What should be the exchange rates for BSL-2 and BSL-3 Clinical & Research Laboratories?
Consensus is 6 to 8 ACH.
What are the number/Cubic Foot of viable bacteria & fungi in BSL-2 & BSL-3 Laboratories?
Typically, the same as outside air numbers, except when BSL- 3 lab supply air is HEPA filtered to Class 100,000 [100 CFU per cubic meter].
Most of the below information was abstracted from the Control of Biohazards Course Laboratory Design Lecture handout.
NIH Design Manual.
B.1 Space Ventilation Rates in BSL3 Laboratories: BLS3 laboratories shall be provided with a minimum of 6 air changes per hour.
This minimum air flow shall be maintained at all times, including unoccupied periods.
Certek Modular BSL-3 Facility.
All levels of biocontainment, animal and agricultural containment. http://www.certekinc.com/products/custom-built-modular-laboratories/.
Most BSL-3 Labs do not have HEPA-filtered supply air.
Certek BSL-3 laboratory is up to International Standard Organization (ISO) Class 8. HEPA supply & exhaust air.
ISO Class 8 Cleanroom Information.
Information on ISO 14644-1:2015 class 8 Cleanroom Classification.
Federal Standard 209E equivalent: Class 100,000.
EU GMP Grade equivalent: D.
Air changes per hour required: 5-48.
Typically measured micron sizes: 5.0µ and 0.5µ.
Microbiological Active Air Action Levels: 100 cfu per cubic meter Microbiological Settle Plates Action Levels: 50 cfu (90mm plate, 4 hours).
It is understood that these are recommendations only and you have the discretion to assign levels based on your manufacturing process and method of analysis.
National Institutes of Health. Biosafety Level 3 Laboratory Certification Requirements.
11. Verification of air change rates (ACR) in containment spaces.
In no case should the ACR be less than 6/hr for labs and 10/hr for animal facilities.
JHU BSL-3 Lab Gilpin checklist negative pressure. Air Pressure Differentials.
Anteroom shall be at 100 cfm negative with respect to an adjoining space.
Containment laboratory shall be 100 cfm negative with respect to the anteroom.
Usually 6-8 ACH, single pass, constant volume [no variable air volume] air in the 1990’s.
Designing a Modern Microbiological / Biomedical Laboratory.
Jonathan Y Richmond Editor. 1997 American Public Health Association, Washington DC ISBN 0-87553-231-4.
Chapter 8. Designing Laboratory Ventilation. Gregory F DeLuga.
Page 183: “There is no way of reliably knowing what specific chemical or airborne substances will be present and at what concentrations in most laboratory rooms. Furthermore, laboratories can be subjected to unpredictable combinations of airborne agents, thus making the situation still more complex and indeterminate. For these reasons, no scientifically based process exists to determine the appropriate ventilation rate necessary for a given laboratory room.”
Page 186: Table 1 – Minimum air changes per hour (ACH).
ASHRAE HVAC Applications 1995 & ANSI/ASHRAE Standard 62-19895.
Biochemistry 6 to 10.
Animal 10 to 15.
Air Change Rates
Jon Crane formerly at CUH2A ABSA biosafety forum 03Nov07
“I wanted to further explain my comment that “Studies over the past 25 years have shown that air change rates are not effective at reducing biological contamination in laboratories” (Jon Crane, Applied Biosafety, 12:3, 143).
First I want to emphasize as I stated in the article that “the most common words in containment facility design are “it depends.” In other words, a single answer rarely covers all the issues for all containment facilities. Be sure to examine the applicability of the information provided below for your specific project needs before you implement them.” I believe that every containment situation should be evaluated independently as to the specific needs of the facility. The conclusions in the following discussion of air change rates might not apply to every circumstance. For example, the air change rate is important if you are trying to:
1) Create a classified clean room environment. In these cases, very high air change rates, supply filtration and laminar flow are combined to get down to very low overall particle counts. There are extraordinarily interesting issues that occur in design if you are trying to combine an enhanced BSL-3 facility with a class 100 clean environment. It would take a separate paper to describe the issues that must be resolved in such a case. The fact that a biosafety cabinet combines clean and containment in a micro-environment makes all of our lives simpler. (By the way, calculate the air change rates in your biosafety cabinets and imaging trying to use the same rates in your facility. It may surprise you.).
