Pfizer Animal Health Group Upgrades and Expands Facility with Orbital Welding and State-of-the-Art Equipment
Pfizer Animal Health Group Upgrades and Expands Facility with Orbital Welding and State-of-the-Art Equipment
This case study highlights how Pfizer Animal Health Group expanded its facility and made improvements to an existing plant in preparation for the production of a new injectable endectocide called Dectomax. Orbital welding was used for the new 316L stainless steel WFI, clean steam, and CIP/SIP piping. All process piping for the Dectomax product, which includes the product transfer lines from the holding tank area to the filling suite, were joined by orbital welding. To assure that the completed piping systems would be fully cleanable and sterilizable, all welds were inspected on the inside surface with a video borescope. This inspection verified that each weld was fully penetrated, uniform, smooth and crevice-free. All welds were fully documented and videotaped records maintained for FDA approval.
Lee's Summit, Missouri, October 1995
Pfizer's Animal Health Group is in the final stages of a facility upgrade and expansion, which began on a project-by-project basis several years ago.
The recent improvements are part of a general plan to assure compliance with continuing changes in cGMPs. Improvements to the plant include the installation of a new sterile fill line and new packaging equipment that will be used for all injectable pharmaceuticals manufactured at this facility.
Even the new vacuum lines (HVAC) are orbitally welded stainless steel. The existing boiler room was expanded to accommodate a new WFI storage tank and a clean steam generator which were installed next to the existing ones so that the latter could remain in operation during the shutdown. A new vapor compression still supplies the WFI system.
Part of the expansion is dedicated to the production of a new product, called Dectomax Injectable. Dectomax is a long lasting endectocide with a broad spectrum of activity against both internal and external parasites in cattle and swine. The new portion of the facility includes two Dectomax compounding areas with two huge new tanks. A Dectomax staging area and a new utility room which services the new area are also part of the new construction.
Sterile Fill Line and Packaging Equipment
Figure 1. Welding operator preparing to weld tubing on the new sterile fill line.
Ronald Johnson, Process Development Manager for the North American Animal Health Division, has spearheaded the installation of the new sterile fill line and the new packaging equipment as well as the expansion for the production of Dectomax. Although the first purchases were planned as early as 1985, each project waited for funding approval which was completed one project at a time. For the past two years, the Process Development Group has been actively working on unifying the project concept with the goal of continuous process improvement. In accord with Pfizer corporate policy which tries to go well beyond the minimal regulatory requirements, the new systems have been designed with worker safety, environmental and health considerations in mind. The conversion of many of the operations associated with filling and packaging from manual to automated systems should greatly improve productivity.
On the new packaging line, the first WFI drop is supplied to the washer for cleaning bottles prior to filling. After the bottles are washed, they go through a new state-of-the-art depyrogenation and sterilization tunnel. The tunnel operates at a temperature of 350° C. This temperature is much higher than needed for sterilization, i.e., killing all of the bacteria present, but is necessary to destroy pyrogens or endotoxins, as required for injectable products. Bottles are filled in the new sterile fill area in the clean filling room, then capped and sent to the new packaging area.
Top-of-the line equipment and materials were selected for the upgrade and expansion in keeping with the intention to upgrade the Animal Health production facility.
Orbital welding was used for the new WFI, clean steam and CIP/SIP piping. All process piping for the Dectomax product which includes the product transfer lines from the holding tank area to the filling suite were joined by orbital welding. All the product lines have CIP/SIP capabilities and process vessels have a clean steam drop that was orbitally welded. Orbital welding has become the standard method of joining piping for pharmaceutical applications because of the smooth inner weld bead which is essential for cleanability.
Piping systems materials were selected to provide excellent corrosion resistance and a very smooth surface finish. Type 316L stainless steel tubing contains about two percent molybdenum to provide additional corrosion resistance compared to type 304. Both the fittings of 316L stainless steel and the tubing were electropolished on the inside surface (ID) to provide a 20 µ inch RA finish (equivalent to .51 µ meters or 180 grit). The effective application of the CIP/SIP technology demands that the inner piping and weld joint surfaces be smooth and free of crevices that could harbor bacteria.
During welding, the molten stainless steel weld puddle must be protected from atmospheric oxygen to retain its bright clean finish. Even trace amounts of oxygen and/or moisture in the purge gas can leave slight amounts of discoloration or "heat tint" on or near the weld which is undesirable. An excessively oxidized weld would inevitably lead to corrosion of the piping system in service. At this jobsite, the argon used for purging the orbital welds and the inside of the tubing during welding was supplied in cryogenic dewars. The phase change from liquid in the dewar to the purge gas results in a very clean grade of argon suitable for biopharmaceutical applications.
The contractor has been on-site since 1993 and the superintendent has been in charge of the fabrication and orbital welding of new piping systems for the past eight years.
