Operations Excellence: Process Analytical Technology (PAT) to Play Key Role in Advancing Operations Excellence

Three meetings of the BioPharma Operations Excellence Consortium, facilitated by Tefen Operations Management Consulting, were held recently. The east coast meeting was hosted by Genzyme at its headquarters in Cambridge, MA; the west coast Chapter met at the Genentech campus in South San Francisco, CA; and the European forum held its meeting in Frankfurt, hosted by Aventis.

Amir London

A major focus at all three meetings was to discuss the current adoption level of Process Analytical Technology (PAT) and advanced software solutions in the industry, as well as the expected impact of such technologies on future advancements in operations excellence.

In general, a recent industry-wide survey conducted by Tefen and Millipore Corporation indicated that more than 50 percent of the 100 industry-leading organizations who