USP 797: A work in progress-Part 2

By Hank Rahe, Containment Technologies Group

Editor’s note: Hank Rahe’s look at General chapter <797> Pharmaceutical Compounding – Sterile Preparations continues this month. For part one, please see CleanRooms, July 2005.

Facilities requiring compliance with USP 797 can be placed into two broad categories: a cleanroom that supports higher air quality environments such as clean benches and biological safety cabinets; and barrier isolators, which are not required to be placed into a cleanroom.

The facility, however, is only one of the key elements that provides for the sterility assurance of aseptically compounded preparations. The ability to clean and sanitize the environment, proper personnel training in aseptic techniques, the selection of appropriate personnel attire, and the use of the correct ingredients and components must all come together to ensure patient safety.

The current requirement for the air quality of the compounding cleanroom is ISO Class 8, with a proposed change to ISO Class 7. An ISO Class 5 environment is required inside the cleanroom for the compounding of the preparation delivered to the patient. The design of the cleanroom and materials of construction are discussed in the chapter.

Chapter 797 describes two types of cleanroom design: One is the traditional pharmaceutical type with the cleanroom for compounding supported by an anteroom. This design has the ability to provide proper pressure differential and airflow in order to minimize contamination. The second design is a single room in which products are compounded, personnel are gowned and material is prepared. In the single-room design, the compounding and preparation areas are separated only by an imaginary line.

The engineering design of the air-handling systems for the two types of cleanroom should be significantly different since the single-room approach does not have a physical barrier to separate the anteroom and preparation areas. The gowning and preparation areas in the single-room design have the potential to spread particulate contamination if the air-handling returns are not properly located. The location of the return ducts for this type of room should be designed to direct the contamination away from the compounding area. The air returns should be located low in the walls and be used to pull the airflow towards the door and gowning area. This will help to control the contamination and protect the critical area in which the compounding is to take place.

The cleanroom air-handling system must be HEPA-filtered. A common question is: How many air changes are required? The answer depends on the particulate load created by the activities and the equipment in the room. Factors affecting particulate generation include the number of personnel, the amount of materials being transferred, and the equipment being used in the cleanroom. Personnel generate a significant number of particles and the amount of particles released into the cleanroom environment is a function of proper garments and gowning procedures and the training of the individuals in appropriate cleanroom conduct.

The single-room design will require more air changes because the gowning activities and movement of personnel in and out-even without gowning and material movement-will significantly increase the particulate load.

Both room designs require a positive pressure differential between adjacent areas to influence the airflow to move to the area of lesser air quality. To achieve positive pressure the rooms must have a door and be sealed properly. A number of cleanroom designs before USP 797 could be more accurately described as “clean zones,” which were partly enclosed with HEPA filtration created by a fan filter module located in the ceiling.

Hard-wall construction is required with either epoxy-coated gypsum board or modular panels that are locked together and sealed. The ceiling can be inlaid panels that are caulked to the support frame and around the perimeter. Floors should be sheet vinyl with heat-sealed seams and coved to the walls. The surfaces must be able to withstand cleaning and sanitizing materials.

Ledges, such as door and window frames, and utility piping should be designed to minimize the surface area that will collect contamination. Penetrations should be sealed. Lighting fixtures should be smooth, flush-mounted and sealed.

Key to the engineering design of any cleanroom is an understanding of the activities that are taking place in the area, including frequency of movement, number of personnel and the amount of materials moving in and out of the space. The use of a pass-through for materials coming into the cleanroom can minimize personnel movement. If carts are used for transfers, they should be restricted to given zones so that the wheels do not spread contamination.

The equipment required for operation of the pharmacy cleanroom should be selected with two factors in mind: the ability to clean and sanitize the surfaces; and the amount of particulate the equipment generates. Items such as computers, printers, compounding equipment, refrigerators and freezers are necessary to properly compound preparations, but each adds to the potential for contamination and must be thoughtfully selected and positioned in the cleanroom.

In summary, gowning techniques and the level of gowning are particularly critical for contamination control. An aseptic environment, however, requires not only particulate control but also more importantly the proper sanitization or decontamination of materials. Good aseptic techniques are critical for the manipulation of materials in the critical zones where the preparations are compounded.

The next article in the series will address ISO Class 5 equipment for compounding sterile preparations.

Hank Rahe is director of technology for Containment Technologies Group and is a member of the CleanRooms Editorial Advisory Board. He can be contacted at [email protected].


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