The orbital welding system includes a microprocessor-based Model 207 power supply equipped with a cooling unit (207-CW), a Model 9-2500 and a Model 9-4500 weld head manufactured by Arc Machines, Inc. in Pacoima, California. The Model 207 allows for the storage in memory of up to 99 weld programs with parameters for welding tube and pipe sizes from 1/8 inch up to 6 inch schedule 5 pipe (10.3 - 168.3 mm). To weld a particular size of tubing, the operator enters the number of the weld program for that particular size and configuration, and with the tubing installed and the purges set, pushes the "Sequence Start" panel switch to initiate the weld sequence. An arc is struck and a rotor inside the weld head carries the tungsten electrode around the tube circumference to complete the weld.
Figure 2. New sterile fill line at Pfizer Animal Health facility.
Figure 3. Flow control panel for CIP/SIP system. Welds are done orbitally except those to the plate.
Figure 4. Welding operator inspecting the inside (I.D.) of a weld with a video borescope. The weld is displayed on a video monitor.
The weld program executed by the welding power supply controls the amount of welding current, pulsation rate, travel speed and time required for the weld of a particular size and wall thickness. The power supply keeps a running count of the number of welds done on each weld program as well as the total number of welds done by the machine. At this site, welds from 1/2 inch to 2 inch OD (12.7 - 51 mm) were done with the Model 2500 weld head, while welds from 2- 1/2 to 4 inches OD (64 - 102 mm) were done with the Model 9-4500.
Prior to welding, it is sometimes necessary to manually "tack" the pieces to be welded together to hold them in position to make the weld. Tacking for this application was done with a "Lift Arc" welding machine. The arc is started as the torch is lifted from surface which avoids tungsten inclusions in the weld that might result from touch-starting of the arc. Purging of the tube ID during manual tacking was done with welding grade argon. The contractor was able to reduce the amount of pretacking considerably below that required for a manual welding installation by using long tangent fittings designed for orbital welding. These fittings have a somewhat longer straight section allowing them to be held in place for welding by the tube clamp inserts or collets on each side of the weld head.
In addition, a "mushroom" tungsten extender was used to position the electrode asymmetrically in the weld head making it possible to use fittings with a shorter straight section than could be accommodated in the standard weld heads. This reduced the number of welds that required the use of the "E" configuration of the weld head which typically requires that assemblies be pretacked since "E" heads provide support for the tube on only one side. By using the mushroom in the standard heads, and some long-tangent fittings, the amount of pretacking required on this installation was held to only 5 percent of the items welded.
The FDA demands traceability of welds and the maintenance of a weld log so that if a problem with a weld occurs in the future, the source of the problem can be determined and corrected. Prior to installation, each piping system to be installed was shown on a weld map with complete spool drawings showing the system branches and the location of each weld identified by number. As each weld was done, it was listed by number on a Program Welding Log listing the job number, the weld program number used to make the weld, the welding power supply by serial number and the date. This information as well as the tubing diameter and wall thickness, the welder's name and identification mark which was written on the actual pipe next to the weld, were recorded in a Master Weld Log.
The industry standards and specifications that welds are qualified to will determine to a large extent the quality of the piping system. Orbitally welded pharmaceutical piping systems may be qualified to ASME Section IX of the Boiler and Pressure Vessel Code to determine the structural integrity of the weldments. Bend and tensile tests are performed by a qualified testing laboratory to assure that the welded tube meets the minimal tensile strength for the material and that the weld is ductile. Results of these tests are recorded in the Weld Procedure Specification, Procedure Qualification Record and the operator who performed the test weld is qualified in a Performance Qualification Record. Weld acceptance criteria outlined in ASME B 31.3 may be referenced.
The pharmaceutical industry in the USA has traditionally followed the recommendations of the 3A Sanitary Standards and Accepted Practices for permanently installed sanitary product pipelines, cleaning systems and bioprocessing equipment fabrication as formulated by the International Association of Milk, Food and Environmental Sanitarians (IAMFES), the US Public Health and the Dairy Industry Committee and published by IAMFES. Both ASME and 3A Standards were originally written for manual welding but can be applied to orbital welding as well. Several groups are now writing or rewriting standards to apply more directly to orbital welding. In realization that existing standards did not meet the need of the emerging bioprocess industry, the ASME Council on Codes and Standards approved the formation of the ASME Bioprocess Equipment (BPE) Main Committee in 1989 to write a new standard for the design of equipment and components for use in the biopharmaceutical industry. This standard will not conflict with existing standards but references them when applicable and exceeds them when necessary.
Regardless of which codes are referenced, a written standard which includes criteria for weld acceptance should be in-place for any high purity installation. Since a written standard may be open to interpretation, all parties must be in agreement with respect to weld acceptance criteria, before the start of production welding. A sample weld piece made prior to the beginning of the job that satisfies the criteria of both owner and contractor is the best assurance that quality control during the job will go smoothly.
