Presentation on theme: "WELCOME TO THE SEMINAR ON EQUIPMENT VALIDATION"— Presentation transcript:
1 WELCOME TO THE SEMINAR ON EQUIPMENT VALIDATION Presented by: -SHRUTI SHAHM.PharmDepartment of Pharmaceutics and pharmaceutical technologyL.M. College of Pharmacy
2 List Of ContentsGeneral information about equipment validationValidation of autoclaveValidation of ethylene oxide sterilization systemvalidation of radiation sterilization methodValidation of filtersValidation of dissolution apparatus
3 Interpretation of FDA guidelines Technical project manager INTRODUCTIONInterpretation of FDA guidelinesTechnical project managerEquipment Validation reference file
5 DESIGN QUALIFICATION"Design qualification (DQ) defines the functional and operational specifications of the instrument and details for the conscious decisions in the selection of the supplier".
6 Points to be considered for inclusion in a DQ :- Description of the analysis problemDescription of the intended use of the equipmentDescription of the intended environmentPreliminary selection of the functional and performance specifications (technical, environmental, safety)
7 INSTALLATION QUALIFICATION “Installation qualification establishes that the instrument is received as designed and specified, that it is properly installed in the selected environment, and that this environment is suitable for the operation and use of the instrument.”
8 At the installation qualification stage, Equipment management groupSupport groupsPlant engineering group
9 OPERATIONAL QUALIFICATION "Operational qualification (OQ) is the process of demonstrating that an instrument will function according to its operational specification in the selected environment ."
10 The content of equipment qualification 1.Application S.O.P’s2.Utilization List3.Process Description4.Test Instrument Utilized To Conduct Test5.Test Instrument Calibration6.Critical Parameters7.Test Function (List)8.Test Function Summaries
11 PERFORMANCE QUALIFICATION "Performance Qualification (PQ) is the process of demonstrating that an instrument consistently performs according to a specification appropriate for its routine use ".
12 VALIDATION OF STERILIZATION PROCESS VALIDATION OF AUTOCLAVE
13 WHAT IS VALIDATION? STERILIZER Unsterile Sterile product product Objective: guarantee of sterility according to EN 550( SAL = 10 –6 CFU/ piece)
14 Sterility Assurance Level (SAL) Level of microbial inactivationSAL 10-6Number of contaminated packs = = 10-6Number of total packs
15 Log reductionMeans to decrease the microbial population by a factor of 10.6 log reduction reduces the microbial population from 1 to 1oooooo, to get SAL of 10-6
16 Thermal resistance characteristics Z valueD valueFo valueF value
18 Installation Qualification Includes following checks-Mechanical equipment specifications( chamber, valves, traps, strainers)Control and instrumentation specification( programmable logic controller, printer / record controller)Site specification/ utilitiesDrawing verificationApproval documentationChange/ spare partsVendor specification sheets
19 Bill of materialsPreventive maintenance programFactory performance testsStandard operating proceduresOperating and maintenance manualsWeld inspection/ surface roughness documentationControl system documentationInstrumentation and input and output dry loop checksInstrument calibration
20 Operational qualification includes: Power loss recovery testSource code reviewFilter sterilizationLeak/air removal/steam penetration test/vacuum hold testJacket mappingSaturated steam test
21 The Bowie Dick test Steam penetration test Successful test indicates Failure of test indicatesSystem for steam penetration test consists of two components: -INDICATORBARRIERPCDPorous load PCDHollow load PCD
22 The Bowie Dick Test Sufficient time temperature and steam penetration Insufficient air removal and steam penetrationEffect of temperature , no air removal or steam penetrationNo effect of temperature or steam penetration
23 Process challenge device (PCD)Bowie Dick test strips
24 Alternatives to Bowie Dick test Helix testRubber load testElectronic test systemWireless data loggerEmpty distribution test
25 Performance qualification Loaded chamber steam penetration test:-ImportanceTo determine which load items are mostdifficult to sterilizeTo determine which locations within theitems present worse case conditions
26 Methods used to determine worst case locations – a. Thermocouples b Methods used to determine worst case locations – a. Thermocouples b. Steam integratorsDifferent types of thermocouples :-
29 Steam integratorsamount of steam exposure can be determined by measuring the movement of chemical indicator on the integrator strip.It is usually recommended to use steam integrator than using thermocouples because thermocouples can give misleading data.
30 Different types of biological indicators products available in the market
34 Validated EO Sterilization cycle Performance qualificationPhysical performanceQualification (PPO)Product profile (temp &RH), functionality testing,Establishing multiprocessingCapability, packagingTesting, EO residualtestingMicrobial performanceQualification (MPQ)Establish productBioburden level,Select appropriateBI or PCDValidated EO Sterilization cycle
35 Validation of Radiation Sterilization Cycle Main objective is to determine the D value of indicator organism.Bacillus pumilus spores are the USP XX choice as the biological indicator.Mode of radiation is cobalt 60, cesin 136 or electron beam.
