Application Articles

Bulk Powder Containment: Key Factors for High Potency Handling and Processing

Figures 1 & 2: The EHP Hybrid Powder Units by FSI under Factory Test
and Field Certification

Abstract:

Today, many Flow Sciences customers must safely handle powdery materials. The reasons for containing such material cover a robust range of applications:

  • Mixing, blending, and dilution of active pharmaceutical ingredients. (API’s)
  • Dispensing, weighing, and packaging dosing quantities of active pharmaceutical ingredients
  • Quality control sampling of incoming bulk quantities of solid fillers or API’s
  • Grinding, milling, or otherwise changing the texture of raw pharmaceutical ingredients

Recently, pharmaceutical facilities have seen an increase in new API’s. These newer powerful drug ingredients have reached a potency where containment equipment requirements have reached a much more demanding level 3.

Such containment devices usually include one or more of these attributes:

  • A drum access opening in the worktop
  • Some type of waste chute or other means for removal of contaminated materials from earlier procedures
  • A fan/filtration system, typically with bag-in bag-out HEPA filters
  • The containment capacity to keep room levels of materials being processed at or below 1mg - 50ng per cubic meter.
  • A highly trained worker, armed with carefully-written manuals and SOP’s

The writer will flesh out some of the applications for such units and highlight newer products available to face the new challenges of active pharmaceutical ingredients.

Fig 3: The Flow Sciences Hybrid Isolator features a removable glove panel, offering great open sash containment plus highly effective gloved operation for more potent materials.

Factors Needing Control in Powder Containment:

Working with powders can present unique containment challenges:

First, the need to bring kilogram quantities of compound into an environment with a microbalance places in close proximity objects that seldom see each in any other analytical context. We already know this “meeting” has to happen, particularly in weighing or compounding environments. The ultimate mandate is that this meeting must smooth the awkwardness of Goliath, while preserving the accuracy of David!

The correct powder containment device can accomplish this feat. Sufficient airflow keeps powders contained, while the non-turbulent flow isolates one process from other materials in the same workspace. While all this is happening, the device provides an environment with virtually no turbulence or vibration impact on balance accuracy.

Flow Sciences technologies for doing all this have a long history in lab design and the efficiencies of such systems continue to improve4.

Powders spread inside containment spaces not only because of air currents, but also due to the electrostatic properties of the powders themselves. Powders are typically charged in turbulent airflow. They “stick” to surfaces and adhere to the operator’s hands (figures 4 below).

Figures 4: UV Luminescent Powder Shows Possible Electrostatic Transport of Powder. Note operator’s gloves!

Researchers must be able to police the containment work area, leaving gloves and equipment behind as they withdraw their hands from a procedure. We should always preemptively collect and isolate such waste inside the device. Waste chutes, transfer ports, bagging, and the like are all ways to retain and control contamination inside devices which contain powders.

To process with high purity, intelligent airflow design, built-in solutions for debris collection and isolation, and worker training about SOP’s are all important. The following six examples of bulk powder devices illustrate how many new types of containment structures achieve very good results.  

 

Examples of Powder Applications and Successful Containment:

1) The EHP: A Hybrid Isolator with Many Available Options:

Fig 5: The EHP unit Shown with Removable Glove Panel
Fig.6: Improved Multi-Foil Airflow Design
Fan Operates while weighing!

Fig 7: EHP used to weigh powder; rubber seal around drum;
vibration-isolated fan, and stable scale environment

Fig 8: Assorted Features Available on the EHP unit.

In summary, the FSI EHP Hybrid Isolator can handle kilo-sized quantities of powder for weighing and compounding applications. The unit is also suitable for custom compounding pharmaceuticals or weighing quantities of unique materials into dose quantities. The standard EHP containment device can do all this with the proper accessories. It has all the supporting attributes set forth in the abstract and illustrated in Figures 5 through 8.FC

Such a device contains weighing operations. Batching and dosage may proceed with products then transferred to a port for removal. Mixing pre-weighed ingredients for pharmaceutical use is also possible with the EHP unit. The more complex the application, however, the larger the device may become, allowing more equipment and processes to be undertaken simultaneously.

2) The Glovebox Workstation for LFBC (Lateral Flow Bio Containment Isolator)

The LFBC Isolator permits handling and manipulation of API (Active Pharmaceutical Ingredients) and HPAPIs (Highly Potent Active Pharmaceutical Ingredients) where personnel protection and product purity are required.

Fig 9: Assorted Features Available on the EHP unit.     
Fig. 10: The LBFC offers very good containment, lateral flow, and no exhaust option.

The LBFC very effectively isolates highly potent pharmaceuticals from the room environment using a lateral flow shown in Fig, 11 below.  This unit can contain to nanogram levels and from OEB 3-5. Consult FSI about your application, as containment levels can vary based on application and quantity of material processed.

This cabinet is also a Class 1 Biosafety unit certified using ASHRAE 110-2016. Generally usable in BSL class 1, 2, or 3 environments. Provides personnel protection, not product protection.

3) Specialized Compounding, Liquid Dose Preparation from Bulk Powder:

 The custom bulk powder unit shown below represents a more complex customer application. Addition of a measured amount of dry powder to a liquid in a mixing vessel on the right hand side to produce a liquid suitable for IV use.

Designed for personal protection, this unit has added features to facilitate working with powders using a Mettler Toledo XPE-10015 balance and an IKA mixer stand with the vessel top penetrating through the port on the right side of the worktop. This table section contains a black under-counter cabinet with a multiple height slide-out shelf for different size mixing vessels. Viewing panels are transparent acrylic.

Other features include energy-efficient LED lighting, black phenolic base, left side powder drum cutout, top-mount fans, dual HEPA filters with bag- in bag-out filter system (BIBO), iris ports on both sides, minihelic static pressure gauge, and a table with lock-down casters.

Fig. 7: Powder / Liquid Compounding Pharmacy Enclosure

4) Sieving and Drug Compounding Bulk Powder Containment:

Fig. 8: Bulk Powder unit designed to house a sieving machine

This Bulk Powder Station has dual, Bag-In/Bag-Out fan/HEPA filtration systems. Designed to vent and filter small batch sieving machine dust, the enclosure is equipped with a stainless steel lift cart and fitted with 20” bulk powder cutout for loading drums through the work top access hole. Hinged front and lower doors allow for additional equipment and samples. Airfoils, rear plenums, and top-mounted fans maintain laminar airflow across the workspace ensuring minimal exposure to hazardous powder APIs. The polypropylene superstructure is fitted with acrylic panels and built-in LED lighting.

5) Very large quantity unit:

Figure 9: This Bulk Powder unit allows large container to be connected to the left side
of the unit horizontally.

This large quantity unit features three top-mounted HEPA filtration systems. Designed for personnel protection while working with powder substances, the unit also houses a related balance application. The superstructure is acrylic with hinged upper access doors. A waste chute is located on the right side wall.

6) Animal Waste Processing:

In some cases, the “powder” being processed is waste, not ultra-pure ingredients. The stainless steel exhaust hood shown below offers our customers an isolated environment where animal cages are cleaned. Crushed clay absorbent is disposed of down the circular chute into a waste container below.

The coved 300 series stainless steel liner is easy to disinfect after use. Containment testing demonstrated isolation of waste contaminants inside.

Fig. 10: A Bulk Waste Unit, ASHRAE 110 tested, handles cage cleaning byproducts!

7) Stainless Steel Bulk Powder Units

Customers who have a need for very clean interior surfaces or effective contamination removal frequently opt for 300 grade stainless steel interiors. The powder device shown below has been tested and validated per end user requirements before leaving the FSI manufacturing facility.

Fig. 11: Stainless steel units are frequently used with radioisotopes, where interior cleaning is critical!

Are Devices Like These Right for Your Application?

