Containment Solutions for Potent Materials



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Containment Solutions for Potent Materials By Gary Partington Walker Barrier Systems 608-562-7761 gpartington@walkerbarrier.com www.walkerbarrier.com

Why do I need containment? Legal NIOSH (National Institute of Occupational Safety & Health), COSHH (Control of Substances Hazardous to Health UK) Regulatory compliance FDA, MHRA (Medicines & Healthcare Products Regulatory Agency UK) Personnel protection Migration Control If containment is not achieved material migration can contribute to: 1) Quality issues due to contamination 2) Loss of product due to cross contamination 3) Environmental concerns (releases within the manufacturing suite causing immediate clean up and possible stoppage of production) 4) Material migration out of manufacturing areas into the facility requiring isolation of halls, stairways gowning rooms, etc. 5) Occupational exposures 6) Tracking material to other facilities 7) Loss of controlled environment

Containment Strategy 1. Identify and quantify the hazardous materials and the operations 2. Determine the exposure potential to the operator (Risk Assessment) 3. Determine the health risk associated with the degree of exposure for that specific compound (hazard involved & OEL (operator exposure level) 4. Identify the likely type of engineering control system/device that is required

Selection of a Containment Strategy Typical Control Approach with the Extract pyramid

Exposure Potential Hazard Band Factors to consider in selecting the exposure potential The hazard rating of the substance being handled is broken down into bands A to F with F being the greatest hazard. Typical Control Approach The higher the containment, the greater the need for equipment designed for minimal product contact. The best choices to minimize operator contact are Downflow Booths and Isolators

What do I mean by Booths? Not vertical laminar flow enclosures, but recirculating air downflow booths

Downflow Booths; Offering optimum operator protection. Suitable for many applications including; dispensing, sampling, milling, sieving, etc. They can offer proven containment levels of 100µg/m3-10µg/m3 (task duration) What to look for: Air should be delivered from the top plenum Top plenum to extend full width of booth Overhang/buffer zone to minimize air coming into the booth Uniform air velocity across full booth width Exhaust volume of 3,500 4,000m3/hr Need high dust holding capacity filters, backed up by HEPA filters

Downflow Booths Standard Booths can generally guarantee 100µg/m³

Downflow Booths Containment screens for higher containment

Downflow Booths Safe change filtration required when handling higher potency materials for protection of service personnel

Downflow Booths --- Operator Interfaces DO NOT! Lean into the dust source. Work in an uncontrolled manner. Use incorrect tools for the job. Do! Keep your head (breathing zone) as far away from the dust source as possible. Work straight-backed. Work in a controlled manner. Use correct tools for the job. Controlled working over the same time period with a long handled scoop produced a dramatic reduction. Uncontrolled working, using a normal type scoop, over a period of 2 minutes produced: an average Exposure Level (OEL) of 156µg/m³ with a peak of 5660µg/m³. an OEL of 2µg/m³ average over the test period and a high of 9µg/m³. A simple change in working practices can substantially reduce the levels.

Quadraflow Unit Small scale use (1 drum at a time) Air cleanliness classification: ISO Class 5 At Rest Effective product control from spraying/mixing and other small volume operations. Dust in Air Level - Operator Exposure Level (OEL) 10 µg/m³ TWA over operation period. Proven operator protection Compact overall size suitable for laboratory applications. Vibration isolated wheel out work bench.

OEL Study/Data Time weighted average exposure recorded at 0µg/m3. With the booth in a clean empty condition the DustTrak is located inside the red containment line and a background reading taken prior to placebo testing. With the operator dressed in the correct personal protective equipment (PPE) a dispensing test is carried out. During the test product is transferred from a plastic bag into a mill. After the product is dispensed the discharge plastic liner is tied and the milled product bag is removed. The test is then repeated. Time weighted average exposure recorded at 6µg/m3

Downflow Booth Conclusions: Dispensing and Sampling booths are an ideal packaged system for dust containment. Off the shelf laminar flow solutions will never provide the level of workplace integration to achieve good containment. A customized design together with an FAT to simulate the customers application will guarantee a right first time solution. The final step is to ensure detailed operator training and dust in air trials to prove the benefits of the new system. Overall...Booths are a versatile and flexible means of achieving containment and improving operator protection from harmful dusts.

What is an Isolator? Enclosures that are sealed to some standard of leak tightness, that contain within them a qualified controlled environment, at variance with the surrounding conditions. Used for operator safety and product or process safety. Ideal for highly potent and cytotoxic materials. Design Parameters OEL (Occupational Exposure Limit): Start point usually 1µg/m 3 over 8 hr TWA This depends on a number of factors applicable to the process;- Quantity of product handled Dustiness Frequency of cycles / task duration Consequently 10µg/m 3 over 8 hr TWA may be the start point

Design Parameters - Containment Air Flow: Personnel Protection / Airborne Capture Turbulent HEPA Quality 99.997% Pressure: Typically -0.25 inches of water column Breach Velocity: Typically 100 fpm Leak Rate: Typically 0.5% of Isolator volume / hour

Design Parameters Temperature & Humidity: May require separate HVAC Weighing: Analytical balances need special attention Lighting: Typically 45 foot candles at work surface Noise: Typically < 80dBA 3 feet from isolator

Cleaning Simplest: Hand cleaning; care required in design to ensure all areas can be reached without breaking containment. WIP: Simple spray ball / wash lance; controlled & operated on demand locally. CIP: Fully automated cleaning cycle possibly incorporating a number of stages such as atomization, degreasing, rinsing & drying.

Isolator Design Considerations Types of Products to be Produced? Size of Isolator System? (Mock up) Configuration of System? Materials of Construction? Method of Cleaning? Material Compatibility? Turbulent Air Flow? Manipulation-Range of Motion? Transfer of Equipment and Material? Illumination of Enclosure?

