Installation of an Orbitally Welded Hygienic Piping System - A Case Study

Installation of an Orbitally Welded Hygienic Piping System


Image courtesy of ATW Services

In response to increased demand for the production of an asthma drug, an expanded hygienic piping system was installed in a UK manufacturing plant. The system was designed to provide process services for two blow-fill-seal (BFS) packaging machines, and to replace the original hand-welded system with an orbitally welded one. Several advanced design concepts were incorporated into the installation to satisfy the goals of cleanability and sterilizability. The packaging suite was designated as a clean room to prevent contamination of the product during the BFS process. Some of the implemented features, and guidelines for similar projects, are presented in this article.

The pharmaceutical technology industry has developed accepted practices for the design, fabrication and installation of process piping and equipment, such that process systems may operate in a clean and sterile manner. It is also appreciated that the materials of construction must not affect the purity of the product. The material most commonly used for tanks, vessels and piping is stainless steel. Other components, such as gaskets and seals, may be made of other materials if they can tolerate the high temperatures reached during steam sterilization. The fabrication and welding must also be done in such a way that the corrosion resistance of the system is not compromised. The design features discussed in this article, consistent with the goals of cleanability and sterilizability, were implemented in the recent installation of a hygienic piping system at Boehringer Ingelheim's site in Bracknell, UK.

Zero deadleg valves

Zero deadleg valves were used to minimize deadlegs in critical areas of the piping system. In less critical areas, it was permissible for valves to be connected with tees or bends. A deadleg in a piping system is defined as a pocket, tee or extension from a primary piping. The term L/D applies, in which L is equal to the leg extension perpendicular to the 'normal' direction of flow and D is equal to the i.d. of the extension or leg. For pharmaceutical process piping systems, it is desirable to keep the deadlegs to a minimum. Although an L/D of 2:1 is achievable with current design technology for valving and piping, 4:1 is considered acceptable for most bioprocess and pharmaceutical applications. A large L/D makes it more difficult to achieve a sterile condition with steam sterilization because air pockets prevent steam reaching all surfaces:1 If deadlegs exist in a system, some provision should be made for flushing them through.

Effectiveness of the cleaning system

The successful operation of the process depends upon the design and operation of the cleaning system. The use of clean steam for thermal disinfection is suitable in pharmaceutical applications in which steam enters the processing equipment and contamination of the product must be avoided. Clean steam differs from plant steam by the requirement for chemical purity, such that additives (for example, corrosion inhibitors) are not used. Pure steam is similar to clean steam, but must be virtually free of pyrogens or endotoxins and generally uses water-for-injection (WFI) as feedwater.2

Delivering steam at sufficient temperature and pressure to ensure sterilization requires careful engineering.3 The installed process system features a clean steam generator that makes steam from deionized water and sends it to the clean steam header (CSH) at a rate of 150 kg/h at 3 bar. The header volume is 20 L at 2 bar. Outlets from the header supply the mixing vessel and holding tanks with two separate lines for the blow-fill-seal machines (rommelag ag, Buchs, Switzerland). The header design promotes fractionation of dry steam and condensates, so that dry steam is delivered via the manifold and the condensate exits via the bottom through a steam trap. Both the 6 in. diameter CSH, which is enclosed in a 10 in. insulating jacket, and the piping entering and leaving the CSH are insulated to conserve heat.


Figure 1: Details of the clean steam generator and header that deliver clean steam to the process piping and vessels for sterilization. The piping and header are jacketed to conserve heat.

Figure 2: Details of piping system, showing swing bends used to select routing of product. Completely welded systems must be physically connected. Such a design should prevent operator error.

To be effective as a sterilant, clean steam must be delivered dry, saturated and without entrained air. Clean steam condensate must not be allowed to flow back into aseptic process systems during or after sterilization. In this system, connection to the 4 in. drain was made only when dumping water from the system, so that accidental backflow cannot occur. Steam traps were used to remove condensate and air from the system. Engineering of the system, including selection of piping diameters, was based on the temperature calculations for heat loss.

Engineering was also required to determine the details of placement and design of the sprayballs used for cleaning the vessels. The coefficient of discharge through the orifice was calculated to determine the size and number of holes in the sprayballs for the most efficient cleaning. Sprayballs should produce a uniform spray coverage over a defined area of the equipment with no decline in performance, and with ±20% variation in flow rate or ±20% change in pressure at design conditions. The location of the sprayballs must also be planned to avoid thermal shadows if temperatures fail to achieve sterility.

Swing bends

It is desirable for high-purity piping systems to be designed to minimize the number of clamp or hygienic (sanitary) connections and fittings and, if practical, piping systems should be installed in which all the joints are welded. In the Boehringer project, flexible connections, which were initially specified for connecting the piping for sterilizing or charging the vessels, were replaced with a swing-bend design featuring all-welded connections. The new design minimizes operator error, which literally could send the product down the drain.

