Throughout this blog, we’ve highlighted and hit on the corners of every niche in the high purity market. As we’ve hopefully shown, today’s market demand for new, safer, more effective, and cheaper drugs is continually driving process engineers to innovate and develop new ways to make process more flexible, reliable, and robust.
One of the groups pushing the boundaries of conventional high purity processing the furthest are the single-use equipment providers. Innovative single use technologies provide engineers greater flexibility by replacing conventional hard piped systems. The benefits of single-use technologies have been discussed in several of our previous posts. Today’s product-centric post will focus on the Aseptiquik family of sterile connectors and what product offerings are available.
To begin, let’s take a look at the connector that started it all- the original Aseptiquick connector. This gendered fitting creates a sterile flow path through an intuitive three step “click-pull-twist” design. The Aseptiquik’s robust design (including integral lock ring) provides reliable performance and eliminates the need for tube welders or bulky pre-manufactured assemblies. The Aseptiquick connector is made from USP Class VI ADCF Polycarbonate (w/ class VI silicone O Ring) and can be both gamma irradiated (50 kGy) and autoclaved (130 C for 30 minutes). The Aseptiquik connector is available with 3/8” and ½” barbed terminations as well as 3/4” sanitary TC ends.
Now you may be thinking, “Well, what if my flow path is smaller or larger than ½” or 3/8 and I really don’t like having to match up male and female connectors? Then what do I do?”. Those are the challenges the next three products in the Aseptiquick line will address.
So what if you need to make a sterile connection on your thick walled, ¾” tubing that won’t fit in your tubing welder? Well, then you go with the Aseptiquik X brand of sterile connectors. Available in ¾” and 1” hose barb, as well as 1.5” tri clamp flanges, the Aseptiquik X is ideal for high flow applications. Featuring a “Twist-pull-twist” design, the Aseptiquik X’s integral lock rings allow it for use in applications with up to 60 PSI of process pressure. Again featuring similar MOC’s as the Aseptiquik and Aseptiquik S products, the Aseptiquik X can be both autoclaved and gamma irradiated.
So how do you take the best family of sterile connectors on the market and make it even better? You make it genderless. Rounding out the Aseptiquik product line is the Aseptiquik G line of sterile connectors. Available in ¼”-3/4” barbed and ¾” sanitary terminations, the Aseptiquik G simplifies use by eliminating the need to pair gendered parts. This means the guy selling you your single use bioreactor does not need to coordinate with the guy selling you your single use filling assembly to make sure they are supplying the right gender fitting. This also means fewer components that you need to stock in house. The simple “flip-click-pull” design is quickly making a name for itself as an industry leader, offering a full range of flow solutions with the same quality and market availability the Colder name has become synonymous with.
And finally, what do you do if you need to make a sterile connection outside of a laminar flow hood with a line size smaller than three eighths? Well, you could buy a $20,000 tube welder, which doesn’t always work great on those small fluid paths, or you could use the Aseptiquik S connector. Designed for 1/8”, ¼”, and 3/8” flow paths, the Aseptiquik S is a genderless sterile connector designed specifically for small line applications. Featuring an intuitive “flip-click-pull” design, the Aseptiquik S expands on the proven advantages of the standard Aseptiquik. Available with both barb, sanitary clamp, and MPC terminations, the Aseptiquik S is made from the same materials as the standard Aseptiquik connectors enabling the same robust process performance.
To conclude, there are many ways by which drug manufacturers can create a sterile connection. The right selection depends on the needs and preferences of each facility. Colder has created a robust product portfolio to help address the need for intuitive, simple, and cost effective sterile connections. For more information about Colder’s Aseptiquik product family, contact a Holland Sales Engineer today.
Today is a big day for us at Holland Applied. Today we publish our 200th blog post. To commemorate all of the hard work over a dozen different employees have contributed, today’s post will take a look back at all the work we’ve done on this blog, what we want to continue to do with this blog, and our plans for the future.
When we started this blog way back in 2009, our goal was to use the blog to share some of the high purity processing knowledge we’d accumulated over the 50 years we’ve been in the industries. We also wanted to use the blog to solicit new ideas and get feedback on some of the issues in our industry.