There are, as we have seen, many types of powder containment devices designed to house a variety of different processes. Containment (personal protection) depends upon good and useful airflow, which keeps powders away from workers in the lab space, but there is so much more!

Because of electrostatics, workers should follow guidelines for properly using the opening. They must never remove an un-bagged object from the containment area. Since gloved hands can inadvertently bring hazardous powders out of containment areas, gloves and expendables should be kept under containment inside the containment area and be disposed using a waste chute. Ultimately, the work area must be clean after the process is complete. Otherwise serious contamination will occur. If the bulk powder containment device has no waste chute or portal, cleanup is virtually impossible. Beware of poorly designed units that allow no disposal routes from inside the containment area.

Experience with such units has shown that process-specific testing is necessary to demonstrate containment using proper technique by end-users. For this reason, ASHRAE 110-2016 and surrogate powder testing reports using the ISPE APCPPE Guideline1 must be part of the equipment validation procedure. Flow Sciences standard and custom containment equipment always come with documentation similar to that shown here!

Figure 12: ASHRAE 110 containment reports with standard sash opening
Figure 13: Custom unit being tested in 2016 using surrogate powder procedure outlined in ISPE Methods

All Flow Sciences, standard products easily pass both tests. Custom bulk powder containment units are tested with ASHRAE 110-2016 and the ISPE APCPPE Surrogate Powder Guideline2 using the customers’ procedures inside the unit. One such published study showed great containment for a standard Flow Sciences chemical fume hood using both containment tests. Results for surrogate powder and solvent vapor containment showed undetectable powder levels in the lab work area after significant interior powder and solvent exposure was created during the test. 2

 In addition, manuals for all our bulk powder units contain complete instructions for coupling and decoupling large ingredient drums, along with more general techniques necessary for effective containment of materials within the work area.

Figure 14: Manuals for bulk powder units review all techniques necessary for product protection.

Conclusions:

  1. Powder units should allow direct access to large quantities of powdered pharmaceutical materials while providing superior personal protection. Lab containment equipment should not expose workers to mixing, weighing, grinding, sieving, compounding, or other processes within an inadequate containment device.
  2. We should test containment units against contamination release using both ASHRAE 110-2016 and surrogate powder testing using the ISPE APCPPE Guidelines and processes relevant to the specified application.
  3. Powders differ from gases in that they will typically stick to surfaces, including the researcher’s hands and lab coat! Any successful test report by a manufacturer of such equipment should also include a review of cleaning and housekeeping procedures designed to prevent static transmittance of the relevant materials.

Footnotes:

  1. Assessing the Particulate Containment Performance of Pharmaceutical Equipment, Second Edition, 2012, International Society for Pharmaceutical Engineering
  2. Evaluating a Fume Hood for Containment of Solids, Liquids, and Vapors Using ASHRAE 110, HAM, and ISPE Methods, Goodman and Haugen, 2019, available from Flow Sciences, Leland NC
  3. Cyto Solutions, Engineering controls for the Containment of Cytotoxic Materials, Flow Sciences 2019, https://flowsciences.com/containment-engineering-controls-for-cytotxic-hpapi-adc/
  4. Red Lights and Green Lights-The Keys to Superior Containment, Robert Haugen, 2018, Flow Sciences, https://flowsciences.com/the-keys-to-superior-containment-in-compounding-applications/

Malvern Mastersizer 3000 with Aero S and Hydro MV Enclosure

Malvern Mastersizer 3000 enclosure

Malvern Mastersizer 3000 with Aero S and Hydro MV

Process:

Customer required a cart-to-dock enclosure to house a Malvern Mastersizer 3000 with Aero S and Hydro MV accessories while providing personnel protection. The PC was to be stored below the cart on a shelf and the enclosure customized to have an articulating monitor mount field-installed upon delivery. The Mastersizer 3000 uses the technique of laser diffraction to measure the size of particles. It does this by measuring the intensity of light scattered as a laser beam passes through a dispersed particulate sample. This data is then analyzed to calculate the size of the particles that created the scattering pattern. The Mastersizer 3000 software controls the system during the measurement process and analyzes the scattering data to calculate a particle size distribution. It also provides both instant feedback during method development and expert advice on the quality of the results.

Containment:

With dry powder dispersion there is always the possibility of particle damage, because of the high velocity at which the particles pass through the disperser system. The Aero S minimizes this issue by avoiding impaction surfaces. The Hydro MV is designed for medium volume wet dispersion and is suitable for a very broad range of sample types. Automated dispersant delivery of both organic and inorganic dispersants allows optimisation of the dispersion process and accelerates analysis. These devices—the Mastersizer, the Aero S, and the Hydro MV—require Dual HEPA filtration in order to minimize lab contamination.

The enclosure cart with its black phenolic top would seat the units and allow for removal when devices required maintenance, and a vertically sliding sash with the ability to be raised above safe operating zone for equipment loading/unloading. The cart was constructed of white steel a locking mechanism and guide rails for it to inset into the table upon which the enclosure sat. Penetrations in the form of iris ports were added to the polypropylene frame to allow for entry/egress of critical cabling to power the various devices. Front bifold doors in the cart allowed for the PC base to be stored. In order to maintain light across the entire work surface, an LED lighting chase was designed and integrated into the enclosure ceiling.



Dual Operator Glove Box Workstation with Balance Enclosure

Occasionally, containment devices must be made a bit more complex in order to simplify the process taking place inside. Here, a powder ingredient can be manipulated in a 2- stage process involving a Mettler analytical balance and a Senco FC202 glass-jacketed reactor using a dual operator glove box workstation with balance enclosure.

This containment device offers personnel protection during a 2-stage, 2-person process. The hazards and exposure risks of both stages of the process are significant. Complete containment is needed at all times. Removal of product before the process is completed is out of the question.

The client required an enclosed weighing and mixing process involving the manipulation of High Potency Active Pharmaceutical Ingredients (HPAPI) in powder form. The first step of the process was to prepare a weighed powder sample of prescribed mass using a Mettler-Toledo XS204 analytical balance. This prepared sample was then transferred into a Senco FC202 reactor for mixing with a solvent. Operators were to be protected from dermal exposure and respiratory exposure. Operator breathing zone concentration of the HPAPI was limited to ten micrograms per cubic meter of air (<10 ug/m3) expressed as an 8-hour Time Weighted Average (TWA).

FSI determined that a pass-thru chamber between the weighing enclosure and the reactor enclosure would aid in a simpler process flow and prevent loss of product during transfer. The chamber housed a process where Operator 1 (left) transferred weighed product from the left enclosure to Operator 2 on the right. Operator 2 then manipulated the Senco reactor using the 2×2 glove port design on the left side of the enclosure. The pass-thru chamber combined with the 57” [1452mm] height and 2×2 glove port design allowed for safe and efficient completion of the process. Gloves are either of Butyl or CSM. Two ball valves connections are on the enclosure exterior, enabling nitrogen or compressed air addition.

The weighing enclosure on the left featured a top – mounted fan / filter housing which provides single-HEPA filtration and removal of airborne product from the interior of the enclosure. The reactor glovebox on the right featured a lateral flow design, using a side- mounted inlet HEPA filter (left) and a top-mounted inlet HEPA. The two inlet filters work in conjunction to move air laterally across the reactor and into the Single-HEPA filtrated fan / filter housing on the top-right of the enclosure. Exhausted air on both sides of the enclosure system may be connected to house exhaust and/or recirculated into the room.

If you have any questions regarding this containment array, please contact Flow Sciences, Inc. at (800)-849-3429 or send an email to customersupport@flowsciences.com.


For More Information – Contact Us

  • What is being done inside of the enclosure? What type of material (powder, liquid, gas, nuisance odor) is being worked with? How does the material enter and exit the enclosure system? etc...
  • What type of filtration is required? Single HEPA, Dual HEPA, Carbon, House Exhaust, etc... What is the required OEL (Occupational Exposure Limit) for the process, or any other details about containment goals? What is the quantity of powder or liquid, task duration, composition of powder, etc...?
  • What equipment is being worked with? What is the equipment model, size, scope, function, and any other information that will affect the design of the enclosure, including movement, heat output, etc...? *State the specific equipment make and model if available*
  • Drop files here or
  • Are there any additional notes or information that should be considered? Are there any special design requirements?

