hvac system validation

Document Sample
hvac system validation Powered By Docstoc
					Department of Quality Assurance
  Maliba Pharmacy College
                                  1
   Introduction
   Validation of HVAC
   HVAC Qualification
   Validation master plan
   Design Qualification(DQ)
   Installation Qualification(IQ)
   Operational Qualification(OQ)
   Performance Qualification(PQ)
   Validation parameter
   References


                                     2
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



                                                             3
    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)

                                                                4
“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

                                                                 5
   Personnel procedures
   Adequate premises
   Use of closed production systems
   Adequate, validated cleaning procedures
   Appropriate levels of protection of product
   Correct air pressure cascade




                                                  6
   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

                                                7
                                Area 1



                                 Area 2   I
                                          M
              HVAC                        P
Impure air           Pure air             U
                                Area 3    R
                                          E

                                          A
                                Area 4    I
                                          R



10% Return
Air
    Exhaust
    air

                                              8
                                        HVAC
                                       components
            Exhaust Air Grille
                                    Silencer    Flow rate controller       Fan   Filter




                          Weather louvre           Control damper
                                                                           Heater
                                                                       +
                                  Humidifier
Prefilter                                                                    Terminal filter



                             Cooling       Secondary Filter   Production Room
                              coil
                   Heating     with
                   coil     droplet
                           separator

                                           Recirculated air

                                                                                               9
It includes:-

   Commissioning

   Qualification

   Maintenance




                    10
   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



                                                             11
    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

   O&M manuals, schematic drawings, protocols, reports




                                                              12
   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.




                                                               13
    Validation Master Plan
      QUALIFICATION
User Requirement Specification
     Design Qualification
   Installation Qualification
   Operation Qualification
  Performance Qualification
      Re- Qualification.
                                 14
   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

                                                                    15
   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

                                                                 16
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

                                                                    17
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

                                                            18
   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


                                                          19
Test procedure          Maximum time     Objective      Test Parameter
and key aspects         interval
Particle count test     6 months or 12   Verifies       Particle count
Readings and            months           cleanliness
positions               depending on
                        Class
Measure pressure        12 months        Absence of     Air pressure
difference                               cross-         difference
                                         contaminatio
                                         n
Measure supply and      12 months        Verify air     Airflow volume
return air, calculate                    change rates
air change rate
Velocity                12 months        Verify         Airflow velocity
measurement                              unidirectional
                                         airflow and or
                                         containment
                                         condition
                                                                           20
   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.




                                                              21
   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.


                                                                   22
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

                                                               23
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.


                                                                 24
   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.

                                                                  25
   Change Parts and Replacement Parts Verification

   Maintenance Procedures Verification

   Critical Systems Change Request Procedure verification

   Lubricants Verification




                                                             26
   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.


                                                                     27
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.


                                                                   28
   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.




                                                          29
   Testing Equipment Calibration Verification

   Instrumentation Calibration verification

   SOP Verification

   Operation Qualification tests




                                                 30
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)

                                                                    31
   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.




                                                                  32
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




                                                                 33
   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.


                                                             34
   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                             35
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


                                                                         36
   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)


                                                                 37
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




                                                                      38
o   Sample location
      Between adjacent areas connected either by a door or grille.


o Frequency of sampling
    Continuously by gauges / manometer & recorded daily.




                                                                      39
oAcceptance Criteria
  > 10 Pa between classified area & adjacent area of lower
      classification
  > 15 Pa between classified area & unclassified area
oAction
  HEPA filter blockage
  Increase fan speed
  Increase air flow to specific area by altering dampers




                                                              40
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 %

                                                                   41
   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




                                                            42
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.


                                                                   43
   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




                                                                   44
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 minute’s 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.


                                                                    45
   Acceptance criteria:
     Temperature : NMT 27 degree centigrade
     Humidity    : NMT 55 %

   Frequency : Daily




                                              46
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.

                                                                  47
   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




                                                                   48
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.


                                                                49
   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.


                                                                       50
   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)




                                                           51
   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.




                                                            52
53

				
DOCUMENT INFO
Shared By:
Categories:
Tags:
Stats:
views:469
posted:8/8/2012
language:English
pages:53