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1. Versatile hardware easily mounts to vessel discharge port Continuous liner pack is installed Sleeve is pulled Unique DoverPac used to separate E a filled drum Next sleeve is pulled into drum into drum and filled crimping system is rPac Ve Containment Systems b Materials ArmorFlex is ILC Dover s proprietary family of films used exclusively in the DoverPac family of high potency flexible containment products These films pass incendivity testing and are designed and manufactured using FDA amp EU compliant materials Continuous Liner Kit The Continuous Liner Kit includes e Canister Cage Shroud e Pack Protector 12 Band Clamp Sanitary Clamp and Gasket e FlexLoc Clamp 23 Crimp Kit e Turn Table Continuous Liner Pack The canister will attach to the vessel using a transition adapter The transition adapter has a nitrogen purge vent to discharge into an inert atmosphere if required Continuous Bag in Bag out System This system can be supplied with an alpha beta port interface to allow attachment to an isolator as depicted in the drawing This allows the contained removal of product containers samples or waste from the isolator 29 DoverPac Continuous Liner 23 Dia Contained Powder Discharge to Drums verPac Systems ILC crimps have been designed and tested to compress standard diameter liners made with Ar
2. The unrestrained design uses a separate lifting bar when it is supported for vessel charging This is significantly more robust in larger volumes and supported weights than an encapsulated plate In fact customer testing has shown the 100L version to hold 165 pounds 75 kgs Reusable restraints are also available for added support The DoverPac SF is also available with an optional S fold on the neck as shown in Figure 2 This functions as an integral clamp to shut off powder flow when making the connection to the vessel Figure 2 Multi O ring Canister Attachment The interface to the vessel can also be supplied in our ge patented multiple o ring technology This configuration is shown in Figure 3 Attachment of the first liner to the first groove in the canister is made The powder transfer opera tion is completed and the neck attached to the vessel is then removed using our crimp separation method The subsequent liner is then attached to the next groove above the stub and the stub is then bagged out lt r een Li ah CORD boo i m a m pn Standard solutions are also available for DN 100 and 150 flange interfaces A variety of configurations are available Figure 3 including 1L 5L 10L 15L 25L 30L 50L and 100L WHAT ARE THE APPLICATIONS Use of powder transfer devices within existing buffer prep processes whether new or existing operations is gaining momentum as well Figure 4 illustrates just
3. Excellent Very Good Excellent Excellent Continuous liners Very Good Fair Water Distilled Criteria Change in Physical Properties Resistance 0 10 10 20 20 30 gt 30 Very Good Good Excellent Excellent Fair Providing Flexible Containment Solutions to the Pharmaceutical Industry since 1997 DoverPac Sample VverPac 7 Containment Bag out i l Systems Benefits Reliable Process Flow Crimp of a Truly Contained Flexible lranster System ay Verified containment as a system Proven to be lowest cost of ownership ArmorFlex 114 film is Static Dissipative with a permanent antistat confirmed to 2002 72 EC and amend ments FDA CFR 21 and test requirements of EP 3 1 3 Bag out Standard and custom installations CE Marked configurations UN DOT approved configurations Lowest carbon footprint in a complete containment process 14 offloading and charging necks using ArmorFlex for the crimping Sample sleeve can process be designed into any DoverPac for contained tamper proof sampling DoverPac PATENTED Bag Out Sleeves system for high con to maintain tainment connection high contain to the o ring canister ment during Containment proven DoverPac using third party testing change to SMEPAC protocol for lt 1 0 g m3 with results lt 250 nanograms m3 O rings are captured to prevent accidental loss to the process vessel during bag out operatio
4. Transtion Adapter Specific To L Customer Hardware Recommend 24 610 Minimum b gt Other System Components and Accessories Other system components and accessories developed by ILC Dover to support contained pharmaceutical ingredient processing include e Wash In Place Enclosure e Clean In Place System In Line Filter Kit 20 DoverPac Contained Powder Transfer F FLEXIBLE CONTAINMENT TECHNOLOGIES b gt System Description This easy to use system has been proven effective in containing active pharmaceutical ingredients and other hazardous compounds to assure a safe and effective transfer of powders an operational requirement that cannot be achieved with a standard FIBC or big bag The DoverPac contained powder transfer system includes a flexible ArmorFlex liner with restraint for containing powders and a set of hardware that fits the flange of a vessel While specific powders react differently due to their particle size OEB 5 lt 1 0 g m3 levels have been demonstrated on a task basis with results in the nanogram range This is based on proven applications third party testing to the SMEPAC protocols on similar designs and the 100 inflation tests performed on the delivered systems Uses ILC Dover s Patented Technology VverPac Containment Systems Charging Using the Individual DoverPac System Contained processing to protect the operators cGMP processing in
5. WHAT CONTAINMENT LEVEL PROVIDED These types of barriers are designed to enhance the capabilities of the booths and facilities installed and rely on the airflow from the primary source of containment WHY USE THIS OVER OTHER TECHNOLOGIES The cost of ownership ergonomic advantages and speed of delivery benefits of this flexible solution far outweigh those of rigid isolation systems Tools such as Lean Manufacturing come into play more and more For example the time to clean and validate the cleaning are major bottlenecks for processing efficiencies in the plant Being able to minimize this part of the process results in getting products to market faster and at an overall reduction in operating costs when considering labor utilities and waste disposal costs It also supports getting multiple products to market faster within an existing facility without risking product safety Contained Blending Transfer Sleeve DoverPac Continuous Liner Technology OVERVIEW Two methods of containing blenders have been demonstrated Included here are the use of flex ible enclosures and separate disposable powder transfer systems The systems described in this containment guide center around bin blending and V Blender applications in Oral Solids Dosage OSD manufacturing using Transfer Sleeves DoverPacs and Continuous Liners Blending involves the controlled mixing of dry primary powder particles and excipients The powders can range
6. Flexible Enclosure be applied to charging processes as shown in 3 Inner Neck Attachment Figure 3 The flexible enclosure design is either 5 4 Outer Neck Attachment supported by a frame or bungee cords 5 DoverPac FEATURES Standard DoverPac hardware interfaces Standard and custom sizes e Two barriers for containment Product contact with regulatory compliant materials BENEFITS Uses a broad range of solutions depending on containment level needed Tailored to specific batch sizes Figure 3 Provides nanogram levels of protection without high capital costs e Eliminates risk to product WHAT CONTAINMENT LEVEL PROVIDED OEB 5 in the nanogram levels The table below outlines a summary of the results achieved Sample Set N Mean Range Range Standard Standard Coefficient 95 Lowest Highest Deviation Error of Confidence Variation Interval for Population Mean Personal Sample 12 0 077 ug m3 0 014ug m3 0 50 g m3 0 136 ug m3 0 039 1 8 0 00980 to Breathing Zone 0 163 g m3 PSBZ with outlier event PSBZ without 10 0 032 ug m3 0 014 ug m3 0 084 ug m3 0 023 ug m3 0 0074 0 72 0 0156 to outlier event 0 0490 ug m3 WHY USE THIS OVER OTHER TECHNOLOGIES The cost of ownership ergonomic advantages and speed of delivery benefits of this flexible solution far outweigh those of rigid isolation systems OTHER POTENTIAL APPLICATIONS This technology is applicable for charging and offloading most vessels This
7. Process Area Barrier Curtains Contained Blending Transfer Sleeve DoverPac Continuous Liner Technology Contained Blending Flexible Enclosure Technology DoverPac SF Powder Transfer Systems Sentinel Clear Sentinel Clear Hood FAQ s Weigh amp Dispense CrimpLoc ArmorFlex Family Pharma Tek CMO Case Study for Retrofit Containment Technology EZ BioPac FlexiVac Ventilated Enclosure System 63 65 69 71 75 77 81 87 88 90 92 94 96 98 100 101 103 Why Do Our Customers Value ILC Dover gt We keep the cost of making drugs down gt We make the medicine people take safer by protecting the drug product from contamination gt Lower cost of ownership with disposibles vs capital gt No cross contamination eliminates need for dedicated facilities gt We keep the people who make medicine safe gt Lite critical softgoods that are the key to the system gt ILC s products do what they claim and we are there to Support our process after the installation Validated Containment THAT WORKS DoverPac Our flagship product that offers the capability to offload and charge potent compounds Continuous Liners Multiple size continuous liner packs designed to support contained drum loading DoverPac SF Charging system designed to interface with split butterfly valves or sanitary flanges Flexible Enclosures Standard and custom
8. allow clearance for the opening of the lid of the granulator Seven glove sleeves are located to support opening of the lid access to the controls discharge of the materials and bag in bag out of raw materials and the processed powder The frame is used to support the enclosure during operations and can be wheeled out of the way for storage when not in use Figure 5 Figure 7 73 Granulator Containment Technology WHAT ARE THE FEATURES AND BENEFITS OF THIS TECHNOLOGY Features Benefits Retrofit to existing equipment design Provides the lowest overall cost of process Process and Technical areas separated ownership through low capital and operating cost Validaied contamment technology including reduced cleaning and cleaning validation Fastest turnaround of a processing suite for Clear film l subsequent manufacturing campaigns Passive system ae 7 Process is contained without contamination Flexible materials of motor drive shaft and controls with Disposable components flange mount design Adaptable to other equipment Nanogram containment levels achieved Supports visibility for maintenance Does not affect ATEX and Ex ratings Ergonomics maximized Speed of implementation WHAT CONTAINMENT LEVEL PROVIDED OEB 5 with results in the nanogram range This is based on customer test data other proven applications third party testing to the SMEPAC protocols on similar designs and the 100 inflation test
9. ergonomic advantages and speed of delivery benefits of this flexible solution also far outweigh those of rigid isolation systems Tools such as Lean Manufacturing come into play more and more For example the time to clean and validate the cleaning are major bottlenecks for processing efficiencies in the plant Being able to minimize this part of the process results in getting products to market faster and at an overall reduction in operating costs when considering labor utilities and waste disposal costs It also supports getting multiple products to market faster within an existing facility without risking product safety 80 Contained Blending Flexible Enclosure Technology OVERVIEW Two methods of containing blenders have been demonstrated Included here are the use of flexible enclosures and separate disposable powder transfer systems The systems described in this containment guide center around bin blending and V Blender applications in Oral Solids Dosage OSD manufacturing using Flexible Enclosures Blending involves the controlled mixing of dry primary powder particles and excipients The powders can range in properties and potency and if not contained can present cleaning and exposure ISSUES Dry mixing of granular and other processing constitu ents includes a significantly high number of blending steps This includes potent and highly hazardous compounds excipients and materials such as lubricants as processi
10. over another Rather this guide depicts a sampling of flexible containment applications to a variety of styles of equipment as standard and customized containment solutions ee AA Figure 1b 1 Vac Purge Port 2 DoverLoc 77 Contained Blending Transfer Sleeve DoverPac Continuous Liner Technology 78 HOW DOES IT WORK AND WHAT ARE THE APPLICATIONS Three methods of flexible containment using powder transfer systems have been applied to blend ers These include charging and offloading with transfer sleeves charging and offloading with DoverPacs and offloading with a continuous liner system This rugged film provides a safe working environment while enabling the enhancements developed through numerous installations using this flexible containment technology The Transfer Sleeves Continuous Liners and DoverPacs are made from ArmorFlex film This rug ged monolayer film brings regulatory pedigree for materials of contact as well as proven use from multiple process applications The use of flexible containment allows the end user to process contained when needed or follow ex isting open processing procedures when containment is not required In both cases cost savings are realized by modifying an existing design or using an existing piece of equipment with no modifications Charging and offloading with transfer sleeves A transfer sleeve is essentially a flexible chute that attaches to the blender and the pi
11. A lifting bar and hoist are used in order to position the DoverPac restraints over the vessel interface for charging The lifting bar comes in two sizes to accommodate DoverPac sizes Hoists typically are supplied by the customer Lifting Bar Specific To Customer Fogar 4 Securing the liner neck iy 1 ae rT b gt Other System Components and Accessories Other system components and accessories developed by ILC Dover to support contained pharmaceutical ingredient processing include e Wash In Place Enclosure e Clean In Place System e In Line Filter Kit 24 Coaxial DoverPac Nanogram Powder Transfer oe Systems The Coaxial neck DoverPac was originally designed to allow secondary containment to be used with a DoverPac in the late 1990 s for charging and offloading vessels through isolators Given the increase in highly potent API manufacturing the use of this system with either rigid isolators or flexible enclosures is a complimentary processing option OVERVIEW The Coaxial Neck DoverPac serves the dual function of contained transfer and storage system These are available in standard 45 185 400 and 700Liter volumes Custom sizes can also be accommodated 1 Vessel Outlet 2 Flexible Enclosure 3 Inner Neck Attachment 4 Support Frame 5 Outer Neck Attachment HOW DOES IT WORK This system is designed to provide containment to the OEB 5 less than 1 ug m3 with a goal of be
12. Kit Contained separation between vessels and DoverPacs is achieved through a Crimp Separation Kit using ILC s uniquely designed crimp system FlexLoc Clamp Crimps are color coded to assure that the right crimp is selected for the right product Red crimps are used for the 14 necks blue crimps are for the 23 diameter continuous liners and yellow crimps are for the 4 diameter sample sleeve on the DoverPacs A Crimp Separation Kit includes e 200 Crimps e 1 Crimp Hand tool 1 Cutter e 100 Cable Ties 7 Nylon 1 User s Manual Additional spare items can be ordered separately by their individual model part numbers The crimps have been designed and tested to compress the standard diameters liners made with ArmorFlex film Use on any other system will preclude the crimps from closing correctly which could result in operator and product exposures The hand tool applies two crimps at once The cutter is used to cut between the two crimps and then the cap is slid onto the closed crimp body ae Systems ILC crimps have been designed and tested to compress standard diameter liners and sleeves made with ArmorFlex film Position crimp Squeeze tool until crimps are engaged then release tool Cut and separate Install crimp cap on crimp body 19 DoverPac Contained Powder Discharge rPac Ve Containment Systems b gt Typical DoverPac Discharging Arrangement
13. Sleeve on outlet of mill for direct transfer to IBCs or other vessels Transfer Sleeve on inlet of mill with drummed materials being introduced using the DoverPac Drum Transfer System Flexible Containment Solution Guide FCSG 003 50 Drum Sampling Enclosure System OVERVIEW ver Pac Systems Sampling of active pharmaceutical ingredients sensitizers and other highly hazardous compounds for quality assurance purposes is a process that is performed on a routine basis The ability to perform this work in a warehouse or other parts of the facility on a task operation basis and without having to make significant capital expenditures are key in meeting this operational need The Drum Sampling Enclosure DSE system a proven containment solution supports accessing drummed materials with the drum fully contained Some processes advocate the safety of remov ing the drum lid before placing the drum inside the containment device Experience proves the risk exists even with a dual inner liner that cross contamination and operator exposure can occur when the lid can not be removed within a robust flexible enclosure HOW DOES IT WORK The DSE System consists of a Flexible Enclosure and Support Stand Sampling to an integral flexible sleeve bottles or a thief are all proven capabilities The enclosure includes one pair of integral glove sleeves a storage sleeve and sampling sleeve Loops for supporting the enclosure by t
14. This is beneficial for equipment Flange Mount Style that can not be modified to use the flange mounted approach Again the enclosure is supported by bungee cords attached to the pan and includes glove sleeves for access to the equipment The enclosure moves with the operator as is the case with all of our flexible enclosure systems to maximize ergonomics as noted above Pan Mount Style 71 Granulator Containment Technology WHAT ARE THE APPLICATIONS The enclosures are manufactured from clear Armor Flex 113 film that allow room light to illuminate inside the enclosure for easy viewing This rugged film pro vides a safe working environment while enabling the enhancements developed through numerous installa tions Transfer Sleeves are made from another version of ArmorFlex film This is the same monolayer film used in our DoverPacs and as such brings regulatory i pedigree for materials of contact Figure1 1 Enclosure 4 Support frame 2 Pan 5 Glove Sleeves 3 BIBO canister The use of flexible containment allows the end user to process contained when needed or to follow existing open processing procedures when containment is not required FluidAir PharmX Model PX 1 In this design containment is achieved by encapsulat 1 Se ing the entire granulator inside a pan mounted flexible seas 2 Enclosure enclosure see figures 1 In this case the pan is 33 l 838 mm x 60 1524 mm Space
15. a three groove canister was mounted on the blender and the standard canister was mounted on the Transfer Stand shown In addition the stand allows the Operator to reach the valve on the outlet of the blender and the transfer sleeve since this interface is 92 2337 mm above the floor in this installation A transfer sleeve is then used as the contained chute to direct the powder from the blender to the Continuous Liner The Continuous Liner is pulled into a drum that sits on the existing scale in the floor between the blender sup ports This allows for the drum to be weighed as part of the process Input from the operation of this system in cluded this saved us significant cleaning time as we no longer need to hose down the entire suite This is a key in the Risk MaPP logic for supporting operations in a multi process facility by eliminating cross contamination concerns Figure 2a Figure 2b 1 Bin 2 DoverPac 7 LJ f m i J a a 4 C wa Figure 3 3 Transfer Stand 4 Continuous Liner System 1 Blender Mounted Canister 2 Transfer Sleeve 79 Contained Blending Transfer Sleeve DoverPac Continuous Liner Technology WHAT ARE THE FEATURES AND BENEFITS OF THIS TECHNOLOGY Features Benefits Retrofit to existing equipment design Complies with the Risk MaPP initiative Process and Technical areas separated Provides the lowest overall cost of process ownership through low capital
