Introducing Flexible Containment to the Pharmaceutical Industry

Both flexible containment and rigid containment were developed for use in the nuclear industry dating back to the Manhattan project. FabOhio, Inc. has been involved with flexible containment in the nuclear industry as well as heavy industrial applications since we first opened our doors in 1963.

In the early 1990's, the Pharmaceutical Industry embraced rigid containment as a means of solving the problems surrounding potent compound handling, guided by their various contract Architectural and Engineering firms. Unfortunately flexible barriers were not a consideration. Their merit as an isolation methodology with performance equal to rigid solutions was sadly overlooked. As a consequence, many advantages of flexible solutions remained unidentified. Even today there is a legacy of process equipment constrained by rigid wall solutions. The mentality was one of putting the processing equipment inside a secondary rigid wall isolator because the equipment interconnects could not be made leak free. Flexible containment could have reduced the amount of steel and fiberglass barriers in favor of minimal interventions and maximum operator access with significant cost savings.

In the US, it wasn't until a major Pharmaceutical Company was designing a new facility in 1992 that flexible solutions were considered feasible to solve some of their equipment challenges. Project management were slow realize the benefits, but with continuous testing and results showing that flexible barriers could deliver containment performance as reliably as that delivered by rigid containment they finally became comfortable with the concept. With measured performance, at that time <0.2μg/cu.m. emission levels, they were encouraged to adopt flexible containment solutions in places where rigid solutions were impractical. Beginning in early 1993, FabOhio, Inc. was an active partner in the adoption process, providing rapid turnaround for early prototypes and final designs. The client was pleased at the economies of this approach, especially the alternative reduced infrastructure costs achieved by eliminating waste stream handling from the cleaning of rigid containment devices. Conservative estimate of the cost savings exceeded $4 million on a project of ~$200 million with continuing cost savings in operations. In fact the project was delivered on time, validated, for several $millions below budget.

With increasing comfort in the acceptance of flexible containment by their operators, it became the ready solution for many of their ongoing challenges in protecting operators from contact with potent compounds and sensitizers. Within 2 years, this client had generated flexible containment solutions for many of their global manufacturing plants. By 1995, FabOhio, Inc. had developed over 140 discrete designs and shipped multiple fabricated products globally for this client alone. We are proud to have been their partner in proving acceptable use of flexible barriers throughout Pharmaceutical Research and Development, Quality Laboratories, and a wide diversity of manufacturing operations, and more recently in Environmental Control and Biotechnology applications.

Through technology sharing, one of the world's largest Pharmaceutical manufacturers learned of these results. They proceeded to design and implement flexible containment solutions allowing every piece of processing equipment in their pilot plants to be docked to any other piece at a moments notice. With this processing flexibility and fast delivery based on shared CAD drawings, FabOhio, Inc. engineering concepts supported their needs in the most economical way possible.

FabOhio, Inc. also partnered with a ca. 1960's development facility in Europe to deliver a complete flexible enclosure suite surrounding their dry products materials handling. Alternative approaches were bid at >€150,000 and a delivery time of ~6 months. We were able to perform engineering design, fabrication, and installation within 8 weeks and <€20,000. The facility produced their first lots of trial materials safely and on time. Clean up and tear down after processing took 2 days with the operators feeling safe and secure throughout. Monitoring showed the facility to be contaminant free throughout processing and tear down. Proof of capability enabled this formerly open facility to deliver many more production lots rather than being mothballed.

The above provides examples of the successful adoption of flexible containment in a variety of environments. Other successful applications have been utilized where existing containment approaches have failed. When traditional engineering approaches have been embraced for laboratories, air handling systems clean up, utilities, and other key equipment handling areas, i.e. the areas outside the normal concern of functional building design, flexible containment has been the only viable solution for retrofit due to space constraints. Management does not look favorably on expending capital on such remediation. Fortunately FabOhio, Inc. has vast experience in all types of facility retrofit and can deliver solutions that neither break the budget nor stun management.

We have the design and engineering skills, and the ability to deliver the most cost effective solutions on a timely basis. Performance measurements on our installed systems have achieved a statistically robust <0.04 ng/cu.m. emission level, adequate to satisfy visiting Regulatory Agency Inspectors that use of a shared facility for both potent and non-potent compound handling was an acceptable practice in these instances.

