化妆品清洗和消毒培训 课件

1、Disinfection Peter Jay: Bioscience, UR&DPSTrumbull, US 14-16th November 2006BackgroundRecent years weaknesses in cleaning and disinfection have been the major cause of incidents.Recognised that greater emphasis on adherence to best practice principles is required. On site validation of procedures is

2、 a key area that needs to be improved. Incident Learnings - Disinfection (1)Water/Dilute Product Residues Left in Plant. Plant NOT disinfected prior to useMANY incidentsDisinfection procedure NOT validatedOperators INADEQUATELY trained Operator did NOT follow documented disinfection procedureDisinfe

3、ction NOT performed when requiredIncident Learnings - Disinfection (2) Disinfection procedure in a third party did NOT follow an approved practice. INADEQUATE control of shutdown proceduresPortable equipment NOT adequately cleaned and disinfected prior to use.INCIDENT LEARNING - C&DEnsure water/prod

4、uct drains from all areas of plant by good design practice. If non drainable areas are identified, they MUST be managed by disinfection procedures prior to use of the plantUndrainable pipe arrangementUndrainable pump arrangementWater/Dilute Product Residues Left in PlantINCIDENT LEARNING C&DTime Imm

5、ediately 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 this?- Would you drink this?- Would you make product w

6、ith this?Undrainable pipe arrangement - Leaving Dilute Product residues = “BUG FOODWater/Dilute Product Residues Left in PlantUndrainableCleaningandDisinfectionRulesINCIDENT LEARNINGSEnsure Cleaning and Disinfection protocols are documented and operators are trained in the procedures. Regular checks

7、 by local hygienist are required to ensure complianceWHENWHOHOWMUST BE DEFINEDAND DOCUMENTEDTRAINING is keyDISIPLINE IN IMPLEMENTATION is essentialCleaning and DisinfectionDisinfectionDestruction of micro-organisms but NOT usually bacterial spores. Disinfection does NOT necessarily kill all micro-or

8、ganisms 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 - HACCPCan be handled as a GMP or as defined CCPsPreferred route is as CCPsEspecially when starting on

9、HACCPConsider CIP system in HACCP studyConsider where need manual interventionWhy CleanProcessPurpose to remove product soils and residues to produce clean equipment surfaces that will not taint the subsequent production of a differing variant.Microbiological Preparation of the plant surfaces for di

10、sinfection. Residual product left in equipment can prevent effective disinfection:Deactivate some chemical disinfectants.Physical barrier preventing the successful elimination of the micro-organisms by protecting them Remaining product residues will also act as a food source for resident micro-organ

11、isms. Poor cleaning can increase the risk of contamination through the formation of dilute and hence more hospitable product residues (sub lethal preservative levels).Why DisinfectWe do NOT operate sterile processesTherefore some micro-organisms WILL enter the manufacturing plantDisinfection strateg

12、ies are required to prevent the build up of contamination in the plant to a level that will result in out of specification productDisinfection should reduce the microbial load on a surface to a level that will NOT be capable of surviving or growing in finished productDisinfection Equipment must be c

13、lean to be effectively disinfected.Equipment must be drained dry to remain disinfected for any period of time.Disinfection only protects equipment for a limited time.How to DisinfectTwo options:Heat ChemicalsThermal DisinfectionRecommended method of disinfectionTemperatures of 70 degrees for 10 minu

14、tes will effectively disinfect plant (coldest part of plant must reach these conditions)Target temperature MUST be attained at the coldest part of the plant/circuit being disinfected. 10 minute contact time shall NOT be started until all parts of the circuit have reached this temperature. It may tak

15、e in excess of 15 minutes for all parts of plant circuit (varies with configuration/equipment) to reach this temperature.Validation time/temperature is CRITICAL Lower temperatures and contact times will NOT deliver disinfection.Thermal DisinfectionHeat more effective than chemical disinfection in de

16、stroying biofilmsEquipment must be able to withstand high temperatures and be engineered correctly to avoid implosion of tanks. Steam: Rarely used outside US Plants not designed (seals/instruments etc.) to handle steamOnly effective against non spore forming micro-organismsProtection against scaldin

17、g requiredThermal Disinfection Guidelines for the Manufacture of HPC Liquids. This document is available on the Global Hygiene Security Group website under Technical Documents. Chemical DisinfectionRelies on physical contact with micro organismsChemical disinfection difficult on unhygienic plantMany

