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