CleanroomTestingandCertification_inhouseGHPtraining

Theoretical HEPA Filter Collection EfficiencyHEPA Filter Mechanisms 0.3µm 99.999 99.99 99.97 99COLLECTION EFFICIENCY(%) 905010 PARTICLE DIAMETER (MICRONS) 0.1 1.0 10.0Copyright National AirFiltration Association 0.012006 Rev. 2

Typical Air Filtration PrinciplesMinimum particulate removal: 99.97% for particles 0.3 um mass median diameter RELATIVE EFFECT OF PARTICLE COLLECTION MECHANISMS 99 OVERALL EFFICIENCY 98 INTERCEPTION DIFFUSION 95COLLECTIONEFFICIENCY(%) 70 60 50 40 30 20Copyright National Air IMPACTION PARTICLE DIAMETER (MICRONS)Filtration Association 0.1 1.0 10.02006 Rev. 2 0.01

Most Penetrating Particle Size - MPPS• It is: – The most difficult particle for a filter to capture – The size where the filter efficiency is the lowest – Normally 0.3 m mass median or between 0.1 and 0.2 m count median• MPPS is a function of: – Media structure – Airflow velocity 53

Air Filtration Theory Particle Collection Mechanisms• Inertial Impaction : particle inertia causes it to leave flow stream lines and impact on fiber• Interception : particles with less mass stay with the air stream and impinge upon the fiber as they go around it• Diffusion : Brownian motion / diffusion due to molecular bombardment 54

HEPA Efficiency Chart HEPA Filters DO NOT filter out gasses and vapors. They only filter out particulates. 55

Efficiency vs Leak Testing• Classification efficiency testing – Tests the encapsulated filter with hot monodispersed DOP having a 0.3 m mass median diameter – Measures total penetration after total mixing down stream of the filter using a photometer – This is filter manufacturer’s test – Anytime you say efficiency, you must state a particle size• Leak testing – Tests the filter installation with poly dispersed aerosol – Measures local penetration (scanning) – Measure overall penetration (remote filter banks) – These are in situ (Field Test) 56

UPLA Filter Definition: IEST• A throwaway, extended medium, dry type filter in a rigid frame, having a minimum particle collection efficiency of 99.999% (that is, a maximum particle penetration of 0.001%) when tested in accordance with the methods of IEST-RP-CC-007 57

Higher Media Velocity Equals Lower Efficiency and Smaller MPPS50% flow 5899.99993%@ 0.23 mFull flow99.9994%@ 0.16 m

UPLA Filter Efficiency Testing IEST-RP-CC-007• Tested at Rated Flow• Determines Efficiency Rating• Polydispersed Cold DOP or Microspheres Used• Uses Discrete Particle Counter to Measure Penetration• Different than Leak Testing• Pressure Drop Across Filter 59

HEPA - Type C: IEST“ A filter that has been tested for overallpenetration in accordance with section 9.1.1and, in addition, has been leak tested inaccordance with IEST-RP-CC034. Theminimum filter efficiency of the encapsulatedfilter is 99.99% on 0.3 m mass mediandiameter particles (or with a count mediandiameter typically smaller than 0.2 m).” 60

What Do You Think? 61• What happens as the HEPA filter becomes loaded with particulates? A. It becomes less efficient B. It becomes more efficient.• Efficiency increases, and Resistance increases – Particulates stick to particles which are stuck to fibers providing more surface area for filtration while leaving less space between fibers for the flow of air. This increases both efficiency resistance to airflow – Filters are replaced when the resistance approaches the fan’s capacity to deliver the required airflow(Answer is A.)

Variety of HEPA Filters 62

Setting the Record Straight Regarding HEPA Filters• HEPA filters are sealed in both directions• May be used with airflow in either direction• Arrow represents the direction of test challenge• HEPA filters cannot be cleaned• Particles are collected throughout the depth of the delicate fiber structure of the media• Once the particles are captured within the media they cannot be removed 63

PTFE (PolyTetraFluoroEthylene)• An expected micro-porous membrane structure that appears fibrous under magnification.• Positively charged media provides enhanced removal properties for particles smaller than it’s pore structure.• Sub-micron particles must negotiate a ‘torturous’ path to penetrate the membrane. 64

SEM of Typical Membrane Media • Created microstructures in PTFE with structure consisting of nodes and fibrils created by membrane expansion. • Smaller particles are filtered efficiently by a combination of depth and surface filtration principles • MPPS is  0.06 m 65

Benefits of PTFE Synthetic Media• Virtually indestructible (durability)• Higher volumetric airflow rates• Lower differential operating pressure• ‘Non-shedding’ expanded fiber structure• High moisture resistance (hydrophobic)• Higher particulate loading efficiency• Resistant to chemical corrosion• Comparable thermal stability• Outlasts Boro-silicate glass media 66

Effective Services of a HEPA Filter• Collecting contaminants within the HEPA filter media causes it to increase in pressure drop as well as efficiency• Power required to move air through the filter also increases as particles are loaded• Prefilters extend the life of a HEPA filter by capturing larger contaminants, thus preventing surface loading• HEPA filters often remain in service until the fan can no longer deliver the required airflow volume due to increased resistance of the filter• There is no “Expiration Date” on HEPA filters 67

Effect of Moisture and Humidity on HEPA Filters• Should be used in non-condensing environments – Less than 100% relative humidity• Water droplets forming on the media may carry particles through the media – Condensation may leach away resins and binders that bond the glass fibers together• Glass media is inert – Mold can grow on collected particulate in the media under humid conditions 68

