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

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,

Equipment management group

Support groups

Plant engineering 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 10-6

Number of contaminated packs =

Number of total packs

1000000

10-6

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

Fo value

F value

Basic validation approach

Installation qualification
Operational qualification
Performance qualification

Installation Qualification

Includes following checksMechanical 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 :-

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 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

Testing sterile gas filters

Dissolution Apparatus
Validation

Installation qualification
Preventive maintenance
Calibration
SOPs
Utilities
Computerized system
Environmental 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 9.910.1 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 98106 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

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, www.Idcch2m.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