When you observe a bioprocess facility, list the types of valves it employs. Most process valves used in the product are diaphragm valves. Only limited types of other valves may exist due to some reasons found in the validation documents. The reason, why so many diaphragm valves are needed, is not related to any ecological concern but is based on the four features of diaphragm valves that coincide with requirements of the law and engineering and cannot be fulfilled by other types of valves.
In the following sections of the article the reasons for that will be explained as well as the cases of diaphragm valve being unsuitable for the particular process, which is hardly found elsewhere.
Brief response: The diaphragm valve is unlike the other valve types in a way that its internal actuator does not touch the medium as the flexible diaphragm provides proper sealing of the valve stem from flowing of the medium. Therefore, packing and sealing stems are not required so there is no room for the fluid. Additionally, electric polished finishing, the ability to be drained easily due to its construction, and a surface roughness of about Ra 0.38-0.76µm allows diaphragm valves to comply with all sterile processing requirements.
Table of Contents
- The Stem Never Touches the Product
- Zero Dead Leg, and Why That Single Word Decides Everything
- Surface Finish Is a Number, Not an Adjective
- CIP and SIP: Where Diaphragm Valves Earn Their Place
- Weir or Straight-Through: Two Bodies, Two Different Jobs
- The Diaphragm Is the Real Specification
- How It Compares With Ball and Butterfly Valves
- Where They Appear in a Pharmaceutical Plant
- What to Put in a Purchase Specification
The Stem Never Touches the Product
Every other type of valve includes a movable shaft that makes its way through the body material. A ball valve has a stem, a butterfly valve has a shaft, and a globe valve has a spindle. These penetrations all require a sealing system, and seals are always experiencing wear that places them between the process and the outside.
The diaphragm valve eliminates the issue altogether by getting rid of the penetration. An elastomer or PTFE composite is sandwiched between the body and the bonnet while the compressor presses down from the outside. The only thing that contact the product is the wetted part of the diaphragm.
This single change does away with various mechanisms of failure: leaking packing, corrosion of the stem, ingress of product into the bonnet, and even slow leaks that could turn a clean room into a source of trouble.
The drawback of diaphragm technology is the fact that the diaphragm is a consumable part that will ultimately break. What matters is how it breaks. Typically, a worn diaphragm will let the product enter the actuator housing, which can be detected and controlled, preventing the release of process fluid into the environment. Conversely, leaking packing will create ugly droplets on the floor, making detection easy, but marking a contamination event.The difference between a sanitary ball valve and a diaphragm valve comes down largely to that failure path, and it is the reason ball valves stay on utilities while diaphragms take the product line.
Zero Dead Leg, and Why That Single Word Decides Everything
A dead leg is a portion of pipeline or an area where there is a halt in movement. This is a location of stagnant mixture where there won’t be any force effect or cleansing of the space leading to the establishment of biofilm.
Two approaches are utilized in diaphragm valves to minimize the dead leg. First, the shape of the valve prevents a huge it from existing downstream. Furthermore, the drainability of the body is good when placed at the right angle, allowing easy release of the remaining liquid.
People responsible for the usage of regulators are conscious of the advantage of the diaphragms to the other kinds of valves. The old ball type has a cavity surrounding the ball which gets filled with product when the valve is opened. A butterfly type produces a restriction behind the moving of the disc and can be constructed cavity-free but is more costly.
As the dead leg describes the fact of being measured rather than just declared. For example, when branches are connected, ASME BPE stipulates the limitations on the value of the L/D ratio. Thus, the unused length should not be more than two times the diameter.
The second aspect is being drainable. It means that if the conical shape is incorrectly constructed upside down, it will hold product in its cavity even if it is manufactured perfectly. Thus, the direction has to be indicated precisely.
Surface Finish Is a Number, Not an Adjective
The term "polished" has no significance in a purchase order. The only thing that is useful in a validation package is the Ra value, the technique used to achieve said value, and the tool used for the measurement.
The relevant values in the pharmaceutical business match the ASME BPE surface finish definitions from SF1 of Ra 0.38 µm to SF4 of Ra 1.52 µm. The sterile service, for example, as well as water for injection loops and aseptic filling, generally require SF1 or SF2. With regard to purified water or non-sterile API, SF3 is typically adequate. While food products and dairy production rely on 3-A standards, with Ra of 0.8 µm being the most common standard.
Mechanical polishing is able to achieve Ra values between 0.6 and 0.8 µm. Electropolishing, on the other hand, removes the affected surface layer and results in the beneficial Ra of < 0.38 µm while improving the condition of chromium at the surface and enhancing the cleanability and the protection against corrosion. Still, electropolishing does increase the price of the valve by 20-40% and is a must in a sterile technology.
There are two details that should have been taken into account. First, the roughness is measured on the wetted surface, including the weir, and it has to be given for a batch, not for the product line. If a certificate states "electropolished, Ra ≤ 0.4" without any hints as to where the measurement was taken, it has to be treated as a marketing material.
