Skip to content

Vial and Syringe Filling in the BioTech and Pharmaceutical Industries

September 29, 2014

At Holland, one particular area of the biotechnology industry has becoming increasingly interesting to us is final product fill and finish. We’ve found that many of our core competencies have prepared us to help end users and equipment providers deal with the challenges associated with getting final drug product in a jar. As the pharmaceutical industry continues to evolve, increasing pressure is being been placed on filling machine providers by end users to focus on improving the flexibility, reliability, and efficiency of the filling process. This post will take a look at the most common types of pharmaceutical filling equipment and recent trends that are interesting to us.

Rotary Piston Pumps

While pharmaceutical companies are driving vendors towards single use, disposable dosing systems- systems where the entire fluid path is discarded- the most commonly used filling mechanism used today is still the rotary piston pump. Rotary piston filling machines use a matched set of piston and cylinder to dispense precise volumes of liquid. These machines are suitable for a wide range of viscosities, temperatures, and fill volumes. They work well with a variety of challenging products including shear sensitive or low surface tension products. While this has historically been the most popular type of filling machine, drawbacks include the need to disassemble and clean the machine after each use. CIP/SIP of piston pumps can be problematic and they are not offered with completely disposable flow paths.

Rolling Diaphragm Pumps

This type of filling machine is essentially a variant of a piston pump. These systems use a diaphragm to push and pull product in and out of the machine. While historically also stainless steel, recently technological breakthroughs, such as Dover’s Quattroflow quaternary diaphragm pump, have allowed for the use of polycarbonate pump heads and disposable needles, allowing for a fully consumable flow path.

Peristaltic Pump Systems

While originally used for fluid transfer, rather than high speed, accurate dosing, recent advance in servo-drive controls have given machine suppliers the ability to control the motion and position of the peristaltic pump rollers and have integrated feedback from the machines check weighing system. The key advantage to this technology is that it offers complete disposability, with almost no chance from product cross contamination. Limitations of this technology include limited viscosity range, tubing spallation, and somewhat low precision compared to other technologies.

Time/Pressure

These systems incorporate a pressurized product tank and pinch valves to open and close silicone tubing between the bulk tank and filling needle. In these systems, it is critical to control and monitor tank headspace pressure and overall system conditions. That being said, recent advances in the ability to control the aforementioned has allowed time/pressure systems to become just as accurate as pump systems in some cases. Other big pluses to time/pressure applications are very low shear and compatibility with CIP/SIP.

Drawbacks to time/pressure systems can include inaccuracies due to variation of vessel head space, no disposable flow paths, and an increased amount of time to tune in and start a fill for a process that can be affected by temperature or other factors affecting fluid flow properties.

Mass-Flow

The last type of machine we’ll touch on are mass-flow fill systems. These use mass as opposed to volume dispensing via the Coriolis effected. The Coriolis Effect occurs when fluid passes through a vibrating sensor tube. These tubes, which constitute a Coriolis meter will then communicate with a valve controlling discharge through the machines needles. Mass flow dispensing is the type we see least often, due to viscosity and accuracy limitations, with applications primarily limited to opthamalic product fills.

To conclude, substantial progress has been made toward improving the accuracy and control of the filling process. Increasingly robust technology has enabled rapid changed over and flexible lines that allow users to be responsive to changing customer demands. Holland is proud to offer both stainless and single use solutions, including needles, tanks, pumps, and manifolds (all in both stainless and disposable) to help our customers with their unique filling challenges. For more information about your next fill/finish application, contact a Holland Sales Engineer today.

EnviZion- ITT’s Newest Sanitary Diaphragm Valve

September 17, 2014

Exciting things are going on in the pharmaceutical process world. Holland has spent the last week in Lancaster, Pennsylvania learning all about the latest and greatest in diaphragm valve technology- ITT‘s new EnviZion hygienic valve platform. This breakthrough technology features an all new valve body, diaphragm technology, and tool-less top works that will set a new standard for critical process applications where excellent cleanability and seal ability are not just necessary, but essential. This post will focus on just a few highlights of the new valve platform and what these features mean to end users.

