Improving production, maintaining GMPs with a revamped purified water system
A drug manufacturer meets growing production and purity demands by using bead and crevice–free fusion technology to build upon existing polyvinylidene fluoride piping
By John Pregenzer
At a pharmaceutical production facility in Germany, a concept was conceived to optimize production while maintaining actual GMP (Good Manufacturing Practices). To achieve the required plan, production had to be relocated along with the supporting processes. The purified water system, installed with polyvinylidene fluoride (PVDF) piping, had to be modified to supply the necessary water quality to the new location and to ensure a successful and timely installation.
This production facility manufactures oral pills, and due to the product's success, production utilization was near capacity and optimization was required to meet demand. The existing water system had performed to specification, but the company had not made modifications to it. The scope of the work called for an expansion of the existing system while maintaining purity and integrity features. With a tight schedule and little room for error, PVDF had to live up to its reputation as a flexible product ideal for both new and retrofit projects.
The specified water quality for purified water is monitored periodically according to established standards, and PVDF had proven to be an optimal material selection for many years. To maintain the water quality and prevent microbiological contamination, it is sterilized with ozone (0.02 to 0.05 milligrams per liter) and, if necessary, heated to 85° C for further sterilization.
Material selection and fusion
The company selected PVDF for the initial system and the retrofit project because it is free of additives, stabilizers, pigments, is physiologically inert, and is approved by the Food and Drug Administration. Additionally, PVDF has exceptionally low leach out (extractable) values for organic and inorganic substances, and indicates no tendency for micro-organic deposits to grow on the interior pipe surface. With a smooth surface finish of Ra <0.20 µm, PVDF pipe can be steam-sterilized up to 135° C.
Other characteristics include excellent resistance to chemicals, disinfectants and ozone. Most importantly, PVDF doesn't cause rouging, as is often the case in stainless steel systems with a high-ferrite content. Also, PVDF is lightweight compared to stainless steel and does not require costly structural support. Material pricing of PVDF is stable and not subject to the volatile economics of stainless steel, reducing cost of ownership risk.
Installation of the new retrofit system was achieved using the preferred jointing method for pharmaceutical ultrapure water applications—bead and crevice-free (BCF) fusion technology. Using mechanical connections, usually by sanitary design fittings, is not recommended, as they can be sources of contamination and bacterial growth. BCF is a proven method producing seamless welds, much like stainless steel orbital welding. BCF uses a defined and controlled amount of heat in the fusion zone to melt the plastic while an inflated bladder provides internal support to maintain the smooth surface. The expansion and bonding of the PVDF molecular chains permits fusion without any additional materials or heating elements, such as copper coils.
The result of BCF fusion technology is a low-tension fusion joint with high mechanical stability and a smooth inner surface, without any undercutting or dead legs. The excellent surface finish of Ra 0.25 µm in the fusion zone compares favorably to the surface finish of Ra 0.20 µm for premium PVDF piping products. The fusion process is fully automatic and requires neither forming nor passivation of the fusion zone—a costly process required for stainless steel.
The completed installation consisted of nearly 650 feet of 1.25" (40-mm) pipe, 45 elbows, 27 unions, 35 fixed points and 8 zero dead-leg valves. The entire system, including 350 fusion joints, was installed ahead of schedule in only nine working days.
The contractor, who was factory trained and certified by the piping system manufacturer, was able to utilize multiple fusion machines and increase productivity—an extremely important factor in the entire process, as the drug manufacturer wanted as little production interruption as possible.
Testing and validation
During the system's commissioning, the loop was subjected to a leak test at 100 PSI with purified water and rinsed for approximately 90 minutes. The required water quality was achieved immediately following the rinsing process. There was no delay in start-up due to extractables that are common with other piping systems. For validation, the project was documented and qualified, supported by material traceability and fusion weld printouts automatically created by the BCF machine.
For this purpose, a master validation plan was implemented, as well as stipulations and agreements from the individual qualification phases—including a 100 percent visual inspection of the BCF fusion welds from the outside with a light source, and an isometric drawing and future protocol for weld documentation. Endoscopic examinations were not required, which saved time and project cost.
Due to the outstanding water quality and the low particle number resulting from installation of the new PVDF system, the number of chemical, microbiological, and ozone measurements could be reduced following the Performance Qualifications (PQ). Additionally, continuous particle monitoring could also be waived since PQ confirmed a consistent and significantly lower number of particles than specified. Both results were significant improvements over the original system.
Since the start-up of the system, there have been no contamination problems whatsoever. The water quality has been consistently in spec, both chemically and microbiologically, and the particle numbers remain extremely low. Additional sanitization has not been necessary because ozone is periodically added to the water for disinfection—an added advantage of the PVDF system, since it is resistant to ozone.
The completed purified water PVDF piping system installation consists of nearly 650 feet of 1.25-inch pipe, 45 elbows, 27 unions, 35 fixed points, and 8 zero dead-leg valves.
In regard to profitability, the operating costs for the PVDF system are comparable to those for traditional systems, with the added benefit that a much higher value can be realized by the end user with the use of PVDF, without higher product or installation cost.
While there has been skepticism towards PVDF piping systems in pharmaceutical plants for many years, this installation convinced the drug manufacturer that stainless steel does not always need to be the first or only choice in pharmaceutical applications.
After working with and measuring the performance of the PVDF piping system for purified water over the course of one year, the drug manufacturer confirmed that, whenever possible, PVDF will be installed in the future because it offers high quality and purity in the entire system, because of its easy and fast installation with BCF fusion technology, and PVDF's ability to achieve the specified water quality so quickly.
JOHN PREGENZER is manager of product management, George Fischer Piping Systems, a division of George Fischer, Inc. (Tustin, Calif.) He can be reached at: email@example.com