Application Articles

The Value and Importance of Testing

The primary mission of Flow Sciences is to contain hazardous materials. We maintain a laboratory for containment performance verification, relevant standard testing, and product development. 
We test every unique enclosure that is manufactured for reliable performance. 

Merck has chosen many times with us to verify containment performance further through surrogate powder testing.  Recently we have hosted Merck at our facility to complete surrogate powder containment validation on an Analytical Process Isolator, as well as a blending and dispensing containment system.

Once a final design has been decided upon, the unit is manufactured and the containment performance of the engineering control is verified and validated to the essential standards.

It is sometimes desirable/necessary to perform surrogate powder testing to further evaluate enclosure performance using simulated operations. This includes an imitation of the application in our laboratory at FSI headquarters in Southeast North Carolina.

Often, we have customers and third-party Industrial Hygienists come to the facility and mimic the task they will be completing in their lab.  This allows for the actual end users and operators to perform the SOP and test for things like ergonomics and workflow.

If you dispensing highly potent and toxic powders into a charge bag for example, you may want to practice a few times to make sure you’re successful and safe.  This is where FATs (Factory Acceptance Testing), SPT (Surrogate Powder Testing), and SCP (Safety and Containment Program) planning are so critical to improving your odds of success.

We have been fortunate enough over the years to make great connections with industrial hygiene companies around the world that partner with us to perform SAT or FAT.  Companies such as ISS, IES, Safebridge, and others often monitor the testing or run their own samples for third-party validation.

Testing aside, at FSI we also aide in the development of good lab practices and proper SOP during the application.  Moreover, we can provide cleaning protocols to guide decontamination and proper cleaning to prevent containment breaches and cross contamination.

The standard testing, however, can be seen in the graphic below.

ASHRAE 110-2016 compliance testing is the standard for most fume hoods and powder containment enclosures. If the CPT (containment performance target) is below the limit of detection of the ASHRAE test, more testing is needed for accurate containment data.

In ASHRAE 110-2016, the hood will pass at anything below .05 ppm, or 292 μg/m3. If the required OEL (Occupational Exposure Limit) is .1 μg/m3 or 100 ng/m3, that is much lower than the acceptable pass exposure for ASHRAE 110-2016. You can see in the graphic below, surrogate powder testing is needed below the ASHRAE limit of 292,000 nanograms.

Engineering controls are only one part of a comprehensive strategy for containment. A surrogate powder FAT and SAT, that includes Good Lab Practices and SOPs, defines how the end user will interact with the process. This provides for the most reliable indication of expected performance. Compliance with solid SOPs and training combined with an ongoing sampling plan can help sustain consistent containment results.

We look forward to working with you to not only design a containment solution, but also ensure that it will contain the entire process and train operators on how to properly use the engineering control to mitigate exposure and ensure process integrity.


Containment Liability: Choosing Assurance or Insurance

How Top Pharma Companies Evaluate Industry Trends and the Human Element in Containment

ABSTRACT

Engineering controls designed to mitigate exposure and create separation between the operator and the toxic material are available in many different forms, all with their own unique advantages and risks.  This article will look into various forms of containment while asking the question, is your liability assured or insured?

ASSURANCE VS INSURANCE

Assurance is defined as a positive declaration intended to give confidence— a promise.  We know that nothing is guaranteed in this industry due to the variables involved, but assurance can be provided based on known factors and containment is provided to the level of current risk.  On the other hand, insurance is defined as a thing providing protection against a possible eventuality.  That is an interesting term, a possible eventuality, as it is an oxymoron.  The difference in these terms is the timeline and scope: assurance is limited to known factors in the present, and insurance is both known and unknown moving forward. 

In the world of increased potency and operator risk, how can you trust that what will protect you in the present will protect you in the future?  Is assurance enough, or is insurance required?

EFFECTIVE CONTROLS?

Besides the industry trend towards increased toxicity, the most threatening risk to containment performance is the operators themselves and their ability to follow GLP (good lab practices) and their given SOP (standard operating procedures).  In this case, assurance is simply not enough protection “against a possible eventuality.”

