Skip to content

Validating a Single Use Process System- Sterility Claim vs. Microbial Control

August 16, 2016

As we’ve mentioned in this blog before, both at Holland and the rest of the biopharmaceutical process

Holland Provides a Broad Range of Single Use Components for the Biopharmaceutical Industry

Holland Provides a Broad Range of Single Use Components for the Biopharmaceutical Industry

industry, we’re seeing an increasing number of customers switching to disposable process equipment. This can be scary stuff for stainless guys. Customers, however, are finding safety, time, and cost reduction benefits compelling enough to switch to single use systems for applications ranging from buffer formulation and bulk intermediate, all the way to final fill. For many of these applications, microbial control or even sterility is required to ensure system safety and product purity. Today’s post will take a look at one of the most common sterilization methods for single use assemblies, gamma irradiation, and what standards and methods should be followed to call something “sterile”.

To begin understanding why and where a sterility claim may be needed, we need to look at to the origins of single use process equipment. Disposable products were first used in small scale lab applications where time and cost of stainless equipment was prohibitive. As these lab applications developed momentum and scale, there became a need for presterilized products that could be directly incorporated into critical process applications. In order to validate systems and ensure a sufficiently high probability of bioburden reduction and sterility, the bioprocessing industry has turned to standards established for the validation of sterilization of healthcare equipment by irradiation developed by organizations such as the American National Standards Institute (ANSI), the Association for the Advancement of Medical Instrumentation (AAMI), the International Organization for Standardization (ISO), the ASTM, and BPSA guidance.

We’ve talked about gamma irradiation as a means of sterilization in prior posts, so we will now turn our attention to the difference between sterility and microbial control. To be claimed as sterile, industry standards require, “validation of the efficacy and reproducibility of the sterilization process, based on determination of average bioburden and subsequent sterility testing of systems after minimal radiation exposure”. These systems are also subject to routine auditing that examines bioburden and sterility testing results. For prototype or lab systems, the process to make a sterile claim can be cost prohibitive.  As an alternative to the sterile claim, many systems can be simply exposed to a sterilizing irradiation dose of 25 kGy and claimed as microbially controlled. In sum, components or systems requiring zero or low bioburden when applied to a nonsterile process, do not need to be validated as sterile, but simply validated as microbially controlled. We will spend the rest of this post helping explain when validated sterility is required or when microbial control is appropriate.

Let’s revisit the four basic stages we can divide biopharmaceutical manufacturing into. First, we have “upstream” processing where we mix nutrients and producer cells in a fermenter or bioreactor allowing the cells to produce the target molecule. Next, we go to the harvest stage where cells are separated from the target molecule using methods like filtration and centrifugation. Third is downstream processing where a series of separation, purification, and chromatography steps produce a purified bulk drug product. Finally, we have the formulation and fill stage where the purified bulk is sterile filtered and aseptically filled into containers. This final stage is similar to how synthetic pharmaceuticals are manufactured aseptically.

Through all of these stages, it is important to prevent any unwanted microbial contamination. What degree of control is driven by the end user and international regulations which dictate that products and processes claimed as sterile must be validated to prove sterility. What constitutes a validated sterile process? Validation is by definition, “the process of establishing documented evidence that provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes”. A sterile process, then, is a validated method of sterilizing a product such that the sterility assurance level (SAL) is less than or equal to 10-6 (one in a million!). These regulations do not, however, apply processes claimed as microbially controlled, which also may have zero or low bioburden but have not been validated with a defined SAL. What this means in respect to the bioprocessing steps described above is while the assurance of validated sterility is necessary for bulk drug product and final fill single use systems, preparative stages after which product will undergo additional refining (i.e. sterile filtration) can be operated under the tight microbial control afforded by irradiation.

If it is determined that a process must be validated as sterile, there are a few methods most commonly employed. First, we need to figure out what to test. In applications where a single use system is used, it is common that multiple variations of a system are used in a process. In these applications, it is often only necessary to validate a single product from a family known as a “Master Product”. The Master Product is usually the largest product in a family, but it can also be the product which possesses the most components, the greatest number of materials, or even the one that requires the most handling during manufacture. Simulated or equivalent products may also be used. For more information on what equivalent and similar products are, please refer to the BPSA’s guidance on sterilization and validation of single use process systems.