Mock Up Construction It is important to involve the end user in the mock up evaluation

Materials of Construction Spray Wand - Teflon or Polypro Glove Ports - Ultem or Polypro 316L SS Shell RTP Alpha - SS & Polypropylene Gloves - Hypalon, Butyl, Neoprene, Viton Laminated safety glass 304 SS Frame Gaskets - FDA silicone or EPDM Internal corner radius 5/8, Surface finish <22 Ra Polyolefin Casters

Design Features Pass-Through/ Ports for Services or Environmental Monitoring. Optional Yellow Lighting Shelving and Hooks for Storage Hatchback Window

Ergonomics Half-Suit Ultem Molded Gloveports and retainers Gloves made of Hypalon, Neoprene, or Butyl Gloves designed with a double o-ring groove to allow safe glove change-out Lift Stand

AMP1000 (Low Level) Types of Controls This level of control system is referred to as manual. A standard system would contain the following: A single loop Red Lion controller to control pressure Manual valves Switches for Phase selection An Allen-Bradley PICO controller (this is not a PLC) Pilot lights Audible and visual pressure alarms Selector switch for the following modes: Run Clean Stop Some options: Type X purge system for classified environments This system is typically used for the low cost isolator or a simple standard isolator. It can also be easily integrated into a Class I, Division I environment. This has limited capabilities and options.

Types of Controls AMP2000 (Mid-Level) This level of control system is our most common, having many features and greater flexibility for future capabilities. A standard system contains the following: A 6 color, PanelView+ 600 touchscreen An Allen-Bradley Micrologix 1500 PLC Pneumatic valves An emergency stop button Automatic control of all features PID loop tuning Password protection Some options: Type X purge system for classified environments Humidity control Oxygen control Ammonia leak test pressure control This system is will be the most commonly used and will fit most customer needs.

Air Handling Systems Negative Pressure Change Procedure Push Push Filters 99.97% efficient HEPA filters to 0.3 microns particle size

RTP Docking Sequence 1. RTP Alpha flange 2. RTP Beta Flange 3.Beta approaches Alpha 6. Transfer begins 4. Beta sealed to Alpha 5. Double door opened

Ammonia Leak Testing Leak Testing using Ammonia Vapors: Ammonia bottle is placed in isolator Isolator is sealed & ammonia poured into pot Isolator is pressurized to 2 wc Yellow detector cloth is held for 5 seconds over all gaskets, joints and glove ports. If cloth turns blue, a leak has been detected.

Containment Isolator Examples

Containment Isolator Systems Weighing/Dispensing Isolator with Integrated Scale. Mixing Isolator with Integrated Stainless Steel Mix Tank. Synthesis Isolator with tray dryer, filter tank and mother liquor vessel Fitzmill Isolator R&D Isolator integrated lyophilizer

Containment Barrier Systems RadioPharmaceutical Liquid Filling Interface Isolator. Features include: Integrated Base on Filler 350mm RTP for Component Entry Manipulators Uni -Directional Ventilation/Filtration System 1.25 thick 316L Stainless Steel & Lead Glass Construction Customer Nuclear Exhaust

Containment Barrier Systems Spray Dryer Isolator with Yamato Spray Dryer with: 316L SS Construction 270mm RTP with Lock Negative Pressure System with RH Control Spray Wand Weigh Scale Sink for Glassware Washing Inside View Illustrating: #4 Sanitary Finish Spray Nozzle and Cyclone Assembly Push push HEPA Filters Shelf for Liquid Container Sink for Glassware Washing

Containment Barrier Isolator Tablet Press and Support Isolators Tablet Press Tablet Check Isolator Deduster-Metal Detector Isolator Tablet Press Isolator

Containment Barrier Systems Nuclear Glove Box - Examples Plutonium Immobilization Glove Box Uranium Powder Mixing Glove Box with: 304 Stainless Steel & Polycarbonate Construction Airlock with Vertical Sliding Doors Negative Pressure System using House Exhaust Operator Lift System Container Lift System Integrated V Blender

OEL Study/Data Personal Air Sample Results during Dryer Unloading, Sieving & Discharge Sample Number ESAL Sample ID Test Run Sample Type Sample Location Total Time (min) Lactose mg/m 3 1 100 2 1 2 101 2 2 Personal During Operation Operator 1 Personal sample 62 < 0.0160 Personal During Operation Operator 1 Personal sample 60 < 0.0170 Operator 1 Personal sample Average < 0.0165 Operator 1 Personal sample Std. Dev. 0.0007 3 102 2 1 4 103 2 2 Personal During Operation Operator 2 Personal sample 60 < 0.0170 Personal During Operation Operator 2 Personal sample 60 < 0.0170 Operator 2 Personal sample Average < < 0.0170 Operator 2 Personal sample Std. Dev. 0.0000 Task Average for Personal Samples < 0.0168 Task Std. Dev. for Personal Samples 0.0004 Air Sampling Conclusions All personal air samples for both operators were below 0.1 µg/m³ airborne concentration for the duration of the operations performed.

Conclusions : Isolators should be strongly considered for containment of highly potent materials. Off the shelf boxes will never provide the level of workplace integration to achieve good containment. A customized design together with an FAT to simulate the customers application will guarantee a right first time solution. Surrogate testing can simulate process and show dust is completely contained with the isolator. The use isolators and downflow booths for containment of small, fine particles provides greater operator protection and process control.

Thank You Engineer s RISK vs REWARD RISK: Public Humiliation and the death of thousands of innocent people REWARD: A certificate of appreciation in a handsome plastic frame American Glovebox Society 2000 Conference Rodney B. Smith Lockheed Martin 865-576-2152