PhEn-602 Pharmaceutical Facility Design J. Manfredi Notes 9A PhEn-602 J. Manfredi 1
Primary & Secondary HVAC units Primary Primary air handling unit arrangement: One unit is responsible for all of the airflow in the space. Primary-Secondary air handling arrangement: Secondary units provide for majority of airflow. Size of primary air handler is reduced. PhEn-602 J. Manfredi 2
Air Handling System Arrangement Primary air handler provides necessary cooling and heating of air Recirculating air handling units near the clean room provide for the necessary airflow For Class 100,000 and 10,000 spaces, typically a single unit is used. For Class 100 areas, usually use a primary- secondary air handling arrangement. PhEn-602 J. Manfredi 3
Sample Layout # 1 One One single primary air handler to serve the Class 10,000 space No secondary (recirculation) units PhEn-602 J. Manfredi 4
Single primary air handler PhEn-602 J. Manfredi 5
Sample Layout # 2 Mixed Mixed Use one primary air handler to serve both Class 10,000 and Class 100 Spaces One One secondary air handler (recirculation unit) to provide the high volume of flow to the Class 100 room. PhEn-602 J. Manfredi 6
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AIRHANDLING UNIT Primary air handler - relatively small Example of secondary air handlers Return airflow in green Return Airwall Class 100 Region Class 100 Filling Room 90% of room air is recirculated through the secondary airhandlers (VLFM s) PhEn-602 J. Manfredi 8
Other concerns.. Other factors that can affect unidirectional flow clean rooms Thermal Thermal currents: Thermal airflows can act against unidirectional flows (e.g. glassware oven after hot glass is unloaded) Airflow Airflow shading: Dead zone created by obstacle in the way of the unidirectional flow pattern PhEn-602 J. Manfredi 9
Regarding returns from clean rooms: For Class 100,000: Ceiling returns are typically used. For Class 100 and Class 10,000: Low return walls are used. PhEn-602 J. Manfredi 10
Space Pressurization and Control PhEn-602 J. Manfredi 11
PART 211-- --CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS-- Subpart C--Buildings and Facilities Sec. 211.42 Design and construction features. (10) Aseptic processing, which includes as appropriate: (ii) Temperature and humidity controls; (iv) A system for monitoring environmental conditions; Sec. 211.46 Ventilation, air filtration, air heating and cooling. (a) Adequate ventilation shall be provided. (b) Equipment for adequate control over air pressure, microorganisms, dust, humidity, and temperature shall be provided when appropriate for the manufacture, processing, packing, or holding of a drug product. PhEn-602 J. Manfredi 12
PART 211-- --CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS-- Sec. 211.46 Ventilation, air filtration, air heating and cooling (cont). (c) Air filtration systems, including prefilters and particulate matter air filters, shall be used when appropriate on air supplies to production areas. If air is recirculated to production areas, measures shall be taken to control recirculation of dust from production. In areas where air contamination occurs during production, there shall be adequate exhaust systems or other systems adequate to control contaminants. (d) Air-handling systems for the manufacture, processing, and packing of penicillin shall be completely separate from those for other drug products for human use. PhEn-602 J. Manfredi 13
Why is pressurization important? The only way to assure space to space contamination control Examples of applications Sterile or aseptic manufacturing Solids manufacturing Animal holding areas Chemical and Biology Laboratories (NFPA 45) Isolation & Operating Rooms (CDC Guidelines) Semiconductor manufacturing Painting automobiles (or anything) PhEn-602 J. Manfredi 14
How does pressurization control the movement of particles? The jet velocity protects the space, not the pressure!! Pressure, is a measure of jet velocity Pressure and velocity are inter-related related PhEn-602 J. Manfredi 15
Pressure Relationships RULE OF THUMB- 100 FPM Velocity develops ~0.001 wc PhEn-602 J. Manfredi 16
