Successful Bioreactor Installation: What it Takes - - BioPharm International

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Successful Bioreactor Installation: What it Takes


BioPharm International
Volume 19, Issue 8

Additionally, SBBI developed a detailed project schedule with descriptions, dates, assignments, and percentage-completion metrics for each task. The detailed schedule, which incorporated approval times for documents, was essential to maintain the aggressive delivery date.

REVIEWING DESIGNS

During the first few weeks of the project, SBBI generated several key documents for our review and approval. The two most critical were the Piping and Instrumentation Diagrams (P&IDs) and the Master Component Lists (MCL). SBBI required our approval before ordering components with the longest lead time, including the actual bioreactor vessels.

The P&IDs were reviewed to ensure that the proposed design met our requirements. We confirmed that utilities were sized properly, flow paths were correct and sterilizable (as required), components were clearly labeled, and that the vessel had the required ports for additional feeds and instrumentation.

The MCL identified specific manufacturers and materials that would be used in system fabrication. For example, If Cytovance Biologics had a preferred supplier for diaphragm valves (to minimize the different types of spare diaphragms to keep in stock), or supplier for pH and DO probes, those concerns would be addressed in the MCL.

After we approved the P&IDs and the MCL, SBBI issued the functional requirement specifications (FRS) for our review and approval. The FRS provided detailed descriptions for how the bioreactor control software would handle control loops and sequences. The control system included with the bioreactors is a proprietary software developed by SBBI, entitled DCU3.

Control loops, such as pH and the cascade loop for dissolved oxygen (DO), were spelled out in detail within the FRS. Sequences such as steam-in-place (SIP) and clean-in-place (CIP) were also detailed. The FRS listed available alarm functions for the various parameters and readings that are monitored. In addition, the FRS listed valve tables to help Cytovance Biologics employees generate standard operating procedures.

SBBI then issued fabrication arrangement drawings for our review. These documents provided a means for reviewing the system footprint and height, functionality of operator manipulations, and the ability to tie utility connections into the facility.

Next, SBBI issued electrical wiring drawings. These provided the schematic for understanding exactly how the bioreactor systems and various digital and analog I/O, as well as power supplies, were connected.

Factory Acceptance Test (FAT) documents detailed the series of tests to be performed to ensure that the bioreactor system was fabricated per the approved drawings and MCL, and that the system was functionally sound (per the FRS with respect to performance) before shipment was approved.

FAT activities included verification of all drawings, MCL verification, I/O check, calibration checks, alarm testing, control loop checks, sequence testing, a riboflavin challenge, and a sterile media hold challenge. Any non-conformances between expected test results per the approved documents and what was actually verified in the field had to be resolved to our satisfaction before the system could be cleared for shipment.

SBBI's timely generation of these documents, and Cytovance Biologics's prompt review helped maintain the schedule. Weekly project meetings also provided a useful forum for addressing any questions and comments about the documents, from initial generation to final review and approval.

INSPECTING SYSTEMS

Inspection of the systems during their fabrication also reassured us that they would meet our expectations when delivered. Cytovance Biologics was on site to supervise and observe the vessel FAT (at the vessel manufacturer, T&C Stainless in Mount Vernon, MO, http://www.tc-stainless.com/) and at the system FAT (performed onsite at SBBI in Bethlehem, PA). Both FATs were formally executed by SBBI representatives.

The vessel FAT was a one-day test for both the 100 L and 500 L vessels. SBBI verified that they matched specifications per the official vessel P&ID. Test verifications performed included the following:

  • Port sizing, angles, and position
  • Drainability to ensure no pooling at the bottom of the vessels or any ports
  • Interior and exterior finish with a calibrated profilometer
  • Sprayball coverage test

After the vessel FAT was executed, SBBI prepared a final report identifying any nonconformances that the vessel manufacturer needed to address before SBBI would authorize shipment.


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