Design and operation of Biotechnology: Design and operation of biopharmaceutical airlocks

Airlocks help maintain air pressurization differentials and directional air flow between adjacent areas when personnel or equipment pass between them.

by Manuel A. del Valle, PE

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Airlocks provide critical separation barriers in pharmaceutical and biopharmaceutical plants. In addition to separating areas of different environmental air cleanliness classifications, they also divide containment and non-containment areas, and may also operate as equipment “pass-thru” and gowning/de-gowning areas.

Each of the four different airlock types is suited to specific applications and requirements.

Application and proper functioning of airlocks is not a simple matter that can be taken lightly if airlocks are to be an effective barrier to cross-contamination. Cooperation and coordination between the architect, the HVAC engineer, the HVAC control engineer and the owner are a must.

Airlock types and applications

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There are four types of airlocks, each suited to a particular type of application. The “cascading pressure airlock,” for example, is the airlock type preferred by FDA when containment is not an issue. Used to separate clean areas from non-classified areas, pressurized air “cascades” from the cleanest to the less clean adjacent areas. In this application, the same quantity of air is supplied to and returned from the airlock.

In contrast, the “pressure bubble airlock” and the “pressure sink airlock” are used to separate biocontained clean areas from non-biocontained (either clean or non-clean) areas. In the pressure bubble airlock, conditioned air from a clean, non-biocontained source is used to pressurize the airlock. The supply air then dissipates into adjacent areas through the airlock doors, walls and other openings, thus preventing cross-contamination between adjacent rooms and contamination from adjacent areas from entering the airlock. In the pressure sink airlock, negative pressure is maintained relative to all adjacent areas and all the air supplied to and infiltrated into the room is exhausted, thus also preventing cross-contamination between adjacent areas.

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Of the two methods, the pressure bubble airlock is the most commonly used because all particles or dirt are kept out of the airlock at all times, while in the pressure sink airlock, particles and dirt from all adjacent rooms opening into the airlock are continuously passing into the airlock through door, wall or ceiling cracks.

The “potent compound airlock” is a combination of the pressure bubble and pressure sink airlocks. This two-compartment airlock arrangement allows personnel to protect (gown/respirator) themselves before coming into contact with any dangerous materials while at the same time, the product (potent compound) is protected from contamination from adjacent, connected areas. All conditioned, clean air supplied to the gown room is dissipated into the adjacent rooms while all the conditioned, clean air supplied to the airlock room (as well as all infiltration air into that room) is exhausted.

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In general, airlock cleanliness classification and airflow rate (air changes per/hour) should match the cleaner of the rooms being serviced, while also addressing the “cascading” principle. For example, a Class 10,000 room (60 air changes/hour) should be protected by an airlock at the same classification level and airflow rate. An exception to this, however, may be an airlock between a Class 10,000 room and a non-classified (95 percent ASHRAE) filtered area. In this case, the airlock should be classified as Class 100,000 (to maintain the “cascading” principle), while the airlock airflow rate should still be 60 air changes/hour.

RIGHT. Each of the four different airlock types is suited to specific applications and requirements.

One reason to maintain higher airflow rates in airlocks is to prevent cross-contamination between adjacent rooms when one of the doors of the airlock door is opened. Because airlock pressure rapidly approaches that of the opened room, allowing contaminants to flow into the airlock, the second airlock door should not be opened until the airlock airflow has had time to flush the airlock. Typically, one room air change is used although some pharmaceutical companies prefer two. Thus, airflow rate is directly related to the time needed between the opening of the two doors. For an airlock designed for 20 air changes/hour, 3 minutes must pass before the second airlock door may be opened, while by using 60 air changes/hour the wait is reduced to only one minute. In either case, the long time delay only applies when passing from the dirtier to the cleaner rooms and is not needed when going in the opposite direction.

Construction materials

Like the rooms they are protecting, airlock construction materials and finishes are critical to controlling contamination. Floors, walls and ceilings should resist cleaning chemicals and have non-flaking or shedding finishes. Walls are typically constructed of gypsum board on metal studs and finished with epoxy paint, though PVC coatings or stainless steel finishes are also used.

Ceilings should also be constructed of gypsum boards and finished with epoxy with joints between walls and ceilings coved. Doors, windows and lights should be flush, and floors should also have integral coved bases and be constructed of poured concrete with epoxy resin finish or epoxy terrazzo with granite aggregate. Floor sealers should resist cleaning chemicals. Whenever possible, airlock doors should open to the dirtier or biocontained side and should have perimeter seals at the frame and floor sweeps.

Pressurization

To determine the pressure differential required between adjacent rooms of different cleanliness level, both US and European Community (EC) GMPs must be examined. However, because the US Aseptic Processing Guide requires a static pressure differential of 0.05 inches w.g. for both “controlled and critical” areas, while the EC Guide gives a range of 10 to 15 pascals (0.04 to 0.06 in. w.g.), a differential of 0.05 in. w.g. will satisfy both GMPs.

