Orbital Welding Technology for Pharmaceutical Piping Systems

Orbital welding technology for pharmaceutical piping systems

Figure 1. Orbital welding operators installing a stainless steel piping system in a pharmaceutical plant in the UK. (Photo courtesy of A.T.W. Services)

The capability of making a smooth, crevice-free inner weld bead on a repeatable basis, has led, over the past decade, to orbital welding becoming the preferred joining technology for biopharmaceutical process piping.

The expanding biopharmaceutical industry in the USA has placed an increasing emphasis on quality standards and documentation in order to expedite the approval process for new therapeutic products by the FDA (United States Food and Drug Administration).

The approval process requires that the facility in which a new drug is produced must be designed, constructed and commissioned so that it meets the criteria for process validation. Failure to achieve validation on the first attempt can be very costly to the facility owner, so maintaining quality from the design phase throughout the construction process is essential. The quality inherent in orbital welding joining technology is consistent with the goals of the CGMP (Current Good Manufacturing Practices) for achieving hygienic pharmaceutical piping systems that will have no adverse affect on the products that pass through them.

Validating critical process systems

In validating the critical process systems in a new or modified facility, the FDA will seek to determine whether the requirements of three key documents, the CGMP, the ASME (American Society of Mechanical Engineers) B.31.3 Process Piping Code, and the project specifications have been met.¹

Of these documents, the most significant is 21 CFR (Code of Federal Regulations) B211 which specifies how the various components in pharmaceutical manufacturing facilities are to be constructed. 21 CFR B211.65 Subpart D states:

(a) Equipment shall be constructed so that surfaces that contact components, in-process materials, or drug products shall not be reactive, additive or absorptive so as to alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements.

The FDA is very non-specific about how a critical piping system should be constructed, but relies upon the requirements detailed in the ASME B31.3 Process Piping Code and the ASME Bioprocessing Equipment Standard (BPE-97). It should be noted that a code is required by law, while a standard provides generally accepted industry practices.

The ASME B31.3 Process Piping Code gives to the owner the ultimate responsibility for documenting to the FDA that the critical piping systems have been manufactured, fabricated, and installed according to the CGMPs.

Welding is an important aspect of piping system design and fabrication. ASME B31.3 provides acceptance criteria for welds (Table 341.3.2), details the types of examinations required, the number of welds to be inspected, and establishes qualifications for welding inspectors. In 1989, representatives of the emerging bioprocess industry came together with the realisation that existing standards did not adequately meet the need for design and construction of equipment to be used in critical bioprocess piping systems. A consensus was reached on the need for equipment design that would be both cleanable and sterilizable. Special emphasis was placed on the quality of weld surfaces once the required strength was present. The ASME published the ASME Bioprocessing Equipment Standard (BPE-97) in 1997.

Figure 2. Stainless steel piping system installed with orbital welding at a UK pharmaceutical installation. Tank bottoms and piping are sloped for drainability. (Photo courtesy of A.T.W. Services, Inc).

Figure 3. Recent recommendations call for reduced deadleg L/Ds to improve cleanability and sterilisability. Orbital welding is ideal for this application, as shown on this orbital weld of a short sanitary ferrule to a pulled tee.

ASME BPE-97. Qualification to ASME BPE-97 requires that welds be certified to ASME Section IX of the Boiler and Pressure Vessel Code and ANSI/ASME B31.3 Process Piping. This requires that a Q.A. manual and a Q.A. program be in effect with a set of weld standards which reference the BPE Standard. ASME Section IX is done to verify the structural integrity of the weldments. To meet this requirement sample welds are subjected to bend tests to verify weld ductility, and tensile testing is done to assure that welds meet the minimum tensile strength specified for the base material. The results of these tests are documented as part of the WPS (Weld Procedure Specification) Form QW-482*, and the PQR (Procedure Qualification Record) Form QW-483*. Welders and welding operators may be qualified by making acceptable test welds and documenting test results on Form QW-484*. Welder tests require six linear inches of weld or multiple coupons, but not more than four.

