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.
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
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|
|Elbow- TC x TC||EG2C||2CMP||2CMP||GC2C||JC2||2CMP|
|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|
|TC x TC U-Bend||EG2WU||–||–||GC2WU||J2WU||2UMP|
|Eblow- TC x Threaded Bevel Seat||EG2FTR||2FMP-15||2FMP-15||GC2F-15||JC2-15||2FMP-15|
|45- TC x TC||EG2K||2KMP||2KMP||GC2K||JC2K||2KMP|
|Reducing Tee- TC||EG7R||7RMP||7RMP||GC7R||JC7R||7RMP|
|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|
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.
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.
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.
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.
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
In today’s blog, we’re going to revisit a product we’ve focused on in the past- the Quattroflow quaternary diaphragm pump. The Quattroflow series of pumps is one of our newer products offerings that continues to innovate, offering our biopharmaceutical customers scalability, flexibility, and performance that traditional product offerings can’t match. As Quattroflow gains larger market acceptance, they have continued to push the envelope to meet customer demands and bring new products to market. Today we’ll take a look at their latest product offering- a compact version of their popular QF 1200.
For some time now, the Quattroflow pump has been available in the 150, 1200, 4400, 5050, and 20K sizes, with all but the 20K being offered with both stainless and single use heads. The smallest of these sizes, the 150 is offered with an integrated drive and controller standard. This small footprint and wide turndown makes the 150 perfect for lab and low flow applications.
When we scale up to the QF1200, however, the Quattroflow 1200 has traditionally been offered with separate pump and control boxes. The 3 phase, 0.5 HP motor meant that we needed to use a variable frequency drive to achieve the wide ranging turndown the Quattroflow is known for. While this is an effective solution, it meant we would need two enclosures- one for the pump and one for the VFD. This relatively large footprint presented challenges when mounting the QF1200 to a skid or when trying to make room for it on an already crowded lab bench.
To solve this problem, we are now excited to offer the Quattroflow 1200CV. Similar to the QF150, the QF1200CV combines controller, motor, and pump into an all-in-one unit that is perfect for customers with a tight space requirement. The compact version of the QF1200 uses a brushless DC motor that is similar to one used in the QF150 and affords use the same range, turndown, and low pulsation the Quattroflow pump is known for.
Currently offered with a single phase, 220V motor, the QF1200CV is available with an optional 0-5V DC input for speed control (which can be easily scaled to a 4-20 milliamp input). The QF1200CV is available with standard ¾” TC stainless and single use heads. Single use heads are available in both a machined polypropylene as well as an injection molded polyethylene. The polypropylene chamber is ideal for high temperature and SIP applications, while the molded head is economical and ideal for applications where the chamber will be gamma irradiated and disposed of following a campaign. All soft parts for both the single and multiuse heads are fully characterized, made of USP Class VI materials with extractable and leachable reports available.
To conclude, the QF1200CV adds another option and flexibility to one of the most scalable positive displacement pump technologies on the market. If you have questions about your next biopharmaceutical application or to see if the Quattroflow line of pumps is right for you, contact a Holland Sales Engineer today.