In the context of Flexible Containment Barriers, most people think of them as a replacement for a glovebox when in fact Flexible Barrier Technology is a technology all its own. This Technical Bulletin will illustrate the basic tenets of Flexible Barrier Technology as it can impact users. It is best explained by separating the ATTRIBUTES of Flexile Barriers from the APPLICATIONS. The latter evolve solely because of the benefits that the attributes bring with them.
ATTRIBUTES OF FLEXIBLE FILMS AS BARRIER TECHNOLOGY
Flexible films bring a whole new concept to freedom in design and application of a wide range of process isolations at all sizes and scales of development and production. To assist in developing an appreciation of the technology we have documented the different attributes and their impact on the user, enabling the reader to better understand the many benefits devolving from their use.
An overriding factor applies when the flexible containment is intended as a packaging contact material. Regulatory guidelines prohibit certain additives, e.g. some antistat and catalysts used in the film polymerisation process, as well as chemical and physical stability requirements (European MedicInes Agency & FDA). Ultimately the burden of proof lies with the manufacturer to perform short and long term contact stability studies and also establish at least equivalency, and preferably better stability, than the ‘gold’ standard Linear Low Density Polyethylene (LLDPE often referred to as PE). Films most studied are LLDPE, with and without antistat additives and plasticizers, and Polyurethane (PU) formulations having no plasticizer content.
1) Linear Low Density Polyethylene (LLDPE) has good clarity and low vapor pressure, but low tensile strength.
Blooming occurs with time, and opacity increases. Catalyst and plasticizer additives add to the blooming and vapor pressure effects and can cause embrittlement. Virgin LLDPE embrittles below 40°F. Low softening temperature, ~100°F. Requires special care in manufacture to avoid the zipper effect at the heat seals – which increases with film thickness. Unless properly tempered, the integrity of the heat seal is lower than the film. Uses a polymerisation catalyst and anti-blooming additives in the formulation. Resistivity >1011ohms/square, reduced to <1010ohms/square (a European pre-requisite) with antistat additive. Note: Resistance is often cited as Conductance.
2) Polvinyl Chloride (PVC) film has good clarity with detectable odor (vapor pressure) and moderate tensile strength. Antistat and plasticizer additives add to blooming and opacity increases with time.
Embrittles below freezing point of water. Low softening temperature
Resistivity >1011ohms/square, reduced to <1010ohms/square using antistat additive or application of a conductive paint to the exterior surface. Heat sealing causes the film to degrade, becoming weaker than the film due to migration of additives. Classed as a hazardous waste in the EU (REACH Regulations) due to hydrochloric acid emissions during combustion.
3) Polyurethane (PU) has good clarity, flexibility, tensile strenth, and elasticity.
No polymerization catalyst or anti-blooming agent in the formulation. Shelf life of virgin and conductive (antistat added) film >3 years with no measurable deterioration. Remains flexible with high tensile strength at ≤-200°F. Softening temperature ~200°F for transient challenges, but capable of contious use up to 180°F. Tensile strength allows for tolerance to pressure variability (>6 times expansion and recovery under pressure) compared with other films. Low vapor pressure, slightly increased with addition of antistat. Resistance ≥1010ohms/square, which can be lowered using antistat additives. Heat seals have higher integrity than the film. The formulation meets the non-flammable criteria adopted for automobile parts manufacture, allowing for use in countries having flammability criteria, e.g. Japan.
4) Polyvinyl alcohol (PVA) is a rarely used film, however it has two unique properties, a) it is completely resistant to chemical degradation by Methylene Chloride, and b) the formulation used is water soluble at ≥60°F.
Good clarity but easily becomes tacky and watermarked due to skin contact. Vapor pressure is low. Ease of waste disposal by dissolving with >60°F water. Resistance ≤1010ohms/square. Requires chilled shipping and storage. Very pliable but needs care in handling
Design reach and operator height are criteria that often determine film selction, with polyurethane being the most tractable film. Film properties and planned inventory requirements also limit film selection.
