cross contamination prevention in hvac

8/21/2019 Cross Contamination Prevention in HVAC

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Whitepaper

Cross-ContaminationProtection in HVAC

I N D U S T R Y I N S I G H T S

Norman A. Goldschmidt September 30, 2011

Principal, Engineering

www.geieng.com


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Copyright Genesis Engineers 2011 - All rights reserved - Do not reproduce without written permission. 2

I N D U S T R Y I N S I G H T S

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Whitepaper

Cross-Contamination

Protection in HVAC

Introduction

In order to comply with widely established GMP regulations requiring minimizing the riskof contamination caused by recirculation or re-entry of untreated or insufficientlytreated air An evaluation of potential for cross-contamination via HVAC should bepart of the risk assessment in multi-product facilities.

As outlined in the ISPE Risk MAPP guide, two HEPA filters in series within an airrecirculation system (on supply and/or return) can reduce the mass of product in anairstream by an acceptable amount. But this approach is certainly not the only way to achievean acceptable reduction in airborne contamination.

Assuming that the risk potential of the products being processed has been determined, andthat the unit operations and engineering controls have been chosen, the mass of a productthat could contaminate another product via the HVAC may assessed. By establishing the

mass of airborne contaminant product, the reduction in airborne contaminant in theHVAC airstream (due to filtration) and comparing this reduced contaminant mass to themass of the potentially contaminated product, it is possible to determine the potentialconcentration per unit dose.

Employing the filter efficiency rating (ASHRAE Efficiency %) as an adjustment to theairborne mass of particulate has been proposed as a method to achieve this evaluation; this isgenerally unsatisfactory as it provides only a rough estimate without the level of assurancedesired for these critical calculations.

However, by employing a mix of well defined cleanroom testing, Industrial Hygiene andfilter classification techniques, it is possible to perform a quantitative assessment of the crosscontamination protection, or potential, of an HVAC system - with rigor.


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Principles

The risk for cross-contamination from HVAC exists primarily when a drug product isexposed to the air that has come from a room where a second drug is being processed. Thisrisk is tied to the amount of airborne product emitted by the process and is easilyunderstood for a class of compound on a particular piece of equipment, in a particular room.

Assuming that the risk potential of the products (or types of products) being processed hasbeen evaluated; the mass of a product that could contaminate another product via theHVAC may be evaluated by the same method used to evaluate the operator exposure risk:

1. Evaluating the mass or volume of airborne contaminant product in the environment.

2. Evaluating the "protection factor", the reduction in airborne contaminant, afforded bycomponents of the HVAC system.

3. Evaluate the exposure over the potential duration of a batch, accounting for theventilation parameters within the space.

This information alone may be sufficient to evaluate risk, if the quantity of product in the airis sufficiently low. However, a complete analysis would include a further evaluation step:

4. Comparing the contaminant mass to the processed product mass and number of dosesto determine potential concentration per unit dose.

In the following sections we will discuss the methodology and examples of the protectionprovided by HVAC components.

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 airbornecontamination level (normally expressed in mcg/m3) to determine if an environment/PPEcombination 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 fromANSI/ASHRAE standard 52.2 testing performed by filter manufacturers. This standarddetermines the particle stopping capability of filters by particle size. This method allows forextremely precise assessments where the particle size distribution in an airstream has beencharacterized. Where empirical data is not available a set of assumptions may be made basedupon basic information about common pharmaceutical ingredients in order to arrive at anacceptable approximation.


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Where only the overall mass of product in an environment is known, the olderANSI/ASHRAE standard test 52.1 or its Eurovent equivalent can be utilized to effectivelyunderstand the mass reduction (and therefore cross-contamination reduction) capability offilters in the HVAC system.

In the following examples we demonstrate the effectiveness of this method and thesurprising effectiveness of medium efficiency filters at reducing airborne contamination.

Example Mass Reduction through Medium Efficiency Filters

Particle

Size TotalMass units

Fractional

Filter

Efficiency Units

Fractional

Mass units

0.1 1.0E01 mcg x 15.000000% mcg/cm3

= 8.5E02 mcg/m3

0.5 1.0E+00 mcg x 29.400000% mcg/cm3

= 7.1E01 mcg/m3

1.0 1.0E+01 mcg x 48.900000% mcg/cm3

= 5.1E+00 mcg/m3

5 1.0E+02 mcg x 94.100000% mcg/cm

3

= 5.9E+00 mcg/m

3

10 1.0E+03 mcg x 96.700000% mcg/cm3

= 3.3E+01 mcg/m3

Total 1.11E+03 44.80 mcg/m3

Example TotalMassReductionfromMERV11Filtration

Particle


Filter

Efficiency Units

Particle

Mass units

0.1 8.5E02 mcg x 35.000000% mcg/cm3

= 5.5E02 mcg/m3

0.5 7.1E01 mcg x 65.300000% mcg/cm3

= 2.4E01 mcg/m3

1.0 5.1E+00 mcg x 81.800000% mcg/cm3

= 9.3E01 mcg/m3

5 5.9E+00 mcg x 98.800000% mcg/cm

3

= 7.1E02 mcg/m

3

10 3.3E+01 mcg x 99.800000% mcg/cm3

= 6.6E02 mcg/m3

Total 1.37E+00 mcg/m3


Particle


Fractional

Filter

Efficiency Units

Fractional

Mass units

0.1 1.0E01 mcg x 50.000000% mcg/cm3

= 5.0E02 mcg/m3

0.5 1.0E+00 mcg x 92.500000% mcg/cm3

= 7.5E02 mcg/m3

1.0 1.0E+01 mcg x 97.400000% mcg/cm3

= 2.6E01 mcg/m3

5 1.0E+02 mcg x 99.500000% mcg/cm3

= 5.0E01 mcg/m3

10 1.0E+03 mcg x 99.999999% mcg/cm3

= 1.0E05 mcg/m3

Total 1.11E+03 0.89 mcg/m3


This simple analysis shows that a MERV 15 (~95% ASHRAE) filter provides a 3 logreduction in contaminants. More importantly, a MERV 11 (~50% ASHRAE ) gives a 1.5 log(20:1) reduction in airborne contamination.


