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Whitepaper

Cross-Contamination
Protection in HVAC

INDUSTRY INSIGHTS

Norman A. Goldschmidt
Principal, Engineering

September 30, 2011

www.geieng.com

facilities. All information contained herein is copyrighted and cannot be reproduced without permission. technology.INDUSTRY INSIGHTS Genesis Engineers periodically publishes white papers and reports about topics of special interest to the industries we serve. energy management. For academic uses. Copyright© Genesis Engineers 2011 . 2 . our leaders share their perspectives to help both clients and the public at large make high value decisions by having the best available information. please contact us. manufacturing and building systems of every type.All rights reserved .Do not reproduce without written permission. As veteran advisors for major corporate infrastructure.

by employing a mix of well defined cleanroom testing. this is generally unsatisfactory as it provides only a rough estimate without the level of assurance desired for these critical calculations. the reduction in airborne contaminant in the HVAC airstream (due to filtration) and comparing this reduced contaminant mass to the mass of the potentially contaminated product.with rigor. it is possible to determine the potential concentration per unit dose. By establishing the mass of airborne “contaminant” product. 3 . the mass of a product that could contaminate another product via the HVAC may assessed. Assuming that the risk potential of the products being processed has been determined.Whitepaper Cross-Contamination Protection in HVAC Introduction In order to comply with widely established GMP regulations requiring “minimizing the risk of contamination caused by recirculation or re-entry of untreated or insufficiently treated air…” An evaluation of potential for cross-contamination via HVAC should be part of the risk assessment in multi-product facilities. it is possible to perform a quantitative assessment of the cross contamination protection. Industrial Hygiene and filter classification techniques.Do not reproduce without written permission.All rights reserved . two HEPA filters in series within an air recirculation system (on supply and/or return) can reduce the mass of product in an airstream by an acceptable amount. Copyright© Genesis Engineers 2011 . However. or potential. But this approach is certainly not the only way to achieve an acceptable reduction in airborne contamination. and that the unit operations and engineering controls have been chosen. As outlined in the ISPE Risk MAPP guide. Employing the filter efficiency rating (ASHRAE Efficiency %) as an adjustment to the airborne mass of particulate has been proposed as a method to achieve this evaluation. of an HVAC system .

afforded by components of the HVAC system. Where empirical data is not available a set of assumptions may be made based upon basic information about common pharmaceutical ingredients in order to arrive at an acceptable approximation. This risk is tied to the amount of airborne product emitted by the process and is easily understood for a class of compound on a particular piece of equipment. the reduction in airborne contaminant. Comparing the contaminant mass to the processed product mass and number of doses to determine potential concentration per unit dose. in a particular room. 3. Evaluate the exposure over the potential duration of a batch. the mass of a product that could contaminate another product via the HVAC may be evaluated by the same method used to evaluate the operator exposure risk: 1. Methodology The factor of protection from HVAC filtration may be utilized in much the same manner as the protection from Personal Protective Equipment (PPE) is applied to a known airborne contamination level (normally expressed in mcg/m3) to determine if an environment/PPE combination yields and acceptable operator exposure according to the formula: Ambient Concentration mcg/cm3 x Protection Factor = Exposure mcg/cm3 The data needed to determine the protection factor from filtration is available from ANSI/ASHRAE standard 52. if the quantity of product in the air is sufficiently low. a complete analysis would include a further evaluation step: 4.Do not reproduce without written permission.2 testing performed by filter manufacturers.All rights reserved . However. 2. Copyright© Genesis Engineers 2011 . This standard determines the particle stopping capability of filters by particle size. This information alone may be sufficient to evaluate risk. In the following sections we will discuss the methodology and examples of the protection provided by HVAC components. Assuming that the risk potential of the products (or types of products) being processed has been evaluated. 4 . Evaluating the mass or volume of airborne “contaminant” product in the environment. accounting for the ventilation parameters within the space.Principles The risk for cross-contamination from HVAC exists primarily when a drug product is exposed to the air that has come from a room where a second drug is being processed. Evaluating the "protection factor". This method allows for extremely precise assessments where the particle size distribution in an airstream has been characterized.