Buchi B-290 Mini-Spray Dryer Enclosure for API Processing

Purpose: Flow Sciences was approached to design and build an enclosure that could house the Buchi B-290 Mini-Spray Dryer during process. Particle sizes would range from 1 to 25 µm, requiring the enclosure to offer containment down to less than one microgram per cubic meter. The client planned to weigh API and dissolve weighed sample into various solvents which would then be introduced into the Buchi B-290.

Process: 50 grams of powder would be dissolved in 725ml methanol outside of the enclosure. Liquid will then be brought into the enclosure in a sealed container and fed into the peristaltic pump of the B290. The maximum amount of powder dissolved in liquid of API at one time is 50g. Upon connecting to the B-290, the client would be spray-drying at a rate of 15mL/min. Upon completion of the cycle, the client planned to remove the collection vessel, seal it with a cap, and remove the vessel from the enclosure via a pass through on right side. The client would then disassemble the glassware and spray down with a misting wand to get as much powder off as possible and then bag out through a continuous liner what glassware was to be sterilized in the cleaning room. All glassware was to be misted, wiped, and then double bagged. Once complete, the client would transfer the product to another room, disassemble all glassware, replace the HEPA filter, and take everything to a cleaning room.

Equipment: Due to its strength and chemical resistance, polypropylene was chosen for the superstructure and a removable sash door designed with 10” oval glove ports. In order for visual clearance around the entire enclosure, acrylic viewing panels were incorporated into all four sides, with glove ports on both ends to help facilitate cleaning and process assistance. Due to the equipment inside the enclosure, the size of the enclosure was quite large—90” exterior width and approximated 50” deep. BIBO Dual HEPA fan filter units were placed on the top of the enclosure, requiring 968 CFM at the thimble connections connected to house exhaust to maintain 100 LFPM at the face opening, and 842 CFM if recirculating.

Given the weight of the Buchi, as well as the other equipment that would be placed inside the enclosure, FSI designers made a table with a cutout for a cart that would lock into place inside the enclosure. Using this method, the Buchi would be rolled in and out of the enclosure on the table for ease of cleaning and service between cycles.

The client also wanted the base to be a drillable material so the air pump could be brought outside of containment and moved below for easier cleaning. Engineers designed a solution that would move the pump outside of the enclosure by adding more iris ports, connections, and hoses. Also, a sink was designed for the glassware allowed easier access while cleaning.

A one-to-one ratio mock-up made of MDF and acrylic was created and sent to the client who wanted some design changes. The client wanted the pass thru to be bigger so it could fit a 1 liter bottle that is 9.25″ tall out through it. Also, the client wanted a glove port in the upper door so that the customer could reach the top of the B-290 for removing and cleaning parts. They wanted the glove port on right side lowered by 2″ for better ergonomics and wanted the rear plenum split into four pieces for easier cleaning.

In lieu of adding a glove in the door, a fifth glove was added to the draft shield in the center. The entire enclosure’s height was reduced by two inches due to facility constraints. An N2 fitting for the pump was also added.

Evaluation & Testing: Between July 12th and July 18th, 2019, factory acceptance testing was performed on the enclosure in the presence of the client to measure equipment compatibility with the process and to determine the containment effectiveness during simulated operations. Overall performance indicated that the enclosure met the specifications determined. During surrogate powder testing, no individual sample exhibited a TWA exposure of more than 0.316 ng/m3., far better than 1 µg/m3 requested.

Findings: These exposures, well below the CPT, indicate that with good laboratory practices, this enclosure is highly effective at providing containment for compounds with Occupational Exposure Limits (OEL)s < 1000 ng/m3.


For More Information – Contact Us

  • What is being done inside of the enclosure? What type of material (powder, liquid, gas, nuisance odor) is being worked with? How does the material enter and exit the enclosure system? etc...
  • What type of filtration is required? Single HEPA, Dual HEPA, Carbon, House Exhaust, etc... What is the required OEL (Occupational Exposure Limit) for the process, or any other details about containment goals? What is the quantity of powder or liquid, task duration, composition of powder, etc...?
  • What equipment is being worked with? What is the equipment model, size, scope, function, and any other information that will affect the design of the enclosure, including movement, heat output, etc...? *State the specific equipment make and model if available*
  • Drop files here or
  • Are there any additional notes or information that should be considered? Are there any special design requirements?

Fitzmill L1A & Quadro Comil Glovebox

Glovebox Workstation

Glovebox and Comil

Glovebox and Fitzmill

Process:
Flow Sciences was approached to design a glovebox that would enclose milling processes done by either a Fitzmill L1A or a Quadro Comil.

Containment Design:
A panel interface on the right side of the glovebox allowed for the connection of either piece of equipment that would sit on a custom-designed cart to fit each jet mill model. The interchangeable side panel allowed for use of either unit and minimized shutdown time before substitution. The FSI design allowed interface with either machine by using two separate interface plates!

Comil and Connection Plate

Fitzmill and Collection Plate

The L1A panel allows the operator free access to the control panel of the L1A while the outlet blower line runs into the enclosure. Additionally, this panel features two cavities to allow insertion and support of the L1A “feet.” The Comil panel features a cutout where it can be inserted into the enclosure for use. The pass-through on the left side allows easy access for insertion of product. One quick-disconnect on the front left and right sides of the unit allows connection and use of Nitrogen (N2) and Oxygen (O2) gas sources. Oval glove ports on the front hinged door protects the operator from dermal exposure to product. A guillotine door was chosen for the pass-through connection to minimize impact on the work surface.

A 1:1 MDF and acrylic mock-up was sent to the client, who made extensive revisions that were then applied to the enclosure design. The client wanted to add a drain to the base for waste disposal while increasing the depth and width of the isolator. Another glove port was added for cleaning the unit while under containment and the pass-through size redesigned to accommodate larger containers that would be introduced into the unit.

Test Performance:
The original client’s internal policies stipulated protection from dermal exposure and reduction of respiratory exposure concentration of no more than 1 microgram powder per cubic meter air, expressed as an 8-hour Time Weighted Average (TWA). The client shipped the Fitzmill L1A and the Quadro Comil to FSI for fitting, finishing, and Factory Acceptance Testing (FAT). Under all configurations, containment down to 0.3 micrograms was achieved.


For More Information – Contact Us

  • What is being done inside of the enclosure? What type of material (powder, liquid, gas, nuisance odor) is being worked with? How does the material enter and exit the enclosure system? etc...
  • What type of filtration is required? Single HEPA, Dual HEPA, Carbon, House Exhaust, etc... What is the required OEL (Occupational Exposure Limit) for the process, or any other details about containment goals? What is the quantity of powder or liquid, task duration, composition of powder, etc...?
  • What equipment is being worked with? What is the equipment model, size, scope, function, and any other information that will affect the design of the enclosure, including movement, heat output, etc...? *State the specific equipment make and model if available*
  • Drop files here or
  • Are there any additional notes or information that should be considered? Are there any special design requirements?

HPAPI Processing and Drying Suite

HPAPI Processing and Drying Suite

HPAPI Processing and Drying Suite

Purpose: A two-part enclosure consisting of a Single Pass Air Flow Glove Box Enclosure and a Nitrogen Purge Enclosure was designed to provide protection to the operator and product. The left side uses HEPA-filtered supply air as well as HEPA exhaust to create a clean interior environment, while the right side provides a clean, dry nitrogen environment.