For this installation, all accessible welds were visually inspected with a video borescope. Once completed, the inspector's signature was recorded next to the weld number in both the Program Welding Log and the Master Weld Log. The borescope probe has a mirror on the end that can be held at an angle for a direct view of the weld which is seen on the video monitor.
Figure 5. Quality control precedures for orbital welding include marking each individual weld with the weld number, piping system color code, welder’s name and date.
Figure 6. Top of new WFI storage tank with some associated piping that was instralled with orbital welding.
The inspector looks for a weld bead of uniform width around the entire weld circumference. The weld criteria in effect permitted no evidence of a lack-of-fusion defect, or excessive discoloration resulting from oxidation. In general, the inner weld bead should be smooth and fairly flat, i.e., neither concave nor convex, with respect to the tubing surface with no porosity or other defects which would either affect the structural integrity of the weld joint, or compromise the cleanability or sterilizability of the completed piping system. As each weld was inspected, the weld number and location on the video tape were recorded on the audio portion of the videotape so that any weld in any of the installed systems could be instantly called up and inspected on the VCR and cross referenced with information recorded in the welding logs and the weld map. At this facility it was possible to borescope 99.5 percent of the welds. For the remaining "blind" welds, test coupons were done before and after each weld to assure that the actual weld would be good, and the voice recording of the location of the weld by number and video frame was recorded.
Next to the weld on the pipe, the number, date, welder's name and color code for the piping system was marked for each weld. This extensive quality control makes it possible for the FDA or other interested party to call up a weld number from the weld map or master log and view the entire inside (ID) surface of the weld on the video monitor almost instantaneously. A total of well over 2,000 welds have been recorded for this expansion on the Model 207 power supply which includes test coupons performed for QC. After the welding is completed on a piping system, the system is passivated with a solution containing nitric acid to restore the "passivity" of the system enhancing its resistance to corrosion in service. This is particularly important for WFI and clean steam systems since purified water is an aggressive solvent which would otherwise attack the stainless steel. The welded WFI and clean steam piping systems were insulated to help maintain their normal operating temperatures.
Contractor's Assessment of Orbital Welding
Orbital welding provides benefits to four groups of people: the FDA, the craftsmen, the contractor and the customer. The consistent quality and uniformity of welds easily satisfy FDA requirements. Orbital welding adds a measure of prestige to the craftsman and allows him to routinely produce a quality product. For the contractor, orbital welding increases both speed and performance. Less time is needed for buffing and polishing of the welds, since the orbital welds are much smoother in the as-welded condition than manual welds.
This increased productivity means more profit for the contractor. Usually, when speed is increased on the job it means cutting corners on performance or quality. With orbital welding both speed and consistency of quality are enhanced simultaneously which benefits everyone.
When bidding a job based on the time per weld, the contractor has found that for sanitary applications, orbital welding is most economical for the customer. The customer is satisfied because he can more easily meet the FDA requirements and, ultimately he benefits from a piping system that will be cleanable and more resistant to corrosion. This will result in a longer service life for the piping system which will enable the customer to produce a better product for an extended period of time.
By Barbara K. Henon, Ph.D., Arc Machines, Inc.
1. Kearns, J.R. and J.R. Maurer. 1991. Welding guidelines to minimize service degradation of stainless alloys in bioprocess systems. Fifth Annual Bioprocess Engineering Symposium at the ASME Winter Annual Meeting, Atlanta, Georgia.
2. Henon, B.K. welding of WDI and WFI Piping Systems for a Bioprocess Application. Pharmaceutical Engineering, November/December, 1993.
The author gratefully acknowledges the cooperation and assistance of Ronald Johnson, and Frank LaPietra of Pfizer Co., and Bud Hendrix and Steve Hurlburt of Rand and Son Construction Company.
About the Author
Barbara K. Henon, Ph.D. is Manager of Technical Publications at Arc Machines, Inc. She has 11 years of experience in the on-site training of welding personnel and development of welding procedures for applications in the pharmaceutical and bioprocess industry as well as the semiconductor, aerospace, nuclear, and other critical industries. Technical articles by Dr. Henon on welding issues have appeared in industry publications and she has presented numerous technical seminars on orbital welding topics. Dr. Henon received her PhD from the Department of Biological Sciences at the University of Southern California and conducted research in neurophysiology at the Beckman Research Institute at the City of Hope in Duarte, California. She is the Chairman of the ASME Bioprocess Engineering Subdivision, and a member of the ASME Bioprocess Equipment Main Committee and the Subcommittee for Materials Joining which are working on the writing of a new ASME standard for the fabrication of bioprocess equipment and facilities in the US. She is currently involved in a research project with Cal-Chem Corp. and the University of Southern California on the welding, corrosion and passivation of stainless steel tubing.