A Seminar On Validation of Heating, Ventilation and Air conditioning System

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A Seminar OnValidation of Heating, Ventilation
and Air conditioning System

Department of Quality Assurance Maliba Pharmacy
College
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Content

• Introduction
• Validation of HVAC
• HVAC Qualification
• Validation master plan
• Design Qualification(DQ)
• Installation Qualification(IQ)
• Operational Qualification(OQ)
• Performance Qualification(PQ)
• Validation parameter
• References

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Introduction

• 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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What is contamination?

• It is "the undesired introduction of
  impurities (chemical/ microbial/ foreign matter)
  into or on to starting material or intermediate
  during sampling, production, packaging or
  repackaging.
• Contaminants are -
• Products or substances other than the product
  being manufactured
• Foreign matter
• Particulate matter
• Micro-organisms
• Endotoxins (degraded micro-organisms)

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What is cross-contamination?

• Contamination of a starting material,
  intermediate product, or finished product with
  another starting material or product during
  production.
• Cross-contamination originates from-
• Poorly designed air handling systems and dust
  extraction systems
• Poorly operated and maintained air handling
  systems and dust extraction systems
• Inadequate procedures for personnel and equipment
• Insufficiently cleaned equipment

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Cross-contamination can be minimized by

• Personnel procedures
• Adequate premises
• Use of closed production systems
• Adequate, validated cleaning procedures
• Appropriate levels of protection of product
• Correct air pressure cascade

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HVACsystem consists of-

• Air conditioner
• AHUs
• Dehumidifier / Heater
• Filters (Pre HEPA)
• Dust Extractors
• Ducting (For delivery of controlled air)
• Supply Fans
• Smoke Detector
• Dampers
• Humidity / Temperature / Pressure sensors
• Bag Filters
• Heating / Cooling Coils

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Area 1

HVAC
Area 2
I M P U R E A I R

Impure air
Pure air
Area 3
Area 4
10 Return Air
Exhaust air
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HVAC
Exhaust Air Grille
Heater
Secondary Filter
Recirculated air
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Validation of HVAC systems

• It includes-
• Commissioning
• Qualification
• Maintenance

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Commissioning -

• Precursor to qualification
• Includes setting up, balancing, adjustment and
  testing of entire HVAC system to ensure it meets
  requirements in URS.
• Acceptable tolerances for parameters
• Training of personnel

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Conti

• Records and data maintained include-
• Installation records documented evidence of
  measure capacities of the system
• Data design and measurement for, e.g. air flow,
  system pressures
• OM manuals, schematic drawings, protocols,
  reports

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Qualification

• To ensure that equipment is designed as per
  requirement, installed properly.
• Action of proving that any equipment works
  correctly and leads to the expected results.

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HVAC Qualification

• Validation Master Plan
• QUALIFICATION
• User Requirement Specification
• Design Qualification
• Installation Qualification
• Operation Qualification
• Performance Qualification
• Re- Qualification.

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Conti

• Manufacturers should qualify HVAC systems using a
  risk-based approach.
• The qualification of the HVAC system should be
  described in a validation master plan (VMP).
• The validation master plan should define the
  nature and extent of testing and the test
  procedures and protocols to be followed.
• A change control procedure should be followed

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Conti

• Risk analysis to determine critical and
  non-critical parameters, components, subsystems
  and controls
• Critical parameters should be included
• Non-critical systems and components are subjected
  to Good Engineering Practices (GEP)
• Acceptance criteria and limits defined in design
  stage
• Design conditions, normal operating ranges,
  operating ranges, alert and action limits

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Validation master plan

• This document should contain
• Validation policy
• Organizational structure of validation activities
• Summary of facilities, systems, equipment and
  processes to be validated
• Documentation format to be used for protocols
  and reports
• Planning and scheduling
• Change control
• References to documents

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Qualification

• Typical parameters to be included in
  qualification
• Temperature
• Relative humidity
• Supply, return and exhaust air quantities
• Room air change rates
• Room pressures (pressure differentials)
• Room clean-up rate
• Particulate matter, microbial matter (viable and
  non-viable)
• HEPA filter penetration test

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Conduct of test

• Time intervals and procedure to be defined by the
  manufacturer
• Influenced by the type of facility and level of
  protection
• Requalification, and change control Tests
  performed according to protocols and procedures
  for the tests
• Results recorded and presented in report

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Schedule of tests to demonstrate continuing
compliance
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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Design Qualification(DQ)

• First step in the qualification of new HVAC
  systems.
• It documents the design of the system and will
  include
• 1. Functional Specification.
• 2. Technical / Performance specification for
  equipment.
• 3. Detailed Air Flow Schematics.
• 4. Detailed layout drawing of the system.
• Compliance with GMPs and other regulatory
  requirements.