NIOSH’s Hierarchy of Controls prioritizes the most and least effective ways of providing safety.  The engineering control is the most effective option when substitution or elimination is not possible.  This engineering control is an isolation between the operator and the hazard— in our case, containment systems such as gloveboxes or vented hoods from Flow Sciences, Inc.  Decreasing in effectiveness following engineering controls are administrative controls (the way people work) and finally PPE (personnel protective equipment such as coveralls, face masks, etc.…)

What is interesting is that an inanimate barrier is supposedly more effective than the way a capably minded operator performs their work.  Think about that for a minute, and really reflect on what NIOSH is saying.  The human element is unpredictable, that a barrier is more effective at keeping them safe than their own operating procedures and decisions.  The assumed risk of the human element is so evident, it is almost offensive to most sound and intelligent human beings.  One would think that the operator would be more capable of making a decision to protect themselves than an inanimate barrier, right?  NIOSH says not.

THE HUMAN ELEMENT

In most cases, the human element is celebrated as an advantage to a situation heeding the abilities of humans that machines or equipment cannot provide.  In this case, rather, it is viewed with a mostly negative connotation.  In lab safety and containment, the human element is a risk that outweighs that of engineering controls and poses a significant dilemma to safety programs.

However, the human element is still important to maintaining an effective containment program.  Without operators, the work would not be completed, so training and ease of use for these operators is crucial.  As a manufacturer and designer of engineering controls, our responsibility is to provide training and instruction on how to properly use the equipment, but it is ultimately up to the end user to perform their activities to the standards set forth by the safety program.

THE MOST EFFECTIVE SOLUTION

According to NIOSH and the discussions above, the most effective solution is to increase the containment engineering controls to a level beyond the risks of increased toxicity and the human element.  The decision between assurance and insurance is as simple as this: should I contain to the minimum of the known factors, or should I anticipate the risks and contain above?

In the chart below, we can see that in typical logic, risk hazard and containment increase linearly for any application where containment is required.  This thinking is common, but the top companies in the pharma and biopharma industries are looking at it differently.

These industries see that the key to growth and scalability is insurance.  Not only does this provide protection from potential liability concerns, but it also gives the ability to increase toxicity over time while still protecting their personnel or product.

FINDING CONTAINMENT INSURANCE

Now that we understand the importance, let’s discuss the options.  Many systems promote assurance and adequate performance based on the task at hand, but after evaluation these systems do not stand up to the added pressures of the human element, and certainly give no room to increase potency.

In the world today, there are premiere brands that deliver quality product at a price that is above those of lesser quality.  We accept this to be true in many cases such as Apple with phones and Porsche with cars.  The reason they are of higher quality is because the components and engineering involved costs more than inferior parts and rudimentary engineering.  I understand there are outliers, but conventional wisdom tells us that you get what you pay for. While other manufacturers try to minimize manufacturing costs, Flow Sciences has always maintained the goal of maximizing containment performance.

The industry has provided many forms of engineering controls for personnel production that are effective.  Respirator programs work well in some situations, but their protection relies heavily on the human element for proper operation and fitting, and PPE programs are also quite expensive programs to maintain.  “Soft wall” containment has grown in popularity for its low cost and flexibility, but again, the design is subjective to the human element and can easily be misused or damaged during an application.  “Rigid wall” systems are more expensive than soft wall but provide a strong and solid barrier between the operator and the hazard.  The industry speaks of the price of rigid wall quite a bit in comparison to soft wall due to the single use aspect, but from an investment standpoint, the cost of a rigid containment system is less over time if, and only if, the system is purchased for insurance, and not assurance.

FLOW SCIENCES, AN INSURANCE PHILOSOPHY

At Flow Sciences, we have many potential customers ask why we are more expensive in some situations than competitors.  The answer is simple, and those that understand choose to protect their personnel and product with Flow Sciences containment systems.  At Flow Sciences, you get what you pay for, and more.  FSI engineers and manufactures containment systems that perform above and beyond the CPT (containment performance target) to provide safety, but moreover, containment insurance.

Many top pharma clients prioritize the effectiveness of their engineering controls by purchasing systems like Hybrid Isolators and Glovebox Workstations that provide a rigid physical barrier between the operator and the hazard.  This mitigates and controls the human element even further, as well as giving room to increase potency in the future without having to replace their equipment when that time comes.  Being flexible and having that option makes clients adaptable to the market and gives them the highest chance of success in a competitive and time-sensitive industry.

