Barrier Isolation Technology:
An alternative to the cleanroom

by
Hank Rahe,
B.S.I.M., M.S.E.

Investment decisions for equipment and facility design are typically made early in the process of setting up a home infusion facility. These decisions have an impact on present and future capacity and can become a fixed operating cost that reduces potential profits.

The ability to make these expenditures incrementally is a function of the technology used to provide the proper environment for preparing parenteral products.

One of the major up-front expenditures incurred by home infusion facilities is the creation of a controlled environment for the sterile preparation of parenteral products. In addition, there are ongoing expenditures associated with cleanroom operations.

Barrier/isolation technology has recently been introduced in the infusion industry as an alternative means of achieving sterile product preparation. As infusion companies seek ways to reduce their cost structures and improve their competitiveness, this technology may offer significant advantages to providers.

Air Quality Standards

Aseptic manipulation of parenteral products involves two key components. The first is a quality environment capable of maintaining an area with minimum potential for contamination of the product; the quality of the environment is defined by the amount of particles present in the air. The second is proper sanitizing techniques, which when applied to the area will kill any microorganisms that may exist in the environment.

For the critical area of aseptic operations--the immediate work space where the product is actually prepared--it is generally agreed that the air quality should achieve a Class 100 standard. Federal Standard 209E describes this as an area with less than 100 particles of .5 micron size per cubic foot of air volume.

For areas adjacent to critical areas, a lower air quality standard is acceptable. Common manufacturing practice is a minimum of Class 10,000 (areas with less than 10,000 particles of .5 micron size per cubic foot of air volume.) Depending on state regulatory requirements, many hospital pharmacies and home infusion facilities have not yet adopted this standard.

Laminar Flow Technology

Laminar flow technology is the most common method used to achieve the air quality required for aseptic preparation of parenteral products. Particles are removed from the air by passing the air stream through a high efficiency particulate air filter (HEPA filter). To be classified as a HEPA filter, the filter must remove at least 99.97 percent of the particles larger than .3 micron. The effectiveness of laminar flow technology depends upon both filtration and velocity of the air stream. Laminar flow technology is used in both hoods and cleanrooms.

Depending on the types of products to be prepared, infusion therapy providers generally use either horizontal or vertical laminar flow hoods. Horizontal laminar flow units pass air through a HEPA filter located so that the air stream passes over the product's critical zone and directly into the face of the pharmacist. This approach has serious drawbacks, including a dependence on the pharmacist's technique and the need to ensure that objects under the hood do not block the airflow. Another significant problem with laminar flow hoods is that personnel are always downstream of the material being prepared and therefore are constantly exposed to the particulate matter circulated by the air stream.

Vertical laminar flow units pass air through HEPA filters located above the work surface and covering the critical zone. This system lowers the clinician's exposure but still requires procedural techniques to provide adequate protection. The air stream must pass over the hands and arms of the pharmacist resulting in the potential of air currents, which may leave the product unprotected and introduce contamination outside the hood.

Cleanrooms

Cleanrooms are designed to achieve a desired air quality standard by circulating the air through HEPA filters. The classification of the room is indicated by the rate of movement or the number of air changes. Only a certain amount of air can pass through each HEPA filter, therefore the number of HEPA filters is generally considered an indicator of air quality (see Exhibit 1).

Cleanroom construction methods vary, ranging from the portable or modular units to custom fabrication. Each has advantages and disadvantages. Regardless of the construction method, there are a number factors to consider when evaluating the cost of constructing and operating a cleanroom, including:

Construction Materials. The life cycle cost of the cleanroom includes not only the initial investment but also the cost maintenance.

Filter Requirements. How many HEPA filters will be required? Using fewer HEPA filters may reduce the cost of the cleanroom but may not achieve the desired air quality standard.

Layout. The design of the cleanroom should include an anteroom for changing and preparing materials that will enter the cleanroom. The layout should also consider the effect of equipment placement and personnel traffic patterns on the air quality of the room.

Air Return Systems. The location of supply and return air ducts is important because they can form streams of air that leave "dead spots" in the cleanroom. These locations can result in contamination problems. Cleanrooms should be "mapped" to assure uniform air distribution throughout the room.

Heat Buildup. The mechanical systems required to support laminar flow technology are a major source of heat. Additional air condition capacity may be required to compensate for the heat load of both the hoods and the cleanroom systems.

Installation Time. The installation time will vary depending on the construction method used, but it may take weeks and involve significant disruption. If existing facilities are involved, operations may have to be discontinued or relocated during the construction. These indirect expenses should also be accounted for in the cost estimate.

Capital Costs and Operating Costs. Capital costs for a cleanroom include site preparation, utilities, purchase, installation, and certification. Operating costs include the utility costs, supplies (including protective clothing), maintenance, and labor costs (including time spent for clothing changes).

Capital expenditures for hoods and cleanrooms represent a major commitment and risk for the provider. The cleanroom is a major, fixed system that must be operated continuously and hence can represent substantial operating costs. It must be sized to meet anticipated volumes, and depending on the construction method used, expansion required to retrofit. In the event that the company is closed or relocated, the value of the cleanroom is small, since moving the facility generally is not cost effective.