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Conti

• Ensures that design -
• 1. Meets the user requirements.
• 2. Details facility airflow and pressure cascade
  philosophy.
• 3. Takes into account process and personnel flow
  (cross- contamination issues)
• 4. Details materials of construction.
• 5. Details safety requirements.
• 6. Full details of the intended construction
  prior to implementation.
• 7. Details all equipment that must be ordered.

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Installation Qualification(IQ)

• IQ Should include-
• Instrumentation checked against current
  engineering drawings and specifications
• Properly served by the required utilities
• Verification of materials of construction
• Installation of equipment and with piping
• Calibration of measuring instruments
• Operation manuals and spare parts lists to assure
  the proper and continuous operation of the system
• Components are installed at specified location

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Conti.

• IQ Document should contain-
• Instrument name, model, I.D. No., Personnel
  responsible for activities and Date.
• A fully verified installation that complies with
  the documented design. (all deviations will have
  been recorded and assessed.)
• All equipment documentation and maintenance
• requirements would be documented.
• Completed calibration of measuring instruments.

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Conti.

• Calibration verification
• To provide a list of critical instrumentation
  and control panel and to document that they have
  been identified and calibrated in accordance with
  the approved procedure
• SOP verification
• To verify that required SOPs exist in either
  draft or final form and must be current and
  approved for use.
• Utilities Connection Verification
• Utilities supported to HVAC need to be
  verified to assure that they are installed
  properly.

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Conti.

• Change Parts and Replacement Parts Verification
• Maintenance Procedures Verification
• Critical Systems Change Request Procedure
  verification
• Lubricants Verification

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Operation Qualification

• The purpose of OQ is to establish, through
  documented testing, that all critical components
  are capable of operating within established
  limits and tolerances.
• The purpose of OQ is to verify and document that
  an HVAC system provides acceptable operational
  control under at-rest conditions.
• Scope of OQ is to test the individual components
  of the system such as AHU, blowers and others.

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Conti

• Operation Qualification Checks -
• Ability to provide air of sufficient quality and
  quantity to ensure achievement of specified clean
  room conditions.
• Ability to maintain temperature, relative
  humidity and pressure set points.
• Ability to maintain any critical parameters
  stated in the DQ consistently.

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Conti.

• Includes the tests that have been developed from
  knowledge of processes, systems and equipment.
• Tests to include a condition or a set of
  conditions encompassing upper and lower operating
  limits, sometimes referred to as worst case
  conditions.

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OQ also includes-

• Testing Equipment Calibration Verification
• Instrumentation Calibration verification
• SOP Verification
• Operation Qualification tests

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Conti

• OQ protocols to be written and approved prior to
  completion. It includes following
• All relevant SOPs should be in place
• Temperature measurement report
• Humidity measurement report
• Differential pressure measurement report
• Air flow direction measurement report
• Room particle count measurement report
• All maintenance/ cleaning instructions available
• All O M staff to be trained to use and maintain
  the system.
• Sign off. (Compliance Certificate by Engineering
  Dept QA)

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Performance Qualification

• The purpose of PQ is to verify and document that
  an HVAC system provides acceptable control under
  Full Operational conditions.
• PQ should follow successful completion of IQ and
  OQ.
• PQ verifies that the critical parameters, as
  defined in the DQ are being achieved.

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Conti

• PQ Should include -
• Test to include a condition or set of conditions
  encompassing upper and lower operating limits.
• Tests should be conducted under in use,
  condition either or simulated as close as
  possible to the actual process

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Conti

• PQ is used to demonstrate consistent achievement
  of critical parameters over time. ( under
  manufacturing conditions)
• PQ and OQ tests are sometimes performed in
  conjunction with one another.
• Any changes to the HVAC system should be
  revalidated before proceeding to the PQ phase.