As we started writing blogs, we found out it wasn’t quite as easy as it sounded. Writing a blog is a serious time commitment and we found ourselves focusing on products, not the problems these products were created to solve. This made posts dry and boring, and ultimately didn’t bear much benefit for our readers to reap. At one point, we were even subcontracting our blogs as part of a larger marketing program. Look closely at our posts and you should be able to pick out prettily easily which are written by industry experts and which are not.
So after floundering for a few years, and with renewed vigor and enthusiasm, we re-launched our blog about a year ago. This time around, our aim was quite different. Inspired by a few other well-known inbound marketing success stories, we re-launched our blog with the goal of addressing common problems our customers inquire about every day.
We didn’t want the blog to be about products. We wanted it to be about problems. By focusing on the problem and challenges encountered every day in the sanitary process world, we knew we could help people understand where our products fit and how best to use them.
Continually, as we began compiling posts, we quickly started to realize something- we offer a huge swath of products and each Holland employee has their own particular area of expertise. There is no “Sanitary Process 101” textbook. And as we began adding new employees (and bringing current ones up to speed on industry trends), we quickly found out what a great internal resource our digital marketing efforts could be. And not only were the blogs helpful to our customers and staff who read them, but creating the content for the posts also help the authors develop and strengthen their own personal knowledge base.
The response we’ve gotten has been overwhelming. In just a few months, we’ve gone from 30-50 views of our blog per day, to over 250 each weekday. We set another record in June with over 5000 blog views and are on pace to go over 6000 views this month, in spite of the holiday and hectic vacation schedules. We get phone calls every day from customers who found us through our blog or website. Our employees cannot go to a trade show or distributor school without another distributor or vendor saying they saw our blog and used it to help a customer in a specific application.
Going forward, we plan to double-down on this strategy. By helping customers understand the challenges of a rapidly evolving market, we can enable them to effectively solve their process problems. We think we’ll benefit from that by branding ourselves as thought leaders in our industry. Additionally, we plan on refining some of our blog posts and will soon start a monthly newsletter expounding on a few of these topics as well as addressing other industry news. So hopefully you’ve enjoyed reading the first 200 blogs posts as much as we’ve enjoyed writing them. Stay tuned from the exciting things to come.
One of the most common questions we get day in and day out is related to sanitary gasket material choices in some form or another. Every day we will have a customer call in and say, “Can I get price and availability of 25ea 1 1/2” gaskets”?”. Our customer service team, well-trained as they are, patiently ask, “Well what material would you like?”. Their response many times is silence and generally doesn’t exude confidence. If technically savvy users don’t always know why they use a specific gasket material, that’s just what they’ve always done. This post will give an overview of the most common sanitary gasket materials and the pros and cons of each material.
Nitrile Buna Rubber (U) – Buna rubber is by far the most common and economic food grade gasket material. Designated by a red dot, Buna is only recommended to intermittent temperatures of 240 F and continuous temperatures of 210 F. Most Buna rubbers do not carry Class VI compliance. While inexpensive, applications for Buna abound. They are great from use on ambient or potable water lines, and have good chemical compatibility with most moderately aggressive chemicals.
Fluoroelaster (FKM) – Also known as Viton, there are many different formulations and classes of Viton. Featuring yellow and white dots, FKM is an excellent choice in both CIP and SIP applications. While they aren’t as well suited for ultra-aggressive chemical applications, FKM handles oils, alcohols, acids, and alkalis with ease. Most are USP Class VI compliant and have max intermittent and continuous temperature s 410 F and 380 F respectively.
Platinum Cured Silicone (PX) – A favorite among pharmaceutical users, platinum cured silicone gaskets also exhibit silicone’s trademark low extractables and leachables profile. Platinum cured silicone gaskets have excellent high temperature properties. With chemical resistance to a variety of common chemicals, including acids, bases, and steam, the primary drawback is cost- likely the reason we see these primarily used in only ultra-high purity applications.