Film clarity permits unrestricted lighting and viewing.
More rigid and low tensile strength films restrict use by multiple operators due to height, girth, and reach limitations and are less user friendly. Greater flexibility overcomes the typical reach limit of 21 Inches used for rigid containment (American Glovebox Society Publication AGS-G001-2007).
Film flexibility allows several approaches to moving materials and tools into, and out of, the containment zone in a safe manner. While direct access to the containment zone allows for designs without an airlock, most users require a two-way process. This can be achieved using a clean airlock/dirty airlock approach on different sides of the containment zone. Optimal containment factors can be met using multiple connecting airlocks, given that the user has no spatial limitations. Airlock purging can be adopted as supplemental isolation, e.g. when inert or conditioned atmospheres are required. Most common access is through a) bag in/bag out flexible sleeves (developed for waste removal in nuclear applications), and b) precision zippered chambers with attached skirt overlap.
Mounting methods have a profound effect on design. Most common is some form of external support frame made of hot water gradenPVC (especially for prototype feasibility) or steel pipe – often assembled using laboratory clamp and frame parts. Electropolished stainless steel framework is also used for cosmetic purposes. (Non-combustible internal frames create a disposal problem.) A variety of attachment methods are used including folded loops of film along seal edges for tubular steel or PVC pipe insertion, heat sealed grommets, or Velcro strip along seams. Frame supports, or anchoring attachments can be used for mounting on a mobile cart or table. An inflatable frame attached along the seams of an enclosure eliminates the need for a frame, allowing immediate setup and use. Inflatable frames do not require a support, however attachment points may be needed where high airflow or mobile carts are used
Unlike rigid containment technology where it is desirable to have the equipment located inside the enclosure, flexible containment allows for use around the perimeter of the equipment giving ready access to equipment adjustments and multiple sampling avenues. Furthermore the equipment orientation is entirely optional with tools and materials used in horizontal, vertical, diagonal, or even allowing entire equipment train rotation.
Connection to hot surfaces is possible using the appropriate film (PU). Very hot surfaces will require a metal buffer between the flexible attachment and the heated surface to allow heat dissipation, often using a blower to provide air cooling.
Clear films allowing light transmission in both directions provide even illumination from the outside environment and unlimited viewing by the operator(s). Lighting levels are controlled by locating the containment at an optimal distance from available lighting.
Minimal waste is a bonus since the internal enclosure needs only to be wetted using a simple fog/mist approach, or extended misting to moisten dry materials. Use of combustible tools allows the entire enclosure containing tools and process waste to be collapsed by expelling the air, secured with ties, and removed for disposal as solid waste. Excess water (>1% visible) can be absorbed using pet litter. This is an area where internal rigid or non-combustible framework create a disposal problem. Using this approach, i.e. single use enclosure, allows the user to bypass any need for cleaning method validation and testing. Many enclosures can be used and discarded before cost effectiveness is superseded.
The speed with which a prototype can be conceived, sketched, built and delivered is unmatched, often less than 4 weeks once user requirements are defined. Detailed engineering drawing are rarely needed because the expectation is for the user to modify the design to accommodate their needs. Once a prototype design is sketched, a working model can be delivered – usually within ≤4 weeks.
Early development of dispensing glovebags relied on PE film sealed with duct tape, or modification of commercially available simple glovebags, e.g. I2R (now Glas-col, LLC) thin film or asbestos abatement glovebags. The design and fabrication of flexible enclosures equates more to tailoring than engineering. Attempts to be precise are unnecessary since the film flexibility allows for much latitude, and indeed the film requires tempering at workshop conditions before cutting the pattern.
Ventilation is not required unless for operations under special conditions, e.g inert, low humidity, clean room, or exhaust fume purging environments. Flexible enclosures use HEPA filters sealed into the outer skin, or frame HEPA’s for larger enclosures. As a result the entire enclosure is allowed to breathe under stress. Unconditioned environment enclosures do not require a ventilation source or exhaust. Methods are available to capture any noxious materials escaping from the enclosure without the need for ventilation exhaust.