CIP and SIP: Where Diaphragm Valves Earn Their Place
The operational principle of Clean-in-Place is based upon chemistry, temperature, flow and holding time affecting all surfaces. Steam-in-place functions in the same manner but operates with steam, usually at 121 C° temperature or higher than that (e.g. 134 C°), so that steam heats the entire surface area.
Diaphragm valves fit both since there is a simple flow path without any shield. In addition, the chosen diaphragm material may provide required temperature performance. EPDM diaphragm can be applied for operation at 120 °C while a short cycle over 120 °C can also be accomplished with this type of material. In case of PTFE composite diaphragm swelling does not occur, therefore it becomes standard in the pharmaceutical field.
The failure of valve during the SIP process is mostly caused by high temperatures. The elastomer will become so hard that the manufacturer may not be able to identify any defect on the valve even though it might fail. That is why periodic replacement of diaphragm should not depend on revealing abnormalities, but should be implemented upon reaching the set number of cycles.
Weir or Straight-Through: Two Bodies, Two Different Jobs
Both are diaphragm valves and they are not interchangeable.
| Body type | Size range | Flow path | Use it for |
|---|---|---|---|
| Weir | DN8 to DN100 | Raises ridge, slight restriction, drains fully | Water, buffer, media, CIP and SIP lines, most aseptic fluids |
| Straight-through | DN15 to DN80 | Unobstructed bore, taller body | Cell culture media, slurries, viscous broth, particle-bearing streams |
| Tank bottom | DN25 to DN50 | Flush with vessel floor | Bioreactor and vessel outlets, zero hold-up drainage |
| Multi-port block | Project specific | Several seats in one forging | Sampling and transfer manifolds, fewer welds |
The wier design offers minimal dead volume and maximum drain - it is the standard option for anything that needs to be sterile. Its limitation leads to pressure loss, which affects gravity drain but is not an issue for pumped lines.
Straight-through design is for liquids that would clog the wier. The output of a cell culture cell that has solid byproducts would block the exit; the straight-through version would allow liquids to escape. The main drawback of the straight-through version is bigger height, bigger hold-up volume, and lower draining efficiency. Therefore, it should be used only if dictated by the process.
Tank bottom design solves a real problem: it provides zero liquid left at the outlet. In case of bioreactor this means the difference between a drained vessel and a vessel that has to be emptied manually.
The Diaphragm Is the Real Specification
People pay attention to the body and consider the diaphragm as an accessory part, which is incorrect. The diaphragm is the only moving part that is in contact with the working substance of the fluid. It determines the limits of temperature, chemical compatibility, cycle life and validation class.
| Material | Temperature | Chemical fit | Typical life |
|---|---|---|---|
| EPDM | −40 to +120 °C | Water, steam, CIP chemicals, buffers | 1 to 3 years |
| PTFE/EPDM composite | to +150 °C short term | Solvents, acids, oxidisers, SIP duty | 2 to 5 years |
| Silicone | −60 to +200 °C | Low-temperature flexibility, some food service | 1 to 2 years |
| FKM | −20 to +200 °C | Oils, fats, hydrocarbons | 2 to 4 years |
It is vital to be aware of the nature of the composite. Pure PTFE has the perfect chemical performance, but is of no use when it comes to seal applications, because it has no shape recovery properties. By gluing a PTFE face to the EPDM backing, the wetted face acquires chemical inertness and the backing gets the ability to close the seal. It should be noted that the diaphragm complies with the requirements of USP Class VI and FDA 21 CFR 177 simultaneously, which eases the whole certification procedure.
One must pay a lot of attention to the cycle life numbers provided by the suppliers. Instead of meaning cyclic temperatures environment or even a steam cycle at 134 °C, the number in hundreds of thousands usually refers to the bench test conducted at room temperature and normal pressure conditions.The practical guide to diaphragm valve use covers the operating envelope in more detail, including how actuator type changes the closing force and therefore the diaphragm stress.
How It Compares With Ball and Butterfly Valves
A fair comparison, since the other two types are valid before plant parts.
- Diaphragm valve. Zero dead leg valve, no valve bonnets, total SIP (sterilization in place), best draining, pressure limited to approximately 16 bars, normally being Class 150, some restriction of flow at the weir, diaphragm needing to be replaced. Recommended for sterile applications and WFI service.
- Sanitary ball valve. Full bore with quick quarter-turn operation, can withstand higher pressures, cheaper even with smaller units. The ball cavity is undesirable unless cavity-free designs are in use, PTFE seals have poor performance with SIP temperature, and regulators dislike using it for application with sterile products.
- Butterfly valve. Compact with lower cost with high size, low pressure drop. The disc and stem produce a wake and the shape of the seat traps the media product in it, thus being used only for utility or cooling water and not for products.This valve selection reference sets out where each family sits, and it is a useful sanity check before a specification gets frozen.