It should be noted that hot WFI water, circulated at temperatures above 40ºC, may be classified as category M fluid service in ASME B31.3, which includes substances which will do irreparable harm in case of a piping system failure in which the contained process fluid comes into contact with human tissue. Weld and inspection criteria for this category are more stringent than for normal fluid service. 21CFR B211.65, Equipment Construction and B211.67, Equipment Cleaning, state that the materials used must be suitable for their intended use which would include the ability to withstand high temperatures and pressures as well as the ability to hold up to sterilising and sanitising agents. Clearly, orbitally welded stainless steel meets these criteria.

While ASME B31.3 was written with manual welding in mind, ASME BPE-97 recommends the use of orbital or machine welding for bioprocess piping. Manual welding may be used, with the owner’s permission, only when using an orbital weld head would create a deadleg. A deadleg is defined as a pocket, tee, or extension from a primary piping run that exceeds a defined number of pipe diameters from the I.D. of the primary pipe.

In ASME BPE-97 (Table SD-1) a deadleg (L/D) of 2:1 is considered to be an achievable target value for bioprocessing systems where L is the length of the extension measured from the OD of the primary pipe, and D is the I.D. of the extension. Deadlegs are undesirable because they are difficult to clean and maintain in a sterile condition and may represent an unacceptable bioburden to the system. Where they exist, they should be designed so that it is possible to flush through them.

Intelligent use of orbital welding

Figure 4. Left: manual weld taken from an operating pharmaceutical plant. Note lack of penetration, misalignment, discoloration, crevices and protruding material on the product contact surface. Right: orbital weld on 316L stainless steel tubing. Note uniform, even, fully penetrated weld bead and essentially flat weld profile with no concavity or convexity. Parts are well-aligned and the weld has minimal discoloration of the HAZ, meeting most biopharmaceutical specifications.

The intelligent use of orbital welding technology can help to keep deadlegs to the required minimum. Some orbital weld heads have provisions for locating the tungsten electrode close to the edge of the head to accommodate parts with short "stick-outs" such as welding short sanitary ferrules to stubs on transfer panels or to pulled tees, as shown in Figure 3. Narrow weld heads are now in use with reduced axial clearances that make it possible to orbitally weld fittings-to-fittings that could not be welded with standard weld heads.

For areas with limited radial clearances it is important to use a weld head that is as small as possible for the tubing being welded. Contractors tent to use a single weld head to accommodate all sizes from 1 inch to 4 inches, which is practical for most situations. However, some of the joints on smaller tube sizes that have inadequate radial clearance for a large weld head might be accessible with a smaller weld head. In designing piping systems, allowances should be made to allow for placement of orbital weld heads and eliminate insofar as possible the need for manual welds.

The International Society of Pharmaceutical Engineers is publishing a series of ISPE Baseline Guides developed by ISPE in cooperation with the FDA to establish a baseline approach to new and renovated facility design, construction commissioning and qualification. The intent is to document current industry practice for facilities and systems used for production of pharmaceutical products and medical devices and to avoid unnecessary spending on facility features that have no impact on product quality. Volume 4: Water and Steam Guide recommends the use of orbital welding for the installation of pharmaceutical water systems, citing the smooth inner weld bead.⁴

The ASME BPE-97 Standard recognizes the importance of the surface quality of welds for maintaining the cleanability and sterilizability of piping systems. A smooth internal surface finish of the piping system, including the welds, is important for controlling the buildup of biofilm that could contaminate the product.

The Materials Joining part of ASME BPE-97 requires that the weld criteria of ASME B31.3 which prohibits weld discontinuities such as cracks, voids, porosity, undercut, lack-of-fusion, and incomplete penetration that would affect the structural integrity of welds be met but, in addition, provides visual weld criteria that are important for maintaining the hygienic condition of the piping system.

Welds must be fully penetrated with good alignment, with a flat OD and ID profile. An unpenetrated weld has a crevice which may not be reached by CIP cleaning and becomes a refuge for bacteria. Excessive I.D. concavity, convexity, or misalignment, that could interfere with proper draining of the system and allow pooling of fluid where bacteria could gain a foothold presents an unacceptable bioburden to the system.

Discoloration of the weld

Any discoloration of the weld or HAZ as a result of oxidation during welding must be held to a minimum. A light discoloration may be permissible if it is tight to the surface, but the amount allowed (if any) for a particular installation is subject to agreement between the owner/user and the contractor. Discoloration has been shown to be proportional to the amount of oxygen (and moisture) in the ID purge gas which is usually argon. A cryogenic source (dewar or bulk gas supply) is recommended for urging during welding of high purity pharmaceutical water systems.