2) Reduce odor and dander in animal rooms with open caged or loose housed animals to provide an appropriate environment. Air change rates do provide value, however, studies at Penn State University that have been published indicate that even then at relatively low levels air change rates may begin to lose their effectiveness “…in this example, the room initially is contaminated with 100 cfu/m3 and then purged with outside air, which is assumed to be uncontaminated. Results of these calculations show that at 1 ACH, the room can be purged of almost 95% of airborne contaminants in 4 h.
This analysis indicates that doubling or quadrupling the ACH has a great influence on how fast the room can be cleansed but increasing the rate beyond 10 to 12 ACH offers little additional benefit. Obviously, there is some acceptable level of performance above which no gains are likely to be cost-effective.
That is, the cost of moving air for purging contaminants may become prohibitive if the air change rate is too high. To put this into perspective, an ACH of 6 to 12 might be a reasonable goal for any animal laboratory or even a hospital operating room, but any increase above these levels may have limited value. This analysis assumes, as stated previously, that the air is completely mixed. If a facility has poor air-mixing, then there might be benefits from even higher ACH levels. One study on rat rooms found that 172 ACH was necessary to control rat allergens, but such high airflow levels could have prohibitive costs” (Engineering Control of Airborne Disease Transmission in Animal Laboratories, Kowalski, Banfleth and Carey, Contemporary Topics, AALAS, 2002). Keep in mind also that containment caging systems greatly reduce the need for overall room ventilation.
3) Reduce chemical exposure below a set value if chemicals are released in an open environment.
4) Reduce aerosol transmission in patient rooms, waiting rooms, etc.
Conversely, if you have a BSL-4 suit laboratory with no animals or animals in individually ventilated cages, the need for ventilation of the space itself might be minimal as both the personnel and animals would be taken care of with micro-environments (Suits and cages respectively).
If you have a containment facility that has these or other special needs you can look at 1) the aerosol load from both normal operations and the maximum credible event, 2) the safety and operational requirements that would drive the overall reduction and the time for reduction of the aerosols and 3) the effectiveness of the ventilation system design. With those parameters, you can precisely define the ideal air change rates for aerosol control of the design conditions; however, as a practical matter, most facilities will operate well using conventional ventilation system design practices. In addition, rooms are seldom static with perfect mixing. Convection currents, doors opening and closing, furniture, equipment, people movement and animal movement will disrupt the ideal conditions. Containment facilities tend to see a constant change in all these parameters. Remember that heat loads and ventilation equipment requirements are also a factor in dictating air change rates in a containment facility.
I have always tried to look at issues related to the design of containment facilities as to how they impact the day-to-day operation of a containment facility in a practical way. What benefit do you get? What price do you have to pay? In paying the price, does it keep you from getting other features that might provide a higher benefit to safety or operations? To understand the cost versus the benefits you have to dig into the details. In containment facilities, there would be two types of source for aerosol contamination: 1) a constant emission from a process or infected animals or 2) a sudden burst emission from a process or accidental event. Air change rates have a different impact on each of these states.
For a basic containment laboratory with aerosols contained in biosafety cabinets or other primary containment systems the constant emission source is not an issue as the aerosol would be contained within the primary containment device. The concern would therefore be with the sudden release from an accident occurring outside primary containment. (Or from an incident inside primary containment that has enough force to escape the primary containment system.) For these events studies from Penn State and elsewhere have shown that the initial concentration is reduced relatively rapidly with effective ventilation; however, with conventional laboratory systems it would not be rapid enough to prevent exposure to personnel in the space and the mixing is not so absolute to completely remove the aerosol for a significantly longer time period.
Assuming a ventilation system with good mixing, if you had a spill in a room with six air changes or twenty air changes per hour you would have the higher level (70-100%) of the initial aerosol concentration in the room for the time period it would normally take for the users to safely evacuate the space. In any event, the air change rate would have minimal impact on the initial exposure.
