Operations Excellence: BioPharma Consortium Meets in California and the Netherlands

Two quarterly meetings of the BioPharma Operations Excellence Consortium were held over the first three months of 2004. On February 3, the US West Coast chapter of the consortium had its first meeting of the year at Abgenix in Fremont, CA, and on March 25 in the Netherlands, the European chapter kicked off its first meeting, which was hosted by Centocor Leiden.

ABGENIX MEETING

The Abgenix meeting hosted 40 professionals from over 15 companies and focused on contract manufacturing, a hot topic in an industry periodically beset by capacity hortages. In addition to the presentations and group discussions, participants were given a facility tour of Abgenix's large-scale manufacturing plant.

One of the more intriguing sessions of the day was a presentation by Joe Dillon, vice president, supply chain, of Silterra, a semiconductor contract manufacturing organization (CMO) based in Malaysia. Dillon discussed the industry's background and how the consortium discussions reminded him of the semiconductor industry 20 years earlier. He also shared that since the '80s, the semiconductor industry has made major advancements that biopharmaceuticals companies might want to emulate.

As an example, Dillon noted that advanced manufacturing execution systems allow customers of semiconductor CMOs to have full, real-time visibility of their products in the CMO plants. He also mentioned that there are a large number of "fabless" companies that focus on product development and outsource all their manufacturing to CMOs, mainly located in Asia. Plus, according to Dillon, manufacturing technology drives improvement in semiconductors, and, as a result, a semiconductor plant can expect to turn over 33% of its manufacturing equipment every three years. He added that labor only constitutes 5% of the product cost, while the tax advantage is the real driver to building CMOs in Asia. The semiconductor industry can thoroughly inspect each product made, Dillon said. He concluded by noting that although there are many differences between the industries, especially related to regulatory requirements, there are enough similarities that the future of biopharmaceuticals with respect to contract manufacturing might look much like the semiconductor industry.

The other presentations of the day were given by Steve Chamow, vice president, process sciences at Abgenix; Karen Walker, director of quality at Abgenix; Patrick Hanley, Sr., manager of packaging at Genentech; Sid Advant, director of technology transfer and clinical operations at Diosynth; and Allan Harmon, plant manager for Baxter BioScience.

The main focus of the presentations given by Walker, representing the development side, and Advant, standing for the CMOs, was the need to develop frequent communication between the organizations as well as a clear, focused set of expectations from the technology transfer to the development of the quality agreement. Harmon's presentation focused on Baxter BioScience's transition of its Hayward, CA facility to transition from supporting internal customers to opening its doors to external customers. For Baxter BioScience, becoming a contract manufacturer required the establishment of a customer-support organization, as well as improvements to the physical plant to provide added transparency to customers and offer visitors a better understanding of the current manufacturing processes.

Abgenix's Chamow discussed the challenges of increasing efficiency in biologics production as well as the key factors to increasing titer. Most of the newer, large-scale production facilities coming on-line are focused on batch production. A discussion developed about perfusion vs. batch fermentation. From a manufacturing perspective, perfusion production theoretically can be more efficient, requiring smaller vessels and fewer changeovers compared to batch processing. This is especially true for processes where large quantities of material are required and suites can be dedicated to products. Many limitations of perfusion were discussed as well. Current technology and equipment constraints have made large-scale production challenging. Also, perfusion requires a long-term, up-front investment for validation. Instead of running three batches over two months to validate a batch process, one may need three runs over at least six months to validate the perfusion process. Because the biopharmaceutical industry is still young, it is too early to tell which technology will become the standard in the end — but batch processing has a healthy lead.

Hanley kicked off an interesting discussion of Genentech's validation of automated vial inspection for liquid-filled vials. Genentech has been exploring the use of automation, due to the ergonomic risks associated with vial inspection and the significant labor costs and space requirements needed to meet growing capacity demands. The discussion focused on the difficulty manufacturers face in validating current manual inspection processes and identifying liquid particles in products. Hanley went on to describe his company's newly proposed inspection process and how it is being validated against current manual processes. Although the process is not fully validated, Hanley said Genentech expects that in the future, it will be able to significantly limit the growth of the inspection group, be more consistent in its inspection of vials, and, most importantly, dramatically minimize the injury rate.

CENTOCOR LEIDEN MEETING

The Centocor session, facilitated by Tefen's European office, was the European chapter's first meeting, hosting over 30 professionals from 18 companies. The large number of participating companies, all European-based biopharmaceutical manufacturers, demonstrated the need for such a forum and the willingness of organizations to share challenges and improvement initiatives. As it was the group's first meeting, a large portion of the day was dedicated to introductions, development of clear expectations, charter statements, and working procedures.

Pedro Tetteroo, vice president and general manager of Centocor Leiden, delivered the day's keynote address. He presented Centocor's vision and manufacturing strategy as well as the company's successful growth story over the past four years. Tetteroo concluded by emphasizing the importance of operations and process excellence to Centecor's success.

Other presentations were given by Eric Goossens, director of production operations, and Johan Telen, director of process excellence at Centocor Leiden; Jo Dalle, director of manufacturing and Wim Croonen, director of human resources at Genzyme (Belgium); Dave Sherwood, director of global quality and compliance at Celltech (UK), and Martin Wrankmore, manufacturing continuous improvement leader at Lonza Biologics (UK). The presentations provided overviews of the companies' current operations excellence programs. The speakers mainly focused on lean operations and Six-Sigma methodologies.

Tefen presented a case study of a successful one-year deviation reduction program it led in partnership with a large, multi-site biopharmaceutical organization, using a Six-Sigma framework. It not only significantly reduced the backlog of open nonconformances (NCs), but it also allowed for the implementation of required infrastructure for continued reduction in NC rates and closure cycle time, including a mechanism for visibility enhancement and elevation of NC reduction ideas from the staff. The program resulted in more than a 35% reduction in the average number of NCs per lot and more than a 50% reduction in average closure time per reported deviation.

OTHER MEETINGS

The East Coast chapter's meeting was held on May 11 at Centocor, Malvern, PA. Meeting highlights will be summarized in a future column.

At press time, the European chapter's next meeting was set for July 7 and it was to be hosted by Serono in its Vevey, Switzerland facility. The next West Coast meeting has not been announced. For more information about the consortium and details on future meetings, please e-mail us at excellence@tefen.com.