In reality, the typical situation in plants is that there is not a single valve type for all areas. We find that diaphragm valves are used in the dosing of raw materials and gull valves to control pure water and services, butterfly valves in the case of large-bore cooling and CIP supply. The specification providing a generalized term for all types of valves is either unreasonably expensive or contradicts the common requirements and is usually both of these things.
Where They Appear in a Pharmaceutical Plant
Fermentation is the process involving the use of a bioreactor and nutrient feed, antifoam addition, harvest line and sampling valve, as well as the formulation in which the bioreactor bottom body is such as to have minimum hold-up.
Water for injection reaches a distribution point at every take-off and every isolation on the loop where the process goes on continuously and there is no dead leg inviting a microbe.
Aseptic filling involves product path, buffer addition, CIP/SIP connection on the filler so that the valve is located inside the aseptic heart, where servicing is made difficult on purpose.
Purification and chromatography involve buffer preparation, elution and column bypass, taking into account that the streams are strong enough to require PTFE facing.
Utility at the boundary refers to a phenomenon such as the clean steam, compressed air and gases where the valve is chosen for being easy to clean, not sterile.The tubing and fitting side of the same system is covered in this look at stainless steel sanitary tubing in biopharmaceutical production, and it matters because a valve is only as cleanable as the tube it is welded into.
What to Put in a Purchase Specification
An essential piece of specification that must be included in a quotation appears relatively short consisting of just eight lines.
Proceeding with the specifications first we come across the body material.316L with carbon content lower than 0.03% having certificate traceability with the heat number reference. The specification shall also indicate body type and size in DN (diameter nominal) as well as tube OD as a body design varies i.e. a weird body, a straight through, a tank bottom and a multi-port block.
Specification for diaphragm line being larger compared to its actual length should include diaphragm material, diaphragm thickness, diaphragm temperature rating and compliance certificates on USP class VI and FDA 21 CFR 177. In the next line of the specification end connections number appears in the specification. The connection types can be either clamp/butt welding/flange/union and standards to be included for clarification.
Actuator is another line that follows, either manual or pneumatic actuator with normal open or normal closed operation and feedback presence. The pressure and temperature ratings have to be specified together. Such action is essential since pressure only does not mean anything without temperature and vice versa.
It is also important to mention documentation which refers to material certification, surface finish report, pressure testing documentation, diaphragm certificate etc. Documentation line is a line where cheap quotes can be distinguished from the correct ones.The wider requirements, including welder qualification and the acceptance criteria for the piping itself, are set out in this overview of pharmaceutical piping under BPE standards.
FAQ
Why are diaphragm valves used?
Due to the fact that diaphragm separates the functioning element from the product which in turn removes the stem sealing and packing, and also thanks to the body being designed in a way to essentially eliminate dead volume, this leads to the product being cleanable and sterilizable in-line which is necessary for sterile manufacturing process.
What types of valves are commonly used in the pharmaceutical industry?
We provide diaphragm valves that can be employed in product and sterile service applications, sanitary ball valves for utilities and purified water, butterfly valves for large bore cooling and CIP piping along with check valves and sampling valves as the need arises. Thus, it could be seen that the equipment is dependent on the service provided rather than being a universal rule for the plant system.
Which type of diaphragm valve is the most commonly used?
The bodies manufactured in sizes DN8 to DN100 are the most efficient. Their dead volume is low, and the bodies drain effectively, unlike any other products. The straight-through bodies are used in the process, where there is a face of solids, otherwise; the bodies would get stuck due to the solid particles.
Are diaphragm valves sanitary?
Certainly, if hygienic construction is applied, such as using 316L and having a surface roughness value between 0.38 and 0.8 micrometers in wetted zones, crevice-free design and also FDA and USP Class VI compliant diaphragm and properly angled body. Regular production of diaphragm valves is not considered hygienic in any way although they may look alike from far away.
Do diaphragm valves need frequent replacement?
The diaphragm is a component that has a limited lifespan. Processing time in pharmaceutical manufacturing is one to three years for EPDM and two to five years for PTFE. Generally speaking, the total number of sterilization cycles is of more importance than the time of elapsing. Having spare materials in stock is necessary because diaphragm failure causes not only a maintenance issue but issues with batches.
References
- ASME — Bioprocessing Equipment (BPE) Standard
- 3-A Sanitary Standards, Inc. — Hygienic Design Criteria
- EHEDG — European Hygienic Engineering and Design Group
- Alfa Laval — Sanitary Valve and Fluid Handling Equipment
- Crane ChemPharma & Energy — Diaphragm Valve Engineering
Conclusion
Diaphragm valves are said to be the leading product in the pharmaceutical field. It does not indicate that it is the best product, but rather a type of valve in which the seal is the wetted element and also releases the stem that facilitates both the creation of packing and cavity. Everything else is based on that fact.
What is more, when obtaining a diaphragm valve, it is necessary to know two figures which describe the functioning of the valve, namely surface roughness Ra and dead leg L/D. If the supplier supplies both those figures as well as the methodology of measurement, this means that the supplier offers a sanitary valve. Otherwise, if he states “polished” only, he offers the just form of the valve.