Drainability


Figure 3: Tank bottoms and piping are sloped to promote complete drainability (image provided by ATW Services).

Drainability is an essential feature of any hygienic piping system. Retained fluid in the piping provides a medium where bacteria could grow, adding an unacceptable bioburden to the system. Retained fluid could also promote corrosion, leading to product contamination. The utilization of gravity has been found to be the most effective method of removing all traces of liquid from a process system. The piping system was therefore designed with falls or slopes to ensure complete drainability. The tong runs of piping leading to drains were sloped to provide a 1:100 fall, which is equivalent to approximately 0.125 in./ft, and the bottoms of the tanks were sloped to ensure that pools of liquid do not accumulate on the vessel bottoms.

Bursting discs

Bursting discs were installed on the holding tanks to provide pressure relief. These devices must also conform to acceptable L/D standards for cleanability. Bursting discs were used in preference to spring-loaded safety valves which, once opened, might not reseal or might open momentarily and lose sterility.

Orbital welding

For critical pharmaceutical piping systems, it is better, when possible, to use orbital welding because of the superior quality of the welds and the repeatability of the process. Orbital welding provides precise control of the heat input into the weld that cannot be duplicated with manual processes and generally results in better corrosion resistance than manual welding. In situations where the use of orbital welding would create a deadleg or an unacceptable L/D, however, manual welding is preferred.

The orbital welding power supply employs pulsed arc GTAW (gas tungsten arc welding), formerly known as TIG (tungsten inert gas). Weld parameters, controlled by the power supply, include primary and background values of pulsed welding current, primary and background pulse times and rpm, which determines the surface travel speed of the tungsten electrode. Each level of the weld programme is precisely timed, where a level change typically implies a change of primary welding current. At the start of the arc, rotation is delayed to allow the formation of a weld puddle or pool, which completely penetrates the tubing wall. The gradual downslope of the current at the end of the weld prevents cracks or craters that might form if the current were cut off abruptly. The power supply at the installation at the Boehringer site was equipped with a water cooling unit, which circulates water through the weld heads and cables during welding to keep them cool.

Three different sizes of weld head were used on the various tubing sizes. With orbital welding, the tube remains in place while an arc is struck between a tungsten electrode and the weld joint. The electrode, installed in the weld head rotor, orbits the weld joint to complete the weld. These weld heads are all of the 'enclosed' type, in which the body of the weld head, filled with an inert gas, forms an enclosed chamber around the entire weld joint. The inert gas, usually argon, forms a shield that protects the outside of the weld joint from oxidation during the weld sequence. The inside of the weld joint must also be purged with inert gas. The enclosed type weld head is particularly suitable for high-purity purging. If a small gap exists between components being welded, it ensures that no air enters the inside of the tube, only argon from the weld head. Tube alignment is critical in pharmaceutical applications where offset of the weld joint members would create a ridge on the inner surface of the tube that would prevent complete drainability.

Piping systems

Orbital welding was specified for the pipe-work that supplies hydraulics to the cylinders on the mould tool (rommelag) because this system, which opens the mould once the ampoules have been made and filled, runs at approximately 100 bar and was thus considered to be particularly critical. To ensure the quality and consistency of these welds, seamless 316L tubing specified to ASTM A269 was used. For tubing that came into contact with the product, pure steam or deionized water, orbitally welded 316L tubing specified to ASTM A270 was used. This tubing had an internally polished bore of approximately 20 Ra maximum (roughness average in micro-inches) or better. These systems included a 2 in. o.d. (outer diameter) line for deionized water, a 0.5-1.0 in. o.d. line for clean steam, and 0.5 in. o.d. lines for compressed air and cold water. The 0.5 in. o.d. stainless steel product line was also orbitally welded. Orbital welding was not used on the non-critical copper chilled-water piping nor on the 4 in. stainless steel drain line, which was welded manually and had no defined internal quality requirement other than to clean and descale. Longitudinal welds from the manufacture of this tubing were also removed. Random samples of tube and fittings were checked to verify surface finish.

Welding in areas of limited clearance. Most pharmaceutical piping systems tend to have a few welds where clearance is so limited that it is not possible to mount an orbital weld head.4 Inevitably, these joints must be welded manually. In the piping system at Boehringer Ingelheim, it was not possible to mount the 9CT-750 weld head on the 0.5 in. o.d. line from the mixing to the holding tanks, so this line was manually welded. A variety of devices exist to enable orbital weld heads to be mounted in areas with limited clearance or to fittings with short stubs or 'stick-outs .' If fittings designed for orbital welding (designated as long tangent) are used, they can generally be welded in a standard weld head without any modification. This requires a straight section of tube or fitting (on both sides of the weld head) of sufficient length to extend from the margins of the tube clamp inserts to the tungsten electrode, which is usually, but not always, located at the weld head centre line. For a 2 in. o.d. tube in a 9-2500 weld head, a straight section of 1.72 in. (43.7 mm) is required. For a 0.5 in. o.d. tube welded in a 9AF-750 head, this distance is 0.70 in. (17.8 mm).