Once we’ve determined which product to test, we need to determine what part of the product needs to be tested. If you’ve used single use processing systems in the past, you know how large these can be and can imagine how difficult it can be quantify bioburden and sterility. In some cases, it is only necessary to test and validate the fluid path. Because the system (ie tubing, bags, ect) can act as its own barrier to contamination, we avoid having to test the entire product and avoid the issue of handling its external surfaces without contamination. Large products can also be sectioned, or split into parts that are easier to test. Each section is then tested and summed to come up with the bioburden of the entire bag.

To test the bioburden of a fluid path or sectioned product, we will partially fill the system with sterile buffer, ensuring all surfaces are wetted, then agitate the article by hand to promote suspension of organisms. The buffer is then removed and tested using standard microbiological methods. Sterility testing is accomplished by a similar method, but a growth media is used in lieu of sterile buffer.

As you can probably tell, validating sterility is anything but quick and easy. Determining whether a process needs to be validated as sterile or microbially controlled is critical in optimizing time and cost requirements for a project, considerations which are ultimately borne by the biopharmaceutical manufacturer. While disposable process equipment offers significant advantages to manufacturers, they are not without significant decisions to be made by all stakeholders. While some applications may only require microbial control, sterile processes must be validated as such. While we covered a lot of ground, the purpose of this post is to help distinguish between sterile and microbial controlled, provide an overview of the sterilization validation process, and discuss where these needs fit into the overall biopharmaceutical manufacturing process. For more questions about your specific application, contact a Holland Sales Engineer today!

Seital Centrifuges and Clarifiers- Applications & Tips for Getting the Most out of Your Craft Brewery

April 18, 2016
Seital Separator

Seital Separator

At Holland, we are committed consistently adding products to our portfolio that will help our customers with their sanitary process needs. By rounding out our product offerings, we are able to deliver novel solutions to complex processing problems our counterparts in the sanitary process equipment industry cannot. Today’s post will focus on one of our newest SPX product offerings- Seital separators and how they can be used in brewing applications to increase productivity and improve beer quality.

To begin, let’s take a look at how a Seital separator works in a beer application- or really any application for that matter. First, the mixture to be separated- usually beer or wort -is pumped in to the centrifuge. It enters the centrifuge through the centrally positioned inlet pipe. A distributor then guides the mixture into the separation area of the system. The separation area is made up of a stack of conically arranged discs. These discs spin at a high RPM. The short distance between discs (coupled with centrifugal force) forces solids through the discs to the outside of the bowl where they are ejected. The remaining beer or wort is then pumped out of the system through the outlet pipe.

So now that we have an idea of how this works, let’s look at why and where we should use a centrifuge for beer or wort clarification. One application where we see clarifiers used in the brewery is following the brew kettle, when the brewer needs to remove the protein and hop solids, or trub, prior to fermentation. In many small breweries, traditional filter media or whirlpools are used to filter the trub. By using a Seital separator, we are able to separate the trub and hop solids with maximum efficiency and yield to get bright and clear wort prior to cooling for fermentation.

Brewers have also found that Seital centrifuges can be gentler to beer than traditional filter media. The advanced sealing systems in the Seital separators minimize O2 pickup. Filter media, such as cellulose or diatomaceous earth, can strip flavor from the beer and have an environmental impact. Why do you think there are so many unfiltered beers on the market today? When used as an alternative to traditional Kieselguhr or diatomaceous earth filtration, we’re able to get the same clear bright beer without stripping out any of the hops characteristics that make a craft beer great. The Seital portable skids are ready for any application where you want all the benefits of filtering without the need for filter media.

Continually, Seital separators properly applied in a brewery quickly pay for themselves. Good, sellable beer is often trapped in the solids that collect in the bottom of fermentation tanks. Seital separators allow for more beer to be recovered from tank bottoms, allowing brewers to ship more beer from the same amount of raw ingredients. This return on investment helps to quickly offset initial cost of equipment.

Another advantage of using a separator is being able to increase production volumes without having to add more people. Seital separators come pre-skidded, prewired, and ready for plug and play use in the brewery. When used with turbidity meters and other automation features, brewers are able to achieve greater repeatability and higher quality standards without having to add additional staff.