18、 commercial disinfectants available. Most are NOT validated against HPC contaminants (especially on surfaces). Recommended chemical disinfectants for HPC plants:Peracetic AcidSodium HypochloriteRoutine Chemical Disinfection - RecommendationsMax. 300ppm Sodium Hypochlorite for 20 minutes or400 ppm Pe

19、racetic 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 and Burkholderia cepacia proved to be most resistant Gram Negative

20、 bacteria to chemical disinfectants (Sodium Hypochlorite and Peracetic Acid).When to DisinfectRequired to destroy micro-organisms which may be accumulating in a process plant. WhenPlant has been idle either for planned downtime (weekend or holidays) or for maintenance.After a contamination incidentP

21、art of a preventative disinfection regimePrior to commissioning new equipment/plantDetection of significant contamination on plant surfacesPreventative DisinfectionFactory should have a planned preventative disinfection schedule to prevent the accumulation of microbial contamination in a process pla

22、nt.Frequency of disinfection is typically based on Susceptibility of the product to contamination.Higher the product risk generally the more frequent the disinfectionDegree equipment complies to hygienic design principlesHistory of incidentsDisinfection Frequency GuidelinePlant AreaProduct RiskFrequ

23、ency DisinfectionMakingHighWeeklyStorageHighMonthlyFillingHighTwo WeeklyMakingMediumThree MonthlyStorageMediumThree MonthlyFillingMediumThree MonthlyThe information is provided for guidance based on current practices. For operations with a history of problems a more frequent regime wouldbe appropria

24、te. 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 DisinfectionBest practiceSchedule and monitor the implementation of dis

25、infection events by building it into the plant control software. Colour 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 disinfected within the next 5 daysRed: Tank must be disinfected when it is e

26、mpty.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 emptied of product before cleaning requiredTime held after equipmen

27、t 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 hoursAnd assess case by caseNever exceed 8 hoursAnd assess case by

28、 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 exceed 8 hoursMedium Risk (3-5)30 Days verified40-90 Days veri

29、fiedNever 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. test requiredHeld in a Pallecon (tote)* before micro. test

30、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 Case by CaseMedium Risk (3-5)90 Days60 Days30 Day

31、s14 DaysDefinitions (Previous Tables)Vessel Storage Tank (Part of the Process Plant).Transit Tank Container where product can be stored (Usually 1 Tonne but size can vary). Often filled by flexible hose/portable pump. Transit container would need to be disinfected prior to filling. PalleconOne use b

32、ag (plastic) held in place in a box. TNT pallecons widely used. Usually 1 Tonne but other sizes available.Often filled by flexible hose/portable pump. Plastic bag can be purchased sterile (irradiated).Drain EffluentEffluent produced during washing or disinfection must be rapidly drained from the equ

33、ipment and the manufacturing area to minimize the possibility of microbiological adaptation in diluted product.“Silicone - Caustic Detergent (1)Work has demonstrated that B.cepacia / Ps.aeruginosa biofilm ex silicone/CTAC (Hair Conditioner) containing products are difficult to disinfectVisibly clean

34、 surfaces NOT good enoughNeed to remove “invisible product residuesA Caustic Detergent will help in the removal of silicone/CTAC residues“Silicone - Caustic Detergent (2)Recommendation:Periodic use of caustic detergent prior to disinfection for Hair ConditionersPost incident STRONG recommendation to

35、 perform caustic detergent wash prior to disinfection for Hair Conditioners (Prudent to do this for other Silicone containing products)Most effective commercial cleaning agents tested are:10% Silox XT (ex TSI). Based on NaOHIn use in Compeigne, France2%: 2% solution of CIP 100 & CIP Additive (ex Ste

36、ris). Based on KOH. Rotation of DisinfectantsSome industries routinely rotate disinfectantsDo you need to do this?If you have a hygienic plant/validated procedures - NOIf you have unhygienic plant/un-validated procedures - Treat the causes. Rotation could be a temporary measure until causes addresse

37、dRotation of biocides has little long term effect; best approach: thorough cleaning with a caustic detergent & physical removal of biofilm then, disinfectValidation of Disinfection:When?New / modified plantChange in protocolNew chemical disinfectantInstalled CIP for thermal disinfectionFrequencyWhol

38、e plant validated annuallyIn modules: Not all at the same timeValidation - DisinfectionHowPhysicalChemicalMicrobiologicalDisinfection Validation - PhysicalThermal (CIP)Stickerspermanent colour changekeep with records as evidenceREMEMBER TIMEThermocoupleREAL TIMEValidation of HeatDisinfection Process

39、Location 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 90 degC10 20 30 40 50 60 70 80 9