Process: The process included wetcake narcotic being oven-dried to a powder to remove water, methanol, ethanol, IPA, DCM, chloroform, acetone, and ethyl ether. After drying in the oven, 9”x13” glass trays were to be moved from the oven to a balance area for weighing. Once the final weight is measured and recorded, the material is moved to the packaging operation.

Equipment: A suite was designed which included flame retardant polypropylene superstructures, a central transfer port, inlet HEPA filtration, dished black phenolic bases, top mount fans with BIBOs and HEPAs, independent hinged doors (24.635 W x 27” H opening), (7x) 10” oval glove ports, 12” H x 16” W access door, FS1650 alarm, minihelic gauge, stainless steel tables, and glass viewing panels. Glass viewing panels and LED lighting to maximize lighting across the workspace. The system had an exterior width of 168”, a depth of 43”, and an interior height of 41”. 245 CFM was required at the thimble connection to maintain 50LFM at center cross section of the isolator, while 216 CFM was measured at the fan to maintain the same LFM at the center cross section. Negative pressure was measured at the mouth of the house exhaust hose at the N2 connection. Multiple glove ports were required due to cleaning requirements, so a design was created to have ports at two different horizontal levels to allow access to the oven controls and oven door in the isolator portion of the enclosure. An N2 generator existed on-site which was hard-piped into the room. Nitrogen is used as an atmospheric replacement during this process. Nitrogen-filled environments can be kept at low relative humidity levels as a consequence of the original purity of the supply. Moisture-sensitive products like nanomaterials and APIs are less susceptible to decomposition in such an environment. Two 0.3 micron cartridge filters were installed on incoming and outgoing N2 to ensure a clean environment.

A custom table for the enclosure was developed as a way of supporting the oven and the enclosure, with adjustable feet beneath the oven that could be used to set height and ensure a proper seal in the wall flange.

Peripheral Equipment: The Binder VDL 115 safety vacuum drying oven for flammable solvents had a max temperature of 100 degrees Celsius, requiring the use of Flametec polypropylene as a material of construction for the Processing and Drying suite. Due to the nature of the materials being manipulated, the oven would typically run within a 50- 60 degree Celsius range. Gasket material was made of high temperature RTV silicone with a maximum temperature rating of 343 degrees Celsius to seal the stainless steel flange to the oven. The Binder VDL 115 oven had two aluminum expansion racks with class 2 independent adjustable temperature safety device with visual alarm— components accessible at the front. The oven needed to able to fully open within the isolator with the door swinging outward from left to right.

Peripheral Equipment Considerations: Completely enclosing the oven created a heat concern, solved by the use of Flametec polypropylene and by installing the oven into the exterior wall and using the custom table for weight support. During on-site installation by FSI personnel, to accommodate an added outer control on the oven, the frame had to be cut by hand on the spot. After installation was completed and validation tests initiated, FSI personnel noted that the interior of the oven was sealed but its exterior shell was not. Particles were coming out of the outside of the oven’s sidewall, which made FSI installers fashion a block-off plate to limit escape of particles during oven processing. The client then revised their internal cleanliness protocol from Class 5 to Class 7 upon this conclusion by FSI personnel.


For More Information – Contact Us

  • What is being done inside of the enclosure? What type of material (powder, liquid, gas, nuisance odor) is being worked with? How does the material enter and exit the enclosure system? etc...
  • What type of filtration is required? Single HEPA, Dual HEPA, Carbon, House Exhaust, etc... What is the required OEL (Occupational Exposure Limit) for the process, or any other details about containment goals? What is the quantity of powder or liquid, task duration, composition of powder, etc...?
  • What equipment is being worked with? What is the equipment model, size, scope, function, and any other information that will affect the design of the enclosure, including movement, heat output, etc...? *State the specific equipment make and model if available*
  • Drop files here or
  • Are there any additional notes or information that should be considered? Are there any special design requirements?

CQ11028 - Memmert VO 200 Vacuum Oven Enclosure

CQ11028 - Memmert VO 200 Vacuum Oven Enclosure

CQ11028 - Memmert VO 200 Vacuum Oven Enclosure

Memmert VO 200 Vacuum Oven Enclosure

         Finding a solution to provide personnel protection when working with Highly Potent Active Pharmaceutical Ingredients (HPAPI) is very tricky. In a business sector where regulations and policies are prevalent, exposure control options are limiting; both physically and financially. Laboratory operations require unwavering precision and physical/financial limitations cannot be avoided in many cases. The information below describes a situation where a containment solution was designed for a benchtop vacuum oven process.

Flow Sciences’ sales process begins by ascertaining information regarding the client’s process and equipment they wish to contain and enclose. From there, proactive and reactive engineering design measures are made in accordance with customer stipulations. The overall purpose of this article is to educate the reader on Flow Sciences’ Discovery process and how it resulted in a containment solution.

         The Memmert VO 200 Vacuum Oven Enclosure was designed to enclose a pharmaceutical vacuum oven drying process for use of the Memmert VO 200 Vacuum Oven. The client stipulated a maximum respiratory concentration of 1 microgram powder per cubic meter air (<1 ug/m3). Flow Sciences collaborated with a distributor to create a Single HEPA-filtrated enclosure with a cutout on the interior left side. Flow Sciences included the cutout on the left side so the oven is able to be connected.

With this design, the operator is able to open the oven door without worrying about hitting anything. This facet of design allows the operator copious space to manipulate product before and after processing. The added ergonomics yield industry-leading utility of space. The additional space increases operator comfort which can improve work quality.

         Let’s address another worry: high temperature. Opening the oven will not negatively impact the integrity of the enclosure’s structure. The phenolic base is more than capable of withstanding the temperature of the outflowing air when the oven door opened. Phenolic doesn’t even begin to thermally decompose until it reaches a temperature of 220 degrees (Fahrenheit) itself. When considering the cooling effect of the fan drawing the heat upwards and the time it takes for phenolic to thermally equalize, there is no room for apprehension in this respect. Additionally, the enclosure features a removable draft shield, which offers the operator protection from dermal exposure with butyl or CSM gloves and the option to complete the operation with open face containment.

         Before the design was finalized, a nonfunctional mockup of the unit was constructed and evaluated by the client at their facility. FSI added the oven “mating” feature to the enclosure design after the client stated that were interested enclosing the sample preparation portion of the operation as well as insertion/removal of product into and from the oven.

         Factory Acceptance Testing (FAT) was performed on the enclosure shortly before shipment to the client. FAT testing included ASHRAE 110 testing protocols with the draft shield on and face the enclosure face.


For More Information – Contact Us

  • What is being done inside of the enclosure? What type of material (powder, liquid, gas, nuisance odor) is being worked with? How does the material enter and exit the enclosure system? etc...
  • What type of filtration is required? Single HEPA, Dual HEPA, Carbon, House Exhaust, etc... What is the required OEL (Occupational Exposure Limit) for the process, or any other details about containment goals? What is the quantity of powder or liquid, task duration, composition of powder, etc...?
  • What equipment is being worked with? What is the equipment model, size, scope, function, and any other information that will affect the design of the enclosure, including movement, heat output, etc...? *State the specific equipment make and model if available*
  • Drop files here or
  • Are there any additional notes or information that should be considered? Are there any special design requirements?

Vented Balance and Fume Hood Array

Vented Balance and Fume Hood Array

Abstract:

Finding a product capable of containing a process where powdered product is converted into an aqueous solution can be tricky. Especially if such processes evolve toxic vapors and gases. In these scenarios, weighing with an analytical balance is typically followed by adding the powder to a stirred liquid. At this point, vapors and gases may evolve.

In this case study, Flow Sciences worked with a customer to develop a two-section containment system that optimized containment while maximizing process efficiency. Such designs become even more essential when high potency active pharmaceutical ingredients are involved.

The device depicted in Figure 1 is an example of the custom product FSI produced for such an application.

Problem:

Our customer had a limited space to perform stirring, weighing, and calibrated solid-liquid mixing operations. Flow Sciences was made aware of chemicals and quantities used in this process.