It is also necessary, however, to determine where to apply the pressure differential, because this will vary depending on airlock type. For example, in cascading pressure airlocks the differential should be between the cleanroom and the non-classified corridor, whereas in both pressure bubble and pressure sink airlocks, it should be between the airlock and the corridor and between the airlock and the biocontained area.

Biocontainment must also be considered for these two airlocks with the biocontainment area always negative to any adjacent non-biocontained areas. This will ensure that in the event that both airlock doors are mistakenly opened simultaneously, any airflow will be from the non-biocontained to the biocontained area. Although the biocontained area is at a cleaner classification level than the corridor, it is also at a lower pressure. Likewise, it can be seen that if the three doors of a potent-compound airlock are inadvertently left open, the airflow will still be from the non-biocontained area (the corridor) to the biocontained area.

Calculation pressurization CFM

Because it depends on the airlock “construction tightness” and door seals, it isn't possible to measure the actual required pressurization CFM (cubic feet per minute) until construction is finished. It is possible to calculate a fairly close approximation. The following “door crack leakage” method has been proven throughout many installations, is relatively simple and provides “conservative” CFM values. For calculation, a “tight construction” (gypsum board ceiling, door seals and closed doors) is assumed.

Using the door crack leakage method, it is assumed that door perimeter and joints (if two leafs) have a 1/8-inch crack and that there is a 1/4-inch crack between the door and the floor. For sliding doors a 1/2-inch crack is assumed around the whole door perimeter.

The calculation formula is then: CFM = CAV where A is the area of crack area in “square feet”, V the velocity pressure in feet per minute (resulting from the conversion of static pressure to velocity pressure to move the air through the door cracks where V = 4005 pressure diff), and C is the pressurization loss coefficient for air movement across a linear crack. Though this value is typically between 0.60 and 0.80, for simplicity of calculation and to be “conservative” on the CFM values calculated, it can be assumed to be 1.0.

The source of conditioned air is also an important consideration. In the cascading pressure airlock, the supply air source can be the same duct branch serving the cleanroom being protected, however, in multi-product, biocontained, or potent compound applications, the source of conditioned air to the airlock/gown/degown rooms should be a clean, once-through source. Typically, air is supplied through ceiling terminal HEPAs or non-induction type diffusers near the cleaner side of the airlock. The return/exhaust is typically located on a low wall, near the dirtier entrance to the airlock.

Air balancing

Procedures for airlock air balancing also vary according to the type of system used. For the cascading pressure airlock, the pressure sink airlock, and the airlock room portion of the potent compound airlock, the supply air minimum CFM must satisfy the clean air classification air changes per hour. The return/exhaust CFMs are then adjusted to obtain the required pressure differential. This means that the pressurization and return/exhaust air quantities on construction drawings are just good guesstimates until the actual CFMs are determined at balancing time.

For the pressure bubble airlock and the gown room portion of the potent compound airlock, the supply CFMs and the exhaust CFMs are temporarily set to the values shown in the construction drawings. The supply CFM is first reduced to obtain design pressurization down to the minimum required to maintain the required air changes per hour. If pressurization is still low, the return/exhaust CFMs are throttled to increase room pressure up to the design value.

A good example of the latter balancing method is the pressure bubble airlock. The minimum supply CFM to maintain 20 air changes/hour in this room is 240. The guesstimated CFM to maintain pressurization is then 500. If the room is tightly built, it will be possible to reduce the supply CFM (down to a minimum of 240) to obtain pressurization.

Temperature control

Airlock temperature control schemes vary depending on both type of airlock and the source of conditioned air. Schemes can include: no dedicated temperature control, dedicated control, and shared control with other adjacent airlocks/gown/pass-thru rooms.

An example of “no dedicated temperature control” is a system where the conditioned air source for the airlock is the supply air branch to the cleanroom with only the cleanroom having temperature control (typically controlling a reheat coil) and the airlock room temperature allowed to float. Though this means that the airlock is slightly colder than the room it protects most of the time, it is typically not a problem because personnel remain in the airlock for only a short time.

An example of “dedicated temperature control” is a “pressure bubble” airlock with multiple, double doors. Here pressurization CFM will be so large that the room could get very cold, and in this case, a reheat coil and thermostat is recommended.

An example of “shared temperature control” is an application having a battery of gown-in/gown-out/pass-thru rooms located near each other, serving different suites. Since all these rooms have similar and constant temperature and cooling/heating loads, one reheat and thermostat could serve all of them.

There are a number of guidelines that must be kept in mind when examining pressurization control schemes for airlocks. First, pressurization is to be maintained when all airlock doors are closed. Second, if two, or all, doors are opened simultaneously by mistake, the direction of air flow from the cleaner to the less clean room must be proven, even though pressure differential cannot be maintained.

Third, the location of the static-pressure probes is critical. For example, with a cascade type airlock, the pressure probes should be located in each room that the airlock is separating, not between each room and the airlock. For pressure bubble and pressure sink airlocks, however, pressure probes are required in all three rooms (each cleanroom plus the airlock). Fourth, a common reference point should be used for all pressure differential readings. Typical locations include the plenum above the ceilings or a common interior corridor.