16. allows operators while dispensing to easily take a spent drum liner with its residual level of powder and stow it until the next drum is attached The residual powder is easily emptied into the next drum maintaining high containment eliminating batch shrinkage A stretch fit ArmorFlex sleeve is used to dock the standard drum o ring canister with the product drum This is a fast and effective process to make a contained connection After the powder is vacuumed from the drum a high containment separation process using the CrimpLoc is performed The drum and the FlexiVac remain contained and are ready to attach the next drum This process has been used with isolators in many applications and proven effective Designed for operator ergonomics the drum connection has a pivoting position to allow the drum to be easily moved into position connected and then removed when empty The FlexiVac system is available with or without a powder pump for compatibility with existing PTS units or other vacuum systems The fully integrated FlexiVac uses dilute phase conveying technology for the best powder transfer possible AR MORFE FILMS ArmorFlex 113 film s superior visual clarity ArmorFlex 114 film delivers permanent static makes this the clear film of choice for flexible dissipative properties while meeting FDA and enclosures and flexible isolators 2002 72 EC requirements for food contact and EP 3 1 3 test conditions Polyethylene base fi
17. be suceess ful from operational and business perspectives Best of all this has been accomplished On an existing non contained design without the need for expensive retrofits past the addition of attachment Mangea This example of how LC Dower is applying the use of highly engineered materials amd state of the ant design techniques i desenbed m detail below HOW DOES THE SYSTEM WORK Enclosure Containment of the BTS 100 is provided by a rectangular flexible enclosure with an an 2 HEPA Filters gled iront surrounding the entire mill head including the inlet hopper outlet nozzle and 3 Integral Glove Sleeves interlock switch Integral glove sleeves are positioned to provide a means of charging 4 BIBO Canister l and collection of product as well as servicing and cleaning the machine Conductive locking castors A single eniro removal paint provides a means for moving product and supplies in and out of the enclosure This entry removel point will support use of a bag in bag caut BIRO deeve of interface with ancillary containment devices such a an in process flexible isolator Figures and 2 The enclosure also incorporates HEPA filters into the design to balance the pressure m the enclosure and allow oto move freely as the operators perform various operations The system is movable via the incorporation of conductive locking castors This al lows safe movement between the processing suites and areas The system is l
18. breach e Pressure control is maintained and monitored by PLC System e Breach control to sense and indicate a pressure drop while changing the operating parameters to maintain a negative pressure PROCESS EXAMPLES Dispense to DoverPac s for charging Dispense to Continuous Liner e Subdivide drums of potent materials lt Sampling from drums Weigh and dispense directly to the process DESIGN OPTIONS No inerting of the system e Low humidity control Alternate transfer options including RTP units and transfer valves Wash in place cleaning Adjustable height base Collapsible frame for storage ARMORFLEX The ArmorFlex family of films has been developed for the specific needs of the pharmaceutical industry including FDA approval for product contact The flexible isolator is manufactured from ArmorFlex 113 film and is typically 8 mil thick This robust material will resist against damage from typical use and is more functional than a hard wall type design ArmorFlex is developed to be resistant to most solvents environmentally friendly for incineration with no chlorides and has a 5 year shelf lite 93 94 CrimpLoc System ver Pac Systems The Premier Closure System In Pharmaceutical Processing ILC Dover pioneered flexible containment for the pharma ceutical industry and continues to innovate processes for better performance We invented the original crimping
19. cleaning validation Product can be transferred between operations without breaking containment No change in validation WHAT CONTAINMENT LEVEL IS PROVIDED OEB 5 with results in the nanogram range This is anticipated given actual customer feedback and third party IH test results from similar designs as well as the 100 inflation dwell tests performed on the deliverable enclosures WHY USE THIS OVER OTHER TECHNOLOGIES The cost of ownership ergonomic advantages and speed of delivery benefits of this flexible solution far outweigh those of rigid isolation systems 60 Mill Containment System Bohle BTS 100 OVERVIEW Particle size reduction is commonly required in pharmaceutical manufacturing Taking mio account today s need to null highly has ardous compounds in conjunction with the need to minimize capital cost spending the i F application of flexible comainment to an existing Bohle BTS 100 sieve design dem onsiraies the use of this containment strategy The Bohle Turbo Sieve BTS is a small volume size reduction piece of equipment ihai is weed in the drag product development sages Typically provided without contain ment options for the end user in the past were limited to installing a rgh isolator or using personal protective equipment PPE Today as denvonstrated in a successful installation at an intemational pharmaceutical munufactuner outfitting the system with flexible containment has proven to
20. includes but is not limited to reactors charging only dryers blenders and granulators Uses ILC Dover s Patented Technology 26 G2Pac lt 100ug m Containment Powder Transfer G2Pac The Smart FIBC Features Durable ArmorFlex liner with groundable restraint type C fli tlh a i i Individual necks with bag out sleeve to support charging and offloading operations Secure dust free hardware interface to process equipment Sized to interface with standard pallet Interfaces with ILC contained separation crimps Benefits Economical containment Supports dust free operation Reduced cross contamination risks Protects operator One person operation b gt Eclipsing the traditional FIBC the G2Pac is engineered to address the issues that arise from uncontrolled processes including compromised 3 E o Feature G2Pac facility cleanliness cross contamination risks Restraint and Liner Yes and employee exposure to unnecessary Charge Offloading Neck Ven hazards G2Pac supports cGMP operations _ ArmorFlex 104 Yes Sizing 700L 560L 185L Integral Bag Out Sleeves Yes for Contained Changeover Interfaces with Contained Yes Separation Crimps 28 b gt System Description a F i i This easy to use system has been proven effective in containing active pharmaceutical ingredients and other hazardous compounds to assure a safe and effective transfer of powders an operational requirem
21. of the enclosure This is a factory packed 35 long liner Once the Continuous liner is filled it is crimped and the bagged out using the BIBO Sleeve on the side of the Enclosure nC Isometric View View from the Glove port side 1 Mobile Frame 4 Attachment to 2 Flexible Enclosure Filter Outlet 3 Glove ports 5 BIBO Canister 67 Contained Offloading of Aurora Filters Processing from Nutsche Filters The basic process steps include 1 pull a length of the Continuous Liner down from the pack 2 open the valve on the filter outlet to allow powder transfer to the liner 3 when filled twist and crimp the liner 4 place the filled section of the liner into the bag out sleeve and then twist and crimp the BIBO Sleeve This is then moved to the next step of the process PEA U RES BENEFITS e Validated containment technology nanogram containment levels achieved e Clear film on enclosures e visibility during operation e Passive and ventilated systems available e Containment to a broad range of requirements e Flexible materials Ergonomics maximized e Disposable components e Reduced cleaning and cleaning validation e Retrofits to existing filters e Low capital and operating cost Speed of implementation WHAT CONTAINMENT LEVEL PROVIDED OEB 5 with results in the nanogram range This is based on proven applications third party testing to the SMEPAC protocols on similar designs and the 100 inflation tests performe
22. savings over rigid isolation systems Significant reduction in cleaning time waste and validation expenses Integral sampling sleeve Static dissipative film with groundable restraint type c 17 DoverPac Contained Powder Discharge Basic Offloading b Materials Process Steps Details are available in a databook upon request Offloading Canister and Transition Adapter The canister pictured at the right shows the set up on a straight transition adapter at ILC s test facility While canisters typically are 316L stainless steel Hastelloy canisters also are available This unit has an initial liner attachment typically 5 or 10 grooves depending on process requirements and available height and 1 groove for the cleaning sleeve or clean in place CIP sleeve attachment The canister is supplied with a 12 sanitary flange on each end This allows for a common design for attach ment to vessel specific transition adapters and our CIP tundish The custom transition adapter is fitted with a flange on one end that interfaces with the vessel flange or valve that is in line on the vessel flange The opposite end is a 12 sanitary flange that interfaces with the canister is used to allow powder flow directly into the vessel without accumulation on the hardware The adapter also is fitted with a vacuum flange port with a 1 2 sanitary flange for attachment to the vacuum and nitrogen sources to allow
23. system and now we have created the CrimpLoc System This NEW system is the next generation to provide high containment and a secure closure when using the DoverPac Continuous Liner and other ArmorFlex film solutions Less hand force and more ergonomic One Tool for all Crimp Sizes Uses the same Crimps as the existing ILC Dover Crimp System Light weight Key factors to consider for closure of in process pharmaceutical packaging Containment Quality Ergonomics Safety No plastic shards from separation cut Validation Operator Ease of Use CrimpLoc System ILC Dover creating what s next Twist and Tie ILC Dover Crimping CrimpLoc Automated Crimping The CrimpLoc System is a complete kit to provide the secure closure for ArmorFlex film packages Current users can upgrade to the CrimpLoc and realize the benefits of the new design New kits are available including the CrimpLoc tool Cutting Tool and Crimps One CrimpLoc tool is needed for the range of ArmorFlex closures offered by ILC Dover ArmorFlex size Crimp Designation 23 Diameter Blue 14 Diameter Red 4 Diameter Yellow Crimp Removal Tool The latest innovation for safe removal of the crimp The crimp remains in one piece so no risk of contami nation upon opening 95 ArmorFlex Family a VverPac Containment Systems z P Hia F P At l hott Os 7 ArmorFlex Family of Films
24. the product and to add design features that improve the overall reliabilty of the product One such example is the fact that all DoverPacs employ strong overlap seams even in 3 dimensional intersection areas e g where the fill neck enters the main body of the liner It s this attention to design and manufacturing detail that makes DoverPac the first and only choice for containment ArmorFlex Family of Compliant Static Dissipative Films Toy ppe ad Bencine Con ry gg ent _ Systems One of the key elements of our DoverPac line of products is the ArmorFlex material These films are custom formulated by ILC to deliver superior elongation performance nearly 500 for ruggedness and high strength This feature coupled with a unique blend of safe and effective anti static additives allows all of the DoverPac products to deliver reliable high level containment From the original ArmorFlex 104 to the most recent film ArmorFlex 114 we pioneer the advancement of flexible materials This is evidenced by the introduction of ArmorFlex 114 the first permanent non blooming static dissipative film to meet the 2002 72 EC and amendments Directive and EP 3 1 3 ArmorFlex 104 Film a ver Pac Containment Systems ArmorFlex 104 Film Passes incendivity testing Designed and manufactured using only FDA compliant materials Verfied quality and reliability No animal der
25. the face of the dryer to the outside of the door An enclosure made from the rugged ArmorFlex family of films is then attached to the flange and a supporting frame assembly The door is within an enclosed environment when loading and unloading the trays with the drug product The trays drug product and associated process tools can either be preloaded into the enclosure or bagged into the isolated area via bag in bag out BIBO canisters or larger drum ring attachment canisters The steps outlined below represent a typical example of this type of process 1 Attach the enclosure to the support frame using the bungee cords supplied Also attach the enclosure to the BIBO canister 2 Preload trays into the enclosure or bag in after the enclosure is attached 3 Attach the enclosure to the flange on the dryer using the tape and V Groove trim method developed by ILC and open the dryer door 4 Load the bags of wet cake material into the enclosure through a bag in sleeve 5 Scoop material from the bags onto the dryer trays load the trays into the dryer and close the dryer door for processing Portable Tray Dryer 6 After the drying process is complete open the door remove the trays 1 Enclosure within the enclosure and scoop the powder into plastic bags which in 2 Frame turn will be placed into a bag out sleeve Alternatively the powder can be 3 BIBO Canister scooped directly into a DoverPac Continuous Liner or Transfer Sleeve 4 Por
26. were seen on the outside of the restraint In order to be successful BNL adopted our Drum Transfer Station CHARGING TO VESSELS The Transfer Sleeve between the bottom of the DTS and the inlet of the next piece of equipment is depicted in Figure 6 This uses our standard technology of multiple groove o rings and bag out techniques The Transfer Sleeve between the enclosure outlet and the process equipment inlet will be sized using our standard 12 hardware In this case we will be able to use our unique crimp system for contained separation After processing the Transfer Sleeve will be twisted and crimped closed using the red 14 crimps The hand tool applies two crimps at once The cutter is then used to cut between the two crimps and the cap is slid onto the closed crimp body In addition the DoverLoc a molded clamp that secures the liner at the bottom interface point of the canister sup ports the twisting crimp operation and minimizes cleaning 47 Drum Transfer System Contained Drum Dispensing Feature Flexible enclosure follows operator s movements Lightweight portable design Disposable Third Party proven containment Reduced capital cost over rigid systems Maximized use of contained processing commonality Time to manufacturing readiness is shorter than capital intensive systems cGMP system Modular frame design Proven in customer applications 48 Benefit Ergonomic performance is
27. GHING CAPABILITY Versatile design to use balance load cell system or floor scale systems Accurate weighing along with tare removal of packaging for net weight accuracy e Weighing accuracy is determined by the scale capability and the weights being handled DRUM DISPENSING The system is primarily designed to dispense from drums Easily attach drums using the ILC Dover drum attachment ring technology e Standard design for drum diameters up to 23 Drums can be completely or partially dis charged and then removed from the system maintaining containment for subsequent discharging e ILC Dover Crimping System completes the sate and secure process The scale can be located outside of the containment area so cleaning is not required The System can discharge to a continuous liner sys tem DoverPac or other packaging This frame can include load cells or use a floor scale to assure accurate net weights Weigh and Dispense System STATIC FLEXIBLE ISOLATOR This passive system is proven for high containment Using our robust ArmorFlex 113 flexible film the integrity of the system is secure Testing results consistently report an OEL below 1 0 ug m3 TWA e Systems have been provided up to 200 long with no limit on size capacity DYNAMIC FLEXIBLE ISOLATOR e Designed with a fan and HEPA filter system to provide an additional level of containment pro tection while reducing the risk of any
28. Meeting Your Current And Future Process Requirements ArmorFlex 114 The latest addition to the ArmorFlex Family Complies with FDA 21 CFR Fully compliant to 2002 72 EC and amendments Meets test parameters of EP 3 1 3 Passes USP lt 661 gt Physicochemical Tests for Plastics Passes USP lt 88 gt Class VI 7 day implant Passes lt 87 gt biological reactivity in vitro No animal derived components b gt At ILC Dover we are always creating what s next 5 year shelf life Permanent antistat replaces by listening carefully to our customers migrating additives In response to customer input and emerging Passes Chilworth incendivity tests Tested for solvent resistance DMF filed with FDA regulations we ve developed a robust new film to support our DoverPac Containment Systems This revolutionary film ArmorFlex 104 Continuing to be the most used ArmorFlex film ArmorFlex 114 delivers permanent This space age film continues to be used for static dissipative properties while meeting process and regulatory needs through meeting FDA and 2002 72 EC out the pharmaceutical industry With over 150 000 containment solutions completed from requirements for food contact ArmorFlex 104 this high tech film is a proven standard DoverPacs continuous liners and other containment solutions will be available using ArmorFlex 104 for years to come and EP 3 1 3 test conditions ArmorFl
29. Small footprint does not take up a lot of floor space Enclosure is attached to drum wall allowing lid to be contained Stretch on enclosure interfaces with common size drums but can also be customized One person operation BENEFITS Can be used in any part of the facility e No cross contamination transfer to other parts of the plant Ergonomics and secure operations are maximized with the integrity of ArmorFlex materials e Low capital depreciation and operating costs maximizes true cost of ownership lt Immediate implementation supports Production and Lab processes in any part of the plant Reduced cleaning and cleaning validation Drums can be moved freely without breaking containment WHAT CONTAINMENT LEVEL PROVIDED OEB 5 with results in the nanogram range Even lower to non detectable levels would be expected if the system were to be used in conjunction with an existing down flow booth This is anticipated given actual customer feedback and third party IH test results from similar designs as well as the 100 inflation tests performed on the deliverable enclosures WHY USE THIS OVER OTHER TECHNOLOGIES The cost of ownership ergonomic advantages ease of use integrity of the ArmorFlex material and speed of delivery benefits of this proven flexible solution far outweigh those of rigid isolation systems OTHER POTENTIAL APPLICATIONS This technology is applicable for multiple process steps and includes but is not lim
30. The Breathing Tube is a reinforced design that resists crushing when an operator needs to be working on their back Your typical cleaning SOPs would be used however there is an approved list of cleaning materials that should be followed System Level User Instruction Manuals Filter User Instructions Battery Charging Instructions Recommended Cleaning Solution list Donning Posters and a Training presentation 91 Weigh and Dispense System A NEW era in dispensing technology OVERVIEW This modular design is developed to allow weighing or subdividing materials in a highly contained way while maintaining weighing accuracy The system can be used for weighing and then directly charging into a process vessel or other equipment BENEFITS Modular design to meet specific process demands using proven containment and weighing technology Improved ergonomics over hard wall isolators by utilizing the comfort of the flexible wall system Low capital cost to purchase and install e Accurate weighing system designed for the application and process typically to 5 grams depending on scale capacity higher accuracy available with custom design and scale selection Proven containment using the static or dynamic Flexible Isolator System to less than 1 0 ug m3 The unique drum attachment method provides high con tainment and ease for the operator to dock a drum 92 VverPac Containment Systems WEI
