1. “Technology Requirements in Facility Designing (HVAC System Design)”
2/10/2018

2. Points Covered Area Classifications (USP, EU, ISO)
Air Handling Systems:
. AHU,
. Ducting,
. Filters,
. Terminations, etc..
Building Management System
Validation of HVAC Systems
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3. Part 1
Area Classification
2/10/2018

4. Too Many Cleanroom Standards.... in the past??
Country
Standard Code
Year
Description
Australia
AS 1386
1989
Cleanrooms and Clean work stations
France
AFNOR X44101
1981
Definition of Cleanroom levels
Germany
VDI 2083:3
1993
Contamination control measuring technique clean air room
Holland
VCNN 1
1992
Dust and microorganism classification of air
Japan
JIS-B-9920
Measuring methods for airborne particles in Cleanroom and evaluating methods etc.
Russia
Gost-R 50766
1995
Cleanroom classification, General requirements UK
BS 5295
Environmental cleanliness in enclosed spaces US
FS 209 E
Airborne particulate cleanliness classes in Cleanroom and clean zones
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5. Cleanroom Standards Depicted In Recent Guidelines
FDA Guidance for Industry (Sterile Drug Products) – September, 2004
EU Guide to GMP – Revision to Annex 1 – September, 2003
WHO Good Manufacturing Practices for Sterile Pharmaceutical Products – 36th Report, Geneva, World Health Organization, 2002, Annex 6 (WHO Technical Report Series, No. 902)
ISO Standards First Edition
2/10/2018

6. ISO Standards – A Step Towards Harmonization!
ISO Document
Title
ISO –
Classification of Air Cleanliness
ISO –
Cleanroom testing for Compliance
ISO –
Bio-contamination Control of Surfaces
ISO –
Cleanroom Design & Construction
ISO –
Cleanroom Operations
ISO –
Terms, Definitions & Units
ISO –
Mini-environments & Isolators
ISO –
Bio-contamination Control General Principles
ISO –
Evaluation & Interpretation of Bio-contamination Data
ISO – – 3
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7. Area Classification As In Different Guidelines
Non-viable Particle Count
..\Area Classification Chart_Nonviable.xls
Viable Particle Count
..\Area Classification Chart_Microbiological.xls
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8. Area Classification Comparison
Comparison of different airborne particulate classification systems for clean areas
ISO / TC : International Organization for Standardization Technical Committee;
EEC : European Commission.
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9. Four Grades Of Clean Areas For Aseptic Applications
Type of Operation
Examples of operations A
Terminally Sterilized
Filling of products, when unusually at risk B
Background Environment for Grade A C
Preparation of solutions, when unusually at risk.
Filling of products D
Preparation of solutions and components for subsequent filling
Aseptic Preparation
Aseptic preparation and filling
Preparation of solutions to be filtered.
Handling of components after washing
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10. Still the confusion persists!
Which standards are valid, when and where?
Cleanroom classification, filter classification and testing methods / standards differ
Standards
Cleanroom Classifications and
particle counting in the room
Filter Classes
Testing filters method
US - FDA
US FED STD-209E
IEST-RP-CC001.3
IEST-RP-CC006.2
IEST-RP-CC021.1
IEST-RP-CC034.1
EU / Europe
ISO 14644
EN 1822
Requirements set by ISO are stricter than the requirements on the American (FDA) market
In principle, ISO also sets the requirements for the American market regarding Cleanroom Classifications and Particulate Testing
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11. Part 2
Air Handling Systems
AHU
Ducting
Filters
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12. Air Handling Unit General Layout:..\AHU Schematic Drawing.xls
Basic Components of an AHU:
Fresh Air Intake Unit
Fresh Air Filter
Volume Control Dampers
Pre-Filters
Correct pre-filters protect systems & prolong life of final filters
Blower Assembly
Ensure that the blower capacity is adequate to give you required air volume
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13. Air Handling Unit Basic Components of an AHU (continued):
Coil Assembly
Chilled Water Coil, Brine Coil, Hot Water Coil
Coils should be fixed in such a way that there is enough clearance to compensate for expansion/contraction with rise/fall in fluid temperatures
Drain Pan
Eliminate the potential for standing water in coil drain pans by keeping:
a generous slope to a drain equipped with a trap and a trap primer.
traps deep enough to ensure that water will not be drawn back into the pan.
an air gap between the pipe end for inspection.
sufficient space for continuously sloped drain piping, avoiding high pockets.
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14. Air Handling Unit
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15. Air Handling Unit Basic Components of an AHU (continued):
Secondary Filtration
Typically, semi-HEPA filters (rating 0.3 micron, but efficiency less than 90%) are used
Inspection Doors
All doors in the AHU shall have perfect alignment with the door frames so that there is no space for external air to leak into the AHU through them and thereby cause contamination
Piping
Hydro-testing must be done
Check whether instruments are provided wherever needed & their calibration status
Check pipe insulation
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16. Ducting Some Basics & Essentials of Ducting System: MOC
Galvanized Iron (GI)
Pre-insulated Aluminium sandwiched panels
Check for proper path & routing as per the approved drawing
Provide access hatches for inspection & cleaning
Provide access hatches and prominent identification signs for inspection and cleaning of ducts
Post a log at each such hatch, identifying dates and observations of inspections and cleanings
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17. Ducting Some Basics & Essentials of Ducting System (continued):
Provide Access to Inject Challenge Aerosol for Leak Testing of HEPA filters
Duct Leakage Testing using Titanium Dioxide
All dampers should have easy & smooth functioning & shall clearly indicate direction: ‘open’ or ‘close’
Connection between ducting & AHU should be such that there is no leakage.
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18. Filters
Now we come to a very critical component of the Air Handling System – FILTERS!!!!
2/10/2018