In order to continue to improve the quality of one’s beer, a brewer must be willing adjust and refine their methods of processing. Craft brewers across the country are all discovery new applications where Seital clarifiers can be used to improve the quality of their product and the efficiency of their process. By using them to replace traditional filter media, automated, pre-skidded processing allows brewers to maximize throughput without compromising quality. If you have any questions about whether a centrifuge is a good fit for your brewery, contact a Holland Sales Engineer today.

Quattroflow 1200 Provides Drop in Replacement for Peristaltic Pump

February 23, 2016

Many of our followers may have noticed that we haven’t posted a new blog in a few months. Fear not- we have still been working on plenty of interesting sanitary process challenges. In this post, we’ll talk about a recent tangential flow filtration application and how Holland was able to leverage our unique design and build skills to provide a drop in replacement for process pump that just wasn’t up to par.

In late September, Holland was contacted by an OEM who was working with an end user to improve the performance of an existing TFF skid. This particular OEM manufactures a variety of automated and semi-automated portable single use filtration skids for the pharmaceutical industry.

While no stranger to the Quattroflow line of quaternary diaphragm pumps, the OEM was working with a customer who had an earlier iteration of one of their skids that utilized the popular Watson Marlow line of peristaltic pumps. The end user was having problems with the high pressures and tubing performance and compatibility issues that frequently trouble peristaltic pumps.

So the solution seems simple, right? Well, not so fast. If you’ve been following many of our earlier blog posts, you would know that the Quattroflow pump is a positive displacement pump designed specifically for the bioprocess industry. It is a gentle, low pulsation pump that uses a series is four diaphragms and check valves to push and pull media through the pump chamber. Available in both stainless steel and single use pump chambers, the high-turndown Quattroflow pump is perfect for these applications. So what’s so tough? Let us explain.

This client was using a servo motor to drive the peristaltic pump. As clean room suites tend to be as compact as possible, so does the equipment that goes into clean rooms. Because the skid had already been built, Holland was presented with unique challenge- provide a servo equipped Quattroflow 1200 that was a drop in replacement for the Watson Marlow pump that the skid was designed around.

To do this meant designing and fabricating in house a new mounting block to mount the servo motor to. Then, we had to figure out how where to position mounting holes so we could bolt in our pump where the Watson Marlow used to be. Finally, we had to mount the motor and couple it to the pump. And we had to do all of this without the skid. Pulling dimensions from CAD models, slowly but surely, a design developed.

When it was all said and done, about five weeks later, we finished bolting the motor to the mounting block and the mounting block to the base plate. Pushed the two halves of the Love Joy couplings together (located inside of the motor mounting block) and bolted down the QF1200 ring drive, and just like that, we had a Quattroflow 1200 pump with servo drive that was ready to stand in for a Watson Marlow pump that just could do the duty.

Sci Log QF1200 Assembly-REV2

Drawing of Quattroflow  1200S with Servo Drive

By implementing a solution that bridged several core competencies at Holland, including technical expertise, design, and fabrication the end user was presented with a solution that, after calibrating the servo drive, allowed for the replacement of a non-performing technology with a performing technology in less than 20 minutes, preserving the benefits of overall skid design.

So the next time you have a technical question about a Quattroflow or are trying to tackle a difficult design challenge, contact a Holland Sales Engineer. We’d be happy to help.

Waukesha Universal Series PD Pump Notes- QR Codes, SPX Connect, & Training Videos

February 15, 2016

Waukesha Universal Series PD Pump Notes- QR Codes, SPX Connect, & Training Videos

Waukesha U2 Pumps Mounted on Polished Round Tube Bases

Waukesha Universal 2 Sanitary PD Pumps

If you’ve been following our blog, you know that one of our favorite products to help our business partners with are Waukesha sanitary centrifugal and positive displacement pumps. Waukesha, the longtime leader is sanitary pumping technology, continues to innovate, offering new features and services to further enhance an already proven product platform. In today’s short post, we’ll highlight a few new things SPX is offering, including where you can find maintenance videos and the new SPX Connect smartphone application.

End users- We have a question for you- have you ever had a piece of equipment you are unfamiliar with go down and everyone looks to you to get it back up and running so production can continue? Most of us know the feeling. We don’t have much choice but to dive in, flip through the product manuals, and speak with customer service representatives or applications engineers. Manuals are often vague or unclear, sometimes you don’t even know if it’s the right one. And even though at Holland we’re all trained to help our customer’s troubleshoot basic PD pump problems, sometimes it can be difficult to communicate. We just can’t always see what you see.