The ITT Pureflo Envizion Sanitary Diaphragm Valve

The ITT Pureflo Envizion Sanitary Diaphragm Valve

Let’s start by looking at the most striking new feature of the EnviZion sanitary valve- the radically new tool-less top works.  The bonnet for all EnviZion valves are mounted to the valve body with a simple twist and secured with a few turns of a locking cover.  The rest of the “tools” needed for assembly are all within the bonnet itself.   This simple assembly process also engages the most innovative feature of the EnviZion valve platform.  A thermal compensation system that ensures a 360 degree active seal at all times – even following SIP.

So what does this mean for end users? Well, first and foremost, it means the valve does not need to be retorqued following an SIP cycle. Let me repeat myself: NO MORE RETORQUING. What else does this mean? It means we’re going to eliminate a tremendous amount of downtime and almost eliminate the possibility of losing a batch of valuable product due to a valve leak because the Teflon diaphragm creeped. By minimizing downtime, we maximize uptime, effectively increasing the capacity of the system. This is key in the highly competitive BioPharmaceutical market where capital costs and building design need to be allocated as efficiently as possible. These two features- decreased chance of leakage and increased productivity- make the valves extremely economic when viewed from a total cost of ownership perspective.

What else does this tool-less bonnet design mean? I’ll give you a hint- it’s another “E” word- ergonomic. It means no more tools, nuts, or screws in classified product spaced. The EnviZion valve makes it quick and easy to change out diaphragms in hard to reach places. Changing diaphragms is in fact so quick and easy now that end users may be able to consider bringing diaphragm change out in house, instead of relying on outside contractors.

Continually, by eliminating tools, we eliminate the need for some of them in our clean room. Diaphragm valves are commonplace in clean rooms and other classified areas. By eliminating the need for torque wrenches and fasteners, we eliminate one more thing that can compromise the area- another big expense.

ITT Pure Flo Envizion Valve with a Pneumatic Actuator

ITT Pure Flo Envizion Valve with a Pneumatic Actuator

So this new technology is great, but what does it mean for existing processes? Fortunately, the EnviZion sanitary diaphragm valve platform uses BPE standard over all lengths, making retrofit and replacement of current problem valves a breeze. Overall, valve footprint of the EnviZion is very comparable to existing valves. The EnviZion platform is available now in sizes 1/2″-1″, with the 1.5″ and 2″ version coming online in the near future. All standard block bodies, including sterile access, GMP, zero dead leg, and ISG configurations are available. Both manual and pneumatic actuators are available, as well as industry standard automation and controls packages. The EnviZion platform will also utilize the same materials of construction, including the diaphragm materials, used in ITT’s current line of Pure-Flo valve, which should help ease compatibility and validation concerns.

To conclude, the new EnviZion sanitary diaphragm valve platform is an exciting, new technology that builds on the decades-old, tried-and-true diaphragm valve technology. With this valve, ITT is able to offer a product that expands on the success of it’s Pure-Flo product line and provide an innovative solution to common process headaches. The EnviZion valve gives users another tool to increase profitability and assure product purity. Aside from the top works, there are some other key features to the valve, including body and diaphragm design that will be the focus of future posts. For more information about the all-new EnviZion valve, contact a Holland Sales Engineer

Pharmaceutical Filling Needles: How to Reduce Dripping and Solve Other Common Problems

September 4, 2014

A tremendous amount of this blog has focused on how we can optimize a process to get a product to the final filling stage, but little of the information available to consumers today focuses on the specific challenges that can occur during the final fill process. Specifically, we’re referring to the lack of information available about filling needle design. Whether you’re filling a vial or a bottle, each product and application is unique. For many applications, a blunt needle tip will suffice. But for more challenging products, we may need to revisit the needle geometry. This post will highlight some common challenges during filling, needle tip geometries, and the problems they address.

