Presentation on theme: "WELCOME TO THE SEMINAR ON EQUIPMENT VALIDATION Presented by: - SHRUTI SHAH M.Pharm Department of Pharmaceutics and pharmaceutical technology L.M. College."— Presentation transcript:
WELCOME TO THE SEMINAR ON EQUIPMENT VALIDATION Presented by: - SHRUTI SHAH M.Pharm Department of Pharmaceutics and pharmaceutical technology L.M. College of Pharmacy
List Of Contents General information about equipment validation Validation of autoclave Validation of ethylene oxide sterilization system validation of radiation sterilization method Validation of filters Validation of dissolution apparatus
INTRODUCTION Interpretation of FDA guidelines Technical project manager Equipment Validation reference file
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".
Points to be considered for inclusion in a DQ :- Description of the analysis problem Description of the intended use of the equipment Description of the intended environment Preliminary selection of the functional and performance specifications (technical, environmental, safety)
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.
At the installation qualification stage, Support groups Plant engineering group Equipment management group
OPERATIONAL QUALIFICATION "Operational qualification (OQ) is the process of demonstrating that an instrument will function according to its operational specification in the selected environment."
The content of equipment qualification 1.Application S.O.Ps 2.Utilization List 3.Process Description 4.Test Instrument Utilized To Conduct Test 5.Test Instrument Calibration 6.Critical Parameters 7.Test Function (List) 8.Test Function Summaries
PERFORMANCE QUALIFICATION "Performance Qualification (PQ) is the process of demonstrating that an instrument consistently performs according to a specification appropriate for its routine use ".
VALIDATION OF STERILIZATION PROCESS VALIDATION OF AUTOCLAVE
WHAT IS VALIDATION? STERILIZER Unsterile product Sterile product Objective: guarantee of sterility according to EN 550 ( SAL = 10 –6 CFU/ piece)
Sterility Assurance Level (SAL) Level of microbial inactivation SAL Number of contaminated packs = 1 = Number of total packs
Log reduction Means to decrease the microbial population by a factor of log reduction reduces the microbial population from 1 to 1oooooo, to get SAL of 10 -6
Thermal resistance characteristics D value Z value F value Fo value
Installation Qualification Includes following checks- Mechanical equipment specifications ( chamber, valves, traps, strainers) Control and instrumentation specification ( programmable logic controller, printer / record controller) Site specification/ utilities Drawing verification Approval documentation Change/ spare parts Vendor specification sheets
Bill of materials Preventive maintenance program Factory performance tests Standard operating procedures Operating and maintenance manuals Weld inspection/ surface roughness documentation Control system documentation Instrumentation and input and output dry loop checks Instrument calibration
Operational qualification includes: Power loss recovery test Source code review Filter sterilization Leak/air removal/steam penetration test/vacuum hold test Jacket mapping Saturated steam test
The Bowie Dick test Steam penetration test Successful test indicates Failure of test indicates System for steam penetration test consists of two components: - INDICATOR BARRIER PCD Porous load PCD Hollow load PCD
The Bowie Dick Test Sufficient time temperature and steam penetration Insufficient air removal and steam penetration Effect of temperature, no air removal or steam penetration No effect of temperature or steam penetration
Process challenge device (PCD) Bowie Dick test strips
Alternatives to Bowie Dick test Helix test Rubber load test Electronic test system Wireless data logger Empty distribution test
Performance qualification Loaded chamber steam penetration test:- Importance To determine which load items are most difficult to sterilize To determine which locations within the items present worse case conditions
Methods used to determine worst case locations – a. Thermocouples b. Steam integrators Different types of thermocouples :-
Steam integrators amount 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.
Different types of biological indicators products available in the market
Performance qualification Physical performance Qualification (PPO) Product profile (temp & RH), functionality testing, Establishing multiprocessing Capability, packaging Testing, EO residual testing Microbial performance Qualification (MPQ) Establish product Bioburden level, Select appropriate BI or PCD Validated EO Sterilization cycle
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.
A five step approach for validation 1.Determine the microbial load on preirradiated products. 2.Determine the D value for natural flora on the product. 3.Determine the D value to determine that the natural flora is not more radio resistant than the biological indicator. 4.Determine the D value for the BI spore strips placed within the product. 5.Determine the D value for the BI, whether it varies as a function of the dose rate.
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.
Validation of sterilizing filtration system Four major elements of the validation process:- Physical/chemical compatibility Binding and adsorption filter characteristics Bacteria retention capacity Integrity of the process filtration installation
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.
Integrity testing of the filters Aerosol penetration tests Bubble point test Testing sterile gas filters
Apparatus 1 Vessel: 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.
Apparatus-2 Vessel: 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.
Apparatus-3 Reciprocating 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.
Apparatus-4 Materials 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.
Apparatus-5 Vessel: 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
Apparatus-6 Vessel: 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.
Operational qualification System suitability (calibration) -using USP calibrator tablets. -Test is considered successful -Each of the vessel contained within dissolution apparatus. -HPLC or UV/V -Acceptable peak resolution and elution time.
Validation of automated versus manual procedures Software/hardware communication Operator interface functions Stress/boundary/challenge testing Data integrity System security
Temperature distribution study Temperature mapping
Rotation speed study
CONCLUSION At the acceptable installation and operational qualification, the dissolution apparatus is considered validated and acceptable for use to perform dissolution testing.
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
List Of References 1.R.G. Lewis, Practical guide to Autoclave Validation, pharmaceutical Engineering, July/ August,2002, ch2m.com/papers/IDC 2002%20autoclave.pdfwww.Idc- ch2m.com/papers/IDC 2.Validation of ethylene oxide sterilization cycles, E.O-ster-cycles.pdfwww.istron.com/docs/validation-of E.O-ster-cycles.pdf 3.www.ravenlabs.com/bis.htmlwww.ravenlabs.com/bis.html 4.www.pall.com/ biopharm_3911.aspwww.pall.com/
4.www.pharmatech.com/pharmatech/article detail.jsp?id www.pharmatech.com/pharmatech/article 5. valtest.htmlwww.mss-ct_co.uk/ 6. Guidelines for Validation Radiation Sterilizationwww.sterigenics.com B.T loftus & R.A Nash, Pharmaceutical process validation, page no
11. List Pagewww.ISO.org/iso/en/catalouge Introduction to a validation of dissolution apparatus, Sharon m averell frost, Dissolution Technologies, feb 2004, vol Gke steri record