Oxygen concentrations in the low parts per million range in argon will usually produce welds with light or no discoloration assuming the purge time is sufficient and there are no leaks in the purge system. Purifiers are available that bring the oxygen (and moisture) levels to the low parts per billion (ppb) range which will usually, but not always, produce welds with no visible discoloration. Purge procedures, including flow rates used on specific weld heads and for ID purges, specified levels of argon purity, and discoloration criteria for welds are detailed in the project specification that is prepared by the architect engineering firm and the contractor in advance of construction.

In validating a piping system, the most important determinants of water quality monitored by the FDA are the (live) bacterial count and endotoxins which are produced from (dead) bacterial cell walls.⁸ Full-penetration crevice-free welds with a smooth I.D. surface are important for meeting these qualifications.

Inspection and documentation

Figure 5. AMI Model 8-4000 weld head welding a stainless steel elbow to a tube. This narrow weld head provides reduced axial clearances, increasing the number of joints that can be accommodated with orbital welding equipment. This head is water-cooled to permit a high duty cycle.

An inspection plan detailing the types of examinations to be made shall be agreed to in advance of the job by the owner/user and contractor. ASME BPE-97 requires that all welds be inspected visually on the OD, and that a minimum of 20% be selected at random for internal inspection with a borescope. The reject rates for orbital welding in biopharmaceutical applications have been extremely low.

By refining their standard operating procedures which are detailed in the project specifications, mechanical contractors have documented reject rates for orbital welding as low as 0.2%. The ASME BPE-97 Part SD Design for Sterility and Cleanability lists the kinds of documentation that may be used to verify conformance with sterility and cleanability. The kinds of documentation shall be agreed to at the outset of a design project by the owner/user and the manufacturer (installing contractor).

These would typically include (but not be limited to) material handling procedures, welding procedures, mechanical and electrical polishing procedures, installation procedures, surface finish certifications, shop passivation procedures, mill test reports (MTRs) on tubing, etc.

Figure 6. Weld schedule print-outs can be used as part of the weld procedure documentation package.

It would also include detailed instructions for receiving, inspection of incoming materials, fabrication, cutting, end-preparation, cleaning of weld components and provision for a clean area set aside for welding. Tracking of tubing material heats and control of diameters and wall thicknesses for specific applications should also be defined.

This information would be detailed in the project specification listed in ASME BPE-97 Part SD Design for Sterility and Cleanability shall also be retained by the owner/user for a period of at least three years.

Corrosion resistance of orbital welds

Validation of a piping system for high purity water proceeds in three phases: 1) at system start-up, 2) when the system is up and running, and 3) after a period of operation of about a year. Water samples must be collected and analysed at specified intervals to demonstrate that the system produces water of acceptable quality on a continuous basis.

Weld quality is most important for the long-term successful operation of the system. Rouging, a form of corrosion sometimes associated with welds in pharmaceutical piping systems, is fairly common and may affect water quality. When properly welded with an adequate purge of the joint I.D. and passivated after welding, orbital welds on 316L stainless steel have pitting potentials equivalent to those of unwelded tubing which is indicative of good corrosion resistance.⁵

Use of orbital welding in biopharmaceutical industry

Orbital welding, which uses the GTAW process, is used in the biopharmaceutical industry for piping systems which have direct or indirect contact with the product and may also be used for other, less critical, systems. These include WFI (water for injection), clean steam, and product lines. It is also used for connecting tanks and vessels to the piping systems, in construction of equipment such as multi-effect stills, and to connect bioprocess equipment mounted on skids.

Typical tubing diameters for biopharmaceutical applications are 1 to 4 inches OD, but 1/2 inch OD tubing for instrumentation tubing supplying bioreactors was welded orbitally by B. Braun Biotech. Autogenous welds up to 7 inches in diameter can be done in enclosed orbital weld heads, but larger tube and pipe sizes require the use of orbital welding equipment with filler wire capabilities.

Power supplies are microprocessor-controlled. The weld parameters controlled by the power supply include primary and background welding currents, pulse times, rotor travel speed (RPM), level times, rotation delay, and purge times. These are recorded on a weld schedule for each size and wall thickness of tube or pipe and stored in the power supply memory. They are easily recalled for welding and the schedules can be modified for different heats of materials or for tube-to-fitting welds and the changes stored in memory as needed.