Wouldn’t it be helpful if there videos that showed Universal 1 and Universal 2 pump assembly and disassembly? Fortunately for you, SPX offers helpful YouTube videos that detail everything from gear case assembly, shimming, seal replacement, and bearing housing maintenance. The links to these videos can be found on our website as well on SPX’s YouTube page- just search “SPX Corporation”, or click the link below:

The second program we’d like to highlight is SPX’s new SPX Connect smart phone app and QR codes. If you’ve purchased a new Waukesha PD pump or Ecopure seal-less centrifugal pump, you might have noticed a QR code on the pump name tag. This QR code isn’t some fancy tool to track pump casings through Kanban flows. Rather the QR codes are a full functioning tool end users can leverage to prevent downtime and give you 24/7 access to the information you need to get your pump back up and running.

Using the free SPX Connect smartphone app, anyone can scan the QR code and identify basic information about their pump, including model, displacement, maximum pressure, and maximum speed. The app can also be used to access pump literature, manuals, and the service videos we talked about earlier in the post. All of this information can easily be shared with colleagues directly from the app. The app allows you to select from a list of common parts and services to submit quote requests and even saves a history of all the pumps you’ve searched, allowing you to quickly retrieve accurate information about what could be any one of a dozen pumps throughout a facility.

So there are a quick couple of tools you can use the next time you have questions about your Waukehsa PD pumps. Have a question you can’t answer in one of the videos or the SPX connect app? If so, a Holland Sales engineer would be happy to help you out.

What is WFI (Water for Injection)?

September 15, 2015
Typical Multi-Effect WFI Still

Typical Multi-Effect WFI Still

Water for injection by definition is water that is intended for use in the manufacture of parenteral (i.e. injectable) drugs whose solvent is water. The USP (United States Pharmacopeia) defines this as highly purified waters containing less than 10 CFU/100 ml of Aerobic bacteria. These waters should also have fewer than 500 ppb of total organic carbon, fewer than 0.25 EU/ml endotoxins, and a conductivity of less than 1.3uS/cm @ 25 C.

Now that we have the textbook definition out of the way, we’ll spend the rest of this blog post delving a little deeper into WFI, how it’s made, and common pieces of process equipment used to make up WFI.

To begin, let’s start by looking at how Water for Injection is made. The USP allows WFI to be produced by one of two means; either distillation or reverse osmosis. Prior to making it to the still, however, supply water has to go through extensive pretreatment. Pretreatment usually includes various filtration steps, removal of chlorines through the use of activated carbon beds, and percolation of water through ion exchange resins to remove residual ionic compounds. What is the purpose of all this pretreatment? By pretreating the water, we effectively reduce the conductivity of the water, as well as the level of organic contaminants.

Once the water makes it through these pretreatment steps, it goes to the still. What happens in a WFI still? Distillation, of course. When water is distilled, it heated until it is a vapor, stripping the heavier ions, particulates, and endotoxins from the water. There are both single and multiple effect stills and which one is best for you is determined by how much WFI you are trying to generate. There are also vapor compression stills available that can make WFI.  Regardless of what kind of still you are using, the basic process is the same- the water vapor is passed through a series of tubes and recondensed, resulting in WFI.

You can also get WFI from a process called reverse osmosis. In reverse osmosis, or RO, water is forced through a semi-permeable membrane and the pores in that membrane reject dissolved ions, salts, and organic compounds. This is filtration on a molecular and ionic level. The quality of water, temperature, PH, and flows rates are all critical in RO as the membranes used can foul easily. Reverse osmosis systems rely on booster pumps to increase pressure across membranes, storage tanks, and sophisticated controls for bulk WFI preparation. RO systems are capable of producing 600-50,000 gallons per day of WFI.

So what is done with WFI after it is produced to ensure the water stays at water for injections quality? It either needs to be used quickly (usually same day) or put in a state that allows it to maintain its efficacy. How do you make sure WFI stays as WFI? You need to minimize microbial growth. This is accomplished by maintaining it at high temperatures and keeping it in motion.  Normally WFI is kept at 90 degrees C and recirculated through a distribution loop at a minimum velocity of 5 feet per second.