The design and engineering involved in these units have been prioritized to provide containment insurance and flexibility in a marketplace that so badly needs it.  Pairing these systems with other containment technologies such as rapid transfer ports and powder transfer valves gives a complete solution for highly potent applications and processes. Click on the above units from Flow Sciences’ newly launched standard product line of Hybrid Isolators and Glovebox Workstations to see specific features and benefits or reach out today to discuss your application and view the hundreds of task specific systems Flow Sciences has engineered.  Our containment engineers are available for no-cost consultations to make sure that your engineering control will be the most effective system available, and moreover, provide the containment insurance that you need.


Glovebox Workstation with RTP

Safely Containing Cytotoxic Compounds Throughout a Weigh and Dispense Process

Integrating a DPTE® transfer system to the Flow Sciences, Inc. Glovebox Workstation

Allan Goodman, Ph.D., Lab Manager;
Stephen Janz, VP International Sales & Business Development


Glovebox Workstation with RTP

Background

A client’s containment application required a method to provide containment of highly cytotoxic compounds throughout a process of weighing, dispensing and sample transport. A Flow Sciences Glovebox Workstation enclosure would provide process containment, however effective sample transport containment between laboratory locations was needed.

 

The Challenge

The client needed an “interim containment” solution for the process which involved powders classified as Highly Potent Active Pharmaceutical Ingredients (HPAPI). This required a leak free interface between the Glovebox Workstation and the containment device which would be utilized for sample transport between two enclosure locations. Client safety policy stipulated that the operator’s respiratory exposure concentration, or Occupational Exposure Limit (OEL) expressed as an 8-hour Time Weighted Average(TWA), would be less than 500 nanograms per cubic meter air (<500 ng/m3). Some clients express this as a Containment Performance Target (CPT) for the enclosure or process of <500 ng/m3 per 8 Hour TWA.

 

The Solution

Flow Sciences designed the enclosure utilizing a Getinge DPTE® Alpha Rapid Transfer Port (RTP) to enable contained sample transport. This solution built upon Getinge DPTE® Beta Containers (DPTE® PE Container) already in use at the facility. The Beta containers were being used for safe leak-tight transfer of cytotoxic products from one contained work area to another. To maximize the functionality of existing, validated re- sources, the Flow Sciences enclosure used a Getinge DPTE® Alpha port fit with the DPTE® Beta containers.

The negative-pressure enclosure provided personnel and product protection through HEPA Filtration and four (4) 10” oval glove ports on the front of the unit. Specifically, “personnel protection” entails employee protection from respiratory or dermal exposure. The Glovebox Workstation is a ‘closed’ system comprised of a polypropylene superstructure, integrated gloves and HEPA filtered air into and out of the enclosure. The 99.99% efficient inlet HEPA filter combined with the bag-in/bag-out dual HEPA exhaust fan-filter unit allows smooth airflow into and through the enclosure, while providing an interior cleanliness level of ISO Class 5 or better.

 

The Solution in Action

After product is weighed, it is containerized for transport. An inherent exposure hazard still exists in the event of a catastrophic spill event during transport. Secondary containment during product transport is provided by the DPTE® Beta containers, thereby serving as an engineering control for this hazard.

By incorporating a DPTE® Alpha port on the side of the enclosure, the process is enabled to securely transfer weighed, containerized HPAPI product directly into the Beta Container by performing the following steps in chronological order:









The Result

The Flow Sciences Glovebox Workstation contains toxic powder substances and the operations that involve them, to levels well below the Occupational Exposure Limit (OEL) stipulated by the customer (<500 ng/m3). Exposure risk during transfer and transport of the product between different locations was controlled by the leak-tight DPTE® container system integrated into the client’s weigh, dispense and sample transport process.

Ray Ryan, President and CEO 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 that industry need”.

This case study serves as an example of a project where Flow Sciences used a recognized transport solution in conjunction with our proven containment systems to fit the specific needs of the client.


Contact Us for More Information

  • 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?

    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.


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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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              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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              • 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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                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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                    • 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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                      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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                      • 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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                        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:


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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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                          • 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...
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                          • 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
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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.

                            Additional Information:


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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...
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                            • 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?

                              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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