To begin, why is needle tip geometry so important? Let us explain. In final fill applications, our goal is to fill both accurately and quickly. We also want to minimize product loss and ensure final product sterility and viability. In order to achieve these goals, we want to avoid foaming of product in the vial or dripping through the needle. Product characteristics such as density, polarity, and surface tension all greatly impact the ease of filling a product. Other products may not be compatible with steel or may be oxygen sensitive. Selecting the right tip geometry can be as much art as science, so let’s look at a few of these properties and needle tips styles we can use to make our lives easier.

Example of Blunt, Straight-End Tip Filling Needles

Example of Blunt, Straight-End Tip Filling Needles

Let’s start by looking at the most common needle geometry- the blunt, straight-end tip. Blunt needles are the “standard” needle type provided by most machine OEMs. The blunt needle will dispense liquid directly into the bottom of a container. Problems that are likely to occur with blunt tip needles can include dripping, foaming, and wicking- particularly with hydrophobic and low surface tension products.

One tip geometry we can use to combat this is the basket tip type needle. These are used in applications where foaming and dripping occur, usually because a blunt tip needle can’t support the fluid column (even when the tubing is properly occluded). A basket tip needle has a larger combined surface area for fluid to exit, reducing the flow rate, but better supporting the fluid column. The basket design directs fluid towards the sides of the container, allowing soapy or foamy products to cascade down the sides of the container like a waterfall without foaming or splashing.

Building on this design, a showerhead type needle will also help with foaming, dripping, and high density hydrophobic products. Showerhead needles are especially helpful with larger fill volumes and usually not feasible with smaller needles. Showerhead needles work by directing product flow in as many as six individual streams. In high volume fills, this greatly reduces the fill times of foamy or soapy products, allowing operators to run product pumps at full speed without issue.

While hydrophobic, oil based products tend to run through the needle head, some products will actually adhere or wick to the needle tip. To combat this, Teflon coated or even solid PEEK needles can be used. Teflon is known for being incredibly slick and won’t interact with a hydrophilic solution. An FEP coated needle effectively strips away extra liquid before it can accumulate in the needle head, throwing off fill volumes.

A final filling challenge we’d like to highlight is metal sensitive products. Specifically, halogen based and high salt content products. Halogens are notorious for attacking and destroying even passivated stainless steel. This is a problem for obvious reasons. To combat this, a variety of halogen resistant coatings can be used to product the steel needle stock. By eliminating halogen related corrosion, we maximize needle life and mitigate corrosion associated risk.

To conclude, final fill and finish is often as much of an art as it is a science. While there is plenty of information available about all of the steps leading up to the needle, very little attention has been paid to optimizing the filling needle design itself. If you have questions about your pharmaceutical filling needle, contact a Holland Sales Engineer today.

The Effect of Slip on Sanitary Pump Performance

August 26, 2014

This post will touch on a topic we’ve discussed a few times in the past- the low slip design the Waukesha Universal series of sanitary positive displacement pumps. Previous posts have talked about how the external circumferential piston design of the Waukesha Universal series makes it nearly perfectly positive and efficient at viscosities over about 250 cps, but why is this important? Outside of efficiency, the low slip design of the Universal series pump allows us to accomplish four useful things- it allows us to pump low viscosity fluids in low NIPA systems, it allows us to pump from vacuum vessels, self-prime, and meter fluids. This post will look at each of these four benefits and why they are important to system performance.

Waukesha Univeral Pumps can be Run at Slow Speeds, Minimizing Shear

Waukesha’s Unique ECP Rotor is More Efficient than Lobe or Bi-wing Designs, Resulting in Less Slip

To begin, the low slip design of the Waukesha Universal series of pumps allows us to efficiently pump low viscosity fluids when net inlet pressure available (NIPA) is also low. When pumping low viscosity fluids in low NIPA systems, slip can greatly reduce pump capacity and increase energy requirements. At low pump speeds this generally isn’t an issue, but if pressure differential across the pump causes excessive slip, little or no flow may result. At higher speeds, internal pump losses may be high enough to limit flow. In a high slip, low efficiency pump design, high velocities of fluids within the chamber can create localized areas of low pressure. If this pressure drops below the vapor pressure of the fluid being pumped, flashing can occur and vapor will fill the pump cavities, destroying the ability to sustain uniform flow.