To ensure there is no contamination of entering or building up in the distribution system, the piping is normally highly polished, at least 20 Ra, often with electropolish.  Any ventilation or vent filters are usually sterile membranes of at least 0.2 uM. Vent filter, commonly found on tanks, are often heat traced or steam jacketed. Why is that? Well, when WFI comes in from the still, it can be very hot. The heat can cause it to flash off and enter the filter. Once the steam makes contact with the vent filter, which if not heat traced will be cooler than the tank, the vapor will recondense and cause the vent filter to blind. When you go to pump that tank out, you would then pull a vacuum and could cause the tank to collapse.

Other common pieces of equipment used to ensure system integrity include double sheet shell and tube heat exchangers and weir type diaphragm valves.  EPDM is probably the most common gasket material we see in a WFI system.

Because the conductivity of WFI is so low, it is considered “ion hungry”, ready to leach ions out of any surface it comes in contact with. That makes the water very abrasive. That means we use centrifugal pumps with single or double mechanical seals and hard seal faces, the most common and robust being either silicon carbide or tungsten carbide.

So to recap, what is WFI? WFI is highly purified water that contains less than 10 CFU/100 ml of Aerobic bacteria. These waters should also have fewer than 500 ppb of total organic carbon, fewer than 0.25 EU/ml endotoxins, and a conductivity of less than 1.3uS/cm @ 25 C.

Why is this important? Well, because as the name implies, WFI is the water, combined with active ingredients used to make drugs that are injected into our bodies. It is also used a the final rinsing agent for any component that comes in contact with the drug such as vials, ampules, caps and stoppers.  How do we make it? Through a series of steps aimed removing ionic and organic contaminants with the final steps being distillation or reverse osmosis.

Once we make it, what do we do? Keep it hot and moving, use it or lose it. We store and transport WFI using ultra high purity process equipment like highly polished tubing, diaphragm valves, sanitary centrifugal pumps with single of double mechanical seals, and double sheet shell and tube heat exchangers.

Any questions? If so, contact a Holland Sales Engineer today.

The Tri Clamp & Sanitary Flange Dimension Guide

June 15, 2015

In previous posts, we’ve discussed how hard it can be to identify what size sanitary flange aka Tri Clamp you have. Today’s post is short and sweet- a simple drawing that should help you correctly identify the size of all of your sanitary fittings.  You can download a copy of this in the Resource Center section of  the fittings page of our website



Sanitary Fitting Part Numbers- A Cross Reference Guide

June 5, 2015

Have you ever ordered a 2CMP and received a EG2C or a GC2C? Do you know why? In previous posts, we’ve talked a lot about sanitary fittings, what they are and what makes them sanitary. One of the things people struggle with the most, however, is providing the correct part for a fitting and recognizing equivalents. Being able to tell what’s what and who’s fitting is equivalent to who’s can help you the next time you’re in a pinch and need a parts for a job the next morning. Even at Holland, where we deal with these parts all day every day, we forget from time to time. So for today’s post, we’ve put together a useful cross reference guide that will help you identify your sanitary fitting and the different part numbers each manufacturer assigns to them.  You can download a copy of this in the sanitary fittings section of our website.