Recommendation:

Flow Sciences proposed joining an open-face powder enclosure with a bag-in bag-out filter and fan (thimble connection to building exhaust) with a polypropylene vertical sash fume hood exhausted to the building exterior.

This arrangement became more defined with multiple phone calls and emails until all parties agreed to the process array depicted below:

Key materials of construction were stainless steel, polypropylene, and anodized aluminum. A deep stainless work space in the fume hood section had hinged doors for final product access and removal.

Successful ASHRAE 110-2016 testing (4 Different Sash positions) completed prior to Product Shipment:

Conclusion:

Flow Sciences worked with our customer and devised a unit containing both a HEPA-filtered weighing enclosure and a polypropylene fume hood. A sliding connecting pass-through was also constructed. The weighing enclosure contained the weighing process with HEPA filtration and the fume hood contained the stir plate solvent addition operation. This construction permitted containment of both liquid and powdered substances in two different processes. Process flow was maximized with this design scheme. The weighed powder could be moved from the HEPA balance section to the fume hood through the sliding door, where solvent mixing took place.

All this was done with demonstrated containment in our test room using ANSI / ASHRAE 110-2016.


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Particle Analysis Suite

Particle Analysis Suite

Particle Analysis Suite

Professionals in the field of laboratory sciences occasionally encounter a situation where they must enclose several processes requiring the manipulation of product in two or more “phases”. But here’s the catch: some processes are comprised of 2 “phases” while others are comprised of 3 or more. The purpose of this document is to demonstrate the capability of Flow Sciences’ products to facilitate flexibility in a dynamic laboratory work environment. While the following text describes the original purpose behind the design of this enclosure suite, the real intention of this article is to convey the message that Flow Sciences’ product line offers consumers the flexibility to change their operations without compromising the safety of those performing them.

The Particle Analysis Suite was designed to enclose a vacuum cleaner filter changeout process on a Nilfisk vacuum unit as well as a Sympatec HELOS/BF Laser Diffraction Analyzer. The lower section of the middle enclosure is intended to house the Nilfisk vacuum system while the left/right enclosures house the laser diffraction devices. The client stipulated a respiratory exposure concentration of less than one hundred nanograms powder per cubic meter air (<100 ng/m3) during the filter replacement procedure. This exposure is expressed as an 8-hour Time Weighted Average (TWA) in the breathing zone. A non-functional, fiberboard mockup of the enclosure suite was shipped to the client so they could make additional considerations prior to finalizing the design. After the client analyzed the area with mockup installed, Flow Sciences worked with the client’s facilities and health/safety departments to incorporate more versatility of use. Flow Sciences’ resultant decision was to add guillotine pass-thrus on each side of the sliding sash enclosures to allow interchangeability of the configuration of enclosure; the option

of using any permutation of 1, 2, or 3 enclosures was now possible. To add to the versatility, tables with locking casters were added to the sliding sash enclosures. A Double Safe Waste Chute is on the side of the draft shield enclosure to facilitate waste load-out.

The removable draft shield enclosure was subjected to two “phases” of Factory Acceptance Testing (FAT) in FSI’s in-house laboratory. During one phase, the enclosure was tested with the draft shield in place. During the other phase, it was tested without the draft shield. Surrogate Powder Testing produced results proving the enclosure contained to an average respiratory exposure concentration of 30 nanograms per cubic meter (ng/m3).

Flow Sciences is known for their flexibility and their unique reception of customer needs. The FSI mantra of “…developing a containment solution to fulfill a particular industry need” does not exclude multi-stage processes. Multi-task systems are built for a multitasking world with a seemingly never-ending influx of information.

SKU: 5324


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Oncology Workstation with Ezi-Dock CSV6 HPAPI Transfer

Oncology Workstation with Ezi-Dock CSV6 HPAPI Transfer

 

The Oncology Workstation with EziDock CSV6 HPAPI Transfer was designed to provide personnel and product protection while working with powder substances. It was determined due to the high OEL that a glovebox workstation would best suit the application, and an Ezi-Dock high containment transfer system was integrated into the black phenolic base. The Ezi-Dock transfer system was used due to its capacity to handle hazardous chemical and pharmaceutical products. A containment level of 50 ng/m3 was required.

Powders contained in drums would have to enter the workstation via a passthrough, which had to be large enough to handle multiple dimensions. The door opening in the front of the passthrough, as well as the sliding door which allows entrance into the glovebox work area, had to be congruent. A list of all container sizes was procured and the passthrough was designed to fit over 70% of the proposed containers.

Due to strong cleaning materials that would be used, the viewing panels of the workstation were made of glass as opposed to acrylic, as the potency of the cleansers would craze the lucite material. The single glass panel in the polypropylene frame that contains the glove ports would be affixed to the enclosure via gas shocks. Efforts were taken by the design team to limit the weight of the door in order to ensure longevity and proper function of the hinges and shocks, as well as make the cleaning operation simple enough for one operator. The design team’s precautionary solution was to fabricate a door that was 70 pounds—15 pounds less than the original concept. Other design considerations included increasing the door width to decrease interference with the grooved seals around the edges. The pull of the fan in operation also yielded an issue with the top plenum, which was too light to stay seated. Rabbit edges were designed for a flush fit, and the thickness of the material was increased.

The customer requested that the door angle reach 140-150 degrees when open, knowing that containment would only be provided if the unit was completely closed. The 140-150-degree request of the door was to allow for entry/egress of the powder weighing equipment and containers, in order to facilitate an easier, and more thorough cleaning process. An electrical duplex was added to the back wall with two single outlets and a Roxtec connection besides the outlet on both sides.

Overall performance during acceptance tests indicated that the enclosure met required specifications. The enclosure passed all requirements for ASHRAE and AIHA/ANSI standards and recommended practices and met the CPT of 50 ng/m3. The results indicate that with good laboratory practices, this enclosure is highly effective at providing containment for compounds with Occupational Exposure Limits (OEL)s < 100 ng/m3.

For more information on the Glovebox Workstation series – Click Here


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Genevac EZ2 Elite

Genevac EZ2 Elite Evaporator and Powder Handling Suite

Genevac EZ2 Elite Evaporator and Powder Handling Suite

            Flow Sciences, Inc. was tasked with designing a modular containment unit that would house a Genevac EZ2 Elite Evaporator and allow for transfer of materials post-manipulation into a separate, connected balance enclosure for weighing. The Genevac equipment required a level, sturdy work surface and a 2” air gap between the evaporator and the bench edge, according to manufacturer installation materials. The Genevac Evaporator was to be housed in a unit alone that connected via a square pass-through to a separate unit where powder handling could commence. Environmental health and safety officers established standards for the lab which required that bag-in/bag-out Dual HEPA filtration be utilized. Due to facility constraints, particularly ceiling height (3.5 feet was designated the maximum height of the enclosure in order to allow for 18” clearance from the ceiling), prohibited the usage of top-mounted fan/filtration systems, so a rear-mounted option was designed. In addition to height restrictions, there was also a depth restriction of six feet and a length restriction of eight feet.

            After using the Genevac, the client’s operating procedure stipulated that material removed from the enclosure would be housed in vials 2.25” high with a one-inch diameter on trays that measured 5”L x 3.5”W x ½”H. The Genevac also produces waste which is evacuated into a 500mL bottle that is eight inches high and four inches in diameter. These dimensions were crucial and influenced the pass-through design between the two enclosures. The Genevac was measured and designers compensated for the 50mm clearance required on all sides for proper functionality and safe usage.

            Due to its resiliency to a variety of cleaning materials, a polypropylene structure was chosen coupled with acrylic for the draftshield, viewing panels, and sliding door. Using a hybrid isolator as a basis for design, as the hybrid units effectively contain using airfoils and plenums to create laminar airflow across the work surface and reduce eddies and turbulence. The fans/filters were moved to the rear of the unit and acrylic panels were placed in the ceiling of enclosure to allow for a better view of the workspace. The draft shield with oval glove ports engineered to be removable from the unit that would house the Genevac to allow for ease of cleaning and for proper equipment installation.