1E+00 mcg/m3 3 = = 5.1E‐02 6.4E‐01 mcg/m3 0.9E+00 3.80 mcg/m3 94. a MERV 11 (~50% ASHRAE ) gives a 1.300000% mcg/cm 1.1E‐01 mcg/m3 = 5.5µ Units 1.5E‐02 mcg/m3 mcg x 3 97.0E‐01 mcg x 0.3E‐01 mcg/m3 x x 3 = = 7.Where only the overall mass of product in an environment is known.100000% mcg/cm 3 96.0E‐01 Fractional  Filter  Efficiency units mcg 1.1E‐01 mcg x 65. Example –Mass Reduction through Medium Efficiency Filters Example ‐ Total Mass Reduction from MERV 11 Filtration Particle  Size 0.1µ Total Units 1.0µ 1.900000% mcg/cm = 7.11E+03 This simple analysis shows that a MERV 15 (~95% ASHRAE) filter provides a 3 log reduction in contaminants.0E‐02 mcg/m3 x = 7.6E‐02 mcg/m3 mcg/m3 1.0E+03 3 Fractional  Mass 50.800000% mcg/cm 3 99.5 log (20:1) reduction in airborne contamination.000000% mcg/cm 3 = 5. the older ANSI/ASHRAE standard test 52.000000% mcg/cm 3 92.5µ 7.0E+03 mcg mcg units = 8.11E+03 Example ‐ Total Mass Reduction from MERV 13 Filtration Particle  Size 0.700000% mcg/cm x x Fractional  Mass 3 15.000000% mcg/cm x 0.0E+02 1.999999% mcg/cm = = 5.1E+00 mcg x 3 81.0E+01 5µ 10µ 1.0E‐05 mcg/m3 mcg/m3 0.5µ 1.0E‐01 1.9E+00 3.1 or it’s Eurovent equivalent can be utilized to effectively understand the mass reduction (and therefore cross-contamination reduction) capability of filters in the HVAC system.89 mcg/m3 1.0E+01 mcg x 5µ 10µ Total 1.5E‐02 mcg/m3 3 29.1µ Total Mass 1. 5 .Do not reproduce without written permission.400000% mcg/cm 3 48.800000% mcg/cm = 9.0E+00 mcg 1.0µ 1.500000% mcg/cm 0.0E+02 1.0E+00 mcg x 1. In the following examples we demonstrate the effectiveness of this method and the surprising effectiveness of medium efficiency filters at reducing airborne contamination.5E‐02 mcg/m3 3 = 2.0µ 5.6E‐01 mcg/m3 mcg mcg x x 3 99.800000% mcg/cm Total Example ‐ Total Mass Reduction from MERV 15 Filtration Particle  Size Total Mass Fractional  Filter  Efficiency units units = 5.3E+01 mcg mcg 98.5E‐02 Filter  Efficiency units mcg x Units Particle  Mass units 35.37E+00 mcg/m3 5µ 10µ 5.1µ Total Mass 8. Copyright© Genesis Engineers 2011 .500000% mcg/cm 3 99.400000% mcg/cm = 2.All rights reserved .3E+01 mcg/m3 mcg/m3 44. More importantly.

11E‐08 mcg/m Total 3 4.0E‐04 mcg/m3 5µ 10µ mcg/m mcg/m3 3 1.5µ 1.All rights reserved .99900% = 1.0E‐04 1.0E‐11 mcg/m3 3 x 99. far below limits of detection or concern for any material we've encountered.0E‐04 mcg/m3 x 99.0E‐06 Filter  Efficiency units Fractional  Mass units mcg/m 3 x 99.0E‐11 mcg/m3 mcg/m3 1.0E‐04 mcg/m 3 Unsurprisingly.0E+00 mcg/m3 x 99. Return Air Concentration mcg/cm3 x % Return Air in supply = Mixed Air mcg/cm3 The second step is to determine the protection from HVAC filtration according to the formula: Ambient Concentration mcg/cm3 x Protection Factor = Exposure mcg/cm3 Copyright© Genesis Engineers 2011 .99000% = 1. Assuming that the return air is representative of the airborne contamination level (normally expressed in mcg/m3) in the room. two HEPA filters in series yield an 11 log reduction in contamination.0E‐09 mcg/m3 5µ 10µ 1.1µ Fractional  Mass 1.Do not reproduce without written permission.99990% 99.5µ 1.Example –Mass Reduction through HEPA Filters In Series Filter Array Evaluation Example ‐ Total Mass Reduction from HEPA Filtration Particle  Size Fractional  Mass Fractional  Filter  Efficiency units Fractional  Mass units 3 x 99. 6 .0E+02 1.0E‐04 1.0E‐04 mcg/m 1. reducing airborne contamination from about one milligram per cubic meter to about ten femtograms.1E+03 mcg/m Total 3 Example ‐ Total Mass Reduction from HEPA Filtration Particle  Size 0.0E‐01 mcg/m 0. as measured or calculated.0E‐04 mcg/m3 mcg/m3 x x 99.99990% 99.99900% = 1.99000% = 1.0E‐08 mcg/m3 0.999% = 1.0E‐04 mcg/m3 1.0E‐10 1..0µ 1.0E+01 mcg/m3 x 99.99999% = = 1.0µ 1.1µ 1.0E‐04 mcg/m mcg/m3 4. The first step in the process is to determine the Mixed Air concentration and account for differences between the concentration in the airstream coming from the room where the "contaminant" is being processed and any dilution that may take place prior to introduction into the room "being contaminated".0E+03 3 x x 99..99999% = = 1.0E‐06 mcg/m3 0.0E‐04 mcg/m3 1.999% = 1.

