Aseptic Process Systems
Over the last couple of decades aseptic process systems in the pharmaceutical industry have evolved from small molecule, chemical based systems to large molecule biological processes. With this evolution has come a change in process designs that includes but is not limited to clean in place and sterilize in place systems as well as an increasing regulatory burden. Not to mention the increase in use of disposable systems. It has been suggested that valves, system dead legs and unused piping as well as poor performing elastomers used in gaskets and seals are key areas for improvement in aseptic bioprocess systems. In as much as the industry still relies on stainless steel based systems, it is important to note that some of the key equipment, most notably, membrane valves, commonly referred to as weir valves and their installation into the process have not changed much in this time.
The following compares today’s membrane valves to the latest generation of aseptic radial diaphragm valve manufactured by Rattiinox S.r.l. The radial diaphragm valve is a design approaching its 25th anniversary. One key difference from membrane valves is that it is based upon a right angle flow path. In this way the sealing point is at the outside limits of the valve. The Rattiinox CAD valve is the latest generation of radial valve and the first engineered around a solid PTFE diaphragm.
An old adage states that the devil is in the details. Another adage states, that if you want to clean it, don’t hide it. In the case of membrane valves, the devil is in the small areas of the valve that are very difficult to clean quickly and reliably. The reason is that all membrane valve designs result in several areas that include an asymptotic “dead leg”. This has been known for some time. The asymptotic angle is such that it approaches zero the closer it is to the seal point. This creates an area of low velocity and low turbulence. Both conditions inhibit quick and thorough cleaning. Another feature of membrane valves is that the valve design incorporates a dead leg into the body. This is unavoidable because of where the valve seals. By contrast the Rattiinox CAD valve incorporates stationary, open seal points that facilitate cleaning. There is no place for product entrapment. The turbulence created in the valve also helps reduce the possibility of biofilm formation.
The CAD valve diaphragms are precision machined from solid virgin PTFE block. This material is well known for its broad chemical and heat resistance and very low E&L profile that is well understood. The diaphragms are internally supported by a mirror polished stainless steel armature that also acts as a pressure contrast system, providing support against high pressure and vacuum. The CAD valve diaphragms also have a much longer life compared to flat membranes. Testing above one million cycles at temperatures above 150°C has been achieved with no discernable wear. At the same time sealing to pressures at 6 bar at -60°C is standard.
There are literally hundreds if not thousands of valve styles available however this number shrinks dramatically when discussing valves suitable for today’s sanitary and aseptic processes. Almost by default, membrane valves constitute the vast majority of valves currently used in sanitary process design for pharmaceutical systems. It is suggested that this tool kit is outdated because of the new demands placed on these systems. Some will argue that today’s process systems do not need to be aseptic because of final terminal sterilization steps. However, this line of reasoning does not take into account the costs due to lost product and additional work as well as the costs involved with repeated occurrences of membrane failures and elastomer material breakdown due to chemical attack from CIP and SIP steps. It seems it would make at least as much sense to strive to reduce or eliminate these occurrences and the resulting deviations as much as possible.
Because most every valve in a system can be considered unique simply because of where it is placed, Rattiinox has developed over 100 different versions of the CAD valve across the various sizes from ½” to 4”. This allows system engineers flexibility to select the correct valve for every location to insure there are no dead legs and to achieve the ultimate goal of full drainability and product recovery. Tank bottom outlet valves and take off valves on high purity water systems are well known applications for radial valves. However there really are no aseptic process applications were the CAD valves’ superior geometry and drain-ability are not improving the overall process. It is interesting to note that skid systems designed with CAD valves tend to have a smaller foot print and overall lower system volume which is certainly a benefit when dealing with today’s high value drug products.
Forward thinking engineers should realize that problems, especially those that are repeat offenders are opportunities for improvement and should be catalyst for change. Valves with poor performing diaphragms, and to a large extent gaskets that deform and stick, are often considered normal conditions because of the frequency that these issues occur. However there are solutions to these issues and it involves using the correct materials and designs. Our industry will continue to rely on stainless steel systems for large scale GMP production. It only makes sense to improve these systems to be easier and faster to clean and more reliable to sterilize, operate and importantly, validate. There is a new right way to a better end result which can be achieved by paying attention to the details.