For filter replacement, customer was instructed to leave at least 22.75” clearance at the rear of the unit. The Genevac containment unit was made slightly taller to accommodate the equipment and allow for more freedom of operator movement in using the evaporator. Upon filling the tray with evaporated samples, the operator would open a sliding door to the passthrough where the tray would then be placed. Another sliding door in the second, connected unit allowed for the weighing operator to ensure containment was achieved in their area before allowing the samples into the balance enclosure.

            Factory Acceptance Testing was performed on the enclosure to measure overall performance and to determine the containment effectiveness during simulated operations. Overall performance indicated that the enclosure met the specifications determined by a company. During surrogate powder testing, no individual breathing zone sample exhibited an exposure of more than 34.7 ng/m3.


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API Process Development System

The API Process Development System was designed to provide personnel and product protection when working with powder and liquid substances. The enclosure housed a Mettler Toledo Easy Max 102, vacuum oven, and IKA LR 1000. The unit required a stainless steel base to allow for intensive cleaning protocols with shelves underneath to assist in recirculating the chiller and vacuum pumps needed to operate the process equipment. Operators needed access from the rear of the enclosure for cleaning purposes and there would need to be enough space for movement of equipment inside the enclosure.

The initial task of the process required the weighing of Active Pharmaceutical Ingredient (API) powder utilizing a Mettler Toledo balance. Proper use of the balance required 12-14” of usable linear width within the enclosure. The powder was then to be placed into liquid suspension by way of a magnetic stirrer—this would preserve the structure of the API without any dissolution. A liquid suspension of powder API can also deliver a higher concentration of API than an equivalent volume of liquid solution. Solvents used were ethanol, acetonitrile, and esthers—some of which had flammable potential. Less than one liter of solution would be in a beaker at any given time. The suspension would then be transferred into a Mettler Toledo Easy Max 102 reactor, a unit that is 26” wide, 30” tall, and 30” deep. Additionally, the unit requires 25” of vertical operator access. The Easy Max 102 utilized a chiller unit connection so feed and return lines were integrated into the enclosure.

The process continued as the API solution was then filtered by vacuum filtration onto a filter paper disk that was to be dried in a vacuum oven. Oven dimensions were 15” width, 16” depth, and 21” height—a vacuum pump was needed so a connection for the pump exhaust line to the system exhaust was engineered. An N2 line connected to the oven for gas purge. Upon removal from the oven, the sample was manipulated by the IKA LR 1000—a 20” wide, 30” tall, and 20” deep unit. The LR 1000 uses a sealed glass reaction vessel to mix powders into a dry or wet cake.

A system was engineered since the sample would need to be contained throughout the process. The sample could only enter or exit the system clean. Given the length of physical travel that the sample would endure through the numerous process steps—and the material of construction requirements given the nature of the different substance manipulations—the design had a substantial number of considerations. Polypropylene was chosen for the superstructure.

The API powder entered via a pass-through into a Flow Sciences Hybrid Isolator as mobility inside the enclosure was as important to the operators as safe containment. However, in order for the sample to be removed, a glovebox workstation was designed for a secondary cleaning of the sample before exit via the final pass-through.

The resulting enclosure had a 252” exterior width, a 30” exterior depth, and a 101” exterior height—including the custom stainless steel table with shelves. A deflector shield was integrated into the table where the vacuum pump was positioned to minimize sound pollution in the lab. The system had inlet HEPA filtration, a black phenolic base, and acrylic viewing panels with a hinged door style. The draft shield with glove ports was removable for cleaning. Bag-In/Bag-Out filtration with dual HEPA filters and top mount fans were coupled with vent kits and five thimble connections for connection to house exhaust. A 6” solid waste port with continuous liner was ported into the base. LED lighting and acrylic viewing panels maximized lighting across the workspace, and iris ports and electrical outlets were installed where needed inside for the process equipment.

In general performance tests, the enclosure passed all requirements for ASHRAE and AIHA/ANSI standards and recommended practices and met the CPT of 1000 ng/m3. During surrogate powder testing, no samples from outside of the enclosure exhibited measurable amounts of naproxen sodium above 0.51 ng/m3 TWA. Additionally, task maximum concentrations did not exceed 5.42 ng/m3. These exposures were well below the CPT of 1000 ng/m3.

See this unit on TaskMatch


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Glovebox Workstation with RTP

Transporting HPAPI Product with Containment

Applying the DPTE® transfer system to the Flow Sciences Glovebox Workstation


Glovebox Workstation with RTP

The purpose of this document is to serve as a case study where a containment device was designed to facilitate “interim containment”, or containment during the portion of a process where the product isn’t inside the enclosure. Rather, the product is intermittently contained between Point A (enclosure) and Point B (another enclosure or otherwise contained atmosphere). In this scenario, Flow Sciences designed an enclosure featuring a Getinge La Calhene DPTE® Alpha Rapid Transfer Port (RTP).

 

Background information regarding the client’s process and equipment was provided, which affected the decision-making process leading up to the engineering design of the enclosure. This includes a discussion on engineering decisions and development of design, level of containment, verification testing, and an explanation of how the Getinge La Calhene Alpha RTP combines with a transport capsule to yield leak-free containment during transport.

 

A client was in need of a containment enclosure for an analytical weighing and solution-preparation operation involving Highly Potent Active Pharmaceutical Ingredients (HPAPI) in powder form. Their goal was to transfer product from an enclosure to another enclosure. Internal policy stipulated that the operator’s 8-hour respiratory exposure concentration, expressed as an 8-hour Time Weighted Average (TWA), be less than 500 nanograms per cubic meter (<500 ng/m3) in the breathing zone. Consultative discussions revealed to Flow Sciences that the client was using a Mettler analytical balance for weighing operations. Additionally, it was ascertained that the client was utilizing polyethylene DPTE® Beta Capsules (DPTE® PE Container) in other parts of the facility. The Beta containers were being used for safe transfer of cytotoxic product from one contained work area to a distant other.

 

When the basis of the design was submitted to the Flow Sciences design team, it was decided that the enclosure could be designed to include a Getinge La Calhene Alpha port to coincide with the Beta containers that the client already owned.  As a result, the enclosure incorporated a 24” x 14” Inlet HEPA and 24” x 14” Dual-HEPA Top – Mount fan / filter housing used in conjunction to create lateral, laminar flow across the work surface.  After air is captured by the inlet HEPA filter, the negative pressure top-mounted fan causes the air to slowly move laterally across the workspace. As a result, the statistical interferences of cross-contamination and product loss are attenuated.

 

When implemented into its practical environment, the enclosure seamlessly integrated into the client’s process flow.  After product was weighed, it was containerized for transport.  Even while containerized, an inherent exposure hazard still existed in the event of a catastrophic spill event during transport. Containment during product transport is yielded synergistically by the combination of the Alpha and Beta Rapid Transfer Ports, thereby serving as an engineering control for this hazard.  The client possessed DPTE® PE [Beta] Containers.  Now, as a result of the incorporation of an Alpha port on the side of the enclosure, operators were able to safely insert weighed product into the Beta Container by performing the following steps in chronological order:









In Flow Sciences’ in-house laboratory, the enclosure was tested in accordance with ISO 14644-1 – ISO Class 5 for particles ≥0.3µm/m3. The average result was 2,276 particles with a diameter greater than or equal to 0.3 micrometers per cubic meter air (2,276 particles with diameter ≥0.3 µm per cubic meter air). Additionally, the enclosure provided personnel protection through its negative-pressure containment design and four (4) 10” oval glove ports on the front of the unit. Specifically, “personnel protection” entails employee protection from exposure via the respiratory and dermal routes of exposure. Similar enclosure models in the Flow Sciences Glovebox Workstation (GBWS) series were evaluated internally using surrogate powder testing. During this test, lactose powder was manipulated into the interior of the enclosure while three operators performed operations similar to that of its real-world application. Air samples were taken in the breathing zone of the operator and in several locations throughout the Flow Sciences laboratory. Upon interpretation of the exposure data, Flow Sciences validated that the GBWS series contained down to a respiratory exposure concentration of 30 nanograms per cubic meter (30 ng/m3), expressed as an 8-hour Time Weighted Average (TWA). Compared to the Occupational Exposure Limit (OEL) stipulated by the customer (<500 ng/m3), the validated containment level is sixteen-times (16x) lower; or 6% of the stipulated OEL.