19. Effective Uni-directional Flow with the help of HEPA filters
Criteria for selection
Type of Application/Pore Rating
Types of Filters
HEPA Filters
MOC of Media: Micro fiberglass
MOC of Separators: Aluminum/Craft Paper/ Separator less/ Minipleat
Type of adhesive: Polyurethane adhesive
Pre-Filter
MOC of Media : Non-woven synthetics / washable
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20. Filters Filter Testing – 2 phases At Manufacturer’s site
Clean Absolute Filter Media
Filters
Filter Testing – 2 phases
At Manufacturer’s site
- Determining Most Penetrating Particle Size (MPPS)
- Leak Test
- Overall Efficiency
At Site after installation
Dust on the inlet side of a used Absolute Media
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21. Filters
Filter
Specification
Chart
The Installed HEPA Filter
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22. New Standards from CEN TC 195 - Air Filtration 1
Filters
New Standards from CEN TC Air Filtration 1
HEPA & ULPA Filters
􀂾EN Requirements for testing & marking
􀂾EN Aerosol Production
􀂾EN Testing Planar Filter Medium
􀂾EN Scan testing the filter element
􀂾EN Testing the efficiency of the filter
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23. Filters
HEPA & ULPA Filters
EN Factory Test
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24. EN 1822 compared with Euro vent 4/4 NaCl
Filters
EN 1822 compared with Euro vent 4/4 NaCl
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25. 2/10/2018

26. In-situ Testing (General)
Filters
In-situ Testing (General)
Select test method, aerosol, and acceptance criteria
Determine challenge up-stream
Scan test final filter face for leaks
Determine acceptance or rejection
Carry out remedial work. Agree before repairing filters
e.g., BS 5295:1989 does not allow repair, but the new ISO EN to 3 family of standards will subject to manufacturer’s approved method
Re-test
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27. Building Management System
Part 3
Building Management System
2/10/2018

