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
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.”
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
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
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
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
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
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.
40.
41. Integrity testing of the filters
Aerosol penetration tests
Bubble point test
Testing sterile gas filters
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
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
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