 

The GBWS is capable of containing today’s most toxic powder substances and the operations that involve them. Ray Ryan, Founder and President of FSI states “Flow Sciences is a solution based company. Sometimes we have the solution on our shelves, but most of the time we have to develop a solution to fulfill a particular industry need”.  This case study serves as a prime example of a project where Flow Sciences used a recently developed containment device and augmented it to fit the specific needs of the client. In this case, Flow Sciences fulfilled a need for temporary mobile containment of HPAPI product through the incorporation of the Getinge La Calhene Rapid Transfer Port system.


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Stainless Steel Mettler Balance Enclosure

Application: Powder Weighing and Dispensing with Getinge La Calhene Alpha-Beta Ports

 

This stainless steel enclosure is designed for powder dispensing applications for facilities performing powdered Highly Potent Active Pharmaceutical Ingredient (HPAPI) weighing and dispensing operations. Particularly, it was designed for operations conducted in facilities operating under the stipulations of current Good Manufacturing Practices (cGMPs). The working space allows operators to freely conduct the operation by weighing a large batch (100 grams or more) of powder, dispensing the powder into a container, sealing the container, and cleaning the enclosure after use. Additionally, two ball valve fittings (3/8” NPT) are located on the right side of the enclosure for connection to inert gas sources. This connection is advantageous for sample protection by facilitating dehumidification and deoxidization of the sample environment for powder substances with attributes incurring the need for inert gas (e.g. pyrophoric powders, hygroscopic powders, high reactivity with oxygen, etc.).

After filling the bag with powder, the operator has the capability of moving the bagged powder from the enclosure to another enclosure with protection from exposure during transport. This function is made possible through the usage of an integrated Alpha Getinge La Calhene Rapid Transfer Port (RTP) on the right side of the enclosure. The incorporation of the Alpha RTP facilitates safe transfer by allowing the attachment of a Beta RTP conjugate capsule to the Alpha RTP. Following attachment, the operator is able to transfer the desired amount of powder (or aqueous solution*) from the enclosure interior, through an opening created by the Alpha/Beta connection, and into a Beta RTP capsule. From here, both the Alpha and Beta conjugates are sealed and the Beta capsule is used as a transport vehicle to the other enclosure. Referring back to the previous paragraph, the enclosure also allows for the transfer process occur, in reverse, after the Beta capsule is transported to the next enclosure or RTP-compatible device.

When designing the enclosure, Flow Sciences also considered ease and efficiency of process flow. Thus, its interior layout accommodates space for 1-2 analytical balances as well as sufficient working space around each balance for safe and effective use during your operation. Specifically, the operator is provided with ample room to move their arms to weigh, removed weighed powder, and dispense the powder into the bag.

After Factory Acceptance Testing (FAT), the enclosure was proven to contain down to an 8-hour Time Weighted Average (TWA) concentration of 100 nanograms per cubic meter of air (ng/m3). The actual level of containment was proven to be 0.06 ng/m3.

The “Containment Target”, as depicted in the image above, is the respiratory exposure concentration specified by the customer. The “Surrogate Powder Testing Result” is the actual exposure concentration result from air samples taken during performance validation testing conducted by FSI. The surrogate “contaminant” sampled during the FAT was a powder substance with attributes similar to that of the actual contaminant.

When designing the enclosure, Flow Sciences also considered ease and efficiency of process flow. Thus, its interior layout accommodates space for the Hydro SV and the Mastersizer 3000. Specifically, the operator is provided with ample room to move their arms to fill the cuvette, insert the cuvette into the Mastersizer 3000, and perform analysis; all while retaining space for wiring connections.

*Note:If the Occupational Exposure Limit (OEL) or Occupational Exposure Band (OEB) for the pertinent HPAPI contaminant(s) are lower than 1 microgram per cubic meter of air (1 ug/m3), dissolution of the sample into an aqueous solution is an alternative method to reduce the risk of overexposure during RTP transport.

 

            Additional Information:

Click here for more information regarding Getinge La Calhene RTP Ports.


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Stainless Steel Malvern 3000 Enclosure

Application: Small Volume Liquid Dispersion Analysis with Getinge La Calhene Alpha-Beta Ports

 

This stainless steel enclosure was designed for small volume liquid dispersion/particle size distribution analysis methods involving Highly Potent Active Pharmaceutical Ingredients (HPAPIs). Particularly, it was designed for operations conducted in facilities operating under the stipulations of current Good Manufacturing Practices (cGMPs). The working space allows operators to freely fill the Hydro SV cuvette with the aliquot, insert the aliquot into a Malvern Pananalytical Hydro SV, and insert the Micro SV into a Malvern Pananalytical Mastersizer 3000 for liquid dispersion particle distribution analysis. Additionally, two ball valve fittings (3/8” NPT) are located on the right side of the enclosure for connection to inert gas sources for propulsion of the sample into the Mastersizer 3000 for analysis.

After the analysis is complete, the operator has the capability to transfer and transport analyzed product from the enclosure to another enclosure with protection from exposure during transport. This function is made possible through the usage of an integrated Alpha Getinge La Calhene Rapid Transfer Port (RTP) on the right side of the enclosure. The incorporation of the Alpha RTP facilitates safe transfer by allowing the attachment of a Beta RTP conjugate capsule to the Alpha RTP. Following attachment, the operator is able to transfer the desired amount of powder (or aqueous solution*) from the enclosure interior, through an opening created by the Alpha/Beta connection, and into a Beta RTP capsule. From here, both the Alpha and Beta conjugates are sealed and the Beta capsule is used as a transport vehicle to the other enclosure. Referring back to the previous paragraph, the enclosure also allows for the transfer process occur, in reverse, after the Beta capsule is transported to the next enclosure or RTP-compatible device.

After Factory Acceptance Testing (FAT) and surrogate powder exposure simulations, the enclosure was proven to contain to a Time Weighted Average (TWA) concentration below the customer’s specified parameter of 100 nanograms per cubic meter of air (ng/m3). The actual level of containment was proven to be 0.06 ng/m3.

The “Containment Target”, as depicted in the image above, is the respiratory exposure concentration specified by the customer. The “Surrogate Powder Testing Result” is the actual exposure concentration result from air samples taken during performance validation testing conducted by FSI. The surrogate “contaminant” sampled during the FAT was a powder substance with attributes similar to that of the actual contaminant.

When designing the enclosure, Flow Sciences also considered ease and efficiency of process flow. Thus, its interior layout accommodates space for the Hydro SV and the Mastersizer 3000. Specifically, the operator is provided with ample room to move their arms to fill the cuvette, insert the cuvette into the Mastersizer 3000, and perform analysis; all while retaining space for wiring connections.

 

*Note:If the Occupational Exposure Limit (OEL) or Occupational Exposure Band (OEB) for the pertinent HPAPI contaminant(s) are lower than 1 microgram per cubic meter of air (1 ug/m3), dissolution of the sample into an aqueous solution is an alternative method to reduce the risk of overexposure during RTP transport.

