no delay(i.e.immediately)Maximum Holding Times Rules Finished Product CONDITIONS FOR PRODUCT BEING HELDPRODUCT RISK RANKINGHeld in a Vessel*before micro.tes
28、t requiredHeld in a Pallecon(tote)*before micro.test requiredHeld in a Transit Tank*before micro.test requiredHeld in a tanker before micro.test requiredVery high Risk(9-10)Assess Case by Case(Must be 7 Days)7 DaysNot PermittedNot PermittedHigh Risk(6-8)30 Days30 Days14 DaysHome Care only.Assess Cas
29、e by CaseMedium Risk(3-5)90 Days60 Days30 Days14 DaysDefinitions(Previous Tables)lVessel lStorage Tank(Part of the Process Plant).lTransit Tank l Container where product can be stored(Usually 1 Tonne but size can vary).lOften filled by flexible hose/portable pump.lTransit container would need to be
30、disinfected prior to filling.lPalleconlOne use bag(plastic)held in place in a box.TNT pallecons widely used.Usually 1 Tonne but other sizes available.lOften filled by flexible hose/portable pump.lPlastic bag can be purchased sterile(irradiated).Drain EffluentlEffluent produced during washing or disi
31、nfection must be rapidly drained from the equipment and the manufacturing area to minimize the possibility of microbiological adaptation in diluted product.“Silicone”-Caustic Detergent(1)lWork has demonstrated that B.cepacia/Ps.aeruginosa biofilm ex silicone/CTAC(Hair Conditioner)containing products
32、 are difficult to disinfectlVisibly clean surfaces NOT good enoughlNeed to remove“invisible product residueslA Caustic Detergent will help in the removal of silicone/CTAC residues“Silicone”-Caustic Detergent(2)lRecommendation:lPeriodic use of caustic detergent prior to disinfection for Hair Conditio
33、nerslPost incident STRONG recommendation to perform caustic detergent wash prior to disinfection for Hair Conditioners(Prudent to do this for other Silicone containing products)lMost effective commercial cleaning agents tested are:l10%Silox XT(ex TSI).Based on NaOHlIn use in Compeigne,Francel2%:2%so
34、lution of CIP 100&CIP Additive(ex Steris).Based on KOH.Rotation of DisinfectantslSome industries routinely rotate disinfectantslDo you need to do this?lIf you have a hygienic plant/validated procedures-NOlIf you have unhygienic plant/un-validated procedures-Treat the causes.Rotation could be a tempo
35、rary measure until causes addressedlRotation of biocides has little long term effect;best approach:thorough cleaning with a caustic detergent&physical removal of biofilm then,disinfectValidation of Disinfection:When?lNew/modified plantlChange in protocollNew chemical disinfectantlInstalled CIP for t
36、hermal disinfectionlFrequencylWhole plant validated annuallylIn modules:Not all at the same timeValidation-DisinfectionlHowlPhysicallChemicallMicrobiologicalDisinfection Validation-PhysicallThermal(CIP)lStickerslpermanent colour changelkeep with records as evidencelREMEMBER TIMElThermocoupleREAL TIM
37、EValidation of HeatDisinfection ProcessLocation points for thermal disinfection.The operators place the stickers at numbered points on the plant(i.e.within the yellow boxes)and once the time temperature criteria has been met,they take the sticker and put it into a record book10 20 30 40 50 60 70 80
38、90 degC10 20 30 40 50 60 70 80 90 degCBeforeAfterREAL TIMEDisinfection Validation-ChemicallTitrationl50%of original concentration:Repeat Disinfectionl50-90%:Improvement Plan The following can be used for disinfection(or water treatment validations):Chemetrics V-2000 Multi-Analyte PhotometerWater tes
39、ting using portable handheld LED photometer-uses specific kits to measure a broad range of analytes in water-uses disposable sample vessels(vacu-vials)to avoid cross-contamination/dirty vessels affecting reading-can store up to 100 readings and download data to PC-see for more info-Unit cost:Approx.
40、$1600;Reagent cost$2 per testChemical Validation(1)Chemical Validation(2)Chemetrics V-2000 Multi-Analyte PhotometerAssays include:Chlorine(free/total)ppm:0-4ppmChlorine dioxide:0-11ppmOzone:0-1ppmPeracetic acid:0.4-4ppmFormaldehyde in water:0.4-8ppm(other kits are also available,see website)Validati
41、on Disinfection Microbiological(1)lThis can be performed in a number of ways:lSurface Detection of Contamination:Environmental MappinglFor example:l Pressure Relief Valvesl Filter Basketsl Instrumentation Inletsl Pig Launch/Receiving Stations lElastomerslEtc.The target is 25 cfu/plate(for flat surfa
42、ces,the procedure is to swab a 10 by 10cm square area)with no Gram negatives(or objectionable organisms).NOT REAL TIMEValidation Disinfection Microbiological(2)lRinse water checkslFirst product packed post disinfectionlFirst bottles packed on fillerManual Cleaning and DisinfectionlSmall items of equ
43、ipment often need to be fully dismantled for effective cleaning(and subsequent disinfection).lDesignated area conveniently and permanently established for the cleaning and disinfection of all mobile vessels,pumps,hoses,pipes,valves,other fittings,utensils,and any other ancillary equipment.lCleaning
44、and disinfection shall be done in a purpose built hygienic wash bay.Wash Bay lHygienic surface coverings which are impervious to hot water and disinfection chemicals lEasily cleaned and fully drainablelClearly segregate clean from dirty equipment;lSeparated into two areas,lWet area for cleaning and
45、disinfection.lDry area where the cleaned and disinfected equipment is stored for drying prior being reassembled lStore cleaned and disinfected equipment/fittings on a designated rack Wash BaylCleaning of disassembled plant items is generally carried out using warm/hot water with subsequent disinfect
46、ion of the equipment using chemical disinfectant solutions.lWater should be of good microbiological quality(same as Process Water)lIf disinfecting solutions are used the equipment is usually rinsed with treated water(same microbiological quality as process water)prior to drying.lDisinfectant solutio
47、ns must be regularly changed to ensure they remain at effective concentrations.HoseslCleaned hoses hung off the floor in a manner that will allow any remaining liquid to drain.lDisconnect hoses not in use;drain,clean,disinfect,dry.lDo not let hose ends contact floor or drains.Use supports to hold ho
48、ses during flushing.lHandle connections and gaskets with washed/cleaned hands.Documentation Documented Cleaning+Disinfecting Procedures must include HowWhenWhoWhatInclude pumps,hoses and utensils etc.These often get forgotten!Include validation requirementsRecords/TrainingRecords of when and who con
49、ducted cleaning and disinfectionIn order to ensure that hygienic procedures are implemented,all personnel need to be trained in the principles of hygienic manufacture and specifically in the cleaning and disinfection procedures they are responsible forBiofilm ImplicationsBacterial BiofilmsBiofilms a
50、re microbial“communities”that form on surfaces(or interfaces)Most bacteria can form biofilmsOver time biofilms can expand and become more complexBiofilms are much more resistant to chemical attack than free floating cellsBiofilm resistance is a result of many mechanisms including:Extrusion of protec