Installation by inflating the enclosure using clean air, or the inerting gas, when it is removed from its overpack allows for immediate use once supported.
Because the film formulator blows the film into a large bubble which is raised to >20 feet in height during film annealing, collapsing, folding, cutting, and winding, all films have potential surface contamination which must be cleaned if a particle free environment is needed. This is done once the enclosure is assembled and tested according to AGS Publication AGS-G008-1997 Section FABRICATION, 5.3 Testing and Inspection, plus an additional inflation leak test. The enclosure is partially collapsed by venting through the HEPA filter, then wiped clean by PPE protected operators, and finally totally collapsed and sealed into one or multiple overpacks depending on customer requirements. The overpacked bag is sealed into the shipping container for dispatch according to customer requirements.
Assembled enclosures sealed in their shipping container can be radiation sterilized before shipment. PU can be sterilized by gamma, X-ray, or electron beam conditioning. LLDPE has limitations since gamma radiation will generate minute holes in the film, consequently electron beam is the more secure conditioning.
Purchase of quality traceable film stock, inventory control, and documentation records are the most expensive contributory cost of a flexible enclosure. Additional costs are labor, packaging, and shipping. Once a final design is approved, bulk purchasing for inventory storage affordsa discounted price. Despite this, disposable flexible enclosures are an economical option to consider at every level of drug implementation, from R&D, animal testing, dispensing and dosing, health care worker protection, pilot plant development and scale-up, production, inspection, sampling, to final packaging and overpack shipment. In an industry where validaion for regulatory requirements is rife, the disposable enclosure eliminates many steps along the quality path undergone by the rigid containment approach. It is rare to find an item that can solve your processing issues without going to the trouble of creating purchse orders. However credit card purchases have become the most expedient method for many users.
APPLICATIONS OF FLEXIBLE BARRIER TECHNOLOGY
As the reader will discover, approaching flexible barrier use, design, and fabrication is an entirely different, and less costly venture than the alternatives, i.e. airflow control, rigid, etc. The entire process is easy to perform. With conceptual needs identified, it is a simple matter to sketch (not design) an enclosure, critique it from a user viewpoint, scale it, and deliver it to the fabricator. The fabricator will often discuss with the user regarding feasibility, economy in design, and prior experience. With this information in hand, a unit cost can be developed. Once approved, the product can be delivered to the user within a few weeks. For this reason, a prototype is recommended. After testing, and when a final design is approved, the fabricator will discuss further costs, volume purchase and delivery frequency. In all, a much simpler, rapidly expedited containment solution than any other approach – especially for companies requiring fast turnaround for manufacture of different products and even different clients. Cleaning, validation, and disposal are reduced to either the minimum or absent.
Performance testing of flexible containment efficacy has repeatedly shown capability equal to glovebox enclosures using appropriately designed containment barriers, while eliminating the cleaning and storage footprint demands.
As we proceed through the application aspects it will become apparent that the attributes free the user from many previous constraints:
The light weight and absence of utility requirements allows for flexible enclosures to be either fixed or mobile. This feature becomes of value when applied to a) multiple users and transportation within a facility or laboratories, b) contained storage in a utility room or warehouse, c) production floor testing and instrument/sensor calibration, d) quality sampling during process validation, e) parts disassembly and transport for cleaning.
The ease with which flexible enclosures can be transferred from test bench to a mobile cart, and back, overcomes procedural requirements that were the bane of instrument technicians, laboratory and maintenance workers, etc. The only supplemental requirement is a flat surface to support the flexible base of an enclosure.
Flexible enclosures have been used successfully for in-process piping repair or modification. They have proven cost effective when installed in rooms carrying contaminated liquid flow outside the processing area, and provided a safe way to change filters in piping conveyance of liquids and dryer exhaust air. Their use in maintenance operations is unsurpassed due to their adaptability to virtually any environment.
