Cross Contamination Prevention in HVAC

Whitepaper
Cross-Contamination
Protection in HVAC
INDUSTRY INSIGHTS
Norman A. Goldschmidt
Principal, Engineering
September 30, 2011
www.geieng.com
INDUSTRY INSIGHTS
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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.
As outlined in the ISPE Risk MAPP guide, 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. But this approach is certainly not the only way to achieve
an acceptable reduction in airborne contamination.
Assuming that the risk potential of the products being processed has been determined, and
that the unit operations and engineering controls have been chosen, the mass of a product
that could contaminate another product via the HVAC may assessed. By establishing the
mass of airborne contaminant product, 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, it is possible to determine the potential
concentration per unit dose.
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; this is
generally unsatisfactory as it provides only a rough estimate without the level of assurance
desired for these critical calculations.
However, by employing a mix of well defined cleanroom testing, Industrial Hygiene and
filter classification techniques, it is possible to perform a quantitative assessment of the cross
contamination protection, or potential, of an HVAC system - with rigor.
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. 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, in a particular room.
Assuming that the risk potential of the products (or types of products) being processed has
been evaluated; 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.
Evaluating the mass or volume of airborne contaminant product in the environment.
2.
Evaluating the "protection factor", the reduction in airborne contaminant, afforded by

components of the HVAC system.
3.
Evaluate the exposure over the potential duration of a batch, accounting for the
ventilation parameters within the space.
This information alone may be sufficient to evaluate risk, if the quantity of product in the air
is 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 doses
to determine potential concentration per unit dose.
In the following sections we will discuss the methodology and examples of the protection
provided 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 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 52.2 testing performed by filter manufacturers. This standard
determines the particle stopping capability of filters by particle size. This method allows for
extremely precise assessments where the particle size distribution in an airstream has been
characterized. 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.
Where only the overall mass of product in an environment is known, the older
ANSI/ASHRAE standard test 52.1 or its Eurovent equivalent can be utilized to effectively
understand the mass reduction (and therefore cross-contamination reduction) capability of
filters in the HVAC system.
In the following examples we demonstrate the effectiveness of this method and the
surprising effectiveness of medium efficiency filters at reducing airborne contamination.
Example Mass Reduction through Medium Efficiency Filters