Effect of Volumetric Balance on Pressurization PhEn-602 J. Manfredi 17
What Factors Affect Ability to Pressurize How porous the room is; how large or small the crack area is Space around door frames Lights Piping penetrations Ceiling tiles Windows What volume of pressurizing air is available; not all air is pressurizing air Habits of staff; do they keep doors closed Maintenance of equipment PhEn-602 J. Manfredi 18
Pressure Levels Units of measure IP- inches of water column (visualize) Metric- Pascals PA Typical Pressure Levels Class 1 or Class 10 Semiconductor clean rooms; greater than 0.25 wc Pharmaceutical: -0.1 to +0.25; typically 0.05 or 0.03 increments between spaces Laboratories, animal spaces, and isolation rooms; 0.01 to 0.005 inches, space to corridor PhEn-602 J. Manfredi 19
Sterile Mfg. Example Arrows are air flow direction Pressures are gradients between spaces DP indicates monitored pressures PhEn-602 J. Manfredi 20
Differential Pressure Transmitter Selection Parameters Measurement Range Signal Output Accuracy in % Full Scale Stability & Drift Identify your needs Target pressure Accuracy as % of reading PhEn-602 J. Manfredi 21
Referencing Pressure Instruments PhEn-602 J. Manfredi 22
Control Terms Input Devices Output Devices Controllers Open Loop Control Closed Loop Control On/Off Control Continuous Control Control Terms Gain PID (Proportional, Integral, Derivative) PhEn-602 J. Manfredi 23
Typical Clean Room System HVAC PhEn-602 J. Manfredi 24
Pressure Control Methods PhEn-602 J. Manfredi 25
Additional HVAC Facets Finish discussion on calculating load across cooling coil CFM calculation Dehumidification Desiccant vs. Refrigerant-based dehumidification PhEn-602 J. Manfredi 26
Review: Total cooling load across coil includes sensible and moisture load h = h m h o h m = enthalpy of mixed air h o = enthalpy of air leaving coil Q T = 4.5 x CFM x Δh PhEn-602 J. Manfredi 27
Review: Cooling load across coil Total load across the coil is the sum of the sensible load and the latent load. Q T =Q s +Q L PhEn-602 J. Manfredi 28
Review: Sensible cooling load calculation Qs= AF x CFM x ΔT (AF = Air Factor: equal to 1.08) Qs = 1.08 (CFM) ΔT ΔT = temperature difference of air, in degrees F Qs - in Btu/hr PhEn-602 J. Manfredi 29
Review: Latent cooling load calculation If moisture level is given in grains of water per lb of dry air: Q L = 0.69 CFM ΔGrains ΔW = Moisture difference: moisture entering coil, minus moisture leaving the coil, in grains of moisture/lb of dry air Q L - in Btu/hr Most common to work in grains of moisture per lb of dry air Note: 7,000 grains per lb. (4840/7,000 = 0.69) PhEn-602 J. Manfredi 30
Review: Sensible heat ratio (SHR) Ratio of sensible load divided by the total load PhEn-602 J. Manfredi 31
Calculating required CFM for cooling a space When sensible load, supply air temperature and room temperature are known CFM = Q s 1.08 T Where ΔT = T rm -T sa = Temperature difference between room and supply air from air handler PhEn-602 J. Manfredi 32
Calculating required CFM to the space If supply air temperature is known: First find the required supply air temperature needed to meet the required internal sensible and latent heat gains 1. Plot room space conditions 2. Calculate SHR 3. Draw a line from the SHR mark through the standard space condition point ( SHR line ) 4. Draw a line that goes through the room space condition which is parallel to the SHR line 5. Read the temperature where this line meets the saturation line This is the best supply air temperature that would simultaneously satisfy the sensible and latent heat gains in the space. 6. Solve for CFM by using: CFM = PhEn-602 J. Manfredi 33 Q s 1.08 T
Pyschrometric Sample Problem A pharmaceutical company wishes to construct a manufacturing space which will require an HVAC system that functions within the following parameters: Space drybulb temperature = 70 F Space relative humidity = 50% Internal sensible load (Q s ) = 88,000 BTU/hour Internal latent load (Q L ) = 12,000 BTU/hour Minimum outside air flow = 400 CFM Design outdoor air drybuib temperature = 94 F Design outdoor air wetbulb temperature = 74 F Problem 1. Calculate the required supply airflow and temperature 2. Calculate the cooling coil load to provide this supply air using mixed air 3. Calculate the cooling coil load to provide this supply air using 100% outside air PhEn-602 J. Manfredi 34