If sections are shorter or no straight section is available, such as with short radius (industrial grade) elbows or bend the joint must usually be manually tacked in place prior to welding and welded in a head modified for this purpose. In such a head, the housing is removed from one side of the head and replaced with a gas seat to contain the shield gas within the head. The weld assembly is held in the head with tube clamp inserts located on one side of the head only. The tungsten electrode, held in a special tungsten extender, is located to the side of the head, which has the gas seats. In this configuration, it is possible to weld fittings or valves very close to the edge of the weld head. Special tools are available for welding short sanitary ferrules to tubing or fittings in these weld heads. Another type of tungsten extender, called a 'mushroom' because of its shape, has a bar holding the tungsten that can be positioned almost anywhere within the weld head. By using the mushroom, nearly all of the joints in a pharmaceutical piping system can be welded using only standard weld heads.5

It is easier to mount a head on a pipe with restricted clearance if the head is the smallest that can be used for the particular tube size being welded. Many contractors will use a single head size to weld several sizes of tube, such that it may be difficult to mount the head on the smallest tube size because of limited radial clearance between the lines of tubing. In addition, narrower weld heads are now available with water cooling, which should help increase the number of joints that can be orbitally welded in areas with limited axial clearance.

Weld criteria

Fusion butt welds for pharmaceutical applications, whether manual or orbital, should always be completely penetrated around the entire circumference, without excessive concavity or convexity of the outer or inner surface. The weld joint should be purged with a good quality purge gas to eliminate or minimize the appearance of oxidation on the inner surface. Cracks, crevices, porosity and welding dross (stag), which would interfere with complete fusion of the joint, should be avoided. The weld bead should be of uniform thickness, without thin spots, and the arc should not differ from side to side to such a degree that could result in a lack-of-fusion defect. Alignment of the weld components should be such that no ridge is formed on the inner surface of the weld joint, which would affect the drainability of the piping system. For proper alignment, the dimensional tolerances of the tubing and fitting ends must meet material specifications for diameter, wall thickness variations and ovality. In addition, a good machined square-end preparation is a prerequisite for consistent high-quality orbital welds.

Welding quality control

Welding quality control (QC) is the responsibility of the owner, but it is most important that owner and installer have similar expectations and are in agreement on weld quality before the start of a construction project. The best way to accomplish this is to have a written specification for welding and to make test coupons that conform to the specification on the actual materials to be used before the start of the job. On the Boehringer site, test coupons were made, examined for the criteria listed above and retained on file to be referred to in the event that a questionable weld was made. QC procedures required that the lines were labeled with the heat number (cast number) of the tubing, the date of welding, the weld number as it appeared on the ISO drawing, and the piping system number. In addition to being recorded on the pipe itself, all of this information was recorded in a weld log for future reference.

It is most important on a job such as this that all craft personnel are properly trained for the tasks they are expected to perform. The welding procedure, as well as the manual welders and orbital welding operators, were certified to BS 4870 part 4 and EN 287-288. Orbital welding operators received training from the manufacturer of the orbital welding equipment. They must be able to set up the equipment and write weld programmes (or schedules) for tubing or pipe sizes up to 6 in., which is the upper size limit of the orbital fusion welding equipment. Operators must also be able to enter the weld programme into the power supply and make a weld. They must then be able to evaluate the weld and make adjustments in the weld procedure or programme until an acceptable weld is achieved. A major benefit of orbital welding is that once an acceptable weld programme has been developed, the precise control of the process makes it possible to continue to make an unlimited number of similar high-quality welds. If the heat number of the material being welded changes, it is necessary to make a new test coupon and evaluate the weld as above. The only change normally required is an adjustment of a few amperes of welding current.

High-purity purging technology

Orbital welding in the semiconductor industry is used extensively for welding process gas lines for the manufacture of semiconductor devices and integrated circuits. The tubing used in that industry is 316L tubing, electropolished to a surface finish of 10 Ra or better. Purging for welding is done with argon or an argon/hydrogen mixture, purified to a low level (ppb), so that no visible sign of oxidation is present on the inner surface after welding.