VNE Tri Clover/Alfa Laval Waukesha G&H Jensen Steel & O’Brien
Reducing Elbow- TC x TC EGLC31CC 2CMP-31MP 2CMP-31MP GC2C-31 JC1-J31 2CMP-31MP
Elbow- TC x Bevel Seat w/ Nut EG2FPR 2FMP-14 2FMP-14 GC2F-14 JC2-J31 2FMP-14
Eblow- TC x Threaded Bevel Seat EG2FTR 2FMP-15 2FMP-15 GC2F-15 JC2-15 2FMP-15
Tee- TC EG7 7MP 7MP GC7 JC7 7MP
Reducing Tee- TC EG7R 7RMP 7RMP GC7R JC7R 7RMP
Cross- TC EG9 9MP 9MP GC9 JC9 9MP
Standard Clamp EG13 13MHLA P13MHHM GH13FAH K13LG P13MHHM
Double Pin Clamp 13MHHM 13MHHM 13MHHM GC13LAH JC13HC 13MHHM
High Pressure Clamp 13MHP 13MHP 13MHP 13MHP JC13HP 13MHP
Tygon Hose Adapter- TC EG14HT 14MPHT 14MPHT GC14AHT JC14AHT 14MPHT
TC Tank Welding Ferrule EG14W 14MPW 14MPW GC14W JC14AHT 14MPW
TC Welding Ferrule- Long EG14WL 14WLMP 14WLMP GC14WL JC14AHT 14WLMP
TC Welding Ferrule- Medium EG14AM7 L14AM7 L14AM7 GC14AC JC14AM7 L14AM7
TC Welding Ferrule- Short EG2CS 14WMP 14WMP GC2CS JC14X 14WMP
TC x Hose Barb Adapter EG14RT 14MPHR 14MPHR GC14AHR JC14AHR 14MPHR
TC Solid End Cap EG16A 16AMP 16AMP GC16A JC16 16AMP
TC x Bevel Seat w/ Nut Adapter EG17PR 17MP-14 17MP-14 GC17PC JC17-14 17MP-14
TC x Threaded Bevel Seat Adapter EG17TR 17MP-15 17MP-15 GC17TC JC17-15 17MP-15
TC x MNPT Adapter EG21 21MP 21MP GC21 JC21 21MP
TC x FNPT Adapter EG22 22MP 22MP GC22 JC22 22MP
TC Welding Ferrule- Reducing EG31R 31RMP 31RMP GC31R JC31R 31RMP
TC x TC Concentric Reducer EG31CC 31-14MP 31-14MP GC31CC JC31 31-14MP
TC x TC Eccentric Reducer EG32CC 32-14MP 32-14MP GC32CC JC32 32-14MP
TC x Bevel Seat Concentric Reducer EG31PC 31PMP 31PMP GC31PC JC14-C31 31PMP
TC x Bevel Seat Eccentric Reducer EG32PC 32PMP 32PMP GC32PC JC14-C32 32PMP
Thermometer Cap EG23B 23BMP 23BMP GC23B JC23B 23BMP
Lateral Wye EG28A 28AMP 28AMP GC28A JC28A 28AMP
Equilateral Wye EG28B 28BMP 28BMP GC28B JC28B 28BMP


Still can’t find what you need? No worries- we plan to continue to add more tools like this that will make specifying sanitary fittings a breeze. Don’t want to wait for our next blog? Contact a Holland Sales Engineer today.

BPE and 3A Sanitary Fittings- What’s the Difference?

May 14, 2015
2" Elbows, one ASME BPE, one traditional Sanitary. They have the same radius but different length tangents

2″ Elbows, one ASME BPE, one traditional Sanitary 3A. They have the same radius but different length tangents

A topic we’ve focused on a lot in the past is sanitary fittings- both BPE and 3A fittings, but this is still something that comes up a lot as when we talk to customers. People who are not intimately familiar with the industry can struggle to distinguish between regular sanitary or 3A fittings and BPE fittings. This post will cover the similarities and the differences between the two fittings and hopefully clear up a simple misconception.

To start, how are the two similar? Well, both BPE and 3A fittings are considered sanitary. Both are measured in the same way sanitary tubing is- by tube OD. We’ve talked about this in the past. This means you could weld the two fitting types together. The triclamp dimensions for the for the two are also exactly the same- which means whether you’re looking for 3A or BPE fittings, you’re just as likely to confuse 1” or 1.5” fittings. Some of the fittings also have the same overall dimensions. Both the 14WMP and BPE S14WMP short welding ferrules, for instance, have the same OAL.

That is about where the similarities end, we’ll spend the rest of this post highlighting some of the differences between the two.

3A fittings have their roots in the dairy industry. They are marked with the 3A symbol which lets customers know that these fittings are designed specifically for use in the dairy applications. As the industry evolved, an ASME subgroup, known as the BPE, developed their own standards for fittings. These fittings needed extended tangents to accommodate the orbital weld heads used heavily in the autogenous welding procedures used in the joining of pharmaceutical fittings. BPE fittings dimension are requirements are outlined in the Bioprocess Equipment standard. BPE fittings are designed specifically to be fully drainable when properly installed.

Another difference that should be highlighted is material availability. 3A fittings are commonly offered in both 304 and 316 stainless steel. BPE fittings are offered exclusively in 316L SS. The next thing that really sticks out is the end styles. Have you ever seen I line BPE fittings? The answer is no. BPE fittings are available in exclusively butt weld and hygienic triclamp ends. You won’t see the I line, John Perry, or Q line fittings available in other sanitary fitting styles.