31. a completely closed operation to protect the product Available in sizes ranging from 20L to 2000L 100 inflation tested CE Marked Significant capital cost savings over multiple rigid isolation systems Significant reduction in cleaning time waste and validation expenses Static dissipative film with groundable restraint type c 21 DoverPac Contained Powder Transfer rPac Ve Containment gt Systems ArmorFlex is ILC Dover s proprietary family of films used exclusively in the DoverPac family of high potency flexible containment products Details are available in a databook upon request Basic Process Flow of b gt Materials a Contained Flexible Charging System b gt Charging Canister and Transition Adapter The canister pictured at the right shows the set up on a straight transition adapter at ILC s test facility While canisters typically are 316L stain less steel Hastelloy canisters also are available This unit has an initial groove for the canister end cap additional grooves for liner attachment typically 5 or 10 grooves depending on process Canister Attached to ILC Dover requirements and available height and Test Rig 1 groove for the cleaning sleeve or clean in place CIP sleeve attachment The canister is supplied with a 12 sanitary flange on each end This allows for a common design for attachment to vessel specific transition adapters and our CIP tundis
32. and operating cost including reduced cleaning and cleaning validation Validated containment technology Passive system Flexible materials Fastest turnaround of a processing suite for Disposable components subsequent manufacturing campaigns Adaptable to other process equipment Process is contained without contamination No blender shape modifications of motor drive shaft and controls Nanogram containment levels achieved Does not affect ATEX and Ex ratings Ergonomics maximized Speed of implementation No affect on blend uniformity WHAT CONTAINMENT LEVEL PROVIDED OEB 5 with results in the nanogram range This is based on customer test data other proven applications third party testing to the SMEPAC protocols on similar designs and the 100 inflation tests performed on the deliverable systems OEB 1 OEB 2 OEB 3 OEB 4 OEB 5 10 000 to 1000 1 000 to 100 100 to 50 50 to 10 10 to 1 1 to 0 1 0 1 to 0 01 Occupational Exposure Levels above are in g m3 WHY USE THIS OVER OTHER TECHNOLOGIES One of the driving forces of this technology is that it reduces the risk of cross contamination in multi process facilities and it provides safety to the operators in both multi process and dedicated facilities By using this disposable Engineered Control highly hazardous powders are contained at the source which significantly reduces cross contamination risks and cleaning of process suites and rigid containment devices The cost of ownership
33. anister is attached to the valve on the double cone blender A custom enclosure was developed based on this process that included a bag in waste sleeve an ambidextrous glove sleeve a HEPA filter and an encapsulated o ring for securing the enclosure to the canister 84 Contained Blending Flexible Enclosure Technology Figures 5a and b illustrate the charging process These steps include attaching the enclosure to the canister bagging the powder into the sleeve on the enclosure bagging out the stub from the previous enclosure pouring the powder from the jar into the blender placing the waste product back in the sleeve and crimping off the sleeve The enclosure is then folded and placed inside a fabric support shroud while still attached to the blender This protects the enclosure during the tumbling operation and saves the enclosure for use when offloading the blended product Offloading the blender figure 5c includes removing the support shroud unfolding the enclosure opening the valve to discharge the product and crimping off the enclosure so that the contained powder can be taken to the next processing step Figure 5a 1 Collection Area 5 Glove Sleeve 2 Blender Enclosure 6 Blender Canister 3 HEPA Filter 7 Band Clamp 4 Bag in Sleeve Figure 5b Figure 5c 1 Bin 85 Contained Blending Flexible Enclosure Technology 86 Wil An Ea HERR EA TURES FANDER ENERE ORT STECNOCOMOCGN Feature
34. beside the granula 3 Filter tor is maintained inside the enclosure for staging of ie ee U i Enclosure product and materials to support the overall process n AR Three ambidextrous gloves are incorporated into the Canister and flexible enclosure to support ease of operations when Sleeve loading and unloading the granulator and operating the controls A bag in bag out BIBO interface allows materials to be passed in and out of the enclosure without breaking containment The entire unit is sup ported on a frame that includes conductive casters which make the system portable Glatt GPGC2 Fluid Bed Granulator In the application shown in figure 2 flanges were added to an existing design that allows the attachment of the flexible enclosures The two enclosures allow for access to the bowl of the granulator and the filters A telescoping frame supports the enclosure when charg ing and offloading the equipment This frame can be collapsed on itself to allow the enclosure to be folded out of the way when not being operated Collette High Sheer Granulator 10L and 20L Figures 3 and 4 depict this containment system which also uses the flange mount feature to achieve con tainment while separating the process and technical areas A roll away frame supports the enclosure This frame also includes a platform that functions as a table to support the bags of material Figure 2 Figure 3 72 Granulator Containment Technology T
35. better than rigid system Fits a wider range of operator sizes without ergonomic issues of rigid designs Can move to process area when needed freeing room in process suite when not in use unlike a rigid fixed system Better utilization of facilities Significant operational cost savings in cleaning time and validation Engineered process control Protection of operator No product loss of expensive APIs Significant savings of capital budget leaving money for other priorities Operator training minimized across multiple processes Improved speed to market No cross contamination Allows attachment to a process specific frame Improved interface to multiple pieces of process equipment and DoverPac sizes This is a validated system Mill Containment System ver Pac Containment Systems OVERVIEW Milling is acommon operation throughout the Pharmaceutical Manufacturing Process Sizing of powders is a dusty operation and with more potent powders being processed the need for containing this operation becomes even more critical from safety and cross contamination avoidance purposes In addition to contained powder throughput it is imperative that access to the interior of the mill be made available without breaking containment in case the screen blinds for changing to a different mesh impeller change or cleaning Underdrive Mill DoverPac Charging Canister with Transition Adapter Screen Access Enclosure Hardware Outl
36. by allowing you to retrofit existing processing equipment while achieving nanogram containment levels All materials meet FDA standards and the design accommodates cGMP as well as operator ergonomics FLEXIBLE CONTAINMENT TECHNOLOGIES VverPac Containment Systems Flexible Enclosures Allows operators to work in shirt sleeve environment increases efficiency 3rd party validated Nanogram containment levels using SMEPAC guidelines Economical Fast turnaround installation Compatible with a wide range of existing equipment for retrofit Design makes use of existing DoverPac containment details such as crimps bag out sleeves and o ring interface canisters Ergonomics are improved with an increased range of motion Designs support separation of process and technical areas Where applicable entire piece of equipment can be contained 39 Contained Processes Flexible Enclosures Glovebags 40 ver Pac Systems Tablet Press Deduster Flexible Enclosure e Powder added using a DoverPac and canister interface A series of glove sleeves permit easy press operation ol Continuous bag out sleeve supports tablet sampling analysis P Unexpected maintenance can be performed using bag out sleeve and gloves Unique base design interface e Eliminates the need for zippers e Stainless steel construction e Utilities can be plumbed through base e Fo
37. canister can also be provide as an optional method for transfer as shown in the photograph Space is also available to store plastic bags that can be used to contain the documents once all work is com pleted A stainless steel frame is used to support the enclo sure which includes casters to make the unit portable The frame will include a rigid plate to use for support during writing The top half of the frame can be provided as a table mounted system Frames are typically available in 304 or 316L Stainless Steel Other materials can be provided as required The typical document transfer enclosure is sized for dimensions of 24 wide x 24 high x 24 deep Custom sizes are also available FEATURES e Clear film allows use of existing light from the suite gt Passive system meets ATEX and Ex ratings e Re usable for extended campaigns Portable Small footprint does not take up a lot of floor space 43 Document Transfer Enclosure rPac Ve Containment Systems e No cross contamination transfer to documents and then to other parts of the plant BENEFITS Ergonomics are maximized with flexible materials Reduced cleaning and cleaning validation e Low capital and operating cost Speed of implementation Production and Lab processes supported WHAT CONTAINMENT LEVEL PROVIDED OEB 5 with results in the nanogram range This is anticipated given third party test results from similar desig
38. capable of providing contain ment levels to below 1 ug m3 in applications around the world Load crimp into installation tool Position crimp Squeeze tool until crimps are engaged then release tool Cut and separate Install crimp cap on crimp body DoverPac Continuous Liner 23 Dia Contained Powder Discharge to Drums aa Containment Systems p gt Continuous Liner Discharge Arrangement i N Minii UONI k Ha b gt Other System Components and Accessories Other system components and accessories developed by ILC Dover to support contained pharmaceutical ingredient processing include Wash In Place Enclosure Clean In Place System In Line Filter Kit b gt Applications Product offloading from sifters mills blenders centrifuges dryers and other process equipment Bag in Bag out E E 32 lt System Description This easy to use system has been proven effective in containing active pharmaceutical ingredients and other hazardous compounds This system uses a five liner canister which will allow up to five contained changes of the 30 packs before cleaning or canister recovery is required This system also provides the 30 liner packs pre bundled which reduces operator time Its use assures a safe and effective transfer of powders tablets vials tools and trash Uses ILC Dover s Patented Technology Dov
39. ches to our patented multi O ring system can be used Figure 6 Figure 4 55 DoverPac SF WHAT ARE THE APPLICATIONS This system has been proven to be of value in Dispensing from Isolators e Reactor Charging Tank charging for mixing creams e Creating a slurry for later charging into a tank Ver AT Aine I rem e Ad Vin Es Bein Eris 2 Features e Flexible ae E N af lf O A gt Clear Tl n Sanitary Flange Ri Range of Sizes qe N ibis lt ArmorFlex Family of Films a pcan MATS Benefits zl a Can be manipulated to overcome bridging Figure 6 also achieves over 99 5 product discharge Operators can see product without breaking containment lt Interfaces with any Split Butterfly Valve Supports Lab scale through Bulk production e Assures ruggedness static dissipation and material of contact compliance WHAT CONTAINMENT LEVEL IS PROVIDED The containment level achieved is that of the Split Butterfly Valve selected If a configuration is selected that interfaces with a DoverPac multiple o ring canister as in Figure 6 above at the right containment to the OEB5 levels in the nanogram range can be achieved WHY USE THIS OVER OTHER TECHNOLOGIES Reduced cost of ownership Eliminates cleaning and cleaning validation Eliminates waste treatment of cleaning solutions Best product recovery Visual access to drug product being manufactured Liner can be manipulated to overcome bridgi
40. chute of the vessel Once the filtration process is complete the valve is opened and the Operator scoops powder through the chute and into the DoverPac using the glove ports that are supplied as part of the Aurora Filter The DoverPac process outlined above is then followed After processing a Clean In Place CIP tundish is attached to the sanitary flange on the canister by bagging it in with the CIP sleeve Offset canister il 66 B gt j Ai I ua BE SANIMART CLAMPS W GASKETS DoverPac Contained Offloading of Aurora Filters Processing from Nutsche Filters iE ALN i Fy j E i i a i at L a i a5 fo Eo F fan gt _ 7 J A _ r T p d im m E i SLE gm h Flexible Enclosure Offloading Flexible Enclosures are a proven alternative to rigid gloveboxes These can be provided in either a passive system or with a Ventilation System included The enclosure is manufactured from clear ArmorFlex film that will allow room light to illuminate inside the enclosure for easy viewing It is also equipped with a bag in bag out sleeve which is used for introducing product and tools to and from the enclosure without breaking containment In this application a standard 8 multiple o ring canister is attached to the outlet of the filter The enclosure is then attached to the same canister to provide a contained connec tion during the transfer of powder A 14 Continuous Liner is connected to the canister inside
41. cleaning validation Low capital and operating cost Speed of implementation WHAT CONTAINMENT LEVEL PROVIDED Figure 3 2 Enclosure Support Frame 3 Support Table DER 5 wiih results in the nancgram range This is based on customer test data oiher proven applications third party testing to the SMEPAC protocols on similar designs and the 100 inflation tests performed on the deliverable systems WHY USE THIS OVER OTHER TECHNOLOGIES The cost of ownership ergonomic advantages and speed of delivery benefits of this flexible solution far outweigh those of rigid iso lation systems OTHER POTENTIAL APPLICATIONS Successful installations have been provided for similar size reduction equipment inching Quadro and FiteMill systems as well as microfitbers 62 Tablet Coater Containment System O Hara LCM Tablet Coater OVERVIEW Recently delivered for lab scale operations at an International Pharma manufacturer the installation described in this Containment Guide takes the idea of retrofits to another level Here a new piece of equipment was needed but cost savings were realized by modifying an existing design Flanges added to the unit by the original equipment manufacturer OEM allow this end user to process contained when needed and to use existing procedures when containment is not required Containment for the O Hara LCM Tablet Coater is provided by two individual rectangu lar enclosures One
42. clo oe sure after the outer drum liner is removed as depicted here 4 H a i r The outlet canister supplied with the frame is typically our Fi ey a GlovelSleeves a L f 5 5 liner multiple o ring groove system For transfer direct to a a process vessel a Transfer Sleeve is used If filling with a DoverPac Is required the canister supports interface to Multi Use gg this containment technology Sleeve 7 Figure 2 WHAT CONTAINMENT LEVEL PROVIDED OEB 5 with results in the nanogram range This is based on proven applications third party testing to the SMEPAC protocols and the 100 inflation tests performed on the deliverable enclosures WHY USE THIS OVER OTHER TECHNOLOGIES The cost of ownership ergonomic advantages and speed of delivery benefits of this flexible solution far outweigh those of rigid isolation systems APPLICATIONS Given the modularity features designed into the Drum Transfer System contained transfer of drummed powders for the following applications is possible MILLING al 97 a In the application pictured in Figure 3 powder is processed from ILC Dover Drum Transfer sieving a drum through a mill a Quadro Sifter in this example into a Stallion Equipment stainless steel Intermediate Bulk Container IBC An interface to the mill is provided at the outlet of the Enclosure frame using a transfer sleeve A similar sleeve is used to go from the outlet of the mill to the inle
43. components In response to customer input and emerging svear shek lite regulations we ve developed a robust new Permanent antistat replaces film to support our DoverPac Containment P migrating additives Systems This revolutionary film ArmorFlex 114 delivers permanent Passes Chilworth incendivity tests static dissipative properties while Tested for solvent resistance meeting FDA and 2002 72 EC requirements for food contact and EP 3 1 3 test conditions DMF filed with FDA 13 ArmorFlex 114 Film 14 Chemical Acetone Acetonitrile Anisole Butyl Acetate _ Cyclohexane ArmorFlex 114 Solvent Resistance Solvent Contact Recommendations Charging mills with DoverPac and offloading to IBC with transfer sleeves ver Pac Systems Resistance Excellent Excellent Good Good Excellent Cyclohexane Ethyl Acetate 50 50 Dichloromethane Diethylether Dimethylacetamide Dimethylformamide Ethanol Ethyl Acetate HCL 37 4 n Heptane HMDS Isopropanol KOH 50 Methanol 2 Methoxyethanol Methylethyketone Excellent _ Excellent Excellent Excellent Excellent Excellent Excellent Very Good Very Good Excellent Excellent Very Good Excellent Excellent Excellent n Methylpiperazine n Methypyrrolidone Methyl tert butylether Mineral Oil Reagent 3A Alcohol NaOH 50 Tetrahydrofuran Toluene Excellent Excellent Bag in bag out sleeves
44. d on the deliverable systems WHY USE THIS OVER OTHER TECHNOLOGIES The cost of ownership ergonomic advantages and speed of delivery benefits of this flexible solution far outweigh those of rigid isolation systems OTHER POTENTIAL APPLICATIONS AURORA FILTERS are designed primarily for the applied research development and pilot scale operations within the pharmaceutical and chemical industry Containment for offloading in addition to the applications outlined above can be applied via Continuous liner system on outlet for contained filling in drums e Transfer Sleeve on the outlet for direct transfer to IBCs or other vessels 68 Mill Containment System Jet Mills OVERVIEW The process for this application consists of the controlled feeding of a mill through a feeder The powder is introduced into the feeder using a Drum Transfer System After the particle reduction is complete the powder is passed through a Cyclone housing and collected in a continuous liner system The Jet Mill or Micronizer as this style of mill is also called used in this application is a Jet Pulverizer 8 Micron Master In this process air drives the particles which are reduced in size when they impact upon each other Smaller particles flow up the transfer tube to the Cyclone housing while the larger particles continue to be impacted on each other until they are reduced to the desired size see Figure 1 at right The Feeder in this application i
45. d in out through sleeve e Glove sleeves allow full operator access A IBC Transfer e Milled powder or finished product e Tare weighing in process transfer Dispensing device enclosure with transfer sleeve to IBC or downstream process 42 Document Transfer Enclosure verPac Systems OE IR WOE The Flexible Document Transfer Enclosure is designed to allow paperwork used in pharmaceutical processing to be handled in a contained way so that powders are not transferred onto the documents and to areas or individuals that are not protected The enclosure can be manufactured from a clear ArmorFlex or polyurethane film that will allow for room light to illuminate the inside of the enclosure for easy viewing and writing on the documents HOW DOES THE SYSTEM WORK Documents writing implements and baggies for enclosing the finished paperwork are preloaded into the enclosure A set of glove sleeves left hand and right hand are integral to the front of the enclosure at an approximate height of 48 Due to the flexibility of the enclosure the operators will be able to work at heights approximately 5 from the glove sleeve centerline This flexibility is provided by the nature of the films employed and the use of bungee cords that allow the enclosure to move with the operator On the side opposite of the Glove Sleeves will be a zipper that is used as a pass through for the documents A bag in bag out BIBO
