Cost factors for both flexible containment and rigid containment are a serious consideration, Any engineering approach to minimize materials migration including dedicated suites, airlock passageways, and other infrastructure designs, frequently increases both capital and operating costs beyond established budget constraints. Costs associated with permanent rigid containment can be orders of magnitude higher than for flexible containment solutions. This is true of design and installation costs as well as validation and operating costs. Another attribute of flexible solutions is the speed with which a prototype solution can be designed, installed, performance tested, and optimized for permanent installation. Rigid solutions cannot compare with the speed of introduction, training, and testing.
Containment usage of any type can be classified by the application, which can fall into several types:
- Open handling requirements, e.g. dispensing, and in-process sampling
- Equipment isolation where equipment is incapable of total closure
- Major materials transfer such as charging and packaging
- Process line disruptions
- Process turnaround and cleaning
- Maintenance operations
- Equipment transport and storage
- Facility retrofit
- Laboratory handling
- Development processing and scale-up
- Performance testing new equipment
- Shared warehousing and shipping
- Product transport using contract shippers
- Environmental control
When a manufacturing site for either bulk or finished goods is undergoing design as a high potency handling facility, cost estimates are frequently exceeded when operational details come into play. It is normal for a dedicated facility design outcome to result in budget escalation when these discussions occur after initial conceptual design and construction is approved.
Design frequently overlooks the needs of several departments that will impact facility usage, most of which are not normally involved in design considerations. Quality, operations, instrumentation, warehousing, dispensing, maintenance, waste management, emergency responders, and site security all have an interest in building operations, as well as downstream users of packaged goods.
Containment concerns will ultimately affect buildings other than the processing facility. Raw materials, final bulk, and finished goods are handled by several departments outside the scope of a building design team. Facility operations will impact operations in other buildings. The condition in which materials are handled before and after they leave the building must be approached realistically. Potent compound release within the confines of a storage warehouse will create significant problems. Even worse is the potential for materials contamination during shipping within and outside the manufacturing site. Similarly contamination of a maintenance shop during equipment disassembly is a serious problem. These and many other scenarios will occur in buildings that normally have room surfaces incapable of effective cleaning to levels currently required for potent, sensitizing, or other classes of compounds of concern. The impact is greatest when shared services are standard practice.
The possibility of product cross-contamination is always present. Based on client experiences, once the cat is out of the bag it is virtually impossible to put it back – so to speak. We often encounter an already contaminated facility requiring retrofit containment to protect a new process and product from existing materials as well as preventing further emissions.
Design and construction of laboratory and development facilities are not exempt from these budget multipliers. Any facility handling potent or sensitizing materials tends to fall outside the scope of normal Architectural and Engineering (A & E) department experience. This is especially true when outside services are contracted for support such as laboratories, animal and human testing, shipping services, contract research studies, etc. Due to cost escalation, many capital improvement plans have been abandoned in favor of readily available flexible containment solutions requiring minimal space. Routine product users such as hospital dispensaries may also be placed at risk if due consideration to product packaging, shipping and breakages are not addressed.
Our experience with users has been that flexible containment barriers are not a first line approach to containment. The trend is to consider them only after cost projections go out of control. Most A & E departments are still reluctant to use flexible containment as a first line solution.
In one case, a facility construction budget was exceeded five fold before a flexible containment aspect was addressed. As a consequence, the processing areas had an unplanned appearance because adoption of flexible containment was after the design was finalized. Many headroom constraints were overcome using flexible containment. Performance data showed the containment goal was achieved. Neither the operating budget nor engineering design allowed for changes and the facility still operates this way eleven years later.
A second Pharmaceutical Company along with their local A & E contractors toured this facility.With only a two month lead time to apply the learning they succeeded in designing, installing, and operating complete flexible containment enclosures around their open scooping and packaging operation for a high potency drug. The site had no prior experience in handling potent compounds. The entire facility was based on vertical flow process design. The existing processing was uncluttered by walls and barriers. Products from several processing rigs were unloaded and packaged in a shared open space. After some months of operation, FDA inspectors accepted this solution based on much sampling data displaying contained processing with no measurable opportunity for materials emission and cross contamination. Rapid adoption of flexible room isolation enabled the company to launch a blockbuster drug with minimal investment in a >30 year old facility. The early launch enabled market penetration and sales rewards by rapidly establishing the product. A more costly rigid containment has since been installed designed after the flexible prototype.
FabOhio, Inc. often provides flexible containment devices meeting site drawing specifications. We later discover many areas where we had the experience to advise and improve on both flexible and rigid containment installations. We have access to much client data from both prototype and permanent installations dating back to 1993 which allows us to confidently recommend successful installations. Through these shared experiences we have found that there are occasions when flexible containment alone is not the best solution. In such cases we are able to lead clients to workable solutions. Few others have the breadth of experience to anticipate the relative strengths and weaknesses of both rigid and flexible alternatives. Performance data is a scarcity in the public domain.
The lesson learned is that it would do well for A & E departments to consider using subject matter experts experienced in both rigid and flexible containment to advise on appropriate approaches early in the project design phase, always recognizing that budget constraints may be extreme.
The choice between the three primary containment methods can be confounding and often at odds with the needs of some site customers. Examples of these approaches are:
Airflow control – laboratory hoods, biological safety cabinets, remote access barriers (RAB’s) and dispensing booths
Flexible barriers – glove bags, equipment enclosures, room enclosures, and transfer systems
Rigid containment – glove boxes, clean room suites, sterile suites.
Hybrid systems incorporating dual approaches – clean rooms and sterile suites where airflow control is a key factor in overall performance, and as such an integral part of facility validation and continuing operational performance measurements.