36 A five step approach for validation Determine the microbial load on preirradiated products.Determine the D value for natural flora on the product.Determine the D value to determine that the natural flora is not more radio resistant than the biological indicator.Determine the D value for the BI spore strips placed within the product.Determine the D value for the BI , whether it varies as a function of the dose rate.
37 Tests are conducted to determine the effect of minimum and maximum product density on the ability of minimum and nominal radiation dose, to produce desired log reduction in the biological indicator population.
38 Validation of sterilizing filtration system Four major elements of the validation process:-Physical/chemical compatibilityBinding and adsorption filter characteristicsBacteria retention capacityIntegrity of the process filtration installation
39 Bacterial Challenge Test Validates the ability of a filter to provide sterile effluent in a specific pharmaceutical liquid.Bacterial challenge tests are usually performed with an industry standard concentration of 107 CFU of B. diminuta per cm2, using pharmaceutical product, whenever possible, for the most realistic validation.
47 Apparatus 1Vessel: cylindrical, mm high, inside diameter mm, nominal capacity is 1000 ml; sides are flanged at the top.Shaft: positioned so that its axis is not more than 2mm at any point from the vertical axis of the vessel and rotates smoothly and without significant wobble.Materials of construction: shaft and basket components are stainless steel, type 316 or equivalent.Basket position: the distance between the inside bottom of the vessel and the basket is maintained at 25+/- 2mm during the test.
48 Apparatus-2Vessel: cylindrical, mm high, inside diameter mm, nominal capacity is 1000 ml; sides are flanged at the top.Shaft: positioned so that its axis is not more than 2mm at any point from the vertical axis of the vessel.Blade position: the distance between the inside bottom of the vessel and the blade is maintained at 25+/- 2mm during the test.
49 Apparatus-3Reciprocating cylinder: positioned so that during the upward and downward stroke, the reciprocating cylinder moves through a total distance of cm.Materials of construction: fittings are stainless steel, type 316 or equivalent.
50 Apparatus-4Materials of construction: flow through cell composed of transparent and inert material is mounted vertically with a filter system that prevents escape of undissolved particles from the top of the cell. Tube connections are of polytef tubing with 1.6-mm diameter and chemically inter flanged end connections.Cell assembly: cell diameters are 12 and 2.6 mm; the apparatus uses a clamp mechanism and two O- rings for the fixation of cell assembly.
51 Apparatus-5Vessel: cylindrical, mm high, inside diameter mm, nominal capacity is 1000 ml; sides are flanged at the top.Shaft: positioned so that its axis is not more than 2mm at any point from the vertical axis of the vessel and rotates smoothly and without significant wobble.Materials of construction: shaft and blade are a single entity and may be coated with a suitable inert coating. Disk assembly is stainless steel.Blade position: the distance between the inside bottom of the vessel and the blade is maintained at 25+/- 2mm during the test. The disk assembly holds the system flat and is positioned such that the release surface is parallel with the bottom of the paddle blade
52 Apparatus-6Vessel: cylindrical, mm high, inside diameter mm, nominal capacity is 1000 ml; Shaft: positioned so that its axis is not more than 2mm at any point from the vertical axis of the vessel and rotates smoothly and without significant wobble.Materials of construction: shaft and basket components are stainless steel, type 316 or equivalent.Cylinder position: the distance between the inside bottom of the vessel and the cylinder is maintained at 25+/- 2mm during the test.
53 Operational qualification System suitability (calibration)using USP calibrator tablets.Test is considered successfulEach of the vessel contained within dissolution apparatus.HPLC or UV/VAcceptable peak resolution and elution time.
54 Validation of automated versus manual procedures Software/hardware communicationOperator interface functionsStress/boundary/challenge testingData integritySystem security
57 CONCLUSIONAt the acceptable installation and operational qualification, the dissolution apparatus is considered validated and acceptable for use to perform dissolution testing.
58 Questions Give in brief about equipment qualification (EQ). Write about validation of autoclave.What is the steam penetration test?What are the steps required to avoid cold spots in autoclave?Write about validation of ethylene oxide cycle.Which are the installation and operation qualifications for the validation of dissolution apparatus
59 List Of ReferencesR.G. Lewis, Practical guide to Autoclave Validation, pharmaceutical Engineering, July/ August,2002, %20autoclave.pdfValidation of ethylene oxide sterilization cycles, E.O-ster-cycles.pdfbiopharm_3911.asp
60 4.www.pharmatech.com/pharmatech/article detail.jsp?id+128855 5. valtest.html6. Guidelines for Validation Radiation Sterilization7.8.B.T loftus & R.A Nash, Pharmaceutical process validation, page no10.
61 11. www.ISO.org/iso/en/catalouge List Page 12.13. Introduction to a validation of dissolution apparatus, Sharon m averell frost, Dissolution Technologies, feb 2004, vol-1114. Gke steri record