 

Additional Information:


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Stainless Steel FTIR Enclosure

Application: Fourier Transform Infrared (FTIR) analysis with Getinge La Calhene Alpha-Beta Ports

 

This stainless steel enclosure was designed for Fourier Transform Infrared (FTIR) Spectroscopy analysis methods involving Highly Potent Active Pharmaceutical Ingredients (HPAPIs). Particularly, it was designed for operations conducted in facilities operating under the stipulations of current Good Manufacturing Practices (cGMPs). The working space allows operators to freely load samples and accessories (such as those associated with the Thermo Fisher Nicolet spectrometer series) into the spectrometer. A ball valve fitting (3/8” NPT) is located on the left side of the enclosure for connection to an inert gas source for purposes such as sample column purging, deoxidization of sample column, etc. Additionally, there are two NEMA 4X-rated electrical receptacles located inside of the enclosure for connection to a power source and two iris ports (or “glands”) which facilitate data connections from the spectrometer to your computer.

After the analysis is complete, the operator has the capability to transfer and transport analyzed product from the enclosure to another enclosure with protection from exposure during transport. This function is made possible through the use of an integrated Alpha Getinge La Calhene Rapid Transfer Port (RTP) on the right side of the enclosure. The Alpha RTP facilitates safe transfer by allowing the attachment of a Beta RTP conjugate capsule to the Alpha RTP. Following attachment, the operator is able to transfer the desired amount of powder (or aqueous solution*) from the enclosure interior, through an opening created by the Alpha/Beta connection, and into a Beta RTP capsule. From here, both the Alpha and Beta conjugates are sealed and the Beta capsule is used as a transport vehicle to the other enclosure. Referring back to the previous paragraph, the enclosure also allows for the transfer process occur, in reverse, after the Beta capsule is transported to the next enclosure or RTP-compatible device.

After Factory Acceptance Testing (FAT) and surrogate powder exposure simulations, the enclosure was proven to contain to a Time Weighted Average (TWA) concentration below the customer’s specified parameter of 100 nanograms per cubic meter of air (ng/m3). The actual level of containment was proven to be 1.15 ng/m3.

The “Containment Target”, as depicted in the image above, is the respiratory exposure concentration specified by the customer. The “Surrogate Powder Testing Result” is the actual exposure concentration result from air samples taken during performance validation testing conducted by FSI. The surrogate “contaminant” sampled during the FAT was a powder substance with attributes similar to that of the actual contaminant.

 

*Note:If the Occupational Exposure Limit (OEL) or Occupational Exposure Band (OEB) for the pertinent HPAPI contaminant(s) are lower than 1 microgram per cubic meter of air (1 ug/m3), dissolution of the sample into an aqueous solution is an alternative method to reduce the risk of overexposure during RTP transport.

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  • What is being done inside of the enclosure? What type of material (powder, liquid, gas, nuisance odor) is being worked with? How does the material enter and exit the enclosure system? etc...
  • What type of filtration is required? Single HEPA, Dual HEPA, Carbon, House Exhaust, etc... What is the required OEL (Occupational Exposure Limit) for the process, or any other details about containment goals? What is the quantity of powder or liquid, task duration, composition of powder, etc...?
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Non-Sterile Hybrid Isolator

Abstract 

In 2011, Flow Sciences, Inc. was commissioned with providing an isolator for a large pharmaceutical company that was capable of protecting its employees by reducing their exposure below the occupational exposure level (OEL) of highly potent active pharmaceutical ingredients (APIs) in an isolator. Here we describe the unit designed and constructed and the in-house testing results. 

Background 

In the ongoing search for new therapeutic treatments, pharmaceutical companies are developing a new class of active ingredients known as High Performance Active Pharmaceutical Ingredients (HPAPI). As the name suggests, these compounds are highly potent and therefore it is critical that exposure to the pure material is minimal. More commonly associated with oncology drugs, an ‘explosion’ of HPAPIs is predicted over the next 5 years due to the high levels of research currently being conducted in this area. 

Clearly, with the advent of this phenomenon, containment of these compounds from the scientists tasked with working with them is of major concern. One reason for this is the high expense often associated with new equipment designed to handle the task. In order to combat these potentially high capital outlays, many companies are looking at alternative methods of containment, including modification of existing equipment. The Non-Sterile Hybrid Isolator, offered by Flow Sciences, Inc., is one such method of reducing the cost of containment (Figure 1). 

Figure 1. Non-Sterile Hybrid Isolator with bag in/bag out and main chamber. 

The isolator is designed to protect personnel from exposure to chemicals including HPAPIs by fully encompassing equipment used by scientists during processes such as weighing, crushing and bag in/bag out procedures. The isolator has been developed using Flow Sciences’ expertise in fluid dynamics and can be designed and manufactured to fit the customer’s needs. 

Case Study 

In 2011, Flow Sciences, Inc. was tasked by a major pharmaceutical company with the design, construction and installation of a non-sterile hybrid isolator for use by its employees during powder handling operations. The design of the isolator included a bag in/bag out (BIBO) annex and a main enclosure. 

After installation of the isolator, a third party industrial hygiene consulting company, IES engineers, was contracted to perform Site Acceptance Testing (SAT) and determine the effectiveness of the isolator. Using industry accepted testing methods; IES performed sampling of the air, surface and the testing area environment to evaluate the containment performance of the isolator using a surrogate powder (naproxen sodium) during typical operator procedures. The design containment performance target (CPT) for the VBE air samples was set at 75 nanograms of surrogate powder per cubic meter (ng/m3) of air. This value was chosen to provide an additional margin of safety compared to the OEL for an API of 150 ng/m3. Surface samples were collected and used for reference purposes. All of the containment verification testing activities were performed using industry accepted practices.1-3 

Procedure 

Prior to the containment verification assessment, the sampling strategy developed by IES was approved by the client and included typical and maximum use scenarios. The procedures, using naproxen sodium as an API surrogate, were: (1) reference standard development, comprising of: (a) dispensing approximately 500 mg of naproxen sodium into volumetric flasks; (b) development of a buffer capacity, which included dispensing of approximately 1 g of naproxen sodium into 50 mL water, followed by 5 minutes of mixing; (2) minor cleaning procedures of the VBE interior, including a wipe down of the floor surfaces and gloves with methanol and removal of equipment and materials used during the procedures. Each procedure was performed three times establish a greater level of confidence in the containment verification data. 

Airborne samples were collected from personal, source, and area locations. Personal samples were collected within the breathing zones of the operators. Source samples were collected at 200 mm from the potential emission source and area samples were collected at distances no closer than 1.5 m from the process or equipment and at a height of 1.5 m. These samples were then analyzed and exposures quantified. 

Baseline samples were collected for all locations prior to performing the operations. 

As can be seen from the table above, all samples collected for the various zones were well below the CPT of 75 ng/m3 air 3

Summary 

In summary, FlowSciences designed, constructed, and installed a non-sterile hybrid isolator for a large pharmaceutical company to limit exposure of employees to APIs during powder handling operations. Containment Verification Testing of the isolator, using a surrogate powder, was performed at the pharmaceutical company by IES, a third party industrial hygiene consulting company. The test results demonstrated that the isolator provided effective containment of powders to the CPT of 75 ng/m3 for the tasks performed. 

References 

1) American Society of Heating, Refrigerating and Air-Conditioning Engineers, “Method of Testing Performance of 

Laboratory Fume Hoods, ANSI/ASHRAE 110-1995” Atlanta, GA, 1995. 

2) International Society for Pharmaceutical Engineering, “ISPE Good Practice Guide: Assessing the Particulate 

Containment Performance of Pharmaceutical Equipment,” Second Edition, 2012. 

3) Section II: Sampling Measurements and Instruments of the OSHA Technical Manual 

 

Contributing Authors: 

• Steve Janz, Flow Sciences, Inc. 

• Allan Goodman, Ph.D., University of North Carolina, Wilmington; 

• George Petroka, Director BioPharma/EHS Services CIH, CSP, RBP, IES Engineers 

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