Ethylene-Propylene Diene Monomer (EPDM) – Along with FKM, EPDM is among the most commonly used elastomers for sanitary gaskets. Marked with green dots, EPDM offers excellent chemical resistance along with good thermal properties and attractive price point that make it a common elastomer choice in both pharmaceutical, personal care, and food applications. The biggest drawback to EPDM is the materials vulnerability to oil based products. Oil based products causes swelling and deformation of EPDM which can compromise the seal.
Polytetra Fluroro Ethylene (Teflon) – PTFE is worth mentioning in this post mostly for what it is not- an elastomer. PTFE is a plastic and exhibits little elasticity and memory. Due to the lack of “squish factor”, or compression, this leads to difficulty sealing, especially in larger sizes. That being said, the chemical compatibility and temperature ranges of PTFE are unmatched.
While there are additional polymers used in sanitary gaskets- what we call “designer elastomers”- such as Tuf Steel, Viton GF, Viton ETP, and Tuf Flex, the above provides a good summary of the elastomers we get questions about everyday. For help selecting a gasket material for your next sanitary application, contact a Holland Sales Engineer today.
As Holland prepares to head to the Quattroflow distributor council this week in Washington DC, we wanted to use this post as an opportunity to highlight a success we recently had working with a customer to incorporate the Quattroflow quaternary diaphragm pump.
To begin, let me share some background information on the customer. Located in the Midwest, the end user is a contract manufacturer who partners with companies worldwide to manufacture immunology products that are used to treat life threatening diseases such as coagulation disorders and other disorders of the immune system. One of the most important starting materials for this company is human blood plasma, which is processed into drug product at this company’s facilities.
Pumping plasma, or any other protein rich product for that matter, can be extremely challenging. An ideal pump is gentle on the product, imparts a low amount of shear and kinetic energy, has low pulsation, and should also be able to achieve required flow rates and head pressures. Tubing spallation, or a lack thereof, is also critical in order to eliminate fouling of final downstream sterilizing grade filters.
An ideal system also needed to be able to transition seamlessly between the stainless steel bulk tank and a single use intermediate bag that was being used to feed a single use manifold the customer had in place on their filling machine. The pump and motor also needed to be able to interface with the rest facilities DCS via an Ethernet connection. Common electrical components, such as Turck receptacles, were also preferred.
To achieve this solution, Holland specified the Quattroflow 1200S pump and another Dover product, the Colder STC connector with Aseptiquick G sterile connector. The STC by Colder allows us to create a sterile connection between the tank and pump by SIP and then aseptically connect to the single use flow path. The genderless design of the Aseptiquick G required the CMO to only change one fitting on their single use manifold. All sterile connections could now be made without the use of a laminar flow hood, creating a closed system.
The Quattroflow 1200S was ideal because it is a low shear, low pulsation pump, and can achieve flow rates of up to 1200 liters per hour without having to adjust the tubing (as you would in a peristaltic pump). We also liked this pump because of its versatility and wide operating range, allowing us to hit both high and low flow requirements. The QF 1200 also has single use pump heads which may present future opportunities for an entirely single use flow path.
Holland was able to add additional value to this application by incorporating a customer specified motor and VFD by building our own base and control cabinet. We were able to integrate Turk receptacles and a VFD with Ethernet connectivity to supply power to the pump and also provide feedback to the user’s DCS using ports, cables, and protocols already available.
The end result of is the marriage of two specific products paired together to create an innovative solution no one else could offer. The CMO is now able to transfer large volumes of drug product to this filling machine between reusable and single use flow paths in a manner that maximizes productivity and minimizes chances for cross contamination. We also introduced a platform we will be able to work with the CMO on to develop further into an all single use solution.
For questions about your next challenging pump application, contact a Holland Sales Engineer today.
Leachable vs. Extractable- What are they, what’s the difference, and why are they a hot-button topic in single use processes today
With the fast paced evolution of single use technologies for pharmaceutical processing, there are many topics and questions that are becoming increasingly relevant as technology evolves. Chief among them are questions about extractables and leachables. How do we test for them? Is this the best way to test for them? How do we quantify and standardize on acceptable levels? This post will focus on the L & E’s (or E & L’s, depending on who you talk to), what the difference between the two are, and why this is such a big deal in single use technology today.