40、0 degCBeforeAfterREAL TIMEDisinfection Validation - ChemicalTitration50% of original concentration: Repeat Disinfection50-90%: Improvement Plan The following can be used for disinfection (or water treatment validations):Chemetrics V-2000 Multi-Analyte PhotometerWater testing using portable handheld

41、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. $1600; Reagent cost

42、$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)Validat

43、ion Disinfection Microbiological (1)This can be performed in a number of ways:Surface Detection of Contamination : Environmental MappingFor example: Pressure Relief Valves Filter Baskets Instrumentation Inlets Pig Launch/Receiving Stations ElastomersEtc.The target is 25 cfu/plate (for flat surfaces,

44、 the procedure is to swab a 10 by 10cm square area) with no Gram negatives (or objectionable organisms). NOT REAL TIMEValidation Disinfection Microbiological (2)Rinse water checksFirst product packed post disinfectionFirst bottles packed on fillerManual Cleaning and DisinfectionSmall items of equipm

45、ent often need to be fully dismantled for effective cleaning (and subsequent disinfection).Designated 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.Cleani

46、ng and disinfection shall be done in a purpose built hygienic wash bay.Wash Bay Hygienic surface coverings which are impervious to hot water and disinfection chemicals Easily cleaned and fully drainableClearly segregate clean from dirty equipment;Separated into two areas, Wet area for cleaning and d

47、isinfection.Dry area where the cleaned and disinfected equipment is stored for drying prior being reassembled Store cleaned and disinfected equipment/fittings on a designated rack Wash BayCleaning of disassembled plant items is generally carried out using warm/hot water with subsequent disinfection

48、of the equipment using chemical disinfectant solutions.Water should be of good microbiological quality (same as Process Water)If disinfecting solutions are used the equipment is usually rinsed with treated water (same microbiological quality as process water) prior to drying. Disinfectant solutions

49、must be regularly changed to ensure they remain at effective concentrations.HosesCleaned hoses hung off the floor in a manner that will allow any remaining liquid to drain.Disconnect hoses not in use; drain, clean, disinfect, dry.Do not let hose ends contact floor or drains. Use supports to hold hos

50、es during flushing.Handle 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 c

51、onducted 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 BiofilmsBiofilm

52、s are 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 p

53、rotective slime by surface attached cells“Shielding of bacteria within clumps that can contain many thousands of bacteriaSome bacteria attach to the surface,most exist as free floating (planktonic)cellsBacteria form surface structures, these caninvolve more than one species.Clumps of bacteria can be

54、 released which areresistant to chemical attackBiofilms are surface attached microbial communities that are resistant to chemical attack. More likely toform in unhygienic equipment/pipeworkTIMEFLOWBiofilm PreventionMaterial SelectionStainless Steel and Polypropylene Data supports low colonization of

55、 these materialsHigh Water VelocitiesHamper the attachment of planktonic cells to solid surfaces as time is required for attachmentSmooth SurfacesDecreasing surface roughness increases the probability organisms will not attach to surfacesHygienic fittings which are easy to cleanNon-hygienic fittings

56、 provide hideaways for organisms and are nearly impossible to clean“Dealing with BiofilmsPreventative Maintenance by Frequent Cleaning and DisinfectionValidate Cleaning and Disinfection Effectiveness“Control by Biocides (Disinfectants)Pitfall: Planktonic cells are much more susceptible to biocides t

57、han biofilmsBiocides will weaken the biofilmGood Manufacturing Design and Effective Cleaning and Disinfection Procedures Helps Manage the Risk from Biofilm.Avoiding ResistanceB.cepacia (but applies to other Gram Negative bacteria) B.cepaciaWater UntreatedTreated WaterPlantB.cepacia Present - Approx.

58、1% populationTreatment System99.9% reliableFailureLow LevelsB.cepaciaConditions to establish selfHigh NumbersINCIDENTResultTransfer from Water to Dilute Product0123456780102030405060Time at 28C (hrs)Log number of bacteriaInoculation of 102 B cepacia into dilute product (10%) preserved with glydant.D

59、emonstrates rapid recovery and growth rate to achieve high numbers in a short duration.Undrainable Pipe LoopRapid Growth Adaptability : ConclusionsDont let it survive !Dont let it adapt !1 litre dilute residues10 T contaminated productHygienic & Drainable !Adequate Cleaning !Adequate Disinfection !

60、1 litre of Burkholderia cepacia in dilute product residues will put a 10 Tonne batch of product at very serious risk from contaminationBulk Transfer High Risk Raw Materials and Finished ProductsTankersExtremely high-risk operationSite where cleaning and disinfection is done should be audited to ensu