1. SUPPORT AND UTILITIES VALIDATION
Dr. D.Y. Patil College Of Pharmacy, Akurdi.
Presented By,
Asmita Rajendra Magare
M. Pharm 1st year (QAT)
Guided By,
Mrs.Sonali Mhaprle
2. Introduction
•All utilities that could impact on product
quality should be qualified and appropriately
monitored and action should be taken when
limits are exceeded.
•There are different type of utilities in the
pharmaceutical product manufacturing
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3. VALIDATION
To prove the performance of processes or
systems under all conditions expected to be
encountered during future operations.
Validation involves proving-
1. Engineering design
2.Operating procedures and acceptable
ranges for control parameters
3. Maintenance procedures to accomplish it
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5. High-quality water is essential for the
manufacturing of pharmaceuticals. Water is the
most commonly used raw material in
pharmaceutical manufacturing.
Water is directly or indirectly used in the
pharmaceutical manufacturing such as a major
component in injectable products and in cleaning
of manufacturing equipment.
Water is thus an important raw material in
GMP and in validating the manufacturing process.
Pharmaceutical water system
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7. Validation of water system should consist of at
list three phases as follows,
• Phase 1 (investigational phase)
• Phase 2(verification step)
• Phase 3 (verifying long term control)
QUALIFICATION PHASES
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8. • A test period of 2-4 weeks – monitor the system
• System to operate continuously without failure or
performance deviation.
• Chemical and microbiological testing should
include in accordance with a defined plan.
Phase 1
(investigationa
l phase)
• A further test period of 2-4 weeks – further
intensive monitoring of the system
• Utilization of all the SOPs after the satisfactory
completion of phase 1.
• Water can be used for manufacturing purposes
during this phase.
Phase 2
(verification
step)
• Over 1 year after the satisfactory completion of
phase 2.
• Water can be used for manufacturing purposes
during this phase.
• sampling frequencies and tests should be reduced
based on established procedures proven during
phases 1 and 2.
Phase 3
(verifying long
term control) 8
9. It is prepared by Verification of design documentation,
including-
Description of installation and functions
Specification of the requirements
Instructions for performance control
Operating procedures
Maintenance instructions
Maintenance records
Training of personnel (program and records)
Environmental records
Inspection of plant
Finally certification (Sign.) by Engineer, User
(Production) and QA Heads.
COMPLETE DOCUMENTATION
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10. Types of steam system in pharmaceutical industries:
1.House steam-
contains steam generator and
distribution system made of iron or
steel.
Constructed with rusting material.
This system is usually treated with
various substances like amines,
hydrazine or other boiler additives
to arrest corrosion.
2. Clean steam-
It established when steam is
used for directly treating the
product or product contact
surfaces.
Constructed with non-rusting
material. E,g. stainless steel.
This system use either purified
or distilled water as feed water.
Steam System
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11. Steam system validation include the
following steps:
Make a process diagram and identify major
process steps
Define major equipment in the process
Carry out IQ, OQ, PQ.
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13. INSTALLATION QUALIFICATION
1. For clean steam generator
Connect the generator to the reqired utilities and
verify on to their correctness
Tighten flanges or other fittings, clean generator
chemically and passivate generator after installation.
Label the utilities feeding the generator
Carry out pressure testing and record the results.
Check and calibrate all critical processes
instruments.
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14. 2. Distribution system
material of
construction is
as per the
specification
Compare the
design
drawing
All branches
of the
system
should be
labeled
Clean the
distribution
system
Carry out the
pressure test
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15. OPERATIONAL QUALIFICATION
1.Clean steam generator
Acc. To SOP, start up and run the clean steam
generator
Check that all instruments and alarms are working
correctly. Record their status.
Check that the generated steam meet the
specifications and can be produced in quantities
required. 15
16. 2. Distribution system
Test all the use points of the system for
adequate supply of steam under maximum load
or other production condition.
Quality of steam should be tested at all the use
points.
Use point should also be tested to find out that
excess condensate is not present under
operating conditions.
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18. Compressed Air system
2 types of compressed air system are used in the
pharmaceutical industry.
1. Conventional oil lubricated compressors for
operating instruments and machinery where no
contact with product or the environment, where
product is being mfg. is involved.
2. An oil free compressed air system used in clean
room areas.
It contains mainly compressor, dryer, storage tank and
distribution system. 18
19. INSTALLATION QUALIFICATION
1. Oil free compressor
Check specification on purchase order and actual
delivery specification
Verify that no oil or other lubricant is used in the
compressor
Check that all required utility requirements have been
met and connected properly
Check whether pre-start up procedures were performed
Check whether all critical instruments have been
calibrated
Document above all
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20. 2. Compressed air storage tank
Compressed
air storage
tank
Confirm that
the material of
construction is
as per
specification
Check the
capacity of the
tank against
purchase
specification
Carry out a
pressure hold
test .
Examine the
cleaning
procedure
adopted for the
tank .
Check all
pressure rates
for tank
against the
purchase
specification
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21. 3. Distribution system
Confirm the material of construction and design
parameter specified by the company
Compare the drawing of the system with “as-
built” drawing to show whether any modification
have been made and note the modifications.