Now, let’s talk surface finish. Both 3A and BPE fittings have what we consider “sanitary” surface finish. Sanitary surface finishes are generally considered any finish that is 32 Ra or better. 3A fittings meet this spec and often exceed it. BPE fittings, however, come in several additional flavors. The “standard” BPE finish is the #3 PC or SFF1 finish. The #3 finish has a 20 Ra Mechanical ID polish and an unpolished OD. Some BPE fitting lines, such as VNE’s Maxpure, even feature a light OD polish on their PC and PD fittings (which are generally insulated). The most common BPE finish is the #7 or PL finish. This is a 20 Ra mechanical ID finish and a 32 Ra polished OD. These are the fittings you’ll see on an uninsulated pharmaceutical process skid. After the PL and PC finishes, we get into the electropolish finishes- PL and PM. These finishes feature a 15 Ra ID w/ EP and either polished or unpolished OD’s. These additional finish options are the biggest reason why BPE fittings are generally more expensive than 3A fittings.

Another difference you’ll see between 3A and BPE fittings is the availability of lot and material traceable certs. On 304 3A fittings, you can’t even get heat certs and on 316 they still aren’t always available. BPE fittings, on the other hand, almost never ship without them. VNE’s MaxPure fittings even ship with a QR code on the package that allow a smartphone to almost instantly retrieve the MTR. Material traceability and verification are absolutely critical in the pharamcetuical process world.

So there you have it- just a few of the similarities between BPE and 3A fittings. If you’d like to know more about the differences, give us a call.  We also keep the Midwest’s largest inventory of sanitary fittings, tubing, pumps, and valves. Our decades of combined experience will help you to make sure you get the right fitting the first time.

Change Control- A Critical Issue in the Single Use and Pharmaceutical Process Industry

April 29, 2015

At a recent panel discussion of bioprocessing industry experts regarding the evaluation of stainless vs single use process components, one panelist was asked an interesting question- when evaluating a single use validation package, what piece of information do you consider to be the most critical? The panelist’s answer may surprise you. While many in the audience may have guessed USP Class VI testing or leachables and extractables studies, this panelist (a category engineering manager for a major pharma company), responded that vendor change control procedures were most important to her when evaluating a new product for their process. This blog will take a look at the why documentation of change is important and what events can trigger a change

To begin, what is a change and why does control of change matter? The pharmaceutical process industry is one of the most tightly regulated industries in the world. And for good reason- patient’s lives may ultimately depend on the quality of decisions made by the people who are responsible for the quality of products and the processes used to manufacture them. A “change” may be a simple adjustment to accommodate a customer specification, an updated document, a part replacement, or other production change. It may result from a deviation from an SOP or work instruction. A change may be temporary or permanent, routine or emergency.

Because change is an inevitable event in any manufacturing process, control is critical. Changing of a process is complex and communication of the change to key stakeholders can be equally challenging. For that reason, it is absolutely essential that clearly defined systems exist that manage how changes are implemented and how they are communicated to stakeholders.

So what are some common events that may result in the need for a manufacturer to send a change notification to an end user, you may ask? Those may range from benign to the extreme- product discontinuation or recall. A few examples of changes that a manufacturer is generally expect to notify a customer prior to implementing include changes in labels or packaging of a material, change of company name, change in shelf life, or changes concerning storage conditions.

While a simple “heads up” may work for some changes, others require more advanced notification- usually a minimum of 6 months. Examples of these sorts of changes include the change of a critical subcontractor, new edition of an analytical specification or product test method, or change regarding animal origin of a raw material. Other changes, such as changes in test methods, elimination of a test method, change in manufacturing site, change in raw materials, may necessitate notification of stakeholder of 9 months or more in advance of a change.

For a distributor like Holland, it is equally important that we have systems in place to handle changes the companies we represent make. With hundreds of active open accounts, it’s critical that we act have clearly outlined and detailed procedures for handling a change made by a manufacturer and getting that information to our customer’s so they can take appropriate action .

To conclude, at Holland, we understand that manufacturers are being continually pushed to develop innovative, high-quality products at lower costs. Whether it’s to stay competitive or to enter new markets, manufacturers need to make changes to meet customer demands. We understand that having a robust quality system is essential to both our success and our clients. If you have any specific questions regarding our quality systems or change control guidelines, contact a Holland Sales Engineer today.