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Validation Parameters

• Air flow measurement
• Room air changes per hour.
• Filter Integrity Testing (HEPA Leak test)
• Pressure Differentials
• Particulate count measurement
• Recovery test
• Temperature and Relative Humidity
• Air Flow Pattern
• Microbial Count

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Conti

• A. PHYSICAL TESTS
• A1. NON-VIABLE PARTICLE COUNTS
• Equipment
• Optical Particle Counter (Discrete 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.
• Sample Volume
• 1 cubic ft
• Sample Time
• 1 Min

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Conti

• Frequency
• GMP compliance- Quarterly
• Sch M - 6 Monthly
• Acceptance criteria
• 1. Critical environments 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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Conti

• A2. PRESSURE DIFFERENTIALS
• Introduction
• 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.
• Equipment
• Electronic manometer (portable and easy to use),
• Incline manometer

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Conti

• Sample location
• Between adjacent areas connected either by a door
  or grille.
• Frequency of sampling
• Continuously by gauges / manometer recorded
  daily.

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Conti

• Acceptance Criteria
• gt 10 Pa between classified area adjacent area
  of lower classification
• gt 15 Pa between classified area unclassified
  area
• Action
• HEPA filter blockage
• Increase fan speed
• Increase air flow to specific area by altering
  dampers

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Conti

• A3. 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)
• No value may deviate from the mean by more than
  20

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Conti

• Air velocity exceeding the stated value may cause
  excessive air movement affect work zone
  protection.
• Air velocity below the limit may be insufficient
  to maintain critical work zone protection.
• Deviation indicates the blockade of filter
• Solution Alteration of fan speed or HEPA
  filter replacement

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Conti

• A4. 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
• Scan at 1 inch from filter surface.
• Make separate passes at peripheries.

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Conti

• 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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Conti

• A5. Temperature and Relative Humidity
• Use a sling psycrometer to measure the dry bulb
  and wet bulb temperature of the air.
• Check the wick of the sling psycrometer, it
  should be always in wet conditions in order to
  record correct wet bulb temperature.
• Sling the psycrometer in air for about a minutes
  time and record the dry bulb and wet bulb
  temperature.
• Check the wet bulb depression i.e. difference
  between dry bulb and wet bulb temperature.

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Conti

• Acceptance criteria
• Temperature NMT 27 degree centigrade
• Humidity NMT 55
• Frequency Daily

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Conti

• A6.Air change rate
• Measurement of the air supply volume and
  determination of the air change rate (ACR) is a
  measure of the frequency of air turnover in the
  clean room.
• This gives some idea as to how quickly
  contamination may be removed from the clean room
  provided there is acceptable mixing of air in the
  room.
• The ACR can be determined by measuring the mean
  air velocity at the supply HEPAs or grilles and
  calculating the air change rate based on the mean
  air supply volume.

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Conti

• Equipment Anemometer
• Sample locations
• At least four positions are tested
  across the filter or grille face to obtain
  the mean supply air velocity.
• Frequency of sampling
• Sch M - 6 Monthly
• GMP compliance Quarterly

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Conti

• A7. 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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Conti

• Sampling condition
• Sampling in the at rest condition may be
  continued at an agreed frequency to monitor
  baseline contamination levels
• The operational conditions and the activities
  being performed at the time of testing should be
  recorded
• Incubation condition
• Incubation of samples, inverted, at 20 25o C
  for at least 5 days is suitable for the growth of
  mould and fungi.
• Incubation of samples, inverted, at 30 - 350C for
  at least 2 days is suitable for the growth of
  bacteria.

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Conti

• Acceptance criteria for Airborne Bioburden test
• Critical Environment no more than 1
  CFU/m3, or 0.03 CFU/ft3(USP
  monograph)
• Acceptance criteria for Surface Bioburden test
• Critical Environment no more than 1
  CFU/12.9cm2, or 2 in2 (FDA Aseptic
  Processing Guidelines)

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References

• Supplementary guidelines on good manufacturing
  practices for HVAC systems for
  non-sterile pharmaceutical dosage forms. (WHO
  Technical Report- Series, No. 937), Annex
  2.(2006)
• Validation of pharmaceutical process, sterile
  product
• 2ndEdition, edited by Fredrick J. Carleton,
  James P. Agalloco, page no.240-256.

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Thank you