ExampleTotalMassReductionfromMERV11Filtration
Particle
Size
0.1
TotalMass
1.0E01
Fractional
Filter
Efficiency
units
mcg
1.0E+00
mcg
1.0
1.0E+01
mcg
5
10
Total
1.0E+02
1.0E+03
mcg
mcg
units
8.5E02
mcg/m3
29.400000% mcg/cm
3
48.900000% mcg/cm
7.1E01
mcg/m3
5.1E+00
mcg/m3
=
=
5.9E+00
3.3E+01
mcg/m3
mcg/m3
44.80
mcg/m3
94.100000% mcg/cm
3
96.700000% mcg/cm
x
x
Fractional
Mass
3
15.000000% mcg/cm
0.5
Units
1.11E+03
Particle
Size
0.1
TotalMass
8.5E02
Filter
Efficiency
units
mcg
Units
Particle
Mass
units
35.000000% mcg/cm
5.5E02
mcg/m3
2.4E01
mcg/m3
0.5
7.1E01
mcg
65.300000% mcg/cm
1.0
5.1E+00
mcg
3
81.800000% mcg/cm
9.3E01
mcg/m3
x
x
=
=
7.1E02
6.6E02
mcg/m3
mcg/m3
1.37E+00
mcg/m3
5
10
5.9E+00
3.3E+01
mcg
mcg
98.800000% mcg/cm
3
99.800000% mcg/cm
Total
Particle
Size
TotalMass
Fractional
Filter
Efficiency
units
units
5.0E02
mcg/m3
7.5E02
mcg/m3
mcg
3
97.400000% mcg/cm
2.6E01
mcg/m3
mcg
mcg
x
x
3
99.500000% mcg/cm
3
99.999999% mcg/cm
=
=
5.0E01
1.0E05
mcg/m3
mcg/m3
0.89
mcg/m3
1.0E01
mcg
0.5
1.0E+00
mcg
1.0
1.0E+01
5
10
1.0E+02
1.0E+03
Fractional
Mass
50.000000% mcg/cm
3
92.500000% mcg/cm
0.1
Total
Units
1.11E+03
This simple analysis shows that a MERV 15 (~95% ASHRAE) filter provides a 3 log
reduction in contaminants. More importantly, a MERV 11 (~50% ASHRAE ) gives a 1.5 log
(20:1) reduction in airborne contamination.
Example Mass Reduction through HEPA Filters In Series
FilterArrayEvaluation
ExampleTotalMassReductionfromHEPAFiltration
Particle
Size
Fractional
Mass
Fractional
Filter
Efficiency
units
Fractional
Mass
units
99.999%
1.0E06
mcg/m3
0.1
1.0E01
mcg/m
0.5
1.0E+00
mcg/m3
99.99000%
1.0E04
mcg/m3
1.0
1.0E+01
mcg/m3
99.99900%
1.0E04
mcg/m3
1.0E+02
1.0E+03
x
x
99.99990%
99.99999%
=
=
1.0E04
1.0E04
mcg/m
mcg/m3
4.0E04
mcg/m3
5
10
mcg/m
mcg/m3
3
1.1E+03 mcg/m
Total
ExampleTotalMassReductionfromHEPAFiltration
Particle
Size
0.1
Fractional
Mass
1.0E06
Filter
Efficiency
units
Fractional
Mass
units
mcg/m
99.999%
1.0E11
mcg/m3
99.99000%
1.0E08
mcg/m3
0.5
1.0E04
mcg/m
1.0
1.0E04
mcg/m3
99.99900%
1.0E09
mcg/m3
5
10
1.0E04
1.0E04
mcg/m3
mcg/m3
x
x
99.99990%
99.99999%
=
=
1.0E10
1.0E11
mcg/m3
mcg/m3
1.11E08
mcg/m
Total
3
4.0E04 mcg/m
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 ten
femtograms, 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 (normally
expressed 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 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".
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
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/hr x Exposure Duration mcg/hr= Total Product Exposure mcg
Next, an adjustment to determine the exposure per unit is applied, assuming uniform and
full 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 cases
are 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/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...
CrossContaminationPotentialCalculation
RoomAirflowCalculation
RoomVol units
3
1000 m
Airflow
units
20,000 m3/hr
VentilationRate units
x
20 AC/hr
Airflow Units
3
20,000 m /hr
TotalAirborneProductCalculation
Airborne
Airborne
Product
Product
Concentration units
Rate
Units
3
= 2.20E04 mcg/hr
x
1.10E08 mcg/m
TotalAirborneProductAvailableforCrossContamination
Airborne
Product
Rate
units
2.20E04 mcg/hr
Exposure
Duration
x
units
8 hr
TotalProdUnits
1.76E03 mcg
As this example shows, the total contamination available in our example case is less than 2
picograms over an 8 hour shift. Further dividing this by the number of units produced in an
8 hour period will likely yield an inconsequential mass/unit.
Other Factors to Consider

While small particles (<10) are of interest in worker safety, due to their greater respirability,
large (>10) particles are of greater interest in the prevention of cross contamination. This
focus on large particles is due to:
1.
Large particles represent the great preponderance of the mass of particles suspended in
the air.
2.
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).
SettlingVelocitiescm/s
0.1
Particle Size
10
100
1.00E+00
1.00E01
1.00E02
1.00E03
1.00E04
1.00E05
SettlingVelocitiescm/s
The first of these facts is accounted for in our method, which models the mass of the
airborne contaminant, not simply the particle count.
It would be desirable to apply a reduction factor addressing the second item, accounting for
the percentage of available airborne contamination that may be expected to actually settle on
critical surfaces and contaminate a dose. However, since the data necessary to support these
factors is difficult to obtain and particular to each product, absent the use of computational
fluid dynamic models, it is reasonable to neglect this factor and accept the overstatement of
potential contamination as a factor of safety.
Conclusion
The cross-contamination risk inherent in HVAC recirculation can be satisfactorily assessed
using readily available information about the product and/or process, the HVAC system
configuration and standard component performance information.
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.

Cross Contamination Prevention in HVAC

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Whitepaper

September 30, 2011

Genesis Engineers periodically publishes

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

Evaluating the "protection factor", the reduction in airborne contaminant, afforded by

Example Mass Reduction through Medium Efficiency Filters

Example Mass Reduction through HEPA Filters In Series

Unsurprisingly, two HEPA filters in series yield an 11 log reduction in contamination,

Example Max. Airborne Cross-Contamination Potential Calculation

Other Factors to Consider

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