In April 2006, Cytovance Biologics LLC (Oklahoma City, OK), a clinical-scale contract manufacturing and process development
organization (CMO), finished installing two new bioreactor systems into its custom-designed multiproduct cGMP contract manufacturing
facility. The installation was the culmination of a difficult endeavor that began in September 2005, when the bioreactors
were ordered, and ended in March 2006, when the systems were delivered.
This article describes the importance of incorporating critical design elements into the quotation before placing the order,
clearly defining roles and responsibilities, and managing the project effectively. The installation was completed on time
and on budget without any project change orders.
UNDERSTANDING DESIGN OBJECTIVES
Cytovance Biologics required two mammalian cell-culture bioreactors for its newly constructed, early clinical phase cGMP contract
manufacturing facility at the Presbyterian Health Foundation Research Park in Oklahoma City, OK. One hundred liter and 500
L mammalian cell-culture stainless steel units were specified for separate manufacturing trains in dedicated suites. They
needed to be operational by the summer of 2006 to support customer cGMP production batches.
Because Cytovance Biologics is a multiproduct contract manufacturer, there was no single product or process to tailor the
bioreactor systems to. It was necessary to accommodate a wide range of mammalian cell-culture products and processes to maintain
the company's ability to bid on a wide variety of contract proposals. Many design issues were addressed early on, such as
the sizing of the mass flow controllers, the addition of baffles to the bioreactor vessels, and whether the bioreactors would
be capable of running perfusion processes.
The cGMP facility design was completed before the bioreactor design, so it was necessary for the bioreactor system design
to accommodate facility restrictions on dimensions and utility services. Cost and timelines were also concerns because a CMO
must carefully control expenditures. An aggressive budget was set. In addition, it was important that the bioreactors be installed
and validated as quickly as possible to accelerate the acquisition of customer projects and associated revenue generation.
We solicited competitive quotes from three vendors and selected Sartorius BBI systems of Bethlehem, PA (SBBI,
http://www.sartorius.de/). We also hired Certified Facilities Corporation, of Seattle, WA (
http://www.certifiedfacilities.com/), as a design contractor to ensure that our formal quotation included process and facility requirements and provided protection
against change orders because of design alterations. We sought and received assurances from the highest executive levels at
Sartorius that the systems would be delivered within 26 weeks of placing the order.
Finally, we conducted a one-day, face-to-face meeting with Sartorius to tour their facility and identify final bioreactor
MANAGING THE TEAM
Once we formally placed the order, we established roles, responsibilities, and key contacts for each team. At Cytovance, I
was the main point of contact. Steven D. Perry, vice president of manufacturing operations, was responsible for final decisions,
and Debra Greiner-Powell director of quality systems, was responsible for quality assurance on the customer side. Steven J.
Ruhl, vice president of Certified Facilities, was also a key consultant to the bioreactor project team.
At SBBI, Stanley Hawrylo, senior project engineer, was the main point of contact and project manager. Kenneth Clapp, senior
vice president, manufacturing and operations, was responsible for final decisions, and David Koiro, quality control supervisor,
managed quality control on the vendor side.
We instituted weekly update meetings by phone, where we took detailed minutes and established a formalized system for tracking
action items. The meetings were invaluable—they provided a forum for consistent communication for the duration of the project.
The minutes also created a historical record of the project's development, which was reviewed whenever disputes arose. Project
teams from Cytovance Biologics and SBBI participated in the weekly meetings throughout the course of the project.