To begin, an extractable is a chemical entity, both organic and inorganic, that will extract from the components of a process system into a solvent under controlled conditions (usually extreme conditions not encountered in a process). This means high heat, pressure, or even multiple sterilization cycles. It also mean strong acids and organic solvents. Extractables are important because they help us to identify potential leachable.
Leachables, on the other hand, are chemical entities, both organic and inorganic, that migrate from components of a system into a drug product over the course of the system’s life. Leachables can sometimes be found in final drug product, usually in trace level relative to the active pharmaceutical ingredient (API).
So now that we know what E & L’s are and the difference between the two, why is this such a big deal in single use systems today? Well, as single-use systems have been widely adopted for upstream biopharmaceutical processing and have been proven effective process and economic system models, interest has been growing to integrate these technologies with downstream processing. As we get closer to the final drug, FDA and internal quality control becomes more intense. This gets people asking about things like extractables and leachable profiles.
These concerns have prompted a battery of validation studies by both the end users and suppliers of single use components. Most single use component suppliers will now have full profiles of each of their products on hand and available to distributors and end users.
End users are doing validation testing as well. Each of manufacturer does something different from their competitor. They make different products, use different solvents, or autoclave at different temperatures, which means they can’t use “stock” testing to see if it is going to impact there product. Each product- and process- is unique.
The variability and attempts to in the characterize extractables and leachables in the most accurate and robust way is what is driving the discussion today. There is currently no specification or guidance documents by an approval agency that mandates testing protocols or set levels that manufacturers must comply with. Additionally, plastic process component manufacturers are asking questions of both regulators and end users as to why extractables and leachables are so important in single use applications, while stainless systems are seemingly grandfathered in. What do you think you might be able to pull out of a stainless system after hundreds and hundreds of steam and aggressive chemical cycles? The answer? Nobody is really sure because we haven’t done the testing.
While this debate is likely to continue to loom over the industry until there is a guidance document or standard for testing and acceptable levels, the industry as a whole has taken steps to better characterize the products that are being used in process today. For questions about the extractables and leachable profiles for your process component, contact a Holland Sales Engineer today.
Stainless steel is a generic term that refers to a variety of types of steel. But what is it that makes stainless steel “stainless” and why is stainless steel the material of choice for sanitary process components? This post will focus on those questions and provide insight into term that is often oversimplified.
Stainless steel, like all steels, is made primarily from iron and carbon. Steel is make in a two-step process. In the first step, iron ore is smelted in a blast furnace. After the raw “pig iron” is made molten, most modern plants blow high purity oxygen into the molten ore, lowering the carbon content and eliminating other impurities. Steel corrodes because the main metal, iron, is chemically very active and quickly combines with other elements, such as oxygen, causing oxidation, corrosion, and rust.
What makes stainless steel different is the addition of chromium to the soup. When chromium is added to steel, it reacts with the free oxygen to form chromium oxide, which acts give stainless its corrosion resistant properties. This passive- meaning chemically inert- layer is what we’re trying to create or enhance when we passivate steel. In addition to chromium, other elements are added to stainless to enhance different properties and the relative amounts of these elements is what determines the grade of stainless.
Most of the steels used in sanitary process are austenitic 300 series steels- 304 and 316. Superaustenites, such as AL6XN exhibit even better resistance to the corrosive pitting effects of chlorides through the addition of molybdenum.
The other type of steel we’ll see in sanitary process are precipitation hardened martensitic or semi-austenitic steels. These steels, which include 17-4PH feature the addition of elements like aluminum, copper, and niobium which makes the steel extremely strong while still easily machined (weld-ability does suffer slightly, however).
Continually, stainless steel, particularly austenitic steels, have properties in addition to corrosion resistance that make it an excellent choice for sanitary process equipment. We’ve already touched n a few of them, but stainless is strong, durable, easily fabricated, relatively cheap, aesthetically pleasing, and easy to clean. This means we can machine, weld, and shape steel into almost any shape we want. The finished steel product will be strong, durable and perform over a variety of high and low temperatures.
