Moving towards green barrier systems

10-Feb-2015

As the pharmaceutical sector looks to cut costs wherever possible, Dr Johannes Rauschnabel, Chief Pharma Expert, Bosch Packaging Technology, reviews the energy use of RABS vs isolators

Instead of comparing barrier systems solely in terms of costs, the consideration of energy consumption offers another insightful approach – especially as it is in line with the recent trend towards ‘green’ pharmaceutical manufacturing. Depending on a) ambient conditions, b) defined parameters and c) the respective air supply systems, the energy consumption of Restricted Access Barrier Systems (RABS) and isolators varies significantly. For instance, isolator systems can save up to 65% of energy compared with RABS, while active RABS are up to 30% more energy-efficient than passive RABS.

Many highly complex process steps, combined with long development periods and expensive ingredients make the pharmaceutical industry a very cost-intensive business. Pharma has had a reputation of being reluctant to consider more ecological production alternatives. However, being neither immune to rising energy costs1 nor against higher regulatory requirements, the industry is currently rethinking its manufacturing philosophy. In parallel, the use of high-potency pharmaceuticals has grown extensively, causing producers to pay more heed to even safer production processes. Good Manufacturing Practice (GMP) guidelines2 require dedicated facilities to minimise the risk of cross contamination.

Both RABS and isolators are designed to prevent product contamination. RABS provide a physical barrier between the production area and the operator environment. The production area is equipped with a rigid machine enclosure, safety-locked doors and ports with gloves3. Depending on the kind of aeration, RABS can be divided into active and passive systems (Figure 1). Active RABS have self-contained air handling equipment, while passive RABS are sealed to the ceiling of a class B cleanroom.

Figure 1: Schematic of active and passive RABS systems

Figure 1: Schematic of active and passive RABS systems

An isolator, in turn, is a hermetically sealed system with a complete separation of operator and process area. Doors cannot be opened during production, which makes it possible to operate isolators in a class D cleanroom environment (ISO 8, in operation). Isolators are typically equipped with a system for an automated bio-decontamination cycle and an air handling unit (AHU). The latter ensures temperature control by heating or cooling, as well as permanent overpressure control of the process area to avoid ingress of contaminated air.

The main differences between RABS and isolator systems in regard to energy consumption result from the smaller cleanroom space and the classification of the surrounding cleanroom. Isolator systems can be operated in a class D cleanroom, while RABS need a surrounding class B cleanroom (ISO 7, in operation). RABS also require higher air change rates and additional areas for air locks and dressing rooms. Isolator systems can be integrated into the technical building services in various ways. From an energy point of view, it is desirable that as little outside air as possible is conditioned for the isolator. Maximum use of recirculation significantly reduces the outside air flow rate. Depending on how the air is supplied and discharged, an isolator with a system that uses air from the surrounding room to condition the process air can save up to 65% of energy4.

Factors to consider for a comparison

The main sources for energy consumption in barrier systems are cold and hot water, steam and electricity. Cold water is essential for chilling the outside air and for dehumidification. The opposite, humidification, is achieved by pure steam. Electrical power is required for outside air handling and, if necessary, for fans.

Depending on the individual parameters, the energy consumption of active RABS can be approximately one third lower than for passive RABS. While passive RABS are completely supplied by fresh pre-conditioned air, active RABS use pre-conditioned air from the cleanroom. At the same number of air changes, passive RABS show a higher outside air flow rate. This difference relates directly to the reduced amount of steam required for humidification and electrical power needed for outside air handling with active RABS.

Depending on their air handling configuration, isolator systems also consume differing amounts of energy for chilled water, hot water, pure steam and electricity (Figure 2).