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Example Mass Reduction through HEPA Filters In Series

Particle

Size

Fractional

Mass units

Fractional

Filter

Efficiency

Fractional

Mass units

0.1 1.0E01 mcg/m3

x 99.999% = 1.0E06 mcg/m3

0.5 1.0E+00 mcg/m3

x 99.99000% = 1.0E04 mcg/m3

1.0 1.0E+01 mcg/m3

x 99.99900% = 1.0E04 mcg/m3

5 1.0E+02 mcg/m3

x 99.99990% = 1.0E04 mcg/m3

10 1.0E+03 mcg/m3

x 99.99999% = 1.0E04 mcg/m3

Total 1.1E+03 mcg/m3

4.0E04 mcg/m3

Particle

Size

Fractional

Mass units

Filter

Efficiency

Fractional

Mass units0.1 1.0E06 mcg/m

3x 99.999% = 1.0E11 mcg/m

3

0.5 1.0E04 mcg/m3

x 99.99000% = 1.0E08 mcg/m3

1.0 1.0E04 mcg/m3

x 99.99900% = 1.0E09 mcg/m3

5 1.0E04 mcg/m3

x 99.99990% = 1.0E10 mcg/m3

10 1.0E04 mcg/m3

x 99.99999% = 1.0E11 mcg/m3

Total 4.0E04 mcg/m3

1.11E08 mcg/m3

Example TotalMassReductionfromHEPAFiltration

FilterArrayEvaluation

Example TotalMassReductionfromHEPAFiltration

Unsurprisingly, two HEPA filters in series yield an 11 log reduction in contamination,reducing airborne contamination from about one milligram per cubic meter to about tenfemtograms, far below limits of detection or concern for any material we've encountered.

Assuming that the return air is representative of the airborne contamination level (normallyexpressed in mcg/m3) in the room, as measured or calculated...

The first step in the process is to determine the Mixed Air concentration and account fordifferences 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 introductioninto the room "being contaminated".

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 theformula:

Ambient Concentration mcg/cm3 x Protection Factor = Exposure mcg/cm3


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The next step in the process is to determine the ventilation rate or airflow of the room"being contaminated".

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/hrx Exposure Duration mcg/hr= Total Product Exposure mcg

Next, an adjustment to determine the exposure per unit is applied, assuming uniform andfull airborne contribution to the product "being contaminated" according to the formula:

Total Product Exposure mcg / Total Units produced = Max. Potential Contamination/unit

Finally, sensitivity analysis should be applied by testing assumptions around filter integrity

and upset (e.g. spill) cases, to assure that the system is robust and that non-attainment casesare understood, to set process limits.

Example Max. Airborne Cross Contamination Potential Calculation

Starting with an airborne contamination (after dual HEPA filtration) of 1,000 mcg/m3a 100 m3room with a ventilation rate of 20 Air Changes per hour might have a maximumairborne cross-contamination potential as follows...

RoomVol units VentilationRate units Airflow Units

1000 m3

x 20 AC/hr = 20,000 m3/hr

Airflow units

Airborne

Product

Concentration units

Airborne

Product

Rate Units

20,000 m3/hr x 1.10E08 mcg/m3

= 2.20E04 mcg/hr

Airborne

Product

Rate units

Exposure

Duration units TotalProdUnits

2.20E04 mcg/hr x 8 hr = 1.76E03 mcg

TotalAirborneProductCalculation

TotalAirborneProductAvailableforCrossContamination

RoomAirflowCalculation

CrossContaminationPotentialCalculation

As this example shows, the total contamination available in our example case is less than 2picograms over an 8 hour shift. Further dividing this by the number of units produced in an8 hour period will likely yield an inconsequential mass/unit.


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Other Factors to Consider

While small particles (10) particles are of greater interest in the prevention of cross contamination. Thisfocus on large particles is due to:

1. Large particles represent the great preponderance of the mass of particles suspended inthe air.

2. Their lower buoyancy (higher settling rate) makes them more likely to contaminate aproduct by falling out of an airstream as its velocity decreases in a production room (seegraph below).

The first of these facts is accounted for in our method, which models the mass of theairborne contaminant, not simply the particle count.

It would be desirable to apply a reduction factor addressing the second item, accounting forthe percentage of available airborne contamination that may be expected to actually settle oncritical surfaces and contaminate a dose. However, since the data necessary to support thesefactors is difficult to obtain and particular to each product, absent the use of computationalfluid dynamic models, it is reasonable to neglect this factor and accept the overstatement ofpotential contamination as a factor of safety.

onclusion

The cross-contamination risk inherent in HVAC recirculation can be satisfactorily assessedusing readily available information about the product and/or process, the HVAC systemconfiguration and standard component performance information.

Using the outlined method we can quantify the maximum cross contamination potential ofHVAC system designs providing a rigorous method to assure control of airborne cross-contamination risk.

1.00E05

1.00E04

1.00E03

1.00E02

1.00E01

1.00E+000.1 1 10 100

SettlingVelocitiescm/s

SettlingVelocitiescm/s

Particle Size

cross contamination prevention in hvac

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