46. d outer Type C restraint The new FlexLoc clamp an improvement over the original DoverLoc clamp that replaced the original cir clip The Crimp Separation System the replacement for the original twist tie 5 6 tape and cut system for repeatable separation of the liner from the vessel without breaking containment 1 Fill neck with o rings 4 Body saree aa 2 Bag Out Sleeve 5 Bag Out Sleeve aaa 3 Sample Sleeve 6 Discharge neck with o rings 65 Contained Offloading of Aurora Filters Processing from Nutsche Filters The basic operational steps are performed for offloading the filter 1 Aah won Attach the fill neck of the DoverPac to the ILC Dover supplied multiple o ring canister and shuffle up some of the neck to create a clean zone for crimp separation Bag out the stub from the previous liner Open the valve on the vessel and use the sample sleeve to take a sample if required by the process Finish filling Pull down the clean zone twist the neck and apply the crimps Cut between the two crimps and close the caps on the crimps Note that this leaves the stub that will be bagged out with the next DoverPac Repeat steps 1 6 The same process is used to charge the next vessel except there is no sampling sleeve at that point In the application below an offset canister with the capability to offload to three 110L DoverPacs was installed on the sanitary flange of the 8 200mm Cora Valve on the discharge
47. e Product offloading e Tablet offloading e Bag in Bag out 35 Continuous Liner Bag in Bag out Contained Transfer ver Pac Containment OVERVIEW z Systems The DoverPac Bag In Bag Out BIBO system is a family of contained transfer designs for multiple processes The primary components for this validated operation consist of multiple groove canisters docking interface hardware and softgoods in either continuous liner form or discreet liners as illustrated below in the continuous liner application Cantinuous Linger Continuous Linar 14 Continuous Continuous Liner Bag Out Bag in Canister Isolator een Band Clamp with O ring 23 Continuous Beta Flange Drui Linet of Tr Clower Connection System Leolatod This system can be applied to any rigid isolator The use of multiple size canisters allows a broad range of needs to be met systems can be retrofit to existing assets and the BIBO system requires a low capital outlay OPERATION By utilizing the patented multi o ring and flexible containment techniques developed by ILC Dover this system builds on proven DoverPac designs The hardware is docked to the contain ment enclosure either by using the existing aloha beta port hardware or bolting directly to the wall of the rigid isolator The liner is then extended over the item to be introduced or removed from the enclosure and then crimped off to complete the contained transfer 44 Co
48. e brochure Specifically what level of contain ment are you reaching there is mention to nanogram ranges what are they lt 50 ng m3 better worse Do you have test data that would be available for review Does the size of the drum matter i e 30 gallon 50 gallon etc How is the drum lid supported inside of the liner Seems like it would get in the way Is the stand support adjustable regarding height Which film are you using for this system This works as well with plastic or SS drums We have not tested this specific design in ILC s SMEPAC test facility Our intent is qualification by similarity to other enclosures that we have tested like the Drum Transfer Station where our results ranged from non detects to under 500 nanograms We do perform an inflation dwell test on this design as we do with all of our high containment systems We currently have three standard sizes that cover a range of drums 15 to 17 5 381mm 445mm diameter Model FE8615S 17 to 19 5 432mm 495mm diameter Model FE8615M 19 to 21 5 483mm 546mm diameter Model FE8615L Custom sizes can also be accommodated The lid is set up vertically on the side Since this is not a long term application we felt the trade off of leaving it set inside was more cost effective than supporting it with a stand The good news is that you can remove the lid inside the enclosure rather than risking a potential exposur
49. e by removing the lid first The stand is three lengths of square SS stock that are connected by push pins Sections can be removed for gross height adjustment The body is AF113 a clear PE film that has been formulated to meet FDA and the new EU regulations but not tested to date The sleeves BE lt For removal and disposal assume the HEPA filter allows the liner to collapse where is the filter how is it mounted to the liner what size etc The HEPA filter is attached via a screw attachment to a fitting that is welded to the enclosure on the top panel This is one of our standard 85L m 3 cfm HEPA filters What size crimps does the sampling sleeve use red yellow or blue 54 Yellow DoverPac SF VverPac Systems OVERVIEW The original DoverPac SF was launched to be used in conjunction with Split Butterfly valves Figure 1 This system replaces rigid bottles HOW DOES THE SYSTEM WORK The basic DoverPac SF is used either unrestrained Figure 2 with an integral restraint Figure 3 or with a reusable restraint The system can be filled and emptied through a standard 4 100mm DN100 or DN150 integral sanitary flange The design is set up so that the SF can be used with any Split Butterfly Valve Filling and emptying the liner is accomplished by attaching the passive half of the valve to the liner which then docks with the active half of the valve Other sizes have been accommodated as w
50. e to help install it in the correct orientation The FlexLoc functions to prevent powder from going between the inside of the liner and the outside of the canister to minimize cleaning operations The clamp is designed to operate in the offloading and the charging operations Crimp Separation Kit Contained separation between vessels and DoverPacs is achieved through a Crimp Separation Kit using ILC s uniquely designed crimp system Crimps are color coded to assure that the right crimp is selected for the right product Red crimps are used for the 14 necks on the DoverPacs A Crimp Separation Kit includes e 200 Crimps e 1 Crimp Hand tool e 1 Cutter e 100 Cable Ties 7 Nylon e 1 User s Manual Additional spare items can be ordered separately by their individual model part numbers After filling the liner is twisted and crimped closed The hand tool applies two crimps at once The cutter is used to cut between the two crimps and then the cap is slid onto the closed crimp body FlexLoc Clamp ILC crimps have been design ed and tested to compress standard diameter liners made with ArmorFlex film Load crimp into installation tool Position crimp Squeeze tool until crimps are engaged then release tool Cut and separate Install crimp cap on crimp body 23 DoverPac Contained Powder Transfer erPac VI Containment Systems Use of Lifting Bar p gt Lifting Bars
51. ece of process equipment being used to fill or offload the blender Contained attachment is achieved through the use of a multiple groove canister on the blender and on the IBC for example The sleeve is then clamped onto the blender and IBC to support powder flow In the case of a bin blender the bin can be attached to the tablet press or to an interface in the floor of the suite where powder transfer to a piece of equipment on a lower floor is part of the process Gemco V Blender to IBC In the example shown in figures 1a and 1b a 30 cubic foot Gemco blender is being emptied to a rigid IBC The application posed a challenge in lining up for docking with the IBC and in clearances while the blender rotates The system includes a 5 groove multiple o ring canister attached to the V Blender a 2 groove canister clamped to the IBC the Transfer sleeve the DoverLoc and the crimp components The transfer sleeve is also made with an ArmorFlex film Charging and offloading with DoverPacs DoverPacs are a proven method for contained transfer from vessel to vessel This system consists of a liner that is attached to a multiple o ring groove canister By incorporating a fill and discharge neck the same liner can be filled at one process point and discharged into another DoverPacs utilize the crimping system and ArmorFlex family of films developed by ILC Various standard and custom designs are available to fit any process need from lab sca
52. ell Figure 1 The sanitary flange is injection molded and then thermally welded to the liner This is done with a blended lap weld which keeps all of the load in shear and eliminates any possibility of powder hangup or bioburden build up in an otherwise raised lip at the seal area The unrestrained design uses a separate lifting bar when it is supported for vessel charging This is significantly more robust than an encapsulated plate The restrained version is provided when a concern over back pressure exists This design uses an integrated restraint that has been proven to withstand pressure Figure 2 Figure 3 excursions of 0 499 bar with a 2X safety factor A window is included in the restraint so the operator can see that all powder has been discharged into the vessel A variety of configurations are available including e Sizes from 1L 5L 10L 15L 25L 30L 50L and 100L An integral tube for addition of al liquids creating slurry within the r liner or for rinsing out the liner to recover any remaining powder Figure 4 a ee ee eee eee eee ee eee eee eee eee eee eee E The DoverPac SF has also been adapted for cGMP and higher eo containment applications For cGMP a dual tied S folded neck D meee is Incorporated Figure 5 For 2 EE raai an i tenn ae a M ee ee PRE eee a containment needs past that of split butterfly valves a model that atta
53. enclo sures designed to provide containment for a range of process equipment Drum Transfer System For offloading drummed materials in a safe and efficient manner at fixed and varying heights Mill Containment System Critical safety and cross contami nation avoidance during particle size reduction operations Providing Flexible Containment Solutions to the Pharmaceutical Industry since 1997 ver Pac Systems One of our major customers says it best You guys provide the only containment that works As the pioneer of flexible containment systems ILC Dover has collaborated with our customers in the phar maceutical industry to develop a range of validated API containment solutions that interface with a wide variety of process equipment All of our products are designed to be safe effective and user friendly The same knowl edge of flexible film and fabric systems and attention to detail that allows us to be NASA s sole supplier of spacesuits uniquely qualifies us to design and produce unparalleled containment systems Some of the key benefits offered by using flexible containment gt Ability to rapidly upgrade existing equipment to handle potent compounds gt Reduced capital costs gt Increased throughput when compared to other systems gt Improved ergonomics gt Faster project start up gt cGMP through nanogram processing Why DoverPac Containment System v
54. enclosure surrounds the pan access door and the second the exhaust plenum access door The enclosure is manufactured from clear ArmorFlex film that allows room light to illu minate inside the enclosure for easy viewing This rugged film provides a safe working en 1 Coater 5 Filter Change Out Enclosure ronment wle enabing te entanoements 2 Erolasine Support Fiane WIN HEPA For using this flexible containment technology 3 BIBO Canister Support Frame an e 4 Coater Enclosure 7 BIBO Canister with HEPA Filters HOW DOES IT WORK The pan access enclosure is used for product charging and removal as well as sampling cleaning and spray gun maintenance It has one pair of glove sleeves A single entry removal point provides a means for moving product and supplies in and out of the enclosure This entry removal point supports the use of a bag in bag out sleeve or interface with ancillary containment devices such as an in process isolator The enclosure is mounted in such a way that it can be collapsed inward toward the front of the coater This simplifies loading and unloading product through the circular door on the coater The enclosure is fully extended to provide clearance when opening the larger pan access door for cleaning operations The exhaust plenum enclosure is mainly used for cleaning operations It has a pair of glove sleeves and a cleaning wand sleeve It can also be equipped with a storage waste sleeve if desired Both enclos
55. ent that cannot be achieved with a standard drum liner The 23 584 mm diameter continuous liner system is designed to allow continuous offloading of powders into drums This contained powder transfer system consists primarily of a set of hardware that fits the flange of a vessel and a factory packed kit of liners that are delivered in a pack ready to install on the canister Standard systems are supplied in continuous sleeves Sample sleeves are often added as custom applications DoverPac Continuous Liner 23 Dia Contained Powder Discharge to Drums F FLEXIBLE CONTAINMENT TECHNOLOGIES ver Pac Containment Systems 23 584 mm Diameter Continuous Liner Systems Contained processing to protect the operators cGMP processing in a completely closed operation to protect the product One person operation Pre loaded liner material minimizes processing time Inert atmosphere offloading of products Significant reduction in cleaning time waste and validation expenses The system is available in the following sizes Pack Length Number of Drums per Pack 50 10 100 20 150 30 assumes 5 of liner per drum to accommodate drum height and crimping Actual usage will depend on the drum height DoverPac Continuous Liner 23 Dia Contained Powder Discharge to Drums The basic steps for operating this easy to use system are shown in these continuous liner process steps
56. er transfer bag or more importantly when it is discharged at the reactor or mix tank BENEFITS e Open fill design provides an easy target for manual filling without spillage e Significantly less time required per dispense cycle e Minimizes cleaning with fold over neck e Additional parts eliminated e Eliminates the need for additional tools and fixtures It is self standing and self supporting e Custom designs to meet specific process requirements e ArmorFlex 114 film is the standard material for the product contact area This unique antistatic film meets FDA USP and EU regulatory compliance standards Complete Range of DoverPac Products FEATURES EZ BioPac Vessel Connection flange sizes options e 1liter thru 100 liter capacity 5 Liter 1 5 Sanitary Flange e 1 5 thru 6 sanitary ferrule reactor 10 Liter 2 Sanitary Flange charge connections 20 Liter 3 Sanitary Flange e Rinse ports vent filters and other 30 Liter 4 Sanitary Flange process features available 50 Liter DN 100 Sanitary Flange e Smaller sizes have a handle for manual 100 Liter DN 150 Sanitary Flange lifting and larger sizes have lifting loops 6 Sanitary Flange 8 Sanitary Flange 100 FlexiVac OVERVIEW In an effort to provide a better solution for containment to the standard PTS DCS system FlexiVac was developed along with our partners CSV Life Sciences in Italy and Micro Macinazione S A The resulting innova
57. er Pac Containment Systems Multiple O Ring Technology Our patented system of progressively advancing to a new clean zone on a canister allows multiple powder transfers without breaking containment Contained Separation Crimps The use of DoverPacs and Continuous Liners is enhanced by this ILC innovation Our crimps permit reliable repeatable one person contained separation of sample sleeves and charging and discharging necks Flexible Enclosures We know that existing pharmaceutical plants are sometimes cramped and many times not originally designed to support the processing of potent compounds Our custom flexible enclosures permit safe contained operation with a wide range of processing equipment Engineering Systems Service Capability Custom engineered hardware interfaces with your specific processing equipment On site surveys to engineer your application offered Product performance testing and customer training at ILC s contain ment processing suite or on site provided Personal and proactive customer service representatives available Seasoned professional engineering team supports standard and custom containment solutions We are the first to validate flexible containment Manufacturing Each DoverPac is manufactured in a clean working environment using custom sealing equipment designed and manufactured by ILC This approach allows us to control the manufaturing quality of
58. erPac Continuous Liner 14 Dia Contained Powder Discharge to Drums a FLEXIBLE CONTAINMENT TECHNOLOGIES verPac Containment Systems 14 355 6mm Diameter Continuous Liner Systems lt 1ug m contained process ing to protect the operators with results in the 250 nanogram m3 range cGMP processing in a completely closed operation to protect the product One person operation Inert atmosphere offloading of products Significant reduction in cleaning time waste and validation expenses DoverPac Continuous Liner 14 Dia Contained Powder Discharge to Drums Attach neck of continuous liner to canister Install a band clamp Slide the pack onto the canister Install the outer shroud Unsnap the retaining snaps on the pack Pull down liner material to start processing ver Pac Systems Materials ArmorFlex is ILC Dover s proprietary family of films used exclusively in the DoverPac family of high potency flexible containment products These films pass incendivity testing and are designed and manufac tured using FDA amp EU compliant materials System Components The system components for contained discharging as pictured here consist of e 8 Sanitary Flange Five Liner SS Canister used to make contained connection of DoverPacs e 30 Continuous Liner Pack Fabric Outer Shroud Pack Protector 8 Stainless Steel Band 8 Sanitary Clamp 8 San
59. ers tablets vials tools and trash an operational requirement that cannot be achieved with a standard drum liner Containment Levels While specific powders react differently due to their particle size customer testing has shown that these systems are capable of providing containment levels to below 1 ug m3 on a task basis in applications around the world Load crimp into installation tool Position crimp Squeeze tool until crimps are engaged then release tool Cut and separate Install crimp cap on crimp body DoverPac Continuous Liner 14 Dia Contained Powder Discharge to Drums FlexLoc Clamp ra Systems FlexLoc Clamp The FlexLoc clamp is used to secure the neck of the liner to the canister Construction of the molded clamp is of FDA compliant elastomer with integrated stainless steel band clamp The clamp has a molded ridge along one surface to help install it in the correct orientation It functions to prevent powder from going between the inside of the liner and the outside of the canister to minimize cleaning operations The FlexLoc clamp is designed to operate in the offloading and the charging operations Other System Components and Accessories Other system components and accessories developed by ILC Dover to support contained pharmaceutical ingredient processing include e Wash In Place Enclosure e Clean In Place System e In Line Filter Kit Applications
60. es a tumble blending operation for free flowing materials in small volumes As such It can be cart mounted using a pan mount design figure 4 The pan is mounted on a frame asembly with conduc tive casters Overall dimensions of this portable system are 54 1372 mm x 42 1067 mm x 73 3 1861 mm tall Standard features carried over to this design include a BIBO canister for introducing raw materials into the enclosure and passing blended product out for process ing to the next step HEPA filters and bungee cord attachment to support a range of operator heights and integral glove sleeves at optimal processing locations Flexible Enclosure loading and offloading By attaching a multiple groove canister directly to the valve on the blender small volumes of powders can i Figure 4 be charged and removed from a blender using a Flex ible Enclosure Typically used in Lab Scale and Clinical 1 HEPA Filters Development trials this process supports processing in RAMONE ENCO early stages where the acceptable daily exposure ADE and Occupational Exposure Level OEL are often not known yet 3 Glove Sleeves 4 Frame Mounted Pan 5 BIBO Canister sleeve not shown Double Cone Blender Mounted Flexible Enclosure System Here a small volume of powder is charged into the blender from a bottle In order to contain this transfer a flexible enclosure is attached to the blender In this design a 6 150 mm multiple groove o ring c