Pressure test the system to confirm its integrity
and record the result
Examine the cleaning procedures after
installation
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22. OPERATIONAL QUALIFICATION
Check all the use points for the tests mentioned below and
record the results.
Identity
Nonviable particle count
Microbial count
Check several worst-case locations for purity.
Test all instrument and alarms for their operational status and
record.
Test the compressor output for hydrocarbons. 22
23. PERFORMANCE QUALIFICATION
It consist of completing the documentation from various
steps mentioned above and repeating operational testing
as specified in the validation protocol.
In case of the system PQ can be considered as validation.
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24. Heating Ventilation and Air Conditioning
system(HVAC)
HVAC systems can have an impact on product quality
It can provide comfortable conditions for operators
The impact on premises and prevention of
contamination and cross-contamination to be considered
at the design stage
Temperature, relative humidity control where
appropriate
Supplement to basic GMP
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25. Test procedure
and key aspects
Maximum time
interval
Objective Test Parameter
Particle count test
Readings and
positions
6 months or 12
months depending
on Class
Verifies
cleanliness
Particle count
Measure pressure
difference
12 months Absence of
cross-
contamination
Air pressure
difference
Measure supply and
return air, calculate air
change rate
12 months Verify air
change rates
Airflow volume
Velocity measurement 12 months Verify
unidirectional
airflow and or
containment
condition
Airflow velocity
2
5
SCHEDULE OF TESTS TO DEMONSTRATE CONTINUING
COMPLIANCE
26. Air flow measurement
Filter Integrity Testing
Pressure Differentials
Particulate count measurement
Recovery test
Temperature and Relative Humidity
Air Flow Pattern
Microbial Count
2
6
VALIDATION PARAMETERS
27. NON-VIABLE PARTICLE COUNTS
Equipment
Optical Particle Counter .
Air sample is drawn into the instrument & passed through
light scattering device. The signal that this generates is
electronically processed to display particle counts at different
size ranges.
Acceptance criteria:
The particle concentration under the dynamic
condition should not more than 100 particle of
0.5µm and larger per cubic meter (for class 100
area)
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28. PRESSURE DIFFERENTIALS
- Correct degree of overpressure can be maintained
relative to the adjacent areas of lower classification to
ensure that air moves from clean areas to less clean
areas.
- It is calculated by making use of the manometer
attached at the walls of the adjacent area.
- The pressure difference is generally kept between 5
and 20 mmHg pressure.
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29. AIRFLOW VELOCITY
Equipment :- Anemometer
Reading should be taken 10cm from the surface of filter.
Record velocity reading from all the four corners and the
Centre of the filter surface.
Repeat twice at each location
For Grade A laminar flow workstations, the air flow rates
shall be 0.3 meter per second + 20% (for vertical flows)
and 0.45 + 20% (for Horizontal flows)
Solution : Alteration of fan speed or HEPA filter
replacement
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30. HEPA filter integrity test (DOP test)
Purpose :
To confirm that no damage to filter, seals and no leakage of
particles.
Equipment :
1. Aerosol generator
2. Photometer
Acceptance criteria:
An unacceptable leak is defined as a penetration of
0.03% or more of particle, 0.3µm and larger than the
reference calibration curve for 99.97% efficient filter
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31. Recovery test
The recovery of temperature and humidity is
checked. For this, the humidity and temperature are
checked at the off position of the HVAC system.
Then the humidity is increased to 75% and
temperature to 400°C and again the temperature and
humidity are measured after switching on the HVAC
system, and the time required to stabilize the
temperature and humidity is noted.
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32. MICROBIOLOGICAL TESTS
Solid growth media (e.g. settle and contact plates)
Soybean Casein Digest Agar medium can be used for
both Bacteria & Fungi tested.
The recommended size of solid media is 90 mm in
diameter (for settle plates)
55 mm for contact plates.
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33. Air flow or smoke pattern
For the evaluation of this parameter, a titanium
tetrachloride stick is taken and burnt and the burning stick
is placed in front of the AHU. The distribution of smoke
is observed.
It should be uniform.
Particle count
A particle counter is used to conduct the test. Particle
count is taken before the operation as well as during the
working condition.
The particle count should be within the range as per the
standards of Grade A, B, C, and D area.
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34. Validation in pharmaceutical industry” edited by
P.P.sharma ;first edition 2007 ; 193-220.
References
Pharmaceutical validation Dr.Sohan S. Chitlange
First Edition April 2014,Page no :5.1-5.40.
Demand of pharmaceutical facility functionality: Validation
and qualification of HVAC system Anamika Singh, Sapna
Malviya, Anil Kharia, Asian Journal of Pharmaceutics -
April-June 2014 Page no: 125-129.
34
35. Validation Of HVAC Systems In Pharmaceutical
& Biotechnology Facilities Part 1 Brian Scott, Jeff
Hargroves, and Jerry Bauers,Page No:32-37.
Guidelines On Validation – Appendix 6 3 Validation On
Qualification Of Systems, Utilities 4 And Equipment
5 (June 2016) Page No:1-24.
Potdar MA. Pharmaceutical Quality Assurance,
Nirali Prakashan, Pune, Edition II, 2012. Page No:
154-162.
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