Although high-purity purging technology has been the norm for the semiconductor industry, the pharmaceutical industry has traditionally been more lenient in its welding specifications. A light-straw coloured oxidation in the heat affected zone (HAZ) of welds on stainless steel tubing is generally acceptable. However, excessive heat tint or oxidation has been shown to reduce the corrosion resistance of stainless steel6 and has been implicated in the formation of rouge in pharmaceutical piping systems. Rouge consists of the products of corrosion that circulate through a piping system, where it may do little harm or may promote further corrosion and product contamination.7 Hansen et al. found that the pitting potentials of stainless steel tubing declined steeply when the oxygen content of the purge gas exceeded 100 ppm.8 Straw-coloured oxidation occurs at oxygen levels of approximately 25 ppm. Although some loss of corrosion resistance may occur with welding, recent studies have shown that this loss can be minimized by welding with argon gas purified to <0.1 ppm oxygen.9 Although the effects of deep heat tint cannot be reversed by passivation, evidence suggests that chelant passivation can reverse all or most of the changes in surface elements across the weld and HAZ when purified gas is used for the purge.

High-purity purging techniques require an ultra-clean source of purge gas, and this must be delivered to the inner surface of the weld joint without picking up significant amounts of atmospheric oxygen or moisture as it travels through the purge delivery system. ATW Services used a stainless steel diaphragm in the argon regulator, because the standard neoprene diaphragms are somewhat permeable to oxygen. Similarly, low permeability hoses and airtight purge plugs are needed to maintain the low oxygen and moisture levels in the purge gas. These procedures may seem extreme for a pharmaceutical installation, but if they can prevent the occurrence of rouge in the system, it will be worth the effort.

Summary

Pharmaceutical manufacturers are under pressure to produce products safely, at reduced costs and to higher quality standards than in the past. Innovative system design and new manufacturing technologies will certainly play an important role in accomplishing these goals.10 Yet it is important to determine the cost-benefit ratio of new technologies to avoid inflating the costs without achieving the desired effects.

Orbital welding has become the standard method of joining piping systems for biotech and pharmaceutical processes in the USA, but in Europe it is still difficult to convince end-users that orbital welding and advanced fabrication technology is justifiable. A leading contractor in the USA has made more than 100000 orbital welds in critical pharmaceutical piping systems and, through continuous improvements of its standard operating procedures (SOPs), has reduced the reject rates of orbital welds to approximately 0.2%.11 Rework adds greatly to the expense of pharmaceutical installations. Clearly, it is cost-effective to do it right the first time. The quality of orbital welds also facilitates CIP/SIP (clean-in-place/steam-in-place) operations. The smoother weld bead makes cleaning more effective and may allow for longer intervals between cleaning and longer production runs, leading to higher profits. Considerable evidence suggests that orbital welding, particularly in combination with high-purity purging, results in better corrosion resistance of the piping systems. The combination of more advanced design concepts and orbital welding technology should help pharmaceutical companies to build better manufacturing facilities and compete more effectively in the future.

By Gary Littlewood, ATW Services, and Barbara K. Henon, Ph.D., Arc Machines, Inc.



References

  1. J.H. Young, "Engineering Aspects of Steam Sterilization," ASME Bioprocess Engineering Symposium Proceedings, ASME Winter Annual Meeting, Chicago, Illinois, USA (1988).
  2. P.J. Smith, "Design of Clean Steam Distribution Systems," Pharm. Eng. 15(2), 72-79 (March/April 1995).
  3. T. Latham, "Clean Steam Systems," Pharm. Eng. 15(2), 8-19 (March/April 1995).
  4. B.K. Henon, "Welding of WDI and WFI Piping Systems for a Bioprocess Application," Pharm. Eng. 13(6), 18-24 (November/December 1993).
  5. B.K. Henon, "Case Study: Pfizer Animal Health Group Upgrades and Expands Facility with Orbital Welding and State-of-the-Art Equipment," Pharm. Eng. 16(2), 20-24 (March/April 1996).
  6. J. Kearns and J. Maurer, "Welding Guidelines to Minimize Service Degradation of Stainless Alloys in Bioprocess Systems," Fifth Annual Bioprocess Engineering Symposium, ASME Winter Annual Meeting, San Francisco, California, USA (1989).
  7. D. Coleman and R. Evans, "Fundamentals of Passivation and Passivity in the Pharmaceutical Industry," Pharm. Eng. 10(2), 43-49 (March/April 1990).
  8. J.V. Hansen, T.S. Nielsen and P. Aastrup, "Root Surface Quality Requirements - High Efficiency Purging or Pickling? Paper 46, Conference on Duplex Stainless Steels," Glasgow, UK (13-16 November 1994).
  9. B.K. Henon and A. Grant, "Orbital Welding for Hygienic Pharmaceutical and Biotechnology Applications," 15th Annual Pharm Tech Conference, Oxford, UK (March 1996).
  10. J.A. Blanchard and A.A. Signore, "Cost-Effective cGMP Facilities," Pharm. Eng. 15(2), 44-54 (March/April 1995).
  11. K. Gilson, "Why Design Build?" presented at the ISPE Greater Los Angeles Chapter Workshop, California, USA (May 1994).