But to really drive the point home, what makes “stainless” “stainless” is its corrosion resistance. When steel is attacked by the environment, it rusts and pits. These pits create an area where product can be trapped. This isn’t good in a sanitary process. These places are hard to clean and once the passive layer is gone, the steel is compromised and prone to additional attack.
Rusting and corroded steel also dramatically affects the mechanical properties of steel. The first site that is generally attacked are the joints- namely welds. Weld and weld quality have been the subject of previous posts and will be reemphasized in the future. Rust will compromise a system, exposing it to detrimental environmental conditions and comprising system and product integrity.
To conclude the main type of steel used in sanitary process equipment are austenitic 300 series steels. All stainless steels benefit from the addition of chromium which helps create a passive chrome oxide surface layer on the steel that helps reduce chemical attack and corrosion. We’ll elaborate on this topic continually throughout the blog, but don’t let that stop you from contacting a Holland Sales Engineer today.
As a follow up to our last post on plastic vs. stainless fittings, today’s post will focus on the key driver that are causing afundamental shift in the pharmaceutical processing world. By understanding the benefits and alternatives single use provides to stainless, you’ll be better able to identify applications where single use makes sense for you.
To begin, while there are a plethora of micro factors driving that highlight the advantages and disadvantages of specific products, there are a few overarching considerations pushing companies to consider and design for single use. The issues we’ve identified as “macro” factors are as follows:
- Reduced upfront capital costs
- Reduced downtime
- Smaller facility footprint
- Increased flexibility
- Environmental considerations & Reduced utility costs
Let’s take a look at each of these a little more closely:
Reduced Capital Cost
Single use facilities by nature have a lot of plastic and not as much steel. That means no expensive stainless steel tanks and no contractors performing hundreds and hundreds of welds. Plastics bags replace expensive stainless tanks and flexible tubing with connectors replace piping. While there are continuing costs associated with single use, the initial amount of capital required to get a facility making drug is less.
One of the most time consuming tasks performed at a pharmaceutical manufacturing facility is cleaning and validating that cleaning. CIP, SIP, and autoclave cycles all take quite a bit of time and usually need to be performed after each production run. When a system is being cleaned, it is not making drugs, which impacts the total capacity of the facility. By going to pre-sterilized single use assemblies, equipment is discarded after each run and quickly replaced by new manifolds, reducing down time and increasing capacity.
The smaller footprint of single use facilities can be important for two reasons- it can mean that you can buy a smaller (cheaper) building, or it means you can fit more production equipment in your existing facility. Either way, improved titers yielded by modern technology are allowing us to use shrink process equipment and maximize productivity.
As a process engineer, can you imagine a facility where you didn’t have to worry about cross contamination? Closed modular single use systems make this a possibility. No longer do systems need to be tied or looped back to a central utility system. No longer to we have to validate cleaning procedures and have dedicated tanks or systems for each product. Single use systems allow us to run more products from fewer facilities.
Environmental Impact and Reduced Utility Costs
With single use systems, it should be no surprise that there is going to be a lot more trash generated. Doesn’t this have a much more deleterious affect on the environment than stainless systems? Not really- let us explain. Almost all single use components can be recycled or incinerated and used to regenerate heat for a building. Not only that, but plastics tend to be more environmentally friendly that caustic CIP chemicals. In fact, studies show that the most environmentally damaging thing a company does is have its employees drive to work. So if we’re going to be serious about saving the environment, we should focus on ride sharing and public transportation, not the pile of recyclable plastic by the dumpster.
Going along with that, now that we no longer need to CIP, we are able to drastically cut our WIFI consumption. This means we need to less heat to feed our WIFI stills. Most stills consume a tremendous amount of electrical energy and with energy costs in Illinois jumping between 10-20%, reducing energy consumption can be a huge cost savings.
So while there are many micro factors that drive people towards single use systems, it is the macro factors that still dominate managements decision to go one with or the other. The above is not to say that single use does not pose it’s own set of unique challenges, but rather to illustrate the key drivers in the industry today. Contact a Holland Sales Engineer today for more information on this topic.