The next thing the low slip design of Waukesha pumps allows us to do is pump out of a vacuum vessel. Pumping from a vacuum vessel is an example of an extremely low inlet pressure system. Vacuum chambers are typically used to evaporate fluids to hold and process liquids at extremely low temperature. This means we’re going to be operating at or near the fluids vapor pressure in these applications. Because of this, we need to use a pump that is as efficient as possible to allow us to run the pump as slowly as possible. High speeds will create an area of low pressure at the inlet of the pump which can lead to flashing and cavitation, crushing system efficiency and greatly reducing pump life.

As we’ve talked about in previous posts, the clearances in Waukesha pumps are so tight that at higher speeds the pump can even move air. What that means is that the pump can be used to dry prime or actually evacuate the air in the inlet line, reducing pressure, and drawing fluid up the line and into the pump chamber where normal pumping can begin. While not suggested, Waukesha PD pumps can run dry long enough to draw fluid into the pump chamber and begin standard processing. Care should always be taken to ensure the maximum available pressure at the inlet of the pump. Contact a Holland sales engineer for help determining the amount of lift your Waukesha pump can generate.

A low slip Waukesha pump can also be used to meter fluids. If the slip is low, a pump will deliver nearly its theoretical displacement in each revolution. By counting or controlling the revolutions per minute of the pump, we can measure the amount of liquid displaced. In any metering application, it’s important to operate in the metering range of the pump- i.e. the range at which the relationship between change in speed and displacement is linear. System conditions should also be kept constant. We want to maintain constant suction head and minimize the pressure differential across the pump. By coupling this with the efficient design of a Waukesha Universal pump, we can reduce the effect of slip and meter effectively.

To conclude, the low slip design of Waukesha Sanitary PD pumps has further reaching implications than just increasing system efficiency. The low slip design of the Waukesha Universal series of pumps allows us to pump low viscosity fluids with low inlet pressures, it allows us to pump out of vacuum vessels, it allows us to dry prime, and it allows us to meter. If you have more questions about your next Waukesha pump application, contact a Holland Sales Engineer today.

What is a Sanitary Surface Finish?

August 13, 2014

This blog was created to answer common questions about sanitary and high purity process equipment. One question we ask customers every day is, “What surface finish do you require?”. Many of our customers know what they use or what they need, but few understand what an Ra, grit, or micron rating means in terms of surface finish. Not knowing what you need can lead to unnecessarily expensive fittings with extended lead times. This post will focus on what a sanitary surface finish is and specifically the relationship between Ra, micron, and grit.

A profilometer is an instrument that measures the actual metal surface by dragging a stylus across the metal a predetermined length, measuring the distance between the peaks and valleys of the surface.

A profilometer is an instrument that measures the actual metal surface by dragging a stylus across the metal a predetermined length, measuring the distance between the peaks and valleys of the surface.

To begin, when we say “surface finish” what we really mean is surface “roughness”. Surface roughness is a component of a surfaces overall texture. The most common measure of this roughness is a measurement known as the arithmetic roughness mean, or Ra. The Ra value of a surface reflects the average height or irregularities on a surface from a mean line. Think of this as the measurement of the heights of peaks and valleys along a line. The lower the Ra, the smoother the surface.  These values can be measured using a profilometer.  It moved a stylus across the surface of the metal and records the differences between the peaks and valleys.

Most commonly measured in microninches, Ra provides a simple value for us to make accept/reject decisions. We measure the Ra of a sanitary surface with a profilometer. Traditional profilometers use a diamond stylus that is moved along a surface for a specified distance with a specified contact force. This allows the profilometer to measure small surface variations across the sample.

A corollary to the micro inch is the micron. One micron is equivalent to about 39.37 micro inches. Ra values in both micron and micro inch are interchangeable as they both reflect the arithmetic mean of the average centerline deviations of a surface.