Figure 2: Energy consumption of barrier systems

Figure 2: Energy consumption of barrier systems

System A (Figure 3) provides pre-conditioned make-up air to the process AHU, which precisely adjusts the air parameters to the process requirements. While System A discharges the exhaust air to the outside, System B re-uses it for process conditioning during production. System C on the other hand takes air from the cleanroom environment, and recycles or – during bio-decontamination – discharges it.5

Air conditioning, a major energy user

As the aforementioned comparisons show, air conditioning in technical building services is a key factor in the analysis of energy efficiency – especially in the pharma industry with its cleanrooms. Air handling systems control temperature and humidity, as well as the numbers of particles and organisms by means of filtration. By managing the differential pressure between different cleanrooms and filling lines, it is possible to avoid the transportation of particles, viables or contaminated air into the process environment.

One of the most frequently used air conditioning systems is central recirculation/mixed air conditioning6, which conforms to the principle set-up of barrier systems according to the ISPE Good Practice Guide7. These systems are commonly used for a specific production area or a single production line. They are equipped with a common central AHU for all cleanrooms. The supply- and recirculation-air passes through all components (mixing chamber, filter, heater, cooler and humidifier) of the AHU.

Passive RABS have no aeration equipment; they are supplied with air from the cleanroom ceiling and are conditioned by the building services. Active RABS, on the other hand, have their own aeration and filtration equipment and take the air directly from the cleanroom. The unidirectional air flow fans (UDAF) are independent of the cleanroom aeration and are directly placed onto the RABS processing area.

Isolators have a separate outside air conditioning and filtration system with their own recirculation ducts; their UDAF is similar to the one inside RABS. Isolators are generally equipped with a proprietary process AHU, which dissipates internal heat loads and corresponds to the special air requirements of bio-decontamination.

Figure 3: Different isolator systems and air handling configurations

Figure 3: Different isolator systems and air handling configurations

Subject to the isolator system in use, the process AHU can be supplied by an additional outside AHU, while the exhaust air is discharged to the outside. On the other hand, the process AHU may only discharge the amount of air which is necessary to achieve the specified number of fresh air changes, and to control the pressure level inside the isolator by an exhaust fan.

Meaningful investment decisions

A number of pre-defined parameters must also be taken into account for an energy-related calculation of barrier systems. Among these parameters are room size, change of air ventilation, fresh air rate, regulated and unregulated cleanroom temperature, outside air temperature, heat recovery rates, as well as thermal loads.

This specific data can have a large impact on the results and may vary significantly, depending on the local climate or seasonal temperatures. A comparison of the energy consumption of different barrier systems is only possible for a very specific situation and should always be recalculated on the basis of the relevant component characteristics.

Pharmaceutical manufacturers who want to save energy costs through their choice of equipment, or ‘green’ pharmaceutical operations should look to have an individual calculation carried out for each new project, clearly determining the parameters and specifying the goals. Only then can such a comparison offer a meaningful approach on how to integrate energy consumption into investment decisions – and ultimately save costs.

References

1. www.eia.gov/electricity/data.cfm#sales and http://epp.eurostat.ec.europa.eu/tgm/table.do?tab=table&plugin=1&language=en&pcode=ten00114

2. FDA: Guidance for Industry. Sterile Drug Products Produced by Aseptic Processing – Current Good Manufacturing Practice, www.fda.gov/downloads/Drugs/.../Guidances/ucm070342.pdf, September 2004.

3. Jack Lysfjord, Pharma. Engineering, Vol. 25, No. 6, 2005, pp. 1–3.

4. B. Hoffmann; K. Frank; J. Rauschnabel, Pharma. Engineering, 33 No. 6, 2013, pp 70–78.

5. Further options with catalytic recycling during bio-decontamination are not considered here. They do not achieve significant energy savings, as the bio-decontamination phase is short and the required dehumidification before recycling also consumes energy.

6. Further systems used by the pharma industry are: local mixed air systems with central outside air conditioning; straight outside air systems, and recirculation air systems.

7. ISPE Good Practice Guide – Heating, Ventilation, and Air Conditioning (HVAC), 3.15.4 Isolator Systems.

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