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Transcript of WELCOME TO THE SEMINAR ON EQUIPMENT VALIDATION Presented by: - SHRUTI SHAH M.Pharm Department of...
WELCOME TO THE SEMINAR ON EQUIPMENT VALIDATION
Presented by: -SHRUTI SHAH
M.Pharm
Department of Pharmaceutics and pharmaceutical technologyL.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
EQUIPMENT QUALIFICATION(EQ) / VALIDATION
•Design qualification (DQ)• Installation qualification (IQ)•Operational qualification
(OQ)•Performance qualification
(PQ)
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.P’s2.Utilization List3.Process Description4.Test Instrument Utilized To Conduct
Test5.Test Instrument Calibration6.Critical Parameters7.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
Unsterileproduct
Sterile product
Objective: guarantee of sterility according to EN 550
( SAL = 10 –6 CFU/ piece)
Sterility Assurance Level (SAL)
•Level of microbial inactivation
•SAL 10-6
•Number of contaminated packs = 1 = 10-6
Number of total packs 1000000
Log reduction
• Means 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
Thermal resistance characteristics
D value Z value
F valueFo value
Basic validation approach
Installation qualification
Operational qualification
Performance qualification
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 qualificationincludes:
Power loss recovery testSource code reviewFilter sterilizationLeak/air removal/steam
penetration test/vacuum hold testJacket mappingSaturated 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 TestSufficient 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 testRubber load testElectronic test systemWireless data loggerEmpty 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. Thermocouplesb. Steam integrators
Different types of thermocouples :-
Thermograph
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
EZTest product
Validation of Ethylene oxide cycle
Installation Qualification: commissioning data, Empty chamber profile, chamber wall profile, EO cycle
Operational qualification: cycle design, product design, packaging design, load configuration
Performance qualification
Physical performance Qualification (PPO)Product profile (temp &RH), functionality testing,Establishing multiprocessingCapability, packagingTesting, EO residualtesting
Microbial performanceQualification (MPQ)Establish productBioburden level,Select appropriateBI 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
Testing sterile gas filters
Dissolution Apparatus Validation
Installation qualification
Preventive maintenanceCalibrationSOPsUtilitiesComputerized systemEnvironmental conditions
Apparatus 1
Vessel: cylindrical, 160-210 mm high, inside diameter 98-106 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, 160-210 mm high, inside diameter 98-106 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 9.9-10.1 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, 160-210 mm high, inside diameter 98-106 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, 160-210 mm high, inside diameter 98-106 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
Temperaturemapping
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 References1. R.G. Lewis, Practical guide to Autoclave
Validation, pharmaceutical Engineering, July/ August,2002, www.Idc-ch2m.com/papers/IDC 2002%20autoclave.pdf
2. Validation of ethylene oxide sterilization cycles, www.istron.com/docs/validation-of E.O-ster-cycles.pdf
3. www.ravenlabs.com/bis.html
4. www.pall.com/ biopharm_3911.asp
4.www.pharmatech.com/pharmatech/article detail.jsp?id+128855
5. www.mss-ct_co.uk/ valtest.html
6. www.sterigenics.com, Guidelines for Validation Radiation Sterilization
7. www.labcompliance.com/equipment
8.B.T loftus & R.A Nash, Pharmaceutical process validation, page no-29-93.
9. www.bioqc/wetsterilization.ppt_24feb 2005
10. www.smartsensors.com/mtr.htm
11. www.ISO.org/iso/en/catalouge List Page
12. www.sgmbiotech.com
13. Introduction to a validation of dissolution apparatus, Sharon m averell frost, Dissolution Technologies, feb 2004, vol-11
14. Gke steri record