One thing that is not necessarily equivalent to Ra? Grit. Grit is a measure of abrasive grains per given area. The specification of a grit reference does not necessarily equate to a consistent surface finish. A specific grit is used by a mechanical polisher to achieve a desired Ra. In order to achieve that finish, the right tool needs to be chosen and utilized properly. Selecting and using the right tool is much more an art than a science and is a skill that takes years of practice to acquire- that’s why Johnny Polish gets paid the big bucks.

So why is surface finish important? Smooth, crevice and pit free surfaces, i.e. ones with low Ra readings, are essential to ensure there are not entrapment areas where product can build up and grow nasty things. Entrapment areas can be difficult to clean, allowing bacteria to accumulate. This is obviously undesirable in high purity applications.

Historically, 32 Ra has been the standard sanitary surface finish for the high purity industry. With the advent of stricter regulation of the pharmaceutical and biologics markets, and subsequently process components, increasingly smoother surfaces are being required. Now, process equipment used in a pharmaceutical application will generally need to comply with ASME BPE standards that dictate a maximum surface roughness of 20 Ra or better, depending on the application.

Standard Grit (Reference Only) Ra (uin) Ra (um) Common Name
60 985 6.3 Mill Finish
180 32 0.8 Sanitary Finish
220 20 0.51 Pharma/Biotec Finish
320 10 0.25 Ultra High Purity

Hopefully this post serves as a good refresh on what a sanitary surface finish is. If you don’t want to read all of my typos, check out the table below for an overview or contact a Holland Sales Engineer today about any of your sanitary process component questions.

How to Size a PD Pump for a Range of Viscosities

August 7, 2014
Waukesha Universal 2 Pump Side Mounted on a Stainless Steel Frame, with Motor, Gear Reducer and a Variable Frequency Drive

Waukesha Universal 2 Pump Side Mounted on a Stainless Steel Frame, with Motor, Gear Reducer and a Variable Frequency Drive

At Holland, we size pumps for sanitary applications every day. We also work with many customers who are having issues with pumps someone else sized for them. This experience has made us well aware of many common oversights made when selecting a rotary positive displacement pump. One of the most common errors made when sizing an ECP pump, such as the Waukesha Universal 1 or Universal 2 series pump, is failing to take into consideration the range of product viscosities the pump will handle. This post will focus on that issue and what steps we can take to ensure adequate drive speed range is selected to handle a variety of products.

To begin, a sanitary process system may require that the same pump handle both viscous and thin products. A simple example could be a shampoo process- imagine a facility wants to transfer shampoo from one tank to another and then follow the transfer with a system water flush. An excellent pump for this application is the Waukesha External Circumferential Piston pump. The Universal 1 and Universal 2 pump, utilizing Waukesha Alloy 88 rotors, have long slip paths compared to other PD pump types, allowing them to handle both thick and thin fluids. Initial pump selection, however, must consider the RPM required for both thick and thin products.

Why do we need to consider both products? As products become thinner, or less viscous, the fluid tends to “slip” back through the pump. While the U1 and U2 series pumps are nearly perfectly efficient with fluids over 300 cps, some “slip” does occur with thin fluids. This “slip” must be compensated for with additional motor RPM. Optional pump features, such as front face or hot clearance rotors and CIP features only exacerbate this problem. Other challenges, such as high pressure conditions that also increase slip should also be considered.

Additionally, pump condition and wear should be considered as well. The tolerances on brand new pumps tend to be much tighter than used pumps. This wear opens clearances and increases slip, decreasing displacement capacity. We will need to increase pump speed to compensate for this.

To avoid these issues, it is critical to ensure we are able provide enough speed for the low viscosity product and enough torque for the high viscosity products. PD pumps are driven by motors coupled to gear reduction units. A gear motor uses a series of gears to increase torque, resulting in decreased shaft speed. We want to avoid using a drive that is “maxed” out when running the thick product and can’t spin fast enough to move our thin product. If we don’t have a large enough gear reduction, however, we will be unable to generate the torque to move the high viscosity product.