Fifth, to allow for temporary airlock door openings, there should be a time delay before an audible and visual alarm is activated. The pressure differential range before alarms are activated can be set at ± 0.02 inch w.g.

Once the above guidelines are met, a decision must be made whether to use static or dynamic pressure-differential control. In static control systems, pressurization is adjusted during the test and balance phase of the project. In this phase, balancing dampers are manually set and locked in position once pressurization is obtained. Follow-up, re-balancing can then be done every six months. HEPA filters can also be checked at these times, or at least once a year.

Dynamic pressurization controls can be adjusted in a number of ways. The simplest (and least costly) approach is to manually set the supply air damper to obtain design CFM and automatically controlling a motorized return/exhaust damper to maintain a specific pressure differential across the airlock. A more complex method is the use of constant-volume boxes at the supply and return exhaust ducts to the airlock. These are set to maintain a specific pressure differential across the airlock.

References

  1. Commission of the European Communities. The rules governing medicinal products in the EC. Vol IV. Good Manufacturing Practice for Medicinal Products. Luxembourg: Office for Official Publications of the EC, 1992. ISBN92-826-3180-X.
  2. ISPE Baseline Pharmaceutical Guide Volume 3 – Sterile Manufacturing Facilities First Edition/January 1999. ISPE, 3816 W. Linebaugh Ave. Suite 412, Tampa, FL 33624; Phone: (813) 960-2105; Fax: (813) 264-2816.
  3. 1999 ASHRAE Handbook – HVAC Applications American Society of Heating, Refrigerating and Air-Conditioning Engineers, Inc.; 1791 Tullie Circle, N.E., Atlanta, GA 30329; (404) 636-8400.
  4. Guideline on Sterile Drug Products Produced by Aseptic Processing, Center for Drugs and Biologics, Food and Drug Administration, Rockville, MD, June 1987.

Manuel A. del Valle, PE, is director of HVAC design at the South San Francisco office of Fluor Daniel, an international design, build, maintenance company. He has published a number of articles and lectured at various seminars of national and international associations on HVAC design for pharmaceutical/biopharmaceutical plants. He has been designing HVAC systems for pharmaceutical/biopharmaceutical plants since 1971.


Airlock pressurization CFM calculations

In the following examples based on four airlock types, it is assumed that all doors are 3' x 7', that each airlock is 8' x 10' x 9' high, and that the airlocks are Class 100,000 with an air flow rate of 20 air changes/hour. The required supply CFM becomes: CFM = Vol x ACHR/60 = (8 x 10 x 9) x (20)/60 = 240.

For the cascading pressure airlock, to maintain pressure differential across the clean and the non-classified area, assume one of the airlock doors is open. The pressurization CFM for a pressure differential of 0.05 w.g. is then: CFM = A x V or CFM = 0.24 sq. ft. x 896 FPM = 215 (say 210). With both airlock doors closed, the CFM leak between the cleanroom and the airlock is the same as between the airlock and the corridor. Therefore, the return CFM of the airlock is the same as its supply CFM or 240.

For the pressure bubble airlock, the pressurization CFM for each door is different. For the corridor door: CFM = A x V = 0.24 x 896 = 215, say 210 (for a pressure differential of 0.05 w.g.). For the cleanroom door: CFM = 0.24 x 1201 = 288, say 290 for a pressure differential of 0.09 in. w.g.). The airlock minimum supply CFM is still 240 (see above), but to satisfy air pressurization it will have to be bumped up to 500 (210 CFM + 290 CFM). The exhaust CFM will be zero because it is assumed all supply air will be dissipated as pressurization CFM.

The pressure sink airlock will also have different pressurization CFMs for each door. The corridor door pressurization CFM = 0.24 x 1201 = 288, say 290 (for a pressure differential of 0.09 in. w.g.), the biocontained room door pressurization CFM = 0.24 x 896 = 215, say 210 (for a pressure differential of 0.05 in. w.g.). The minimum supply CFM to the airlock is still 240 CFM but the exhaust CFM becomes 740 (290 + 210 + 240).

In the potent-compound airlock, each door will have a different pressurization CFM requirement. For the door between cleanroom and airlock: CFM = 0.24 x 801 = 192, say 190 (for 0.04″ w.g. pressure diff.); for the door between airlock and gown: CFM = 0.24 x 1444 = 347, say 350 (for 0.13″ w.g. pressure diff.); and for the door between gown and corridor: CFM = 0.24 x 896 = 215, say 210 (for 0.05″ w.g. pressure diff.).

The minimum supply CFM to the airlock and the gown room will be 240 CFM each, but the gown room will require 560 CFM (350 + 210) to satisfy pressurization requirements. The gown room return will be zero and the airlock exhaust 780 CFM (190 + 350 + 240).

This paper was presented at CleanRooms West '99 in San Jose, CA. For a copy of the conference proceedings, which are available for $95, please call 603-891-9267.

For more exciting conference sessions on contamination control, be sure to attend CleanRooms East 2000. Visit www.cleanrooms.com for more information.

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