61. escribed in this guide center around wet granulation which involves the massing of a mix of dry primary powder particles using a granulating fluid The powders can range in properties and potency and are subjected to a variety of additional steps including sieving drying and milling Used for lab scale and production operations at multiple International Pharma manufacturers our contained Granulator applications take the idea of retrofits to another level Here a broad range of existing and new equipment are supported as a tool to eliminate the risk of contained powder processing HOW DOES IT WORK Two methods of containment have been applied One uses flanges that are added to the piece of process equipment that then have a flexible enclosure attached to the flange in opera tion The second is to totally encapsulate the granulator with a pan mounted flexible enclosure Equipment Mounted Enclosures Separate the Process and Technical Areas The use of stainless steel flanges added to the granulator enables the containment of the process area The enclosure is attached to the flange and includes glove sleeves bungee cords and HEPA filters These features support access to the equipment while maximizing ergonomics and support operators from the 5th percentile female to the 95th percentile male Pan Mounted Enclosures Encapsulate the Entire Granulator Pan mounted enclosures allow the entire piece of process equipment to be contained
62. et Canister ee ee HOW DOES THE SYSTEM WORK The configuration shown in Figure 1 consists of the basic mill with modifications to support the attachment hardware needed for the standard DoverPac charging and offloading systems In addition a flexible enclosure interface is provided between the base of the charging canister and the mill s inlet housing Safety is maintained as provided in the base mill design Safety Grids are included in the inlet and outlet canisters In addition the interlocks are relocated to the Charging Canister and Screen Access Enclosure Ring In the event that a screen blinds during operation the mill is turned off and the screen is accessed using the enclo sure shown in Figures 2 3 and 4 This is accomplished by Applying the Lifting Shroud to the canister e Removing the protective shroud from around the enclosure used when the enclosure is in the stowed Figur i position only not shown in this document Inserting hands in the integral glove sleeves in the enclosure and opening the tri clamp e Hoisting the canister and using the glove sleeves again to remove the impeller and screen The enclosure is manufactured from clear ArmorFlex film that will allow room light to illuminate inside the enclosure for easy viewing It is also equipped with a bag in bag out sleeve which is used tor housing the tool needed to loosen the bolt that secures the impeller and bagging out the screen as re
63. ethods of flexible containment using enclosures have been applied to blenders These include containing the entire blender in an enclosure using an enclosure and flanges attached to the blender to separate the process and technical areas and charging and offloading a blender with an enclosure attached to the valve on the blender The enclosures are manufactured from clear ArmorFlex 113 film that allows room light to illuminate inside the enclosure for easy viewing This rugged film provides a safe working environment while enabling the enhancements developed through numerous installations using this flexible containment technology The Bag in Bag out BIBO Sleeves and DoverPacs are often used to transfer powders into and out of the enclosure The Sleeves and DoverPacs are made from another version of ArmorFlex film and as such brings regulatory pedigree for materials of contact The use of flexible containment allows the end user to process contained when needed or follow existing open processing procedures when containment is not required In both cases cost savings are realized by modifying an existing design or using an existing piece of equipment with no modifications Separating the Process and Technical Areas of the Blender In this method flanges are added to the piece of process equipment usually by the original equipment manufacturer OEM A Flexible Enclosure is then attached to the flange The use of stainless steel flan
64. ex Family ArmorFlex 114 Solvent Resistance Solvent Contact Recommendations Chemical Acetone Acetonitrile Anisole Butyl Acetate Cyclohexane Cyclohexane Ethyl Acetate 50 50 Dichloromethane Diethylether Dimethylacetamide Dimethylformamide Ethanol Ethyl Acetate HCL 37 4 n Heptane HMDS lsopropanol KOH 50 Methanol 2 Methoxyethanol Methylethyketone n Methylpiperazine n Methypyrrolidone Methyl tert butylether Mineral Oil Reagent 3A Alcohol NaOH 50 Tetrahydrofuran Toluene Water Distilled Criteria Change in Physical Properties 0 10 10 20 20 30 gt 30 VverPac Containment Systems Resistance Excellent Excellent Good Good Excellent Excellent Excellent Excellent Excellent Excellent Excellent Excellent gt Very Good Crimp Separation Continuous Liner System DoverPac Very Good a Excellent ILC Ireland operating since 2007 Excellent ILC Ireland located in County Cork has been providing standard products Yoy Geo from this facility for 4 years Estab Excellent lished to support the pharmaceutical Excellent industry in Ireland the facility ware Excellent houses all standard products offered by ILC Dover DoverPac s continuous Excellent ie liners crimps etc are readily avail Excellent able for immediate delivery with the Excellent convenience of all customs clearance Excellent completed ILC Ireland is committed EeGIIGRE ILC Ireland facili
65. examining new methods yields new discoveries Table of Contents Why Do Our Customers Value ILC Dover 5 Validated Containment THAT WORKS 6 Why DoverPac Containment System 7 ArmorFlex Family of Compliant Static Dissipative Films 8 ArmorFlex 104 Film 9 ArmorFlex 113 Film 11 ArmorFlex 114 Film 13 DoverPac 15 DoverPac Contained Powder Discharge 17 DoverPac Contained Powder Charging 19 Coaxial DoverPac Nanogram Powder Transfer 25 G2Pac lt 100ug m3 Containment Powder Transfer 27 DoverPac Continuous Liner 23 Diameter Contained Powder Discharge to Drums 28 DoverPac Continuous Liner 14 Diameter Contained Powder Discharge to Drums 32 Continuous Liner Bag In Bag Out Contained Transfer 36 Antistatic Drum Liners 38 Contained Processes Flexible Enclosures Glovebags 39 DoverPac Document Transfer Enclosure 43 Drum Transfer System Contained Drum Dispensing 45 Mill Containment System 49 Drum Sampling Enclosure System 51 Drum Sampling Enclosure FAQ s 53 DoverPac SF 55 DoverPac SF BioPharmaceutical From Lab Scale Through Production Processes 57 Tray Dryer Enclosure Technology 59 Mill Containment System Bohle BTS 100 61 Table of Contents continued gt 3 Table of Contents Tablet Coater Containment System O Hara LCM Tablet Coater Contained Offloading of Aurora Filters Processing from Nutsche Filters Mill Containment System Jet Mills Granulator Containment Technology
66. f 1000 and the HP system is rated with an APF of 25 How many sizes of hoods are there The hood is designed and NIOSH approved as a one size system Can wear standard personal protective gear in the hood What types of filters are available Yes the head top supports the use of equipment such as hard hats hearing muffs and safety glasses as needed The system has NIOSH approvals for the option of using two High Efficiency Particulate HE or three OV CD CL HC HF SD HE filters What airflow does the PAPR provide The powered air purifying respirator PAPR delivers 8 scfm 230 LPM of filtered air This is 33 more than the minimum flow required by NIOSH What is the advantage of all this added air flow What keeps the hood from rising Aside from increased protection for the worker the added flow provides additional prevention of lens fogging as well as cooling to the head and torso as the air passes from the internal duct in the hood across the breathing zone and down into the Tyvek suit The outer bib includes four adhesive tabs These tabs adhere to the up when it is inflated 90 Operator s Tyvek suit creating a shear mode resistance to any lifting load Additionally a portion of the air from the blower is exhausted to the room which balances the comfort and protection features of the system Sentinel Clear Hood FAQ s What type of batteries are used with the Sentinel XL system Ho
67. f our flexible enclosure systems to maximize ergonomics as noted above Chitra V Blender In this design the containment is achieved by encapsulating the entire blender inside a flexible Figure 2 enclosure The enclosure is of the pan mounted style see figure 2 where the pan is situated on Pmelosure eh the floor of the process suite In this case the 2 BIBO Canister 5 Glove Sleeves pan is 53 5 1359 mm x 74 5 1892 mm 3 Support Frame The enclosure height is 75 5 1918 mm Multiple sets of gloves are incorporated into the flexible enclosure to Support ease of operations when loading and unloading the blender and operating the controls A Bag in Bag out BIBO interface is included to allow materials to be passed in and out of the enclosure without breaking containment The entire unit is Supported on a frame PK Blendmaster A similar design contains the PK Blendmaster in Figure 3 The pan is 56 1422 mm x 61 1549 mm and the overall height is 81 2057 mm Operational features such as integral glove sleeves located at key process points a BIBO canister HEPA filters and bungee cords are incorporated into the design Figure 3 1 HEPA Filters 6 Enclosure Support 2 ArmorFlex Enclosure Frame 3 Glove Sleeves 7 Base Tray and 4 Bag in Canister Enclosure 5 PK Blender Existing Mountngmange Contained Blending Flexible Enclosure Technology PK Blendmaster Yoke Blender The Yoke Blender provid
68. films are regulatory compliant Disposable Eliminates concern of cross contamination due to pneumatic effect of low end films leaking Bolt on or RIP Interfaces available Reduced cleaning and cleaning validation costs Reduced process time and cost by eliminating multiple RTP canisters Eliminates RTP seal maintenace 37 Antistatic Drum Liners b DoverPac static dissipative drum liners provide you with the confidence to safely transfer and store a wide range of API s and other powders As the pioneer of flexible containment systems for the pharmaceutical industry ILC Dover offers drum liners constructed from our durable ArmorFlex film the same material used in our DoverPac API containment system VverPac Containment Systems Static Dissipative Drum Liners Features Clear durable film Chilworth tested passes incendivity testing Available in all ArmorFlex films Up to 5 year shelf life based on film selected Contained Processes Flexible Enclosures Glovebags Fit check on lab scale fluid bed dryer ILC Dover s flexible enclosures take the concept of a traditional flexible glove bag to a new level Using the same reliable fabrication techniques and proven containment design features found on our DoverPac family of products we ve produced a line of flexible enclosures adaptable to a wide range of existing equipment These enclosures save time and money
69. for the equipment the film clarity and the elastic suspension attachments simplify the process for their operators e Custom designed with ILC Dover s engineering expertise Pharmatek custom designs enclosures for each process train unit WHAT CONTAINMENT LEVEL IS PROVIDED ILC Dover Test OBZ TWA Comment Enclosure System Material g m3 No of operators Granulator Lactose 0 0026 0 0027 Operation 2 Granulator Lactose 0 0027 0 0331 Cleaning 2 Drying Oven Lactose 0 0026 0 0028 Operation 2 Drying Oven Lactose 0 0026 0 0037 Cleaning 3 Operator Breathing Zone 8 Hour Time Weighted Average WHY FLEXIBLE Based on surrogate monitoring testing conducted by Kasai Consulting Pharmatek s facilities in San Diego achieved the nanogram containment values shown at left Flexible Enclosures prevent cross contamination and help assure operator safety in Pharmatek s development and manufacturing operations ie ILC DOVER creating what s next Pharmarek o_O PHARMACEUTICAL CHEMISTRY DEVELOPMENT 99 EZ BioPac lt Contain State of the Art Powder Transfer for Biotech as Systems Applications Typically for Media Prep and Buffer Prep Ss OVERVIEW i ILC Dover has developed a new powder transfer process to solve issues related to contamination and reduce the fill time of each powder bag The EZ BioPac is proven to reduce contamina tion that typically occurs during filling a powd
70. g arm of the lifter Twist and crimp the Drum Transfer Sleeve for disposal of the drum Attach a new sleeve to a new drum and attach the sleeve over the stub remaining from the previous drum Pull the stub into the enclosure to allow a clear pass through for the drum and repeat the process steps above 45 Drum Transfer System Contained Drum Dispensing HOW DOES THE SYSTEM WORK The Enclosure Frame sits on a series of bases offering a modular approach to processing drums in a con tained fashion This provides the benefit of processing into various mills DoverPacs and other vessels The entire assembly is mobile and can be wheeled over the piece of process equipment to be charged The castors used here are conductive Two wheels are locking while the other two pivot for steering The enclosure functions as a flexible isolator It is attached to the frame at the drum inlet ring and the outlet canister Bungee cords are used to attach the enclosure to the frame and allow the enclosure to move with the operator to take advantage of the system s built in flexibility The drum lifting unit is provided as part of the system The lifter is pneumatic powered to lift and tilt the drum into position The unit is a stainless steel construction and meets cGMP requirements The maximum lift capacity of the Hepa Filters standard unit is 100 Kg though larger lifts can be provided F K The drum s inner liner can then be accessed from the en
71. ges added to the blender enables the containment of the process area This then keeps the controls motors and other components of the technical section of the equipment away from the powder being processed to avoid contamination The enclosure is attached to the flange and includes glove sleeves bungee cords and HEPA filters These features support access to the equipment while maximizing ergonomics for operators from the 5th percentile female to the 95th percentile male Globe Pharma Blend Master V Blender In the application shown in figure 1 flanges were added to an existing design that allows the attachment of the flexible enclosures The frame is included to support the enclosure This frame is on casters so it can be moved out of the processing suite and stored when not being operated The overall enclosure is 58 1473 mm x 44 1118 mm x 70 1778 mm tall Figure 1 1 Enclosure 4 Glove Sleeves 2 Support Frame 5 BIBO Canister 3 Attachment Flange and Sleeve Contained Blending Flexible Enclosure Technology Containing the Entire Blender Pan mounted enclosures contain the entire piece of process equipment This is beneficial for equipment that can not be modified to use the flange mounted technology described above The enclosure is supported by bungee cords attached to the pan and includes glove sleeves for access to the equipment The enclosure moves with the operator as is the case with all o
72. h The custom transition adapter is fitted with a flange on one end that interfaces with the vessel flange or valve that is in line on the vessel flange The opposite end is a 12 sanitary flange that interfaces with the canister For flanges smaller than 12 a conical transition adapter is used to allow powder flow directly into the vessel without accumulation on the hardware The adapter also is fitted with a vacuum flange port with a 1 2 sanitary flange for attachment to the vacuum and nitrogen sources to allow inert processing b gt Purge Vacuum Arrangement Note Common vacuum purge supply connection to HEPA filter provides backwash function to extend filter life 22 DoverPac Contained Powder Transfer Ver Pac Systems This hardware is supplied with a 240 grit 15 RA internal finish and a 180 grit 32 RA external finish Other materials and finishes also can be provided Please note that for vessels that normally operate under pressure a valve is required to isolate the liner from the vessel while the vessel is under pressure This pressure rated valve is normally supplied by the customer and installed between the vessel and the transition adapter FlexLoc Clamp The FlexLoc clamp is used to secure the neck of the liner to the canister Construction of the molded clamp is of FDA compliant elastomer with integrated stainless steel band clamp The clamp has a molded ridge along one surfac
73. he stand are added to provide the attachment mechanism for the bungee cords The combination of HEPA filters and bungee cords support the flexibility of the ergonomic design Operationally the following basic steps are employed 1 Sampling tools are preloaded into the 14 350mm diameter sleeve and the open bottom of the enclosure is stretched over the drum and then taped to the drum wall 2 The integral grommets on the top of the enclosure are connected to the support frame to provide the operator with space to work using the supplied bungee cords 3 The drum lid is removed and placed along side of the drum but remains inside the containment area The inner drum liners are then opened 4 The sample is taken via the 4 100mm sleeve using the process desired scooping directly into the sleeve or a sample bottle that is placed in the sleeve or using a standard sample thief and depositing that sample in the sleeve or a sample bottle The samples can then be removed from the enclosure through the 4 100 mm diameter sleeve by using the ILC Dover developed Crimping process 5 The inner drum liner is resealed and the drum lid is put back into place without breaking containment 51 Drum Sampling Enclosure System Ver Pac Containment Systems REATORES e Clear film allows use of existing light from the process area Static dissipative film e Re usable for repeated sampling Tamper Proof sampling Portable
74. his style of granulator includes a separating cover as part of the top driven mixer and chopper with a removable bowl The enclosure and flange are elongated on the lower front face of the equipment to support the movement of the process area without breaking containment ProCepT Mi Pro 1900 Containment of the Mi Pro Mixer Granulator figure 5 is achieved by a flexible enclosure surrounding the process chamber and staging area forward of the control system con nection column A single pair of glove sleeves is provided to charge and collect product from the process vessel A single entry removal point using replaceable bag in sleeves provides a means for moving product and supplies in and out of the enclosure The enclosure also includes integral HEPA filters to balance the pressure in the enclosure and allow it to move freely as the operators perform various operations Figure 4 The enclosure is attached to a stainless steel base pan with vertical attachment flanges A small attachment canister with liquid tight connec tors provides a method of introducing utilities into the contained area An external frame supports the enclosure and the bag in canister RapidMix 100 Granulator This granulator is a fixed installation as op posed to a mobile de sign As seen in figures 6 and 7 the granulator is placed on a floor pan that is 85 2159 mm by 54 1372 mm The overall height of the enclosure is 88 5 2248 mm to
75. ical chemistry develooment combined with their state of the art HP C facilities ensures their customer s molecules move efficiently from discovery to clinical trials Pharmatek focuses on preclinical and early phase development amp manufacturing of small molecules and peptides Compound Selection Formulation Development Preformulation Drug Product Methods Specification Prototype Stability cGMP Manufacturing Packaging Labeling Method Qualification Release amp ICH Stability GLP Formulation Support CTM Storage amp Distribution API Method Development HOW DO FLEXIBLE ENCLOSURES WORK Flexible Containment Enclosures are designed using two basic methods flange mount and total encapsulation The flange mount approach is used for the tray dryer where the flange is added to the face of the dryer outside of the door An enclosure made from the rugged ArmorFlex family of films is then attached to the flange and a supporting frame assembly The door is within an enclosed environment when loading and unloading the trays with the drug product Flange Mount Flexible Containment Selected for Tray Dryer Process Train Containment in CMO Operations The trays drug product and associated process tools can either be preloaded into the enclosure or bagged into the isolated area via bag in bag out BIBO canisters or larger drum ring attachment canisters For the wet granulation process Pharmatek selected the total encapsulati