.76E‐03 mcg As this example shows. Cross Contamination Potential Calculation Room Airflow Calculation Room Vol units  3 1000 m Airflow units       20. to set process limits. 7 .The next step in the process is to determine the ventilation rate or airflow of the room "being contaminated". sensitivity analysis should be applied by testing assumptions around filter integrity and upset (e. Mixed Air Concentration mcg/cm3 x Airflow m3/hr= Supply Air Product Rate mcg/hr Then the period of exposure in the room "being contaminated" is accounted for as: Supply Air Product Rate mcg/hr x Exposure Duration mcg/hr= Total Product Exposure mcg Next.20E‐04 mcg/hr x 1.. assuming uniform and full airborne contribution to the product "being contaminated" according to the formula: Total Product Exposure mcg / Total Units produced = Max. to assure that the system is robust and that non-attainment cases are understood. Example – Max.000 m /hr  Total Airborne Product Calculation Airborne   Airborne  Product  Product  Concentration units Rate  Units 3 = 2.000 mcg/m3 a 100 m3 room with a ventilation rate of 20 Air Changes per hour might have a maximum airborne cross-contamination potential as follows.g.000 m3/hr Ventilation Rate units x 20 AC/hr = Airflow Units 3     20. the total contamination available in our example case is less than 2 picograms over an 8 hour shift. Airborne Cross-Contamination Potential Calculation Starting with an airborne contamination (after dual HEPA filtration) of 1.All rights reserved . Potential Contamination/unit Finally.Do not reproduce without written permission. spill) cases.10E‐08 mcg/m Total Airborne Product Available for Cross‐Contamination  Airborne  Product  Rate  units  2. Copyright© Genesis Engineers 2011 .20E‐04 mcg/hr Exposure  Duration x units 8 hr = Total ProdUnits 1. Further dividing this by the number of units produced in an 8 hour period will likely yield an inconsequential mass/unit. an adjustment to determine the exposure per unit is applied.

large (>10µ) particles are of greater interest in the prevention of cross contamination. absent the use of computational fluid dynamic models.00E‐02 1.00E‐05 Settling Velocities cm/s  The first of these facts is accounted for in our method.00E‐04 1. Using the outlined method we can quantify the maximum cross contamination potential of HVAC system designs providing a rigorous method to assure control of airborne crosscontamination risk. which models the mass of the airborne contaminant.1 Particle Size µ 1 10 100 1.Do not reproduce without written permission. It would be desirable to apply a reduction factor addressing the second item. since the data necessary to support these factors is difficult to obtain and particular to each product. accounting for the percentage of available airborne contamination that may be expected to actually settle on critical surfaces and contaminate a dose.00E+00 1. it is reasonable to neglect this factor and accept the overstatement of potential contamination as a factor of safety.All rights reserved . This focus on large particles is due to: 1.Other Factors to Consider While small particles (<10µ) are of interest in worker safety. not simply the particle count. the HVAC system configuration and standard component performance information.00E‐03 1. Their lower buoyancy (higher settling rate) makes them more likely to contaminate a product by falling out of an airstream as its velocity decreases in a production room (see graph below). However. Copyright© Genesis Engineers 2011 .00E‐01 1. due to their greater respirability. 2. Conclusion The cross-contamination risk inherent in HVAC recirculation can be satisfactorily assessed using readily available information about the product and/or process. 8 . Large particles represent the great preponderance of the mass of particles suspended in the air. Settling Velocities cm/s  0.