Manufacturing Immunoglobulins

Back in 2006–2007, GEA collaborated with CSL Behring (Bern, Switzerland) to build the first module of a plant to produce the human blood plasma-derived immunoglobulin (IVIg) drugs Privigen^® and Hizentra^® to treat patients with serious and rare conditions such as immune deficiencies. Two years later, module two was commissioned and, in 2011–2012, the companies teamed up again to design and build a third module in Melbourne, Australia. Then came the next challenge.

The R&D department in Bern had been working hard to improve the immunoglobulin manufacturing process and, as a result, it was decided to integrate this development into the current production system, which meant scaling-up the laboratory process to production scale while maintaining the yield. Having led the previous three projects, GEA Project Manager, Maic Kroll, was the obvious choice to steer this upgrade as he knew the plants very well. He started work on the basic and detail engineering in September 2012 and the project was awarded in April 2013.

“We provided all the mechanical engineering,” explained Maic, “including P&IDs, equipment lists, tank workshop drawings, 3D designs, time schedules, mechanical installation qualification (IQ) and the relevant technical documentation.” He added: “As well as supplying nine pharmaceutical production tanks with all the required valves, pumps, pipelines and instrumentation, we were also contracted to provide the mechanical installation of the system, which was handled by our experienced assembly engineers. During the ‘hot’ phase, we had 20 fitters on site to ensure that we met the customer’s tight time schedule.”

Maic said that the most difficult part of the project was just before Christmas 2013, when all the work had to be done prior to the biannual two-week maintenance break, to prepare the connections between the existing plant and the new one. “That was a tough time,” said Maic: “For most of December, the whole team worked without a break. But, by using small assembly groups that worked well together and remained flexible, we were ready in time.”

Before the holiday, Maic and his team made the connections to the existing system using the cleanrooms that were not in use during the break. “Early in October, we began to identify all the necessary connections and work packages to define the requirements for the fitters and welders during the break, as well as the engineering resources that would be needed to qualify the newly installed equipment,” he explained. This IQ check includes checking that all the connections comply with the approved P&IDs, the valves are in the right place, the slope of the pipes is within tolerance, all water pressure tests are successful, there’s no leakage or pressure loss, the welding documentation is correct and complete, and the pipeline isometrics comply with the installation.

Maic and his team worked closely with the customer and the automation company during this phase. On 6 January, production returned to normal without any problems or product losses. A month later, the project was complete and CSL Behring will now be able to safely commission the new plant alongside the existing system, ready for full production.