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Calculate CFM Qs = (1.08) (CFM) (ΔT)( 88,000 88,000 = (1.08) (CFM) (ΔT)( 88,000 88,000 = (1.08) (CFM) (70( 70-48.79) 88,000 88,000 = (1.08) (CFM) (21.21)( 88,000 88,000 = (22.91) (CFM) CFM CFM = 3841 3845 PhEn-602 J. Manfredi 36
Mixed air entering the coil Mixed-air airflow (CFM) is sum of outside-air (CFM) and return-air (CFM) Weighted average of the dry-bulb temperature of outside-air and return-air CFM ma x T ma = CFM oa x T oa + CFM ra x T ra PhEn-602 J. Manfredi 37
Calculate Dry Bulb Temperature CFM ma x T ma = CFM oa x T oa + CFM ra x T ra 3845 x T ma = 400 x 94 + 3445 x 70 3845 T ma = 278,750 T ma = 72.50 DB PhEn-602 J. Manfredi 38
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Calculating the Cooling Load Across a Coil Q T = 4.5 x CFM x Δh Where Δh = h m h o (enthalpy of air entering the coil minus enthalpy of air leaving the coil in btu/lb) H m : Enthalpy of mixed air entering the cooling coil in btu/lb H o : Enthalpy of air leaving the cooling coil in btu/lb Q T : in btu/hr PhEn-602 J. Manfredi 41
Cooling Coil Load w/ma Q T = 4.5 x CFM x Δh Q T = 4.5 x 3845 x h m h o Q T = (17,302.5)(26.5 19.5) h m @ 72.5 DB & 60.49 WB h o @ 48.79 DB & 48.5 WB Q T = 121,118 BTU or 10.09 Tons PhEn-602 J. Manfredi 42
Cooling Coil Load w/100% OA Q T = 4.5 x CFM x Δh Q T = 4.5 x 3845 x h m h o Q T = (17,302.5)(37.5 19.5) h m @ 94 DB & 74 WB h o @ 48.79 DB & 48.5 WB Q T = 311,445 BTU or 25.95 Tons PhEn-602 J. Manfredi 43
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HEPA FILTER SUSPENDED FROM CEILING GRID WITH GEL SEAL PhEn-602 J. Manfredi 45
Plan View of Clean Room 22 HEPA FILTERS. 2FT x 4FT EACH PhEn-602 J. Manfredi 46
HVAC Design Process Understand the process served Determine and establish the design criteria for each room served Evaluate/establish system Select systems and components PhEn-602 J. Manfredi 47
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HVAC System Components Air handling unit Ductwork Dampers Duct-mounted heating coils Reheat coils Airflow stations Duct-mounted humidifiers PhEn-602 J. Manfredi 49
HVAC System Components Instruments and controls Diffusers Exhaust fans Return air fans - Inline with duct Secondary recirculating fan systems Smoke detectors PhEn-602 J. Manfredi 50
HVAC System Air Handling Unit: Fans to deliver the air. Some have a return fan as well as a supply fan Filter sections to filter the air Contains heating and cooling coils to heat or cool the air Cooling coil also dehumidifies since it removes moisture from the air Heating coil at unit preheats the air to prevent freezing downstream components, such as cooling coil Dampers which control the amount of air brought in from outside or from the return air stream, or to adjust the amount of air that is directed toward the cooling coil Mixing box with dampers PhEn-602 J. Manfredi 51
Fans Forward-curved (Housed) Backward-curved (Housed) Airfoil blade (Housed) Airfoil blade (Plenum) Vane axial Q-Fan (Duct) PhEn-602 J. Manfredi 52
Air Handler Unit Size Based on CFM CFM through the unit is based on the amount of air needed to supply the clean room, which in turn is based on required air change rate. Air change rate is a function of: Required flow to address the particulate gain in the space Required flow to adequately cool the space (i.e. address the heat gain) Required recovery time PhEn-602 J. Manfredi 53
Air Handler Unit Size Heating and cooling coil size is also based on the heating and cooling load of the space and amount of air through the unit. Cooling coils size must be carefully considered face velocity across the coil must be kept low to prevent moisture carryover. For clean rooms, air handling unit size is affected more by the need for keeping particulates low, than it is for cooling and heating Cooling and heating loads are often relatively low compared to the amount of air that needs to be moved for other purposes PhEn-602 J. Manfredi 54