Airflow inCleanrooms 69

Primary Cleanroom Function• Reduce particle concentration – HEPA filtered air supply – Airflow patterns – Positive room pressure• Control particles generated in cleanroom – Non-shedding materials of construction – Proper gowning of personnel – Minimize particle generation sources 70

Particle Movement• Particles follow room air flow pattern – Air streams are particle highways• Gravity has little effect on small particles – Brownian motion keep particle airborne• Large particles fall quickly – Example: Throw pebbles into the air 71

Particle Setting Velocity **Particle Diameter, m Meters / sec 0.3 4.23E-06 0.5 1.00E-05 1 3.50E-05 5 7.77E-04 10 3.06E-03 20 1.20E-02 100 2.48E-01** Spherical particles with a specific gravity of 1.0 in still air at 20 C 72

Dilution to Reduce Concentration• Non-unidirectional flow cleanrooms• HEPA filtered air supply• Room air exchange rate often reported• Poor design may result in pockets where particles accumulate 73

Non-unidirectional Room 74

Room Air Changes / HourRoom Air Changes / hr = Total Air Volume (m3) x 60 min / hr Room Volume (m3)“The direct measurement of airflow volume is usuallypreferable to measurement of airflow velocity and is amore representative test to the final filter air supplyfor non-unidirectional airflow cleanrooms” (IEST RP-6) 75

Airflow Volume Measurement 76

ProblemA room is 4 m x 5 m x 3 m high ceilingsThe room has 3 supply filters with thefollowing airflow volumes: 1. 20 m3 / min 2. 22 m3 / min 3. 18 m3 / minWhat is the number of air changes per hour? 77

AnswerRAC / hr = ( 20 + 22 + 18) x 60 min / hr 4x5x3• 60 Room Air Changes per hour 78

Air Exchange Rate (% Filter Coverage) for Various Cleanliness Classes• No magic number• Particle concentration depends on: – Particle generation rate – Volume of dilution airflow – Ventilation Efficiency FactorParticle Conc = Particle Generation Rate x Ventilation Efficiency Total Airflow Volume 79

50% Ceiling CoveragePOOR LAYOUT BEST LAYOUT 80

Worst Ventilation Efficiency Layout for 50% Ceiling Coverage Return Return Return Return Return Return 81

Room Recovery Tests• For non-unidirectional flow rooms only• Identifies problem areas in design• Fill room with glycol droplets and use multiple particle counters to measure – Report time to see a 2 log reducing in aerosol concentration at all sampled locations• Spearman of Eli Lilly led US research• Consider using photometers 82

Flow Control of Particles• Unidirectional flow cleanrooms – Typically > 80% ceiling coverage of filter media or diffusion screen• Typically used for ISO 5 and cleaner rooms• Sweeps particles from generation source to room returns 83

84

Measure Air Velocity 85

Airflow Visualization Tests• Performed in critical areas (aseptic filling)• Use a neutral density visible aerosol – Water vapor has a short visible span – Low NVR (Non volatile residue) theatrical fog preferred• Look for up drafts and aspiration of particles from surrounding less clean area• Video tape for documentation – Caution with audio and activity visible in recording 86

Acceptable Velocity• FDA is no longer hardcore 0.45 m/s +/-20%• Show documented evidence of facility specific velocities based on airflow visualization• Some determine a performance envelope – Requires at least separate three tests • Minimum or lower limit • Operational set point • Maximum or high velocity limit 87

Typical Airflow Uniformity Specification• 0.45 m/s +/-20% – Compromise of 0.36 m/s or 0.45 m/s for first laminar flow cleanroom at Sandia – From “Non-Mandatory Appendix” of FEDERAL STANDARD 209B, 1973 – Semiconductor cleanrooms design for 0.30-0.33 m/s• No tolerance for outliers• Does not define distance or position• Normal population distribution 88

Effects of Cleanroom Width• Semiconductor cleanrooms use open floor for return air – No restriction on size of room – > 75,000 FFU’s 1.2 m x 1.2 m = 112,000 m2 – Pharmaceutical cleanroom have sidewall returns – Cleans ability issues with raised floor• Distance between returns effects airflow patterns 89

Ducted Terminal HEPA Filter• Filter media is sealed to the inside of the metal housing• No center port for damper adjustments 90

Zero Leak Cleanroom Design• Supply duct with dampers 91• Flex duct to ducted terminal filters – Walkable filters (100 kg man) construction• ePTFE filter media – Very durable / cannot damage media• Cleanroom is positive pressure to all external areas• No gels or seals or center ports that may leak• 10 mm ID tubing to measure upstream challenge concentration

Negative Pressure Plenum Design 92

Positive Pressure Plenum Design 93

References• Institute of Environmental Science & Technology – 5005 Newport Drive, Suite 506 • Rolling Meadows, IL 60008-3841 • 847-255-1561 www.iest.org• National Environmental Balancing Bureau – 8575 Grovemont Circle – Gaithersburg, MD 20877-4121 – 301-977-3698 94

CleanroomStandards : Brief History of Cleanrooms 95

96

97

Before Clean Rooms• 1950’s – USA cold war first to control contamination – For missile guidance system assembly – White rooms and gray rooms• 1957• Invention of the discrete particle counter – 0.5 m and 5 m size with very low sample rate 98

First Clean Room• 1961 – Willis Whitfield of Sandia National Labs used HEPA filters in first horizontal flow cleanroom• 1963 – Federal Standard 209 released • Defined three cleanliness levels – Class 100, Class 10,000 and Class 100,000 99

100