76. iesivetbeysiemi keeps boodih place even while bending Patent pending Unique Skirt exhaust system fully inflates suit to deliver improved protection and comfort Safety glasses and hard hats are readily accommodated Elimination of neckdam improves comfort No suspension system increases Sentinel XL Blower comfort and eliminates sizing concerns Sentinel POWERED AIR PURIFYING RESPIRATOR www doverpac com customer_service ilcdover com Ph 302 335 3911 X506 or 800 631 9567 ONE MOONWALKER RD FREDERICA DELAWARE USA 19946 2080 88 Sentinel Clear Blower with HP Filters and Quick Loc Belt OV AGHHE Filters Adhesive tab system keeps hood in place even while bending p Sentinel XL Blower Integrated blower and battery pack reduces bulk and eliminates battery falling off and snagging issues Quick Loc belt greatly simplifies adjustment and cleaning Operation with two P100 filters vs 3 provides excellent protection while reducing operating costs NIOSH approved OV CD CL HF SD HE filter operation available Low voltage alarm flashing LED and continuous beep alert wearer ILC Dover has been creating what s next for over 60 years To create what s next ILC Dover listens to its customers Our skilled engineering Staff building on years of experience with NASA military and commercial customers translates those needs into high performance
77. ighted average TWA While this draws the powder into a set of filters the airflow is disrupted when an operator is working at this type of station When that occurs eddy currents of air and entrapped powder start to swirl which disrupts containment The barriers described in this guide are a tool in improving this type of application 3 Pair Butyl Glove Sleeve Similarly restricting access to another part of a processing suite has been a demonstrated need as well Here a barrier can be added to a doorway for example to restrict the flow of personnel between the suites HOW DOES IT WORK By isolating the operator s breathing zone from the point of exposure with this form of secondary containment the operator is protected from the product and vice versa 0 4 7 n Pi d iti in rolled up position Rolled up Panel The curtains are manufactured from clear Heo eben pete Pe E of Curtain ArmorFlex 113 film that will allow room EATA Top Aeaee light to illuminate inside the barrier and gt not restrict visibility This rugged film Closed Panel of Curtain provides a safe working environment while enabling the enhancements developed through numerous installations using this flexible containment technology Vinyl Trim can be removed to Typically the ArmorFlex 113 is roll up one or both Curtain sides patterned to interface with the opening to be contained This can be a flat sheet or a three dimensional design The ba
78. ightweight and can easily be moved by personne from the 7 percentile female to the 95 percentile mabe without the need for material handling equipment Installation of the enclosure is accomplished by means of an attachment plate and flange that are secured to the mill drive tube behind the interlock switch This assem bly is attached to the perimeter of the drive shafi tube without modification of the sieve An extemal enclosure support frame is constructed to support the enclosure as well os the bag in canister and product staging table Figure 3 Fi 2 The enclosure is manufactured from clear ArmorFlex film that allows room light to 1 Angled front rca illuminate inside the enclosure for easy viewing This rugged film provides a safe work 3 Bungee Cords ing environment while enabling the enhancements developed through numerous installa thons using this flexible containment technology 61 Mill Containment System Bohle BTS 100 FEATURES e Process and Technical areas separated Clear film Flexible materials Rarofit to existing mills Adaptable to other particle size reduction equipment e Validated containment technology Disposable components BENEFITS Process is comained without contamination of motor drive sha amd controls s Nanogram containment levels achieved Supports visibility for maintenance Does not affect ATEX and Ex ratings Ergonomics maximized Reduced cleaning and
79. in properties and potency and if not contained can present cleaning and exposure issues Dry mixing of granular and other processing constituents includes a significantly high number of blending steps This includes potent and highly hazardous compounds excipients and materials such as lubricants as processing aids As demonstrated by the Risk MaPP principles both current good manufacturing practices CGMP and Industrial Hygiene IH needs can be met by containing the process at the source By employing flexible containment and using the logic diagrams from the Risk MaPP process cleaning is minimized and the operator is protected with this Engineering Control As such processes in multi product facilities can be safely performed without the risk of cross contamination Used for lab scale and production operations at multiple International Pharma manufacturers our contained Blending applications take the idea of retrofits to another level Here existing and new equipment are supported as a tool to eliminate the risks posed by uncontrolled powder processing At no time are the blenders angle of repose affected so as to change the blending performance Note that the powder containment applications described below are based on proven designs supported for customers based on the process equipment that they specified ILC Dover does not have any specific ties to these equipment suppli ers and does not recommend one type of blender
80. inert processing Bag out stub w b gt Purge Vacuum Arrangement _ CUSTOMER J VESSEL a To sample extend sleeve and fill Place crimp cap on crimp body 18 groove for the canister end cap additional grooves for For flanges smaller than 12 a conical transition adapter ver Pac Systems ArmorFlex is ILC Dover s proprietary family of films used exclusively in the DoverPac family of high potency flexible containment products fie E L ia 7 i B 1 Nis ha r Canister and Transition Adapter Attached to ILC Dover Test Rig This hardware is supplied with a 240 grit 15RA internal finish and a 180 grit 32 RA external finish Other materials and finishes can be quoted sepa rately Note Common vacuum purge supply connection to HEPA filter provides backwash function to extend filter life DoverPac Contained Powder Discharge FlexLoc Clamp The FlexLoc clamp is used to secure the neck of the liner to the canister Construction of the molded clamp is of FDA compliant elastomer with integrated stainless steel band clamp The clamp has a molded ridge along one surface to help install it in the correct orientation The FlexLoc functions to prevent powder from going between the inside of the liner and the outside of the canister to minimize cleaning operations The clamp is designed to operate in the offloading and the charging operations Crimp Separation
81. ion It supports Production and Lab processes in any part of the plant gt Reduced cleaning and cleaning validation gt Drums can be moved freely without breaking containment gt Crimping with DoverPac system confirmed as the best possible containment gt Tamper proof sampling achieved 53 Drum Sampling Enclosure FAQ s How is the flexible liner removed from the drum after use Seems like containment would be lost once the tape is removed ver Pac Containment Systems A The containment level stated was for operation and leaving the enclosure on original customer s operation To remove the enclosure the Twist Tie Tape Cut TTTC method would need to be employed due to the film used for the body of the enclosure and the material thickness While the TTTC method can be slightly variable in how tight the bundle is the amount of powder that becomes airborne inside the enclosure will be very minimal If the sampling is done with care the enclosure and the TTTC area should have very little powder and so the containment level should still be excellent with expectations in the nanogram range Have you thought about a DoverLoc type of clamp to give you a positive seal without taping We looked at a flexible strap originally but were concerned that the enclosure might slip out from that type of attachment Does it work equally well with plastic and steel drums you show a fiberpacks in th
82. itary Gasket e 14 Crimp Kit e 8 FlexLoc Clamp This system can be supplied with an alpha beta port interface to allow attachment to an isolator as depicted in the drawing This allows the contained removal of product containers samples or waste from the isolator b gt Continuous Bag in Bag out System 33 DoverPac Continuous Liner 14 Dia Contained Powder Discharge to Drums ver Pac Systems ILC crimps have been designed and tested to compress standard diameter liners and sleeves made with ArmorFlex film 34 Crimp Separation Kit The 14 crimp kit is used to separate the filled drum from the unused pack The 14 Crimp Separation start up Kit includes e 200 Crimps e 1 Crimp Hand tool e 1 Cutter e 100 Cable Ties 7 Nylon e 1 User s Manual Additional spare items can be ordered separately by their individual model part numbers The crimps have been designed and tested to compress the standard 14 diameter liners made with ArmorFlex film Use on any other system will preclude the crimps from closing correctly which could result in operator and product exposures The hand tool applies two crimps at once The cutter is then used to cut between the two crimps and the cap is slid onto the closed crimp body This system has been proven effective in containing active pharmaceutical ingredients and other hazardous compounds to assure a safe and effec tive transfer of powd
83. ited to cGMP access to buffer prep powders e Liquid sampling Dispensing 52 Drum Sampling Enclosure FAQ s At ILC Dover we are always creating what s next by listening carefully to our customers In some cases we are continually improving our offerings using this same voice of the customer commitment The Drum Sampling Enclosure DSE is just such an example ILC first starting supplying drum sampling enclosures internationally in 2002 Based on our patented flexible containment transfer technology we have evolved those original designs to the DSE system that we offer today VverPac Containment Systems High performance features Clear film allows use of existing light from the process area Static dissipative film Reusable for repeated sampling Portable Small footprint utilizes small amount of floor space Enclosure is attached to drum wall allowing lid to be contained Stretch on enclosure interfaces with common size drums but can also be customized gt One person operation gt Crimp separation for containment and sample security Benefits gt Drum lid can be opened after drum is contained gt Can be used in any part of the facility gt No cross contamination transfer to other parts of the plant gt Ergonomics are maximized with flexible materials gt Low capital depreciation and operating costs offers best cost of ownership gt Speed of implementat
84. ived components Complies with USP Class VI No halogenated compounds and safe for incineration b gt ArmorFlex 104 was developed in 1997 and has been in use by pharmaceutical manufacturers globally ever since Proven in myriad applica tions ArmorFlex 104 supports processes from wetcake to dry powder storage and transfer ArmorFlex 104 Film Solvent Contact Resistance arn z Systems Chemical Resistance Acetone Very Good Acetonitrile Excellent Anisole Very Good Butyl Acetate Excellent Property Test Method Results Cyclohexane Very Good i Puncture Resistance Fed Std 191 5120 11 Ibf Cyclohexane Ethyl Acetate 50 50 Very Good Tear Strength ASTM D 624 91 Die C 470 ppi min Dichloromethane Fair Diethylether ven Ceod Tensile Strength ASTM D 412 97 5500 psi min Dimethylacetamide Very Good Elongation ASTM D 412 97 490 min Ethanol Excellent Ethyl Acetate Excellent HCL 37 4 Very Good EN Number Test Results Heptane Excellent j i i 388 HMDS Fair EN 388 1994 Protection against mechanical risks KOH 50 Excellent Methanol Very Good EN 420 1994 Determination of Pass Paragraph 4 4 42 pH value 2 Methoxyethanol Excellent n Methylpiperazine Excellent n Methypyrrolidone Excellent Mineral Oil Very Good NaOH 50 Excellent Reagent 3A Alcohol Very Good CFR Conformance USP Conformance Tetrahydrofuran Very Good 21 CFR 177 1520 Conforms to USP 24 lt 661 gt for 21 CFR 178 3130 b
85. le to full production Conta Bin Blender Charging and Discharging While DoverPacs can be used for charging and discharging any type of blender the wall mounted Bin blender shown is an example of an application with this flexible containment technology In this design the process is supported by the installation of a single 8 200 mm multiple o ring groove canister on the bin which allows for contained powder transfer through one port for charging figure 2a and offloading figure 2b the bin This minimizes the capital expense versus a rigid isolator even further and allows for existing bins to be used without modification Following this step the filled 20L DoverPac is used to charge a capsule filler Contained Blending Transfer Sleeve DoverPac Continuous Liner Technology Offloading with a continuous liner system Utilizing a similar multiple o ring groove canis ter ArmorFlex film and crimping technique as above this system allows contained of tloading into drums Liners are factory packed with standard bundles of 150 45 m 100 30 m and 50 15 m Custom lengths are also provided Gemco V Blender to Continuous Liners Figure 3 is an example of offloading a 30 cubic foot V blender with a Continuous Liner system to drums In this case the rotational clearance did not allow the Continuous Liner canister to be installed directly on the blender as in other applications To account for the clearance
86. llection area This jacket is for use with heat transfer fluids only such as cooling brine hot water Dowtherm Silthane Glycol or similar liquids The remainder of the filters are not considered a registered pressure vessel The Upper Chamber is designed for atmospheric conditions only and the Lower Chamber is designed for atmospheric to full vacuum conditions The CIP Spray ball assembly is designed such that the entire spray ball assembly can be extracted from the nozzle without disassembly within the filter The spray ball components are either Teflon or equivalent to the wetted material of choice However the outlet of the filter is not typically contained This Flexible Containment Solutions Guide outlines several methods of achieving a contained discharge from the Aurora Filter A HOW DOES THE CONTAINED OFFLOADING SYSTEM WORK There are a variety of methods that can be used to achieve contained offloading of an Aurora Filter The designs of the filters are varied so the applications below represent a few of the installed solutions Some customization may be needed depending on the specific filter Offloading to DoverPacs The key components in The DoverPac system include Transition adapter between the vessel and the DoverPac canister o Multiple o ring canister typically separate from the Transition Adapter but these can be combined into one piece of hardware DoverPac which is a combination of inner liner an
87. lm provides excellent solvent resistance e Complies with FDA 21 CFR e Permanent antistat provides better than e Passes USP lt 661 gt Physicochemical Tests 1 x 1011 Ohms per square surface resistivity for Plastics e No incineration off gassing concerns e Passes USP lt 88 gt Class VI 7 day implant lt ArmorFlex is designed for high strength and e Passes lt 87 gt biological reactivity in vitro has a 500 elongation before failure assuring e Passes Chilworth incendivity test to assure the safety from tearing during typical use static dissipative qualities of the flexible isolator Tested for solvent resistance DME filed with FDA ArmorFlex films contain no animal derived components and have a 5 year shelf life CONTAINED DRUM TRANSFER OPTIONS DTS Drum Transfer System VTS Contained Drum Transfer DSE Drum Sampling Enclosure 102 Ventilated Enclosure System FLEXIBLE CONTAINMENT TECHNOLOGIES VverPac Containment Systems Ventilated Enclosure System User friendly control system Stable running conditions Automatic breech condition protection with audible and visual alarms Provide EC GMP Grade A internal conditions Enclosures available in static dissipative Polyurethane PVC or ArmorFlex 113 Polyethylene film System can be offered to provide negative or positive pressure operation Capable of 30 air changes per hour minimum The Ventilated Enclosure System combines the benefits of Inc
88. low 200 nanograms m3 on a task basis To achieve this the secondary containment i e flexible enclosure and the outer neck at the primary connection points are applied Figure 1 shows the offloading set up during exposure monitoring trials The installation sequence follows The top of the enclosure is attached to the first canister on the vessel outlet e The bottom of the enclosure is attached to the canister on the support frame gt The external neck on the DoverPac is then attached to the outlet point of the canister on the frame The internal neck of the DoverPac is pulled up through the lower canister and is attached to the groove on the vessel canister by using the integral glove sleeves on the flexible enclosure Figure 1 Once the vessel is offloaded the internal neck is crimped off and pushed back down through the canister on the frame by using the enclosure to access the neck area The operator then extracts his her arms from the enclosure and crimps off the external neck The crimping process Figure 2 is employed for the contained separation operations This process consists of installing two injection molded crimps into the hand tool twisting the liner neck ratcheting the crimps closed cutting between the two crimps and installing the protective cap Figure 2 25 Coaxial DoverPac Nanogram Powder Transfer u yJ F y 1 Vessel Inlet In addition to offloading vessels the system can l 2
89. morFlex film 30 Crimp Separation Kit The 23 crimp separation kit is used to separate the filled drum from the unused pack The 23 Crimp Separation start up Kit includes 200 Crimps 1 Crimp Hand tool 1 Cutter 100 Cable Ties 7 Nylon e 1 User s Manual Additional spare items can be ordered separately by their individual model part numbers The crimps have been designed and tested to compress the standard 23 diameter liners made with ArmorFlex film Use on any other system will preclude the crimps from closing correctly which could result in operator and product exposures The hand tool applies two crimps at once The cutter is then used to cut between the two crimps and the cap is slid onto the closed crimp body FlexLoc Clamp The FlexLoc clamp is used to secure the neck of the liner to the canister Construction of the molded clamp is of FDA compliant elastomer with integrated stainless steel band clamp The clamp has a molded ridge along one surface to help install it in the correct orientation FlexLoc Clamp The FlexLoc functions to prevent powder from going between the inside of the liner and the outside of the canister to minimize cleaning opera tions The clamp is designed to operate in the offloading and the charg ing operations Containment Levels While specific powders react differently due to their particle size customer testing has shown that these systems are
90. nd Controls Assembly Flexible Enclosure Inlet Filter Outlet Filter behind BIBO canister Pawn Inlet Filter and BIBO Canister Location 104 105 Active in the design and development of pro ducts for both ZOvVernment ana Incustry since 1947 ILC Dover consistently provides solutions to a dynamic and dwerse customer base ILC Dover has been creating what s next for over 60 years To create what s next ILC Dover listens to its customers Our skilled engineering staff building on years of experience with NASA military and commercial customers translates those needs into high performance products We look forward to hearing from you so we can continue to create what s next J ILC DOVER creating what s next www doverpac com customer_service ilcdover com 1 302 335 3911 1 800 631 9567 ONE MOONWALKER RD FREDERICA DELAWARE USA 19946 2080