Air Handling Unit Unit can be constant volume or variable volume Variable volume units have a variable frequency drive that adjusts motor speed to the desired volume (CFM) or duct static pressure (or VAV box) Simpler way of controlling volume through use of vortex damper at inlet to supply fan (less energy efficient since motor and fan speed remains high at low-flow periods). PhEn-602 J. Manfredi 55
Ductwork Sheet metal distribution system Typically galvanized steel (Can be SS) Round or rectangular Different construction types depending on system pressure Low-pressure, Medium pressure and Highpressure duct systems, measured in inches of water static pressure Joint construction is critical Leakage is a major design concern PhEn-602 J. Manfredi 56
Ductwork Typical Spec. is for 1% leakage limit Very tight systems required Leakage tested by pressurizing the duct and checking the pressure drop across an orifice Based on DP across orifice, can determine the flowrate which represents the leakage amount Divide by total flow through unit to obtain percent leakage PhEn-602 J. Manfredi 57
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Ductwork Various methods of duct construction, possibly based on pressure in duct PhEn-602 J. Manfredi 59
Levels of Filtration (AHU) Filters: Reduce particulate load in the space. Protects cooling and heating coils. Extends life of HEPA filters in system Helps maintain cleanliness of ductwork and systems Typically two or three levels of filtration at the air handling unit Initial: Prefilters. 20-30 % Intermediate filters: 80-90 % Intermediate filter is typically bag filter type, with efficiency of about 50% against the 0.5 micron particle). PhEn-602 J. Manfredi 60
Levels of Filtration (AHU) Prefilter: 20 30 % Bag Filter: 90 95% HEPA Filter: 99.97% Prefilter Bag Filter HEPA Filter PhEn-602 J. Manfredi 61
Filter Section Flat 2, 4, or 2 /4 combination Angled 2 and 4 Bag Cartridge HEPA Filter mixing box module PhEn-602 J. Manfredi 62
Levels of Filtration (AHU) Filter efficiencies are staged from low to high as you approach the HEPA section Can feed directly to terminal HEPA filters in the clean room ceiling. Feeding the terminal HEPA s directly, can result in premature filter loading and eventually to filter blinding Can lead to unacceptable pressure reversal in the space. Can have a set of HEPA s in the air handling unit itself as the third level of filtration. May be preferred PhEn-602 J. Manfredi 63
Supply = Return Air + Fresh Air Intake Aseptic Area Filter Arrangement with Two HEPA s in series FRESH AIR AIRHANDLING UNIT HEPA Filter at Airhandler Level Supply duct Return Fan Return Duct Terminal HEPA Filter Return Airwall Class 10,000 Clean Room PhEn-602 J. Manfredi 64
TYPICAL AIRHANDLING SYSTEM - SINGLE HEPA FILTER ARRANGEMENT FRESH AIR AIRHANDLING UNIT Supply duct Return Fan Return Duct Terminal HEPA Filter Return Airwall Class 10,000 Clean Room PhEn-602 J. Manfredi 65
Differential Pressure SUPPLY Blinding 800 cfm 600 cfm HEPA 1 HEPA 2 EXTRACT 750 CFM ASEPTIC ROOM 1 ASEPTIC ROOM 2 EXTRACT 650 CFM CORRECT AIRFLOW DIRECTION PhEn-602 J. Manfredi 66
Example showing reduction in particulate levels - Aseptic area filtration arrangement PhEn-602 J. Manfredi 67
Cooling Coils Types: Chilled water Tonnage vs chilled water flow rate Direct expansion Refrigerant in coil PhEn-602 J. Manfredi 68
Cooling Coils 1/2 1/2 inch and 5/8 inch coils with maximized face areas Removable from the side Cleanable drain pans PhEn-602 J. Manfredi 69
Need for Humidification Product Product requirements hygroscopic materials People People comfort Organism growth control Static Static electricity Requirements for GMP compliance Must be controlled PhEn-602 J. Manfredi 70
Air Conditioning Processes Humidifying Humidifying and Cooling Heating and Humidifying Sensible Cooling Sensible Heating Dehumidifying with Cooling Dehumidifying with Desiccants Dehumidifying PhEn-602 J. Manfredi 71
Humidifiers Types/methods: Steam Industrial steam Pure Pure steam (preferred for pharmaceutical applications Water City City water (tap water) Softened Softened water Deionized water Water Water for Injection PhEn-602 J. Manfredi 72