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.
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.
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
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.