There is no limitation on size. Enclosures range from simple glovebags to hold a flashlight to multiple level manufacturing suite enclosures having personnel uni-flow.
Small but effective enclosures can be secured around piping flanges, sampling valves and openings, valves, valve stems and actuators, and many other small but frequently overlooked applications. These show value by containing moving parts and seals, e.g. in utility and public access areas where process inspection may be less common. The inclusion of a sorbent pad will show accumulation of stains due to leakages even when material flow is absent. Combined HEPA and organics filters sealed into the enclosure will collect released fumes and prevent creation and propogation of fire potential.
Attachment to large items of equipment allows great freedom in equipment selection, e.g. drying ovens in laboratories and pilot plant operations, up to 2-story access to pizza oven style dryers, etc. One of the most common applications is extending the usable life of existing validated, but uncontained, equipment.
Regardless of size, a variety of sleeves or chambers extending from a containment zone make for secure pass-throughs at any size scale. These can be incorporated in vertical or horizontal orientations, e.g. sample delivery from a pan or filter dryer, a granulator, a microwave dryer, etc. This is of value during initial validation of equipment or a process. The design can incorporate overpacking for safe transport of materials or contaminated parts.
Another use of sorbent pads is in surface padding underneath a flexible enclosure to minimize breakage potential and damage to the skin of the enclosure.
Purging conditions can be achieved through attachment of appropriate dry or moist air or nitrogen, helium, or any gas or vapor source. When transporting or storing, either disposable compressed gas bottles or larger movable tanks can be used to maintain conditions.
Setup is best accomplished by inflating a newly unsealed enclosure using the appropriate processing environment gas as the inflation medium. Once inflated, the enclosure can be secured to the support frame ready for immediate use. The frame and load bearing requirements do not differ from most existing work surfaces. For European usage, enclosures can include bonding strips in the seams for electrical grounding.
When used for storage of materials, enclosures can be collapsed in all dimensions to reduce the storage footprint or height. The smaller internal volume will reduce the volume of any purge gas used.
Training in flexible enclosure use is as critical as for rigid containment. All operators having potential need to use a flexible enclosure should receive hands-on training from a responsible party. One of the best methods is to select a non-believer to go through the training routine and then appoint them as the training coordinator. It is amazing how fast they get the belief (and peer pressure) when they realize the difference is working in cumbersome air breathing respirators and suits versus minimal PPE.
Flexible Containment is a much larger topic than most engineers and safety professionals realize. Lost are the constraints that apply to the design of rigid containment, e.g. steel and glass construction, long design lead time, rigid prototypes for testing before design finalization, weight, rigid materials pass-throughs, utility requirements, sealed service connections, limited lighting and viewing, structural load bearing support frame and floors, docking issues, limited mobility, spare parts inventory, maintenance, cleaning/decontamination/validation time and costs, speed of delivery (and vendor validation), design and engineering costs (involving client, design engineer or A&E consultants, site maintenance, and operators), plus costly FOB charges.
These are just a few examples of Flexible Barrier Technology at work. The drop down menu’s under the thumbnail images at the top of our website homepage will lead to multiple images of working applications provided by our clients. Preexisting applications are similar, and in some cases exactly meet, the needs of clients.
FabOhio Inc. has pioneered the development of most user applications and used film attributes for improvement while addressing client needs since 1963. Our collective experience in containment practices exceed 170 years. As a result, we have generated a large database of workable solutions. When approaching a clients needs, this is our first resource that enables us to reduce the design costs to a minimum, while providing quick response. Our construction material of preference is the non-flammable polyurethane because it most fits our clients needs, however we work with other polymer films at clients request. All our materials of construction are traceable to the source, and documentation complies with Government and Pharmaceutical Industry Quality criteria. FabOhio, Inc. undergoes routine quality inspections by external Quality Inspectors and complies fully with their requirements, even as they continue to evolve.