HVAC design for cleanrooms
Know what type of cleanroom is being designed to meet USP Chapter 797.
The U.S. Pharmacopeial Convention (USP) created a document in 2007 that relates to pharmacological practices. USP Chapter 797 (revised in 2008) relates specifically to pharmaceutical compounding - sterile preparations (CSPs). The objective of this chapter is to describe conditions and practices to prevent harm—including death—to patients that could result from microbial contamination, excessive bacterial endotoxins, variability in the intended strength of ingredients, unintended chemical and physical contaminants, and ingredients of inappropriate quality in CSPs in the course of administering the CSP to patients.
Chapter 797 pays particular attention to the provisions, maintenance, and evaluation of air quality, and these requirements, along with design ideas to achieve proper air change rates and air quality, are the focus of this article. The standards contained in USP 797 are applicable to places where CSPs are prepared, including hospitals, patient treatment clinics, pharmacies, physicians' practice facilities, and other locations where CSPs are prepared, stored, or transported.
The project team, including the facility pharmacist, architect, equipment vendor, and HVAC engineer, must be involved in planning the compounding area. Identification of critical area type and placement is important to HVAC design and air distribution. One important item to note is that all CSP areas and anterooms are cleanrooms and require HEPA-filtered supply air. Compounding pharmacies typically have two room types, with anterooms placed between or adjacent to each room:
A cleanroom where hazardous drugs are prepared, such as chemo prep rooms
Cleanrooms where nonhazardous drugs are prepared.
Pressure relationships, airflow, and cleanliness are vital to maintaining the cleanroom condition required in each space. Hazardous drug (chemo) prep rooms are negative to the anteroom. The chemo prep anteroom is positive to the chemo room and positive to the adjacent work space or corridor access.
Cleanrooms with nonhazardous drug preparation are positive to their anteroom, which also is positive to the corridor or adjacent work space. Cleanrooms where radiopharmaceutical drugs are prepared are negative to the anteroom, which is positive to the prep room and the adjacent spaces, similar to the hazardous drug prep rooms.
Criteria affecting the HVAC design of the pharmacy include:
Selection by the user of the critical area type
Design of the ISO Class 7 buffer area at 30 ACH minimum
Design of the ISO Class 8 ante-area at 30 ACH minimum
Pressure differential relationships of 0.02 to 0.05 in. water column between cleanrooms and adjacent spaces
Identification of drug types (hazardous, nonhazardous, and/or radiopharmaceutical) to design positive or negative pressure rooms
HEPA-filtered unidirectional airflow design from the ceiling through high-capacity laminar flow air devices apart from the ISO Class 5 environment to minimize disruption at that environment
The low return air location in ISO Class 7 and 8 rooms
Proper space temperature (+/- 68 F) to provide occupant comfort due to added garb and protective clothing
Ceilings and items penetrating the ceilings such as air devices, light fixtures, and sprinkler heads gasketed or caulked and sealed so no cracks or crevices exist. Additionally, all wall penetrations by devices such as receptacles, switches, and thermostats also must be sealed to keep the room particulate count within established limits.
Specific airflow problems can exist in the design of the space, which can cause major headaches for the design engineer. A 200-sq-ft ISO Class 7 buffer area with a 9-ft ceiling supplied with 30 ACH will require 900 cfm of HEPA-filtered supply air. Chemo preparations typically are done in a Class II Type B2 biological safety cabinet (BSC) which achieves ISO Class 5 cleanroom criteria and serves as the Primary Engineering Control In chemo prep rooms, these cabinets are hard-duct connected and require 760 cfm or more of exhaust. Many rooms have two or more cabinets, and above-ceiling coordination can be an issue. The 30 ACH requirement is easily met, and with all air exhausted through the cabinet, there is no need for the low return/exhaust.
Air supply through high-capacity laminar flow air devices with HEPA filters at the point of discharge can meet the supply air requirement in hazardous drug prep rooms. Many times in renovation projects the existing air distribution system does not have the capacity to provide the 30 ACH required or does not have the capability to overcome the static pressure drop of the HEPA filters at the point of air discharge. Sometimes in-line supply air fans are needed to overcome the added static pressure and dedicated 100% outside-air air conditioning units are needed for proper space conditioning and air supply.
In rooms where nonhazardous drugs are prepared and no BSC exhaust is required, the 30 ACH requirement also can be achieved. Low-return air registers are required with air recirculated and supplied through HEPA filters. In-line supply fans, which may take a portion of the air from the building HVAC system and the remainder from the space through the low return, can supply the required ACH delivering the airflow through high-capacity laminar flow air devices. Another approach is to use fan-powered HEPA-filtered supply air units that re-circulate room air. These unit fans are typically remote-controlled so that specific air delivery rates are achieved. Fans and accessories serving the rooms must be mounted in accessible locations, and the heat gain from such devices also must be taken into account.
As with all spaces, a proper amount of ventilation air from the building system is required for occupant needs, to aid in maintaining proper air velocity (40 fpm) and direction from the ISO Class 7 buffer area to the ISO Class 8 ante-area, as well as to maintain proper pressure relationships. In all cases where HEPA-filtered air is provided, a means of testing the effectiveness of the HEPA filter must be provided through test ports.
Once the HVAC designer has the user-defined PEC and location and type of drugs to be prepared, the systems and space can be properly designed. Knowing the existing HVAC system design parameters during renovation also will provide insight into the airflows available to assist in system design and space pressurization.
Banse has more than 30 years of experience in the consulting engineering field with the past 25 years in healthcare design and engineering. He is a member of Consulting-Specifying Engineer's Editorial Advisory Board .
A few definitions are important to understanding the cleanliness required of such spaces.
ACH : Air changes per hour
Ante-area or anteroom : An ISO Class 8 or better area that serves as a transition area to the buffer area or cleanroom.
Buffer area : An area (ISO Class 7 or better) where the PEC is physically located.
Cleanroom : See Buffer area. An area where concentrations of airborne particulates are controlled to meet specified criteria.
Critical area : An ISO Class 5 environment.
Critical site : A location that includes any component or fluid pathway surfaces or openings exposed and at risk of direct contact with the air or moisture, or touch contamination.
First air : The air exiting the HEPA filter in a unidirectional airstream that is essentially particle-free.
Negative pressure room : A room that is at a lower pressure than the adjacent spaces with a net airflow into the room (e.g., chemo prep rooms and radiopharmaceutical prep rooms).
Positive pressure room : A room that is at a higher pressure than the adjacent spaces with a net airflow out of the room (nonhazardous CSPs).
Primary engineering control (PEC) : A device or room that provides a Class 5 environment for the exposure of critical sites when compounding CSPs.