There were several lessons for CMOs at the recent “BioProcess International Conference,” among them notification from Miriam Monge, vp of marketing and disposables implementation at Biopharm Services, that CMOs must significantly reduce development and manufacturing costs.
“The success of monoclonal antibodies is reflected in the major growth in manufacturing capacity,” said Monge. However, “high capital investment, coupled with high operating costs, and inflexible facilities have contributed to the high price of mAb-based treatments.
“Starting in process development we have to develop efficient, robust processes more quickly,” Monge continued, “and with greater success. We then have to transfer the processes efficiently into flexible, low-cost manufacturing facilities.”
One of the speakers giving tips on how to improve technology transfer was Kristi Huntington, associate technical consultant at Eli Lilly and Co. Her presentation focused on how Lilly Ireland overcame the challenges it faced in transferring production of an inlicensed biologic to a facility that had never before made a biotech product. The production process was not well understood nor was it optimized. “We had limited information and data, and so we had to learn the nuances of the process,” she explained.
First and foremost, she said, the tech transfer team needs to prepare a plan. “This insures up-front alignment of the key players with fewer surprises and a bigger chance of getting the process right the first time.”
Owing to the accelerated project timeline, five teams worked on this tech transfer, although there was not a formal plan which, Huntington admitted, was not ideal. Despite facing significant technical challenges, two batches of API were made within a year. This success is a tribute to the positive attitude and commitment of those involved. “The learning from this tech transfer was priceless for Lilly Ireland,” she commented. “It really set the stage for our upcoming new biotech facility.”
Among the lessons learned was never to underestimate the need for experienced biotech operators, which “is absolutely key to the success of the process execution,” said Huntington. “We also underestimated the technical complexity of the molecule.”
CMOs can also speed up tech transfer by adopting new tools and technologies. Susanne Wallenborg, Ph.D., section manager of R&D, life sciences at GE Healthcare, described the role that high-throughput process development (HTPD) can play in tech transfer. Efficient process development is key to developing a robust and efficient manufacturing process, she said.
HTPD allows exploration of a larger experimental space and supports the definition of a well-established process design space where the critical process parameters that really need to be controlled and monitored are completely understood,” Dr. Wallenborg explained.
Key to HTPD is the GE PreDictor™ plate, a 96-well plate product prefilled with chromatography media. The product can be used throughout downstream processing to screen for binding capacity, wash and elution conditions, adsorption isotherms, and CIP conditions, Dr. Wallenborg said.
But it is not just innovative technology that is important to CMOs these days— organizational culture also plays a role. Fadel Hamed, Ph.D., head of operational excellence at Genentech, said that being “world class is a never-ending pursuit of perfection.” Companies aspiring to world-class status can use operational excellence (OE) to help them to deal with the challenges of the biopharmaceutical business. Dr. Hamed defined OE as the “routine delivery of exceptional performance through a systematic approach to continuous process improvement.”
OE has three stages. In the foundation phase, the infrastructure required to improve current operations is set up; in the incremental phase, operations are optimized to deliver a predictable performance; and the final and most difficult phase, which is known as transformation, sets a company well on the road to being world class. “Most companies will not reach the transformation stage,” Dr. Hamed claimed.
OE at Genentech is based upon a Lean/DMAIC (Define, Measure, Analyze, Improve, and Control) approach, which is a data-driven problem-solving methodology for delivering business results. Dr. Hamed explained that, “variation is the enemy, and we have to control it—Lean/DMAIC gives us a mechanism to do so.”
“OE is about attitude and having a continuous improvement mindset,” he added. At Genentech, it is focused upon reliability, simplicity, and growth. However, one should beware of islands of excellence. What is needed is end-to-end OE throughout the whole organization to identify any weak areas.
With a team of just 10 OE people, Genentech delivered $54 million in savings in 2008. Dr. Hamed explained that 30 different factors have been identified in the failure of OE, and the most important of these is leadership. “Leadership must be committed and accountable,” he concluded.