Also, as a practical matter, there is little difference between six air changes and thirty air changes in the length of time it takes to purge the room to a low level of remaining aerosol, In both cases you get below 5% in less than 45 minutes;
If you have the appropriate containment laboratory, there is not a difference in containment risk if you get to 5% concentration in 20 minutes or a 5% concentration in 45 minutes as the laboratory will appropriately handle the aerosols either by filtration or dilution. If it is necessary to rush into the room quickly after the incident, as in the case of a medical emergency being the root cause of a release outside of primary containment, prudent practice would have the response team wearing respiratory protection. In any case, air change rates would not significantly change the aerosol load at this point. If you can wait to respond, the difference between waiting 20 minutes or 45 minutes would also not likely be significant. Again, however, each facility should address the value of this length of time to their operations.
Based on the above, I don’t see significant benefits for most facilities in increased air changes. I do see significant additional costs for higher air change rates.
For a 5,000 SF laboratory, the difference in cost for heating and cooling as you move from six to twenty air changes would be in the range of $40,000 – $50,000 per year. If the facility is HEPA filtered, there would be an additional large cost for the fan energy to pull the difference in quantity of air through the filters. As air change rates affect filter sizes, duct sizes, air handling unit sizes, exhaust fan sizes, exhaust valve sizes, etc., the first costs for installing the larger system would be proportionally higher as well. These to me become significant enough costs to carefully examine if the minor benefits you might get from higher air change rates would be worth the initial and ongoing costs.
Again, it is important to point out that in some cases the benefit may be worth the cost of the higher air changes. For any specific facility, I am not advocating one answer or the other. I am advocating that you analyze the cost versus benefit for your situation. In my opinion that is the only way you will get the best answer to meet your needs.
As I mentioned in the ABSA Journal editorial, I have run across papers over the years that support the argument that in a containment laboratory, there is little real benefit to safety from increased air changes. One of the older but better papers was by Emmet Barkley in which he examined the impact of various safety measures and engineering controls on the reports of laboratory acquired infections at that time. He stated that “It is difficult to assess the value of air exchange rates as a hazard control factor. It is my general feeling that no ventilation rate associated with conventional mixing and air distribution within a laboratory would substantially reduce the inhalation dose that an individual might be exposed to if infectious materials were accidentally released into this environment. Protection from exposure to burst sources can only be practically achieved using biosafety cabinets. To achieve a similar level of protection through room ventilation practices would require high-velocity laminar flow facilities in which the investigator would always be upstream of the materials being handled. This condition is obviously impractical and terribly expensive.
Conventional ventilation rates (i.e., 6 to 15 air changes per hour) are virtually ineffective in reducing airborne contamination caused by a continuous release of particles. I have, therefore, guardedly concluded that ventilation rate has little relevance as a hazard control factor”.
Everything I have seen or read in the 25 years that I have been involved in the design of containment facilities would lead me to believe that Emmet made a wise assessment of the issue of air change rates related to most containment facilities.
Lastly also remember that air change rates themselves do not create effective ventilation of a space. You can have a high air change rate with poor system design and not get any benefit.”
New Approaches to Pressure Stability in BSL-3 Containment Labs: Minimized Turbulence, Mix of Control Strategies Keep Pressure Relationships on Track.
The golden rule of containment is to always maintain the relationship between exhaust and supply.
Typical room pressurization is guided by a rule of thumb: It takes an offset airflow of 100 to 150 CFM per door to attain the target pressure. “This rule assumes the space is basically airtight with leakage only around the door frame and the door undercut.
Studied four existing BSL-3 labs, each with multiple rooms of a consistent geometry (similar layout and door size, same controls). They collected 874 data points related to flow and differential pressure. The analysis of the data ultimately confirmed the relationship between differential pressure and airflow in the facilities as a function of the geometry of the transfer openings.
With its connections to all spaces, the corridor has a pivotal role to play in the containment strategy for the entire suite. Often regarded as least important, because it does not house primary research, the corridor (or similar anchor space) is actually the hub. “It’s inherently a central anchor from the control standpoint.”It follows that equipping the corridor with the higher performance of a direct pressure control system would enhance containment capabilities of the suite as a whole.