91. ng 56 DoverPac SF BioPharmaceutical From Lab Scale Through Production Processes ver Pac OVERVIEW Containment Systems The DoverPac SF BioPharmaceutical consists of a series of standard and customized applications based on the DoverPac SF Split Flange technology FCSG 007 This expansion of single use manufacturing is designed to meet the needs of speed of implementation ease of facility design reduced validation cost savings over cleaning and cleaning verification and reduced capital costs to the operation HOW DOES IT WORK The DoverPac SF can be attached to a variety of process vessels with by an integral sanitary flange either sealed or clamped to the liner or via our patented multi o ring technology Materials of Contact The ArmorFlex Film is utilized to provide structural integrity as well as meet the rigorous demands for materials of contact Using existing and specific reference monographs key needs such as no animal derived components extractable leachable limits and food contact compliance to name a few are addressed The Sanitary Flange Interface The sanitary flange is injection molded and then thermally welded to the liner Figure Sous We basic design with This is done with a blended lap weld which keeps all of the load in shear and a4 inch 100mm eliminates any possibility of powder hang up or bioburden build up in an sanitary flange otherwise raised lip at the seal area
92. ng aids As demonstrated by the Risk MaPP principles both current good manufacturing practices cGMP and Industrial Hygiene IH needs can be met by containing the process at the source By employing flexible containment and using the logic diagrams from the Risk MaPP process cleaning is minimized and the operator is protected with this Engineering Control As such processes in multi product facilities can be safely performed without the risk of cross contamination Used for lab scale and production operations at multiple International Pharma manufacturers our contained Blending applications take the idea of retrofits to another level Here existing and new equipment are supported as a tool to eliminate the risks posed by uncontrolled powder processing At no time are the blenders angle of repose affected so as to change the blending performance Note that the powder containment applications de scribed below are based on proven designs supported for customers based on the process equipment that they specified ILC Dover does not have any spe cific ties to these equipment suppliers and does not recommend one type of blender over another Rather this guide depicts a sampling of flexible containment applications to a variety of styles of equipment as standard and customized containment solutions 81 Contained Blending Flexible Enclosure Technology 82 HOW DOES IT WORK AND WHAT ARE THE APPLICATIONS Three m
93. ns inlet amp outlet necks 15 DoverPac Proven DoverPac Attachment Liting Bar Spei To Tym C E lt Cu Tee z ee Type Resini DoverPac Contained Powder Discharge b gt System Description This easy to use system has been proven effective in containing active pharmaceutical ingredients and other hazardous compounds Its use assures a Safe and effective transfer of powders an operational requirement that cannot be achieved with a standard FIBC or big bag The DoverPac contained powder transfer system includes a flexible ArmorFlex liner with restraint for containing powders and a set of hardware that fits the flange of a vessel While specific powders react differently due to their particle size OEB 5 lt 1 0 g m3 levels have been demonstrated on a task basis with results in the nanogram range This is based on proven applications third party testing to the SMEPAC protocols on similar designs and the 100 inflation tests performed on the delivered systems Uses ILC Dover s Patented Technology FLEXIBLE CONTAINMENT TECHNOLOGIES VverPac Containment Systems Offloading Using the Individual DoverPac System Contained processing to protect the operators cGMP processing in a completely closed operation to protect the product Available in sizes ranging from 20L to 2000L 100 inflation tested CE Marked Significant capital cost
94. ns and the 100 inflation tests performed on the deliverable enclosures WHY USE THIS OVER OTHER TECHNOLOGIES The cost of ownership ergonomic advantages and speed of delivery benefits of this flexible solution far outweigh those of rigid isolation systems OTHER POTENTIAL APPLICATIONS gt Sampling Dispensing Product Analysis 44 Drum Transfer System Contained Drum Dispensing aa Systems Flexible Containment for offloading drummed materials in a safe and efficient manner is provided by the Drum Transfer System DTS platform at fixed and varying heights OVERVIEW Flexible Enclosure Outer Drum Sleeve DTS Enclosure Frame DTS Base Frame Outlet Canister Lifter OoorFrwWN Figure 1a Fixed Height Lifter Figure 1b Variable Height Lifter The DTS consists of an enclosure attachment frame a Support stand a drum lifter an enclosure an outer drum sleeve and discharge softgoods that are dependent upon your process equipment The basic process steps include Attach the enclosure to the frame Stretch the bottom opening of the Drum Sleeve over the drum and attach the sleeve to the ring on the back of the frame Pull the drum slightly into the enclosure and open the inner drum liner using the integral gloves on the enclosure Scoop pour powder into the process equipment to be utilized Put trash in the empty drum and move the drum back out of the ring with the translatin
95. ntinuous Liner being attached to isolator lt 4 Operator shown bagging out a sample Uses ILC Dover s Patented Technology 36 Continuous Liner Bag in Bag out Contained Transfer arn Systems Accessories and support equipment include a lifting stand to help support the larger canister size crimps and the FlexLoc Crimping tool crimps 4 FlexLoc 44 Lifting Stand APPLICATIONS CURRENT AND POTENTIAL Current applications tool pass through on 22 rigid isolators at one international Pharma manufacturer s site trash bag out sample bottle transfer tablet transfer for testing analysis pre packaged seed API processing after tare weight process Other potential applications document transfer gamma irradiated for sterile transfer operation wall mounted in process suite for contained pass thrus CONTAINMENT LEVEL Nanogram containment levels demonstrated during task based operations see data below Sample Location Duration of Measured Airborne Operation Concentration mins g m3 Source Sample AS 0BH At Bagout Port 31 lt 0 017 Operator 1 PSBZ On Shoulder 31 0 017 Operator 1 PSBZ On Shoulder 30 lt 0 017 Operator 2 PSBZ On Shoulder 30 lt 0 018 Source Sample AS 0BZ At Bagout Port 30 lt 0 017 Finished Product raw materials cleaning materials waste materials FEATURES Beihai S gt Validated system e Minimizes risk during operation Proven and tested softgoods e ArmorFlex
96. nufacturing campaigns e Process is contained without contamina tion of motor drive shaft and controls WHAT CONTAINMENT LEVEL IS PROVIDED OEB 5 with results in the nanogram range This is based on customer test data other proven applications third party testing to the SMEPAC protocols on similar designs and the 100 inflation tests performed on the deliverable systems WHAT ARE THE APPLICATIONS This containment technology can be applied to any Oral Solid Dosage OSD type of processing equipment Applications to myriad Tablet Presses Coaters Dedusters Blenders Granulators Mills Roller Compactors Spheronizers Extruders Fluid Bed Dryers and weighing subdivision processes have been demonstrated successfully WHY USE THIS OVER OTHER TECHNOLOGIES The cost of ownership ergonomic advantages and speed of delivery benefits of this flexible solution far outweigh those of rigid isolation systems Tools such as Lean Manufacturing come into play more and more For example the time to clean and validate the Passive system Flexible materials Disposable components Adaptable to other process equipment Nanogram containment levels achieved Supports visibility for maintenance Does not affect ATEX and Ex ratings Ergonomics maximized Speed of implementation cleaning are major bottlenecks for processing efficiencies in the plant Being able to minimize this part of the process results in getting p
97. on method by working with ILC Dover engineers Solid pan mounted enclosures allow the entire piece of process equipment to be contained The enclosure is Supported by an elastic suspension system attached to the pan and includes glove sleeves for access to the equipment and integrated HEPA filters Based on the suspension system the operator is able to get in close proximity to the process as if containment wasn t even present WHAT ARE THE APPLICATIONS Solid Pan Mount Total Encapsulation Selected for Granulator Flexible Containment enclosures have applicability across Pharmatek s entire high potency process train WHAT ARE THE KEY BENEFITS OF THIS TECHNOLOGY e Prevents cross contamination the enclosures are single use and are dedicated to a specific compound to prevent cross contamination which is of extreme importance to their customers e Supports lean manufacturing with over 100 product runs per year Flexible Containment supports easy product changeover and helps Pharmatek meet stringent EH amp S requirements and project timelines e Superior operator protection proven nanogram level containment reference table below Additional advantages e Durability manufactured using puncture resistant ArmorFlex films the enclosures hold up during the most demanding operations e Improved ergonomics the flexibility of the enclosures in terms of configuration glove sleeves ports and passthrus configured
98. orporates Bag In Bag Out multiple Flexible Containment with a unique light weight ventilation O Ring canister capability unit This system provides all the advantages of a negative or positive pressure isolator providing reduced costs for cleaning and validation with the disposable enclosure that is utilized Incorporates a visual pressure indicator Incorporates Exhaust Filter pressure Typical pharmaceutical process operations with this system drop monitoring include but are not be limited to dispensing sampling mill ing mixing and processing potent compounds Containers solvents and raw material containers can be opened used Available in ATEX and Non ATEX sealed and cleaned within the enclosure rated versions Transportable by one person 103 Ventilated Enclosure System TECHNICAL SPECIFICATIONS Operates on standard European power of 220 240V 50 Hz and United States Power of 110V 60 Hz Automatically operates and maintains an enclosure negative pressure of 15 Pa nominal Audible and visual alarms are set at 25 Pa and 3 Pa to notify operator in case of pressure change outside of the safe operating range or in case of excessive exhaust filter pressure drop Complies with the following Regulatory Requirements gt GAMP 5 gt 21CFR Part 11 gt Machinery Directive 2006 42 EC replacing 98 37 EC gt IEC 60529 gt CE Marking available Frame Assembly Bag In Bag Out BIBO canister Fan a
99. products We look forward to hearing from you so we can continue to create what s next 89 Sentinel Clear Hood FAQ s oy What user operations are approprate for the Sentinel Clear hood What is the difference between Sentinel Sentinel XL POWERED AIR PURIFYING RESPIRATOR The Sentinel Clear hood supports the broad range of pharmaceutical processing operations The hood is designed for comfortable non encum bering use over long operating periods When combined with the Sentinel XL PAPR blower and NIOSH approved cartridges it provides protection from airborne particulates aerosols and organic and acid gas vapors The Clear Hood covers the head and neck and includes bibs that get Clear Hood and HP head tops What are the major advantages tucked into coveralls The HP hood covers the head and face only First and foremost is the field of view the Sentinel Clear offers to the Sentinel Clear hood a 320 degree field of vision Attention to ergonomic detail has also resulted in a system that does not require a headband thus no uncomfortable mechanism riding on your head and no neck dam which eliminates any chocking feeling Are the Sentinel XL Clear Hood and HP systems NIOSH approved What are the assigned protection Yes both have NIOSH approvals The Clear Hood system has been rated with an assigned protection factors for these designs factor APF o
100. programs to assure you will for media and buffer prep always have the right product available at the right time ILC Dover global experts in powder transfer systems which meet cGMP requirements and control cross contamination ArmorFlex a unique anti static film meeting global product contact requirements including stringent USP Class VI and other regulatory directives Compliance Certificates of Conformance to comply with your Quality program bf Id Ask how our options can 100 L DoverPac SF prior to and following be combined to solve your sanitary flange interface specific process needs Gamma Irradiation of 25 50 KGy j i High containment using patented ecco oP a i Complete Range of DoverPac Products DoverPac Vessel Connection SF sizes options 5 Liter 1 5 Sanitary Flange 10 Liter 2 Sanitary Flange 20 Liter 3 Sanitary Flange 30 Liter 4 Sanitary Flange 50 Liter DN 100 Sanitary Flange 100 Liter DN 150 Sanitary Flange 6 Sanitary Flange 8 Sanitary Flange 87 Sentinel Clear Sentinel Clear with ArmorFlex Material NIOSH Approved TC 21C 0848 and TC 23C 2537 Benefits of the Panoramic Hood Clear hood provides 320 panoramic field of view APF of 1000 provided The 8 scfm 230 lpm of air supplied is above the NIOSH minimum of 6 scfm Panoramic Hood 170 lpm Air distribution plenum improves clear vision comfort for the future Ad
101. quired The opening at the top of the enclosure includes an encapsulated o ring that is clamped onto the bottom groove of the canister The bottom of the enclosure has a similar arrangement that is clamped to the interface ring shown in Figure 3 49 Mill Containment System i r i Figure 3 Grooved interface ring Figure 4 Integral glove sleeve for manipulating screen FEATURES BENEFITS gt Validated containment Nanogram containment technology levels achieved e Clear film e Supports visibility for maintenance Does not affect ATEX and Ex ratings e Passive system Flexible materials Disposable components Ergonomics maximized e Retrofit to existing mills Reduced cleaning and Figure 2 Shroud used to hoist canister j Adaptable to other mills gleaning validation and size reduction designs Low capital and operating cost Speed of implementation WHAT CONTAINMENT LEVEL PROVIDED OEB 5 with results in the nanogram range This is based on proven applications third party testing to the SMEPAC protocols on similar designs and the 100 inflation tests performed on the deliverable systems WHY USE THIS OVER OTHER TECHNOLOGIES The cost of ownership ergonomic advantages and speed of delivery benefits of this flexible solution far outweigh those of rigid isolation systems OTHER POTENTIAL APPLICATIONS Continuous liner hardware on outlet of mill for contained filling in drums e Transfer
102. rPac multiple o ring canister as in Figure 3 containment in the nanogram range can be achieved WHY USE THIS OVER OTHER TECHNOLOGIES Reduced cost of ownership Eliminates cleaning and cleaning validation Eliminates waste treatment of cleaning solutions e Best product recovery e Visual access to drug product being manufactured Liner can be manipulated to overcome bridging 58 DoverPac Tray Dryer Enclosure Technology ver Pac Containment i Systems OVERVIEW Tray Dryers are a common method of drying wetcakes and granu lated drug products This is especially true in the early product development phase The issue of containment for this type of process equipment is unique in that open scooping of powder onto multiple trays that get slotted into the dryer one at a time prohibits amass single transfer as with charging a vessel through a nozzle There are many styles of Tray Dryers that drive the Engineering Control here to a custom design However containment is accom plished with a standard set of interface and design techniques The various styles of dryers interfaces door types volumes ergonomics and life cycle costs must all be taken into account in order to meet the need of containing the dryer Included here is whether the dryer is portable or a fixed installation HOW DOES THE SYSTEM WORK The final design may vary from operation to operation but a typical installation includes adding a flange to
103. rk lift compatible allows for easy repositioning e Base can be used to connect to wash in place WIP system Enclosures designed to work with Blending e Milling Tableting e Weighing Subdividing More cost effective than s L e Rigid isolators Downflow booths Lab Scale Analytical Blending Process Train lt New equipment lt Product enters through bag in sleeves Operation of equipment accommodated via glove sleeves Integration of process steps through ILC Dover canister interface Process train can be expanded to include sub dividing milling tableting etc Contained Processes Flexible Enclosures Glovebags anes Systems F E a bean oi eee OREHA milen Weighing and Dispensing e Utilities through pan Used with standard lab equipment A e me ind i Emin m Mill Flexible Enclosures L1A Fitzmill e Powder added at top using DoverPac addition technique or scooped in by hand e Milled powder discharged into DoverPac IBC or vessels Overdrive Mill enclosure with shroud removed and fully deployed to allow use of glove sleeves for Granulator cleaning and maintenance e Mobile frame allows use in multiple suites Clear film and bungee attachments optimize ergonomics ILC Dover pioneers of flexible containment 41 Contained Processes Flexible Enclosures Glovebags ae s Systems Tablet Coater Enclosure peN e Tablets bagge
104. roducts to market faster and at an overall reduction in operating costs when considering labor utilities and waste disposal costs It also supports getting multiple products to market faster within an existing facility without risking product safety 64 Contained Offloading of Aurora Filters Processing from Nutsche Filters ver Pac gt Systems Nutsche Filters are a mainstay in processing in the Pharmaceutical and Chemical industries They typically function by keeping the slurry contents fluidized until most of the mother liquor is filtered through When filtration is complete the cake can be washed by reslurrying the cake After washing the mother liquor can be refiltered and the cake can then be discharged AURORA FILTERS a Division of ALL WELD Company Limited designs and fabricates a line of Nutsche filters for the pilot scale production of active pharmaceutical ingredients These designs typically combine a glove box with a single plate vacuum Nutsche under an inert gas blanket to ensure operator safety and product integrity OVERVIEW Each filter has seven process connections Slurry Inlet Nitrogen Inlet CIP Wash Inlet Vent Nitrogen Inlet for Drying Final Vacuum Outlet and Filtrate Vacuum Outlet Each filter has a large viewing window on the Upper Chamber as well as a small sight glass on the Lower Chamber A Heating Cooling Jacket designed for 50 to 75psi and registered to ASME Code surrounds the cake co
105. rrier is attached using flanges and U Groove channel as a locking mechanism or by grommets Glove sleeves are incorporated into the panel as needed by the specific process These can include right handed left handed or ambidextrous gloves There are myriad flow booths installed and as such no one curtain design fits everyone s needs As such customization is provided to make sure the process and ergonomics are covered correctly 75 Process Area Barrier Curtains 76 WHAT ARE THE APPLICATIONS This type of containment can be an extension of down flow cross flow and laboratory fume hoods In addition doorway restrictions have also been designed to prevent access from one part of a suite to another The use of flexible containment allows the end user to process contained when needed or to follow existing open processing procedures when containment is not required In both cases cost savings are realized by modifying an existing design or using an existing piece of equipment with no modifications WHAT ARE THE FEATURES BENEFITS Features Benefits Retrofit to existing equipment designs Provides the lowest overall cost of process Clear film ownership through low capital and operating cost including reduced cleaning and cleaning validation Passive system oan Supports visibility for maintenance Does not affect ATEX and Ex ratings Ergonomics maximized Flexible materials Disposable components Speed of implementation