So how do we solve this problem? It’s actually not that difficult. First, we size a pump and motor that will spin faster enough to move the high slip product. Then we check that the torque the higher speed motor can generate against the torque required to move the high viscosity product. Finally, we’ll utilize a variable frequency drive and a motor with at least 10:1 constant torque turndown (we need to avoid motor slip as well), which will allow us to effectively adjust speed of the pump to handle the complete range of product viscosities and displacement requirements. Finally, an over speed safety factor will should be considered to compensate for pump wear over time.

To recap, when sizing a sanitary pump for multiple products, it is critical to take into account the viscosities of all products the pump will hand. At Holland, we use our over 60 years of experience sizing sanitary pumps to dictate how much speed compensation is required for a given set of conditions. For help with your next sanitary pump application, contact a Holland Sales Engineer today.

Waukesha Single Seat Valves- An Overview of an Industry Leader

August 6, 2014
Picture of a Waukesha W60 Series Valve Manifold We Fabricated in our Shop

A Waukesha W60 Series Valve Manifold We Fabricated in our Shop

Throughout the past 10 months, we’ve dedicated many posts and countless hours to conveying the advantages the Waukesha Universal series of positive displacement pumps have over other brands in the hygienic market. Today’s post will focus on another best in class product offered by Waukesha Cherry Burrell- the W60/80 line of seat valves and 5 specific benefits they offer over the competition.

First and foremost, all Waukesha valves are designed specifically for the sanitary and high purity market. Waukesha valves are cleanable, featuring 316L wetted parts, minimal cracks and crevices, free draining in multiple positions are 3A and FDA compliant, as well as EHDGE tested. They have options for surface finish upgrades (all the way to 15 Ra w/ EP), as well as a variety of stem seals and seat options to allow for optimal performance in applications with particulate that can challenge valve cleaning. MTRs are also an available option.

The next staple of Waukesha seat valves are heavy duty construction. All bodies are machined from bar with thick walls and laser welded ports. Valve stems are ¾” of an inch and feature multiple bearing support. This rugged design allows Waukesha valves to perform at pressures up to 1220 psi through the use of heavy duty clamps and high pressure adapters.

Waukesha valves are also flexible and have a modular design. The WCB valve line offers a variety of body and port orientations to match up with sometime complicated piping designs. Bodies are usually one piece or two piece clamped. The standard body MOC is 316L, but AL6XN is all available for application with extremely corrosive products. Custom port lengths and center to center bodies are also available to allow drop in replacement of legacy series valves such as Tri-Clover and Sudmo valves.

Continually, the major valve components- the body, stem, adapter, and actuators- are modular in design and all for quick and easy assembly and maintenance. There are a variety of actuators compatible with all Waukesha W60 valves, ranging from fully maintainable to maintenance free actuators. A complete line of control tops is offered as well, including the low cost APV CU4 and the industry leading Burkert 8681- see one of our previous post for more information relating to the Waukesha control top offerings.

All of these benefits- hygienic design, robust construction, and modularity and flexibility- endow all Waukesha seat valve with an exceptionally low total cost of ownership. Their heavy duty design maximizes service life. Waukesha’s extensive distribution network allows for regular preventive maintenance and immediate end user support, while part commonality reduces stocking requirements. The valves modular design results in several multi-use parts and easy training for new operators, again minimizing spare part stocking requirements.

Finally, all Waukesha seat valves are manufactured and supported domestically. Waukesha seat valves are made in Delevan, Wisconsin. They’re so close to us at Holland Applied that we pick up our orders at the factory twice a week. This proximity has allowed Holland and SPX to build a value-added distributor relationship through face-to-face representation and training. At Holland, we are able turn around most spare parts orders in 24-48 hours as well as perform on-site repairs and maintenance. This cohesive relationship between manufacturer and distributor goes a long way to minimizing total cost of ownership for the end user.

So for your next seat valve application, we strongly encourage you to consider Waukesha. At Holland, we can work with you to identify and size the right valve technology and specifications for your application- we do this every day. Contact a Holland Sales Engineer today for more information.

Follow

Get every new post delivered to your Inbox.

Join 183 other followers