Airlocks for cGMP facilities

Free pharmacy material

The use of airlocks is a principle that is well-established in the design of cGMP facilities. Despite the apparent simplicity of inserting small rooms into the plan of a pharmaceutical manufacturing facility, there is confusion regarding their proper use and definition. Airlock seems like a simple enough term, but airlocks have several distinct functions that, although closely related, are freely mixed and often cause confusion. This article looks at these functions and definitions.

Airlocks

Airlocks are an architectural device that helps implement heating, ventilation, and air conditioning (HVAC) control of air classification or quality. Their purpose is to allow a shift between cleanliness levels, for example, from ISO 8 to ISO 7 or Grade C to B. This shift is achieved by maintaining room pressurization (by the direction of air flow through doors) and isolating the levels from each other. This common understanding of airlocks is defined in industry literature (1).

An airlock is a space that provides segregation of cleanliness zones. While always designed for the higher level of cleanliness, when in use, the room will switch back and forth between levels as the doors open and close. When one door is opened, the opposite door maintains the boundary. And when opened to the lower classification level, the airlock effectively downgrades (see Figure 1). Once all the doors are closed, the room re-establishes itself at the higher level. Similarly, when a door is opened, air flows into or out of the room, and the pressurization at the open door goes neutral; the door opposite becomes the new boundary. 

Figure 1: An airlock segregates cleanliness zones. When one door is open, the room becomes the level of the open door, and the opposite door becomes the new boundary, indicated by the red dashed line. Image is courtesy of the author.

Gowning rooms

Whenever there is a change in air classification, a gowning activity also occurs. Personnel are the dirtiest entity entering a cleanroom. Contaminants generated by personnel must be properly encapsulated to restrict particulate counts to the levels appropriate for the cleanliness level in question. Depending on the nature of the process (i.e., oral solid dose, aseptic, biologic), restricting particulates may mean adding more coverage or possibly a change of garments. Upon leaving a cleanliness zone, the potential to carry contaminates out of the higher air classification must also be considered. In any case, a garment adjustment is necessary when moving to a new zone.

Because airlocks and gowning rooms are both required between air classifications, they are often considered the same. There are instances, however, when gowning occurs and a change of air classification does not. A case in point could be a multiproduct facility where containment is crucial. In this example, gowns exposed to product in a processing area need to be considered contaminated and should not be introduced back to a common corridor serving adjacent processing rooms. Given that gowning rooms are not necessarily airlocks, it is important to be clear on the need and purpose of the gowning room and to deploy them accordingly; not just whenever airlocks occur.

Transition spaces

Transition spaces are the odd duck. They are essentially airlocks, but they do not meet the classic definition. While airlocks are indispensable to the proper segregation of air classifications, the term “transition space” is used to distinguish those instances when there is no change in cleanliness level. In these situations, the air classifications on both sides of the transition space are the same, but maintaining pressurization and direction of air flow is still crucial. Such conditions are primarily found where containment is required. A good example is in a biological facility where a transition space is necessary to maintain a biosafety boundary. Both sides may be Grade C, but to properly segregate the adjacent processing rooms or rooms served by a common corridor, it is necessary to confine contaminants to within each room. In an oral solid-dosage facility, containment could be needed where there are adjacent processes using dusty operations. In both cases, the transition space allows for containment within the process room through the control of pressurization and the direction of air flow.

Summary

The term “airlock” is often used loosely, which can result in a lack of understanding of process segregation. The primary role of an airlock is the isolation of cleanliness zones. Like airlocks, gown rooms are always needed when moving between different cleanliness zones, but gowning rooms are needed in other instances as well. For any facility, a gowning strategy needs to be thought through independent of the cleanliness zones and, if appropriate, additional gown rooms provided. On the other hand, transition spaces are functionally airlocks, at least in terms of pressurization. Sometimes, process spaces need to have the segregation that airlocks provide even though there is not a change in air classifications. Again, process segregation is a topic that needs to be thought of independent of the extent of cleanliness zones. Given that these functions are so closely related and even overlap, it is easy to understanding the blending of these terms together as airlocks. When looking at a pharmaceutical manufacturing facility design, however, it is important to recognize that these different cGMP aspects need to be considered based on their own criteria. When these factors are considered carefully and employed deliberately, a more effective facility can be achieved that is both cGMP compliant and operationally efficient. 

Reference

1. ISPE, ISPE Baseline Guide, Vol. 3: Sterile Product Manufacturing Facilities, Second Edition (Bethesda, MD, Sept. 2011.)