28. Part 4
Validation of
HVAC System
2/10/2018

29. For < ISO Class 5 – Biannually For >ISO Class 5 - Annually
VALIDATION
The HVAC system must be Validated for the following tests according to approved protocols and procedures:
-   Filter integrity test (DOP test)
-   Air changes test
-   Air flow pattern
-   Particle count test
- Temperature, Relative Humidity and Differential Pressure test
Sr. No.
Tests
Frequency 1.
Air changes
Biannually 2.
DOP & leakage tests 3.
Non viable Particle count
For < ISO Class 5 – Biannually
For >ISO Class 5 - Annually
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30. VALIDATION Alternative to DOP Filter integrity test (DOP test)
Thermally Generated DOP: an aerosol generated by quenching (condensing) vapor that has been evaporated from liquid dioctyl phthalate by heat. The aerosol mean particle diameter is between 0.2 and 0.4 m with a geometric standard deviation of 1.3.
Air Generated DOP: an aerosol generated by blowing air through liquid dioctyl phthalate at room temperature. When generated with a Laskin-type nozzle the approximate light scattering mean droplet size distribution is as follows:
99+% less than 3.0 m
50+% less than 0.7 m
10+% less than 0.4 m
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31. VALIDATION Filter integrity test (DOP test)
Aerosol Photometer: a light scattering mass concentration indicator. Instruments of this type with threshold sensitivity of at least 10-3 mg/liter for 0.3 m–diameter DOP particles, capable of measuring concentration in the range of 80 to 120 mg/liter, and having a sample flow rate of 1 cfm+10% of air are suitable for leak testing.
Linear readout photometer: a photometer having a linear reading scale graduated from 0 to 100 with a range switch to vary the full scale response in multiples of 10, through at least four decades of response. The instrument shall be capable of indicating 0.001% of a concentration that registers 100% on the highest range.
Logarithmic read out photometer: a photometer having a logarithmic response scale graduated 0, 1, 2, 3, 4, 5 covering the full range of instrument sensitivity without range switches. For this type of photometer, “one scale division” means the first intermediate scale division following the zero.
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32. VALIDATION
Filter integrity test (DOP test)
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33. VALIDATION
Filter integrity test (DOP test)
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34. VALIDATION Air Changes Per Hour ACPH design based on: Room size
Nature of operation
Number of personnel present
Requirement : NLT 20 Air changes / hour
If the number of air changes is more than 20 per hour and HEPA filters and return air risers are installed at strategic locations, then throughout the room mixing of air shall take place and it will not be difficult to get Class B, C and D conditions
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35. VALIDATION Air Changes Per Hour
CFM of air supplied = Velocity x Area of air discharge unit
ACPH = (CFM x 60) / V
where, ACPH = Number of Air changes/hour
CFM = Total supply air flow to space (cu. ft./ min.)
V = Space Volume (cu. ft.)
Note: Velocity of air must be determined using
Calibrated Hot-wire Anemometer
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36. VALIDATION UDF (Uni-direction Flow) Modules
Class 100 is only obtained under the UDF-module (Laminar Flow Unit); the surrounding room must be Class 1000 with a number of air changes set at minimum 20 per hour
Only UDF areas can exhibit Laminarity of
Air Flow
Laminar / Uni-directional
with Perforated Floor
(Low Air Velocity is required)
Perforated Floor Air Riser
Laminar / Uni-directional
with return air riser
(High Air Velocity is required)
Air Riser on Side Wall OR
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37. VALIDATION Turbulent Air flow Laminar / Uni-directional
Results in dilution of dirty air
Laminar / Uni-directional
with return air riser
(High Air Velocity is required)
Air Riser on Side Wall
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38. VALIDATION Air Flow Patterns
Laminarity of Air Flow must be documented by taking Video graph under dynamic conditions
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39. VALIDATION Air Flow Patterns
Laminarity of Air Flow must be documented by taking Video graph under dynamic conditions
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40. VALIDATION Particle Count Test
Optical Particle Counter : a light scattering instrument with display or recording means to count and size discrete particles in air, as defined by the American Society for Testing Materials Standard (ASTM) F50-69
Instruments of this type having a sampling flow rate of at least 0.1 cfm, (and preferably 1.0 cfm), and with size discrimination capability to detect total particle concentrations >0.5 m size and >5.0 m size are suitable for leak testing.
Instrument of this type having a sampling flow rate of at least cfm and with size discrimination capability are suitable for particle counting.
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41. VALIDATION Particle Count Test
3 test states “As-built”, “At rest”, “In Operation”
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42. VALIDATION Recovery (clean up) period : Around
Particle Count Test
Recovery (clean up) period : Around
15 minutes after completion of operation
Major Particle Counter Manufacturers
Lighthouse
Met One
Climet
IQAi
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43. VALIDATION
Other Instruments/Equipment used for Validation
Air Pressure Gauge: an inclined manometer or magehelic gauge capable of measuring 0.01 to 2.0 in water gauge static pressure.
Wet/Dry Bulb Thermometers: instruments used to measure moisture in air so that acceptable dew point can be found.
Smoke Generator: ventilation smoke tube pencil for generating visible smoke filament for air tracer studies.
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44. 2/10/2018

45. Building Management System
BMS has evolved over many years alongside HVAC system
It has adopted “control system architectures & philosophies” to satisfy the need for advanced automation
Deployed in Healthcare companies with modern day solutions based on standard software & hardware design
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46. Building Management System
BMS may cover in its scope a range of computerized systems:
PLCs Programmable Logic Controllers
SCADA Supervisory Control & Data Acquisition Systems
DCS Distributed Control System
Outstations/Controllers &Instrumentation
2/10/2018

47. BMS - Benefits BMS brings several benefits:
Effective control of building related processes & equipment
Real time visibility of BMS performance
Early warning of process deviations
Predictive maintenance planning
Centralized and/or remote control
Optimization of utility costs
Secure management &storage of process & equipment performance data
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48. BMS – Regulatory Environment
Used to control, record, monitor & alarm a variety of processes of varying risks to product
Ability to readily detect product attributes downstream of the process
BMS often cover both regulated & non-regulated processes, concurrently
Can be sometimes difficult & expensive to validate
2/10/2018

49. BMS Validation - Impact Assessment
GEP Only
Parking Facilities
No Impact
Elevators
Office Air conditioning
The design & use of these systems affect their impact!
Chilled Water
Indirect Impact?
Building Management System
Production Air Conditioning
Building Management System
Autoclave
Purified Water System
Direct Impact
BMS Validation - Impact Assessment

50. BMS – Validation Criteria
The criticality of BMS is determined through a risk assessment that considers consequence on product attributes of failure of parameters
This is dictated by the impact of process parameters being controlled on product purity, safety, quality & efficacy, and not the functionality of BMS itself
Validatability of BMS is determined by the direct or indirect impact on the product’s quality, purity, safety etc..
Some of the citations indicate a lack of validation /qualification of controls
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51. 2/10/2018

52. BMS Decision Tree BMS Decision Tree.xls
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53. BMS – Validation
The MHRA inspection findings reiterate the importance of monitoring critical (environmental) parameters while also demonstrating the importance of sterility assurance & cross-contamination risks
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54. BMS BMS Functional Model Process Reporting Control Parameter
Management
Calibration
Management
Data
Logging
Alarm &
Event Logging
Control &
Processing
Monitoring
Process
Measurements/
Outputs
2/10/2018