106. s Retrofit to existing equipment design Process and Technical areas can be separated Validated containment technology Clear film Passive system Flexible materials Disposable components Adaptable to other process equipment No blender shape modifications Benefits Complies with the Risk MaPP initiative Provides the lowest overall cost of process ownership through low capital and operating cost including reduced cleaning and cleaning validation Fastest turnaround of a processing suite for subsequent manufacturing campaigns Process is contained without contamination of motor drive shaft and controls using flange attachment design Nanogram containment levels achieved Supports visibility for maintenance Does not affect ATEX and Ex ratings Ergonomics maximized Speed of implementation No affect on blend uniformity WHAT CONTAINMENT LEVEL PROVIDED OEB 5 with results in the nanogram range This is based on customer test data other proven applications third party testing to the SMEPAC protocols on similar designs and the 100 inflation tests performed on the deliverable systems OEB 1 OEB 2 OEB 3 100 to 50 10 000 to 1000 1 000 to 100 Occupational Exposure Levels above are in g m3 OEB 4 OEB 5 10 to 1 1 to 0 1 0 1 to 0 01 WHY USE THIS OVER OTHER TECHNOLOGIES One of the driving forces of this technology is that it reduces the risk of cross contamination in multi process facilities and it provides safety
107. s performed on the deliverable systems OEB 1 OEB 2 OEB 3 OEB 4 OEB 5 10 000 to 1000 1 000 to 100 100 to 50 50 to 10 10 to 1 1 to 0 1 0 1 to 0 01 Occupational Exposure Levels above are in g m3 WHY USE THIS OVER OTHER TECHNOLOGIES The cost of ownership ergonomic advantages and speed of delivery benefits of this flexible solution far outweigh those of rigid isolation systems Tools such as Lean Manufacturing come into play more and more For example the time to clean and validate the cleaning are major bottlenecks for processing efficiencies in the plant Being able to minimize this part of the process results in getting products to market faster and at an overall reduction in operating costs when considering labor utilities and waste disposal costs It also supports getting multiple products to market faster within an existing facility without risking product safety 74 Process Area Barrier Curtains OVERVIEW Process Area Barrier Curtains are a useful tool in improving the Bungee Cord gt containment levels in existing installations as a method to reduce included with operational exposure risk and to restrict access Examples of these Enclosure types of applications include but are not limited to down flow booth curtains and room access barriers Down flow booths for example work by pulling air across a drum or piece of processing equipment which typically provide a containment level of 100 g m3 on an 8 hour time we
108. s the K TRON Model number K PH M V KT20 feeder This is a 20L twin screw volumetric feeder with a separate control system Figure 1 This equipment was on site prior to this effort Some modifications were required by the customer which included but were not limited to modification of the piping going to the Cyclone and mounting the equipment on the ILC supplied cart HOW DOES IT WORK This system Figure 2 at right provides a contained method of transferring the complete or partial contents of drums to a variety of processes including milling The design will accommodate the charging of several different types of mills with various sizes and shapes though the Jet Pulverizer 8 Micron Master was used in this application In the case of partial transfers the system provides 4 l a contained method of resealing the drum for return to stock The system consists of a flexible enclosure mounted on a mobile stainless steel frame see Figures 3 and 4 on next page Product drums are over sleeved with disposable drum attachment sleeves The sleeves are stretched over the 1 drum and taped to the drum The opposite end of the 2 sleeve is attached to the 23 diameter stainless steel 3 Drum Lifter bag in ring using a band clamp and integrated O rings 4 Drum Transfer System Frame and Platform 5 6 Mill Containment Cart Feeder Inlet Canister This provides a connection interface to attach the Drum Transfer System Enclosure sleeve and introd
109. such an example during the Factory Acceptance Test FAT stage of the project at METO where dispensing to weight operations were being trialed Now that this has been successfully completed process installation efforts are underway 57 DoverPac SF BioPharmaceutical From Lab Scale Through Production Processes Since this was a dispense to weight operation within a tightly controlled tolerance the need to separate the support frame and scale from the drum inverter was needed Figures 5 and 6 show the application of a flexible sleeve with molded sanitary flanges as a method for achieving this need FEATURES Flexible Clear Sanitary DN and multi o ring flange interfaces Range of Sizes ArmorFlex Family of Films Gravity feed No capital Reduced cleaning and disposal BENEFITS Can be manipulated to overcome bridging also achieves over 99 5 product discharge Operators can see product without exposing product Interfaces with any vessel interface Supports clinical through production scale up Assures ruggedness static dissipation and material of contact compliance Figure 5 No expensive mechanical systems eliminates validation of mechanical components simple to use Best overall cost of ownership small footprint Supports Green Initiatives WHAT CONTAINMENT LEVEL PROVIDED Figure 6 Often applied for cGMP containment however if a configuration is selected that interfaces with a Dove
110. t of the IBC Figure 3 46 Drum Transfer System Contained Drum Dispensing Figure 5 Equipment Inlet Canister g Figure 6 In Figure 4 the milled powder is processed into a DoverPac for future charging into a vessel The example pictured uses a Quadro overdrive mill This same approach has been ac complished with the Quadro under drive mill as well as other mills In this application a transfer sleeve would be attached to the discharge canister of the DTS frame and to the inlet canister on the mill SUBDIVIDING Using the DTS a scale can be placed either inside the enclosure or just underneath it between the support tray and the enclosure In this approach the discharge canister was moved to the side to allow room for the scale On a larger size system like the BNL repackaging effort discussed in the next paragraph the DTS was placed around a floor scale so that a tare weight was measured In this instance a Sartorius scale was used but others can be accommodated In this type of application it is important to confirm the interface sizes REPACKAGING We have worked recently with a repackaging company BNL Labs for an application with one of our customers in Ireland In this application drums and bags of intermediate materials were transferred directly into DoverPacs These were for 185L 400L and 700L sizes The customer would have rejected any lot of repackaged materials if any powder
111. table Tray Dryer 7 Crimp cut a remove the contained materials for further processing 5 V groove trim attachment to flange After processing is completed spray mist the inside of the enclosure as part of the overall wash down The flexible enclosure will then be removed from the dryer while wearing personal protective equipment PPE as part of the wash down process 6 Flange Frames are typically supplied in 304 Stainless Steel with a 2b mill finish Other materials can be provided as required 59 DoverPac Tray Dryer Enclosure Technology VAGEIAG SACRE Wehbe Ar Pl CAT OINES 2 Portable and permanently installed Tray Dryers have been fitted with this type of flexible containment technology Features e Clear film allows use of existing light from the process area Bungee cords and HEPA filters allow the enclosure to move with the operator Static dissipative film supports ATEX and Ex operations e Re usable for repeated processing of same drug product Portable or permanent installations supported Customized to specific process and equipment without change to drug product drying process Benefits Ergonomics maximized for visibility operator height and reach e No cross contamination transfer to other parts of the plant e Low capital depreciation and operating costs maximizes true cost of ownership Speed of implementation supports Lab and Production processes in any part of the plant Reduced cleaning and
112. te the process and technical areas as well as systems that encapsulate the entire Jet Mill have been supplied WHAT ARE THE FEATURES BENEFITS Features Process and technical areas separated Clear film Flexible materials Retrofit to existing equipment Validated containment technology Benefits Process is contained without contamination of motors and controls Visibility optimized and use of room lighting achieved Ergonomics maximized Figure 3 Capital equipment costs minimized Reduced cleaning and cleaning validation WHAT CONTAINMENT LEVEL PROVIDED The Occupational Exposure Level for this application was set to be less than 1 ug m3 The flexible containment technology utilized in this ap plication has been proven to be capable of being below this level in third party and customer testing Test results on a variety of powders have shown that containment in the 250 to 500 nanogram range is achiev able WHY USE THIS OVER OTHER TECHNOLOGIES The cost of ownership ergonomic advantages and speed of delivery benefits of this flexible solution far outweigh those of rigid isolation systems Figure 4 70 Granulator Containment Technology OVERVIEW In the pharmaceutical industry granulation is used to create bonds between multiple particles as part of the oral solid dosage manufacturing process Two types of granulation technologies are employed Wet Granulation and Dry Granulation The containment systems d
113. tive solution improves the ergonomics of the system while containment levels have been verified to lt 1 0 ug m on a TWA BENEFITS e Operator motion is less restricted with a flex ible isolator compared to using a hard box style e The Flexi system can be provided stand alone to work with an existing powder pump The filter design and the wand support are designed to work with typical installations Integrated FlexiVac with powder pump is a turnkey system available in non rated electrics or Ex Proof e Can be operated with nitrogen inerting or the stand alone static filters which allow for air flow thus balancing the pressure in the flexible enclosure SQ Containment FEATURES a Sic Operator is aided visually in the wanding process as the flexible wall allows for clear sight into the drum Integral Bag Out sleeves are included which can be used for samples or for the spent liners after a transfer is complete A choice of Allen Bradley or Siemens control platforms are available FlexiVac 101 FlexiVac ver Pac Containment SYSTEM FUNCTIONAL DESCRIPTION Systems FlexiVac features an ArmorFlex 113 flexible isolator that can be attached within minutes This safe isolator system is designed to minimize cleaning requirements while providing high containment The flexible isolator is robust for use on many drums and then disposed The improved ergonomics and head space above the drum
114. to the operators in both multi process and dedicated facilities By using this disposable Engineered Control highly hazardous powders are contained at the source which significantly reduces cross contamination risks and cleaning of process suites and rigid containment devices The cost of ownership ergonomic advantages and speed of delivery benefits of this flexible solution also far outweigh those of rigid isolation systems Tools such as Lean Manufacturing come into play more and more For example the time to clean and validate the cleaning are major bottlenecks for processing efficiencies in the plant Being able to minimize this part of the process results in getting products to market faster and at an overall reduc tion in operating costs when considering labor utilities and waste disposal costs It also supports getting multiple products to market faster within an existing facility without risking product safety DoverPac SF Powder Transfer Systems ver Pac gt Systems Designed for your process Delivered on time Supported by the ILC Dover Team Combining flexible technology with manufacturing expertise to deliver economic disposable solutions to the biopharm industry Robust construction using ArmorFlex to assure integrity even when dropped Custom designs to meet your specific process needs including turnkey systems for weighing powders Powder transfer containers nventory
115. trahydrofuran Toluene Water Distilled Criteria Change in ArmorFlex 113 Solvent Resistance Solvent Contact Recommendations Resistance Excellent Excellent Good Very Good Fair Good Very Good Excellent Excellent Excellent Excellent Very Good Excellent Good Excellent Excellent Excellent Excellent Excellent Very Good Excellent Very Good Excellent Excellent Excellent Very Good Excellent Physical Properties Resistance 0 10 10 20 20 30 gt 30 Excellent Very Good Good Fair ver Pac Containment Sa Soar F B 7 by od a f r A re c ra F 1 Mill impeller and screen change out pTi rE a ay ee _ i Ga The superior visibility provided by AF113 lets you see inside the enclosure as if looking through glass Processing drums Providing Flexible Containment Solutions to the Pharmaceutical Industry since 1997 ArmorFlex 114 Film 4 S ver Pac Containment Systems ArmorFlex 114 Film Complies with FDA 21 CFR Fully compliant to 2002 72 EC and amendments Meets test parameters of EP 3 1 3 Passes USP lt 661 gt Physicochemical Tests for Plastics Passes USP lt 88 gt Class VI 7 day implant Passes lt 87 gt biological reactivity b gt At ILC Dover we are always creating what s next VILE by listening carefully to our customers No animal derived
116. ty to or a superior service with quick responses for process needs Excellent locally in Ireland Very Good Fair Excellent Resistance Excellent Very Good Good Fair 97 Process Train Containment in CMO Operations erPac VI Flexible Containment Technologies are critical to AL containment ystems Pharmatek s CMO Operations 98 OVERVIEW Pharmatek Laboratories Inc is a premier pharmaceutical chemistry development organization supporting the pharmaceutical and biotechnology industries Pharmatek offers development and manufacturing services for highly potent and cytotoxic HP C compounds including e Analytical methods development e Stability storage and testing services Preformulation testing all ICH storage conditions Formulation development e Technical transfer for commercialization GMP manufacturing of phase I II clinical supplies Clinical distribution and fulfillment Handling HP C compounds requires highly specialized facilities and controls As part of Pharmatek s overall corporate safety program they have chosen after careful consideration to integrate ILC Dover Flexible Containment Solutions into their HP C facilities Wet Granulation Dry Granulation Oven Drying Fluid Bed Drying Milling Blending Encapsulation Tableting and De dusting are all examples of manufacturing processes in which Pharmatek has integrated the ILC Dover containment technology Pharmatek s focus on pharmaceut
117. uces the drum into the enclosure 23 Diameter Continuous liner not shown The enclosure containing the Mill and Feeder is mounted on a tray integral to the cart provided by ILC Dover All air and electrical lines are passed through the tray The milled product feed pipe to the Cyclone passes through a single interface ring which includes a groove for enclosure attach ment This ring is mounted to the cart The feed hopper is fitted with a grooved canister to also allow enclosure attachment for the Drum Transfer Station and the Mill The mill enclosure includes three butyl gloves A right and left pair are on the front of the enclosure The third is a bidirectional glove on the opposite side on the enclosure HEPA filters and bungee cords allow for the enclosure to move with the operator which is an ergonomic benefit that is not achieved with a rigid system 69 Mill Containment System Jet Mills The milled powder is collected from the bottom of the cyclone via a 23 diameter 50 foot continuous liner in this application This interface is fitted with a valve to prevent inflation of the liner DoverPacs could be used instead if contained powder transfer to the next step in the process were required WHAT ARE THE APPLICATIONS In addition to the Jet Pulverizer system containment has been proven on other Micronizers Fielded applications include but are not limited to the Microtech Midas Mikronizer 200 Enclosures that separa
118. uffering capacity heavy metals Tes Fev 21 CFR 182 90 non volatile residues residue on ignition thermal analysis and IR a ID identity Passes USP Class VI Criteria Change in Physical Properties Resistance 7 day implant testing 0 10 Excellent 10 20 Very Good 20 30 Good gt 30 Fair 10 ArmorFlex 113 Film VverPac Containment Systems ArmorFlex 113 Film Superior visual clarity ideal for Flexible Enclosures and Flexible Isolators Polyethylene base film provides excellent solvent resistance Permanent antistat provides better than 1 x 1011 Ohms per square surface resistivity 5 year shelf life No animal derived components b gt At ILC Dover we create what s next by listening a No incineration off gassing to our customers In response to operators concerns input we ve developed a new addition to the ArmorFlex family of films AF 113 The clarity of the product makes this the clear film of choice for flexible enclosures and flexible isolators 11 ArmorFlex 113 Film 12 Chemical Acetone Acetonitrile Anisole Butyl Acetate Cyclohexane Cyclohexane Ethyl Acetate 50 50 Dichloromethane Diethylether Dimethylacetamide Dimethylformamide Ethanol Ethyl Acetate HCL 37 4 n Heptane HMDS Isopropanol KOH 50 Methanol 2 Methoxyethanol n Methylpiperazine n Methypyrrolidone Mineral Oil NaOH 50 Reagent 3A Alcohol Te
119. ures also include HEPA filters to balance the pressure in the enclosure and allow it to move freely as the operators perform various operations Attachment flanges running outward from the cabinet around each of the access doors provide a means of attachment for the enclosures This allows for containment to be applied to the process area of the equipment with the technical area segregated from any contamination A bag in canister is mounted on a mobile stand with integral product staging table An external enclosure support frame supports the enclosures without need of ceiling attachment The enclosure also includes a spray wand cleaning sleeve to allow misting of the interior of the enclosure during cleaning Spray mist of the inside of the flexible enclosure and surfaces of the equipment within the contained area eliminates airborne contaminants prior to removing the containment Cleaning of the surface of the equipment is done following normal practices 63 Tablet Coater Containment System O Hara LCM Tablet Coater WHAT ARE THE FEATURES AND BENEFITS OF THIS TECHNOLOGY Features Retrofit to existing equipment design Process and Technical areas separated e Validated containment technology Clear film Benefits lt Provides the lowest overall cost of pro cess ownership through low capital and operating cost including reduced cleaning and cleaning validation Fastest turnaround of a processing suite for subsequent ma
120. w long does the charge last Will get the same flow as the battery charge runs down during use Does the PAPR incorporate a low voltage alarm How much does the PAPR weigh How is the PAPR worn What is the advantage of an integrated blower battery system How rugged is the system How do decon my system after use What documentation is available Sentinel XL POWERED AIR PURIFYING RESPIRATOR Nickel metal hydride NiMH rechargeables which do not exhibit memory effects like NiCad batteries 8 hours Yes the PAPR is equipped with an integrated circuit board that is designed to maintain a steady flow during operation Yes both an audible and visible alarm are included The integrated blower and battery weigh 2 75 pounds The PAPR is supported on the Quick Loc comfort belt The inte grated system sits comfortably on the Operator s hips and does not present any snag hazards An integrated battery is ergonomically more suitable to the wearer with the weight distributed over the Quick Loc comfort belt ver sus having the blower riding on the back and the separate battery riding on the hip thus two points where one has to carry weight An integrated system also does not require a separate cable to attach the blower and battery which can be a snag hazard The entire system has been designed and tested to support vigor ous use in a plant environment One example is the Breathing Tube

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