Support utilities validation.pptx (asmita magare)
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Transcript of Support utilities validation.pptx (asmita magare)
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
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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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VALIDATIONTo prove the performance of processes or
systems under all conditions expected to be encountered during future operations.
Validation involves proving-
1. Engineering design2.Operating procedures and acceptable ranges for control parameters3. Maintenance procedures to accomplish it
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utilities
Water system
Pure steam system
HAVCsystem
Compr-essed
air
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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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SYSTEM QUALIFICATION
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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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• 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 (investigational
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)
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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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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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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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waterWater
pretreatment
Distillation
equipment
Holding tank
Steam generator
Distribution system
Process outline of clean steam
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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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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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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.
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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.
17PERFORMANCE QUALIFICATION
Several tests under
defined load
conditions
It required testing
specified in the
protocol
PERFORMANCE QUALIFICATION
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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.
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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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2. Compressed air storage tank
Compressed air
storage tank
Confirm that the
material of construction is as per specificatio
n
Check the capacity of
the tank against
purchase specificatio
n 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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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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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.
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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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Heating Ventilation and Air Conditioning
system(HVAC)
HVAC systems can have an impact on product qualityIt can provide comfortable conditions for operatorsThe impact on premises and prevention of contamination and cross-contamination to be considered at the design stageTemperature, relative humidity control where appropriateSupplement to basic GMP
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
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SCHEDULE OF TESTS TO DEMONSTRATE CONTINUING COMPLIANCE
Air flow measurement
Filter Integrity Testing
Pressure Differentials
Particulate count measurement
Recovery test
Temperature and Relative Humidity
Air Flow Pattern
Microbial Count26
VALIDATION PARAMETERS
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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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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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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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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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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 HVACsystem, and the time required to stabilize the temperature and humidity is noted.
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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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Air flow or smoke patternFor 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 countA 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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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.
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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 Equipment5 (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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Thank you