Custom Seal Solves Biopharm Bioreactor Problems

• Flowserve solution maintains sterility, cleanability in a mammalian bioreactor by enforcing seal integrity.

When Tarrytown, NY’s Regeneron Pharmaceuticals Inc. purchased a new mammalian bioreactor skid, it had the same high expectations that surround any major process improvement. But during initial startup, it became apparent the vessel wouldn’t maintain sterility reliably, due in part to the design of the OEM bottom-entry agitator seal. According to Regeneron facilities engineering supervisor Kyle Cherry, the reactor was “problematic.”

Leaks Affect Sterilization

“The main issue with the OEM seal was that the sterilization requirement hadn’t been observed and sealing integrity was compromised,” says Cherry.

3D cutaway of Flowserve's ST Seal

Sterilization of the interior vessel bore was absolutely essential. Once this requirement was met, the bioreactor had to cool to a temperature appropriate for introducing the cell culture medium.

The hitch was that the OEM seal faces were not oriented suitably to foster complete sterility. In addition, the port locations were not optimal for total evacuation of air, causing the inner seal to let in water vapor. Because clean steam was used for sterilizing the bioreactor, a moderate flow of clean steam-condensate became the barrier fluid to the mechanical seal assembly during certain phases of production.

Custom-Engineered Solution

Undisrupted production didn’t begin until shortly after the OEM agitator shaft seal was replaced with a custom-engineered design from Flowserve Flow Solutions. While both the OEM seal and Flowserve replacement featured a dual mechanical seal to protect the sterility of the cell culture medium and a secondary sealing device to protect the gearbox, the difference, says Cherry, “is the OEM seal had cleanability issues making it unable to maintain a sterile environment.”

Cross section of Flowserve's ST Seal

“Flowserve customized a model ST seal to address the repetitive seal problems,” says Cherry. The new seal was designed as a dual cartridge seal mounted directly to the gearbox as well as to the bioreactor’s mounting pad. An additional challenge was that the European design and the transverse angle of the drive required detailed field measurement by Flowserve for proper fit and function.

Seal Integrity

Installing the seal as a complete unit provides numerous advantages. The seal requires no handling of integral sealing components, has fewer components to stock and maintain, and includes a complete cartridge that can be aerostatically pressure-tested to ensure integrity before installation.

Relocating the springs outside the process media and contouring critical sealing components to resist pooling also fostered optimal cleanability and sterility. Adding a flexible stator design compensated for misalignment and mixing anomalies that can occur under normal operation.

The new seal maintains absolute containment of the clean steam condensate during each phase of production. By incorporating an internal flow deflector, the primary seal is kept lubricated to eliminate dry run conditions. A Flowserve Bearing Gard II unit was added to eliminate condensate weepage from penetrating the gearbox.

Choosing the Solution

When asked why Regeneron chose Flowserve, Cherry explained that it had engineered sealing solutions for several Regeneron bacterial fermentation reactors over the years, and that those had performed as promised.

In this case, because the reactor was too large for a magnetic drive, a mechanical seal was needed. “Although this is a bottom-entry agitator at a slight transverse angle, and the previous Flowserve-Regeneron projects were for top-entry agitators, Flowserve didn’t seem to have any problem getting the job done,” said Cherry.

Because the seal is in contact with the process medium, mammalian reactors require a high level of reliability. Positive containment is also critical. Cherry said that with the seal and some small piping modifications and procedural changes, “We are able to maintain sterility for extended periods.”

“This issue was an ongoing challenge for us,” he added. “The Flowserve seals team worked closely with our technicians and engineering department on the field retro-fit and came up with the solution we needed.”

Based in Irvine, Texas, near Dallas, Flowserve Corp. (www.flowserve.com) is one of the world’s leading providers of fluid motion and control products and services. Operating in 56 countries, it produces engineered and industrial pumps, seals and valves.