This document provides an overview of equipment validation processes for various sterilization and testing equipment. It discusses the qualification stages of design, installation, operational, and performance qualification. Specific equipment validated include autoclaves, ethylene oxide sterilizers, radiation sterilizers, filters, and dissolution apparatus. Validation procedures for each involve installation checks, qualification tests, process validation, and establishing the equipment is fit for intended use.

2. 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

3. INTRODUCTION
Interpretation of FDA
guidelines
Technical project manager
Equipment Validation reference
file

4. EQUIPMENT
QUALIFICATION(EQ) /
VALIDATION
Design qualification (DQ)
Installation qualification (IQ)
Operational qualification (OQ)
Performance qualification (PQ)

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 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)

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. Equipment management group
Support groups
Plant 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’s
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

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. 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 inactivation
SAL 10-6
Number of contaminated packs = 1 = 10-6
Number of total packs 1000000

15. 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

16. D value Z value
Fo value F value

17. Basic validation approach
Installation qualification
Operational qualification
Performance qualification

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/ utilities
Drawing verification
Approval documentation
Change/ spare parts
Vendor specification sheets

19. •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

20. Operational qualification
includes: loss recovery test
 Power
 Source code review
 Filter sterilization
 Leak/air removal/steam penetration test/vacuum
hold test
 Jacket mapping
 Saturated steam test

21. Steam penetration test
The Bowie indicatestest
Successful test Dick
Failure of test indicates
System for steam penetration test consists of two
components: -
INDICATOR BARRIER
PCD
Porous load PCD Hollow load PCD

22. 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

23. Process challenge device
(PCD)
Bowie Dick test strips

24. Alternatives to Bowie Dick test
Helix test
Rubber load test
Electronic test system
Wireless data logger
Empty distribution test

25. 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

26. –
a. Thermocouples
b. Steam integrators
Different types of thermocouples :-

28. Thermograph

29. 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.

30. Different types of biological indicators products
available in the market

32. EZTest product

33. 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

34. Performance qualification
Physical performance Microbial performance
Qualification (PPO) Qualification (MPQ)
Product profile (temp & Establish product
RH), functionality testing, Bioburden level,
Establishing multiprocessing Select appropriate
Capability, packaging BI or PCD
Testing, EO residual
testing
Validated 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 the microbial load on preirradiated
1. Determine
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.

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 compatibility
Binding and adsorption filter characteristics
Bacteria retention capacity
Integrity 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.

41. Integrity testing of the filters
Aerosol penetration tests
Bubble point test
Testing sterile gas filters

42. Testing sterile gas filters

45. Dissolution Apparatus
Validation

46. Installation qualification
Preventive maintenance
Calibration
SOPs
Utilities
Computerized system
Environmental conditions

47. 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.

48. 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.

49. 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.

50. 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.

51. 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

52. 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.

53. 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.

54. Validation of automated versus
manual procedures
Software/hardware
communication
Operator interface functions
Stress/boundary/challenge
testing
Data integrity
System security

55. Temperature distribution study
Temperature
mapping

56. Rotation speed study

57. CONCLUSION
At 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 References
1. 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

60. 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

61. 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