Barrier/Isolation Technology

Barrier/isolation technology represents an alternative to laminar flow technology and cleanroom construction as a means of achieving an aseptic environment.

It is generally accepted that people are a major source of contamination in the product preparation environment. Studies have shown that by removing personnel from the area in which aseptic manipulation takes place, increased sterility assurance levels are achieved.

The concept forms the fundamental premise behind barrier/isolation technology. This technology was first used in the nuclear industry over forty years ago. Since that time electronics and pharmaceutical manufacturers have actively pursued the applications of this technology due to its performance and cost effectiveness. In the past two years, barrier/isolation technology has been introduced into the hospital pharmacy and home infusion markets.

The barrier/isolation workstation for sterile drug preparation is a closed environment that uses solid stainless steel walls rather than air movement to create a critical zone for product handling. A hard clear plastic wall is also used to allow compounding personnel for viewing operations. The area is completely contained, offering protection to both the pharmacist and the product. The solid barrier eliminates the procedural requirements of a "set back" and the need to place materials within the work zone in a manner that does not block the laminar flow. This freedom of placement allows more efficient work flow and productivity equal to or exceeding traditional hoods.

A HEPA filtration system is also used to condition both entering and exiting air to remove initial particles and particles that may be generated by the materials being used in the unit. Because the air filtration system of the unit is not being used to provide a barrier, high velocity is not needed, thereby reducing energy cost, noise levels, and heat loads. In many cases, the air is recirculated within the unit; in addition, a small quantity of air is discharged to maintain a pressure differential between the interior of the unit and the environment in which it is located. This pressure differential is used as a back-up if the security of the system is breached. When product protection is the highest priority, the pressure differential can be positive; or, as in the case of handling cytotoxic preparations where the protection of the pharmacist is the most critical, the differential can be negative.

Compounding Technology

As with the use of a conventional hood, the manner in which mateirals are introduced into the unit and how people interact with the product are crucial to ensuing aseptic preparation conditions. To help eliminate these potential sources of contamination, the product is introduced in the workstation using an airlock system to separate the critical area and the outside while also allowing additional items to be introduced during operations. Glove ports are also used to allow compounding personnel to manipulate the product without exposing either the product or the pharmacist.

As materials are transferred into the workstation, they must be sanitized using a spray-down method. Using this procedure, tests show that typical particle counts inside a barrier/isolator workstation approach Class 1 in routine operations and are still well within the Class 100 requirement within a few seconds of introducing the product into the primary chamber.

Proper sanitization is a necessary part of any successful aseptic operation. This involves both the use of proper methods and sanitizing materials. The workstation design should be accessible and easy to sanitize, allowing the use of contact sanitizing agents. Typical sanitizing materials include alcohol and hydrogen peroxide.

Implications for Home Infusion

Barrier/isolation technology offers a cost-effective, flexible choice for both large and small home infusion therapy providers.

The totally enclosed environment of barrier/isolators combined with HEPA filtration creates Class 100 conditions. Large volumes of air are no longer required, therefore the size of the mechanical air systems is reduced, which in turn creates less noise and heat than laminar flow technology. Because the system is smaller and can be turned off when it is not in operation, operating costs are also reduced substantially. Integrity of the product can be increased because compounding personnel are moved from the critical zone and are only able to manipulate the product through glove ports.

The capital costs and operating costs of barrier/isolator systems can be less than a cleanroom. In some cases, the reduction in operating costs can cover the leasing costs of the barrier/isolation system with no additional expenditure. Barrier/isolator systems may also offer tax advantages, since they represent equipment rather than a fixed facility.

The barrier/isolator approach allows incremental growth of the facilities without disrupting existing operations. The number of workstations required for a given facility is based on volume and mix of product. High-volume and multi- location providers can control start-up as well as ongoing expenses by incrementally adding workstations as demand grows from location to location. This ability offers a significant competitive advantage. Lead times for equipment can be as short as six weeks, allowing expansion to meet demand. In some cases, installation and certification can be completed within a matter of hours.

Time studies have shown that barrier/isolation systems are slightly more efficient than conventional hoods not in cleanrooms. When the in and out time of a cleanroom operation is considered, the advantages of barrier/isolation workstations are even more striking.

Organizing and transferring materials into the workstation using a tray system is the key to workflow efficiency. Internal disposal systems for sharps and packaging materials can also enhance efficiency and safety. Workstations have been developed for both large volume admixtures such as TPNs and smaller packages such as piggybacks and disposable syringes.

In summary, barrier/isolation technology can offer a cost-effective alternative to laminar flow technology for providing a Class 100 environment. Cost advantages are achieved through reduced capital costs, reduced operating costs, reduced investment in disposable supplies such as personnel protective clothing, and controlled expansion. The operational advantages are flexibility of location, less heat, and noise in the working environment and the ability to turn the unit off when not in operation.

Hank Rahe, M.S.I.M., M.S.E., is director of technology for Containment Technology Group, Inc. (317-862-5945), a manufacturer of mobile workstations for the preparation of sterile products using barrier/isolation technology. Rahe has more than 27 years experience in the pharmaceutical industry, specializing in aseptic product preparation.