FabOhio,Inc. stands ready to assist you with your containment needs. Contact us at (740) 922 4233 to discuss your specific challenges and we will give an honest appraisal of the feasibility for the use of flexible containment within your facilities. We can provide a full service of engineering design, installation, operator training, and performance testing at a realistic cost.

With increasing comfort in the acceptance of flexible containment by their operators, it became the ready solution for many of their ongoing challenges in protecting operators from contact with potent compounds and sensitizers.

Posted on May 13, 2015 .

General background discussion

Flexible containment has evolved into a mainstay for control of the work environment in the pharmaceutical industry. Whether handling dry powdered products, processing rigs, process waste systems, or controlling waste material releases from cleaning of process equipment and rigid isolators, flexible containment has proven to be an economical and readily disposable technical advance.

The early adoption was a painful decision for management, but with a solid basis of data from test trials using a wide configuration of glovebag and other flexible isolator designs, their reluctance rapidly evolved into a grudging acceptance. The appearance was always a stumbling block because it did not meet the expected industry image of grit polished stainless steel equipment. However, parallel testing of rigid isolators and flexible isolators showed the flexible versions to be equal in emission control capability. The difference was in the cleanability aspect. Flexible isolators merely require wetting of the inside before removal and disposal. Validation of cleaning becomes a non-issue. Not so simple for rigid isolators.

Rigid isolators require a time consuming validated cleaning regimen which is tied in to rigid piping, storage installations, and process automation. Early results using Niacin as the test agent usually gave adequate cleaning performance when viewed under Ultra-Violet (UV) light. More recent tests using milled Acid Yellow as the contaminant highlighted the poor performance of rigid containment cleaning practices.

This finding is a common factor. The issue is one of method sensitivity. Whenever a test procedure is improved we discover new challenges. In cleaning tests, Niacin is observable at low percentile concentrations under UV light. Acid Yellow is observable to concentration below 50 ppb under the same test conditions. The difference is orders of magnitude in observed sensitivity. Surface cleanability remains a highly subjective area.

The same issue has arisen with emission testing of flexible isolators and other forms of barrier isolation. When testing first started in 1993, the analytical test limit was 0.2μg/cu.m for a water insoluble test agent having a dustiness index of 11%. In 1997, milled water soluble lactose (<3 micron diameter) was adopted as the test agent with an improved detection limit of 2ng/cu.m, although the dustiness index was only 3%. Recent advances have lowered this detection limit to 0.2ng/cu.m. Clients have documented statistically valid performance for our flexible isolators at <0.04ng/cu.m when used for handling a dried Active Pharmaceutical Ingredient. This reflects a cumulative improvement in measurement of 5,000 since inception.

Throughout this evolution, our products have always performed to below the current detection limit as long as they were installed and used properly. Even with orders of magnitude improvement in test methodology, our original flexible isolator designs perform to below the latest method limits. We feel confident that we have consistently achieved our goal of providing our clients with a highly cost effective technology that both protects the worker and meets the more stringent quality requirement of controlling materials migration.

The added values of flexibility in installation, no-risk low cost disposal, and lack of need for an infra-structure system further recommends widespread use of flexible barrier technology in many applications throughout the industry.

Our first major client was a partner in developing new applications. With increasing comfort in the acceptance of flexible containment by their operators, it became the ready solution for many of their ongoing challenges in product contact with potent compounds and sensitizers. Within 2 years, this client had generated flexible containment solutions for many of their global manufacturing plants. By 1995, FabOhio Inc. had developed over 140 discrete designs and shipped multiple fabricated products globally for this client alone. We are proud to have been their partner in proving acceptable use of flexible barriers throughout Pharmaceutical Research and Development, Quality Laboratories, and a wide diversity of manufacturing operations, and more recently in Environmental Control and Biotechnology applications.

FabOhio Inc. stands ready to assist you with your containment needs. Contact us at (740) 922 4233 to discuss your specific challenges and we will give an honest appraisal of the feasibility for the use of flexible containment within your facilities. We can provide a full service of engineering design, installation, operator training, and performance testing at a realistic cost. Many of our services are of such low cost that they eliminate the need for purchase orders. Credit card purchasing has become an everyday occurrence.

We will be providing further details of the evolution of flexible barrier solutions in our next information release.

Posted on May 13, 2015 .