Print-outs from the power supply may include the weld identification number, the operator’s name, and the serial numbers of the power supply and the weld head. This information can be used in conjunction with the welding log as part of the documentation package.

Latin America

Figure 7. Orbital welders at Fiocruz Instituto de Tecnologia em Imunobiologicos vaccine plant near Rio de Janeiro in Brazil.

The use of orbital welding is expanding in Latin America. Fiocruz Instituto de Tecnologia em Imunobiologicos used orbital welding in the fabrication of a new building used for the manufacture of vaccines. Orbital welding was used for joining the WFI piping, the DI loop piping, as well as service piping for cold water, air, and steam systems. Type 316L stainless steel tubing was used for both WFI and DI water systems. Cold water is used for washing glassware used in the plant, hot DI water is used for rinsing the glassware, and air for drying it.

Engineering contractor, Termo Engenharia Ltda, wanted to upgrade its welding procedures and standards to a level that would satisfy the FDA in the USA since Fiocruz intended to export its products. The installation was very successful and Fiocruz is planning to use orbital welding on another new facility at the same location.

Other Latin American pharmaceutical users of orbital welding include Schering do Brasil, and orbital welding is being used in plants for the manufacture of cosmetics and other hygienic applications such as breweries, dairies and juice packagers throughout Latin America.

Productivity

Productivity is typically higher for orbitally welded systems than for comparable manual installations. Productivity gains are achieved through reduced time to weld each joint as well as lower reject rates and reduced need for rework. Thus orbital welding is eminently suitable for "fast-track" construction projects without sacrificing quality.

Summary

During validation, the FDA will examine all the documentation to make certain that procedures outlined in the project specification have been followed and properly documented in accordance with the CGMP. Orbital welding done in compliance with the ASME Bioprocessing Equipment Standard, which by reference includes ASME B31.3 Process Piping and ASME Section IX of the Boiler and Pressure Vessel Code, is a key component in achieving pharmaceutical piping system validation in a timely manner.

The repeatability of the process makes it possible to achieve crevice-free welds with a smooth surface that can be maintained in a clean and sterile condition on a routine basis. The smoother surface decreases the affinity for colonization and growth of microorganisms and increases the efficacy of CIP.

Similarly, the controlled heat input of orbital welding combined with the use of proper purging technology and passivation results in welds that are comparable in corrosion resistance to unwelded base materials. Thus orbitally welded systems, installed with proper fabrication techniques and documentation, are in compliance with 21 CFR B211 Subpart D facilitating piping system validation as well as providing excellent performance in service.

By Barbara K. Henon, Ph.D., and Eng. Angel Brond, Arc Machines, Inc.

References

1. Lohnes, J. Codes and standards: Critical process piping systems requirements as keys to success. InSPEct. ISPE San Diego Chapter Newsletter, Issue #4, 1999.

2. ASME B31.3 Process Piping Code (1996 Edition) ASME, 22 Law Drive, Box 2900, Fairfield, New Jersey 07007-2900, USA.

3. ASME Section IX of the Boiler and Pressure Vessel Code.

4. ISPE Baseline Pharmaceutical Engineering Guides Vol. 4. Water and Steam Guide. Draft Working Document (Revision B) Revised October 30, 1997.

5. Grant, A., B.K. Henon, and F. Mansfeld. Effects of purge gas purity and chelant passivation on the corrosion resistance of orbitally welded 316L stainless steel tubing. Pharmaceutical Engineering, January/February, March/April, 1997.

6. Henon, B.K. Orbital welding in compliance with the new ASME Bioprocessing Equipment Standard (ASME BPE-97). Pharmaceutical Engineering, January/February, 1999.

7. Henon, B.K. and Angel Brond, Orbital TIG provides right connections for vaccine plant. Welding and Metal Fabrication, April, 1998.

8. FDA Guide to Inspections of High Purity Water Systems

9. An introduction to the ISPE Baseline Guides. Pharmaceutical Engineering. January/February, 2000.

This paper was originally presented at the Latin American Pharmaceutical Show, Centro Costa Salguero, Buenos Aires, Argentina, 28, 29, and 30 March, 2000.