National Welding Month- The History of Welding

April 16, 2015

Welding Piping Hangers on a Sanitary Skid Using the Manual TIG Technique

For our next spurt of blog posts, we’re going to focus on one of mankind’s greatest inventions-welding (welding actually ranked #10 on Scientific American’s list of greatest inventions back in 2013). With April being National Welding month, we’re going to take a few posts this months to talk about the history of welding and then focus more specifically on sanitary welding and welding in the high purity process industry.

The history of welding goes back to the Bronze Age. Man’s first attempts at joining metal were done mostly through a process known as forge welding. It works by heating the metal pieces until they glow red and soften. When they’re soft enough, the welder mashed the two parts together with a hammer and allowed them to cool. This type of metal working was popular up until the Industrial Revolution when new forms of welding were devised to meet industries evolving needs.

While the history of welding is interesting, we’ll spend the rest of this post focusing on the common welding techniques of today and where we see them used.

The easiest place to start is the welding process we’re most familiar with- arc welding. Arc welding is a type of welding that uses a power supply to create an electric arc between an electrode and a base material to melt the metals together at the welding point. There are two main methods of arc welding- consumable and non-consumable electrode methods. An example of consumable welding is gas metal arc welding (GMAW), also known as MIG (metal/inert-gas). This is a semi-automatic or automatic process in which a continuously consumed wired is fed and acts as both the electrode and filler metal.  At Holland we use MIG welders to join structural material, like stainless steel skid frames.

The most common type of welding we see in the high purity industry is another form of arc welding that uses a non-consumable electrode and separate filler material to join two parts. Known as gas tungsten arc welding (GTAW) or tungsten/inert-gas (TIG) welding, TIG welding is a manual process that uses an electrode made of tungsten, an inert gas mixture.   TIG welding may or may not use separate filler material to affix joints. This process is especially useful for welding thin materials, but because it is a manual process (with the exception of orbital welding, which we’ll touch on later), it requires a significant amount of skill and can only be accomplished at relatively slow speeds, relative to MIG or other welding processes.

Welding a High Purity Piping Component  in Our Shop Using a Computerized Orbital Welder

Welding a High Purity Piping Component in Our Shop Using a Computerized Orbital Welder

As we just mentioned, another method of TIG welding common throughout the biopharmaceutical industry is orbital welding. Orbital welding is an automatic process whereby an arc is rotated mechanically 360 degrees around an unmoving work piece. This technique does not use a filler material.  By taking the human out of it, we see consistent, high quality welds that require little operator intervention. Orbital weld beads end up being so smooth and consistent that BPE guidelines don’t even make us polish ID welds.  Most of the high purity welds we create for bio pharmaceutical skids and modules are automatic orbital TIG welds

Now that we’ve talked about arc welding, we’ll spend the rest of the post focusing on some processes that are less common in the high purity industry, but pretty cool nonetheless.

The first process we’ll touch on is friction welding. Friction welding uses pressure and movement to generate the heat we need to cause welding to occur. Friction welding is commonly used to join dissimilar materials. This is helpful in aerospace applications where we might want to join a lightweight aluminum part with a high strength steel. Because of the large difference in melting points between aluminum and stainless, arc welding procedures would be useless and a mechanical connection would be required. But friction welding provides a full strength bond with no additional weight.

Next, let’s look as laser welding. We do see laser welding from time to time in the sanitary industry. Laser welding is a process that uses a high power laser beam to provide a concentrated heat source, allowing for narrow, deep welds and high welding rates. Because of its speed, laser welding is commonly used in high volume applications. Laser welding provides high quality welds and the focused beam results in small heat-affected zones, resulting in little distortion of the part.

Finally, we’ll talk about ultrasonic welding. Ultrasonic welding is cool because it is commonly used to join plastics and dissimilar materials. Ultrasonic welding uses high frequency ultrasonic vibrations applied to work pieces held together under pressure to create a weld. We think ultrasonic welding is interesting for its potential uses in affixing single use needle hubs to cannula.

This is by no means a comprehensive list of welding techniques, but a brief overview on a few processes that we see in our industry or just think are cool. We’ll spend the next couple of posts discussing sanitary hand and orbital welds a little more closely. If you have any questions about your sanitary welding application, contact a Holland Sales Engineer today