“Under direct control, if something happens in a lab, the corridor acts as a workhorse, absorbing, minimizing, or mitigating pressure fluctuations. The other rooms aren’t affected, and the problem doesn’t propagate.”
A further potential enhancement is a primary-secondary valve configuration for corridor supply air. The larger secondary valve provides the requisite air volume, while the smaller primary valve enables fine-tuning for space pressure control.
With the corridor under direct control, the other rooms in the suite can operate effectively under progressive offset control. Clements and Stanford point out that the mix of control types should be systematic throughout the facility, with all procedure rooms operating one way, and all corridors another.
Air change rates recommended in various standards and selected projects
Standard/Guideline. Recommended Air-Change Rate.
ANSI/AIHA Z9.5-2003. The specific room ventilation rate shall be established or agreed upon by the owner or his/her designee.
NFPA-45-2004. Minimum 4 ACH unoccupied. occupied “typically greater than 8 ACH.
ACGIH Ind. Vent 24th Ed. 2001. The required ventilation depends on the generation rate and toxicity of the contaminant-not on the size of the room in which it occurs.
ASHRAE Lab Guide-2001. 4-12 ACH.
OSHA 29 CFR Part 1910-1450. 4-12 ACH.
Project. Specified Air-Change Rate.
UC Santa Cruz Bio-Med Building. 6 ACH occupied, 4 ACH unoccupied.
UC Davis Tahoe Center. 6 ACH occupied, 4 ACH unoccupied in low-risk labs.
UC Berkeley Li-Kashing Building. 6 ACH.
Energy Efficient Laboratory Design: A Novel Approach to Improve Indoor Air Quality and Thermal Comfort.
Farhad Memarzadeh-1, Andy Manning-2, and Zheng Jiang-2.
1-National Institutes of Health, Bethesda, Maryland and 2-Flomerics, Inc., Marlborough, Massachusetts. Applied Biosafety Vol. 12, No. 3, 2007.
The results of this study show that chilled beams improve thermal comfort and can be operated at reduced Air Changes per Hour (ACH) while maintaining a comfortable environment in occupied zones expressed as the Predicted Percentage Dissatisfied (PPD).
To obtain a similar level of thermal comfort, a higher ACH is required in a ceiling diffuser system with cooling panels and bench exhausts.
The following conclusions can be drawn from this study:
1. Chilled beams improve thermal comfort and can be operated at as low as 4 ACH (without a fume hood in the laboratory) while maintaining very satisfactory average PPD (around 10%) in the occupied zones.
To obtain a similar level of thermal comfort, 6 ACH is required for ceiling diffuser system with two sets of cooling panels and bench exhausts.
2. The presence of an operational fume hood slightly improves the thermal comfort in the room.
3. The average concentration in the occupied zone caused by the bench top spills increases when the primary flow rate decreases but is not very sensitive to the change of primary air flow rate. The chilled beams improve the removal effectiveness of gases and airborne particles by generating a better mixed condition in the room than ceiling diffusers.
4. The chilled beams in the cases studied are seen to have an insignificant effect on the hood containment.
5. Using chilled beams with a fume hood, satisfactory thermal comfort and air quality can be achieved at 6 ACH (100% Outside Air) in comparison with an all-air ceiling diffuser ventilation system at 13 ACH (70% Outside Air), which indicates a 22.5% saving in annual energy costs for cooling and ventilating a typical lab in the Washington, DC area.
It should be noted that the use of chilled beams is not intended to be applicable to all types of laboratories and should not override the contaminant controls that are appropriate for this type of laboratory, particularly with respect to the use of appropriate biosafety cabinets (BSCs) and/or fume hoods, and the handling of hazardous materials on the workbenches.
Finally, the usefulness of the chilled beam system may not be beneficial from a cost standpoint in scenarios where the room flow rate is already low, and energy costs are relative to other occupied spaces.
Study on contaminant distribution in a mobile BSL-4 laboratory based on multi-region directional airflow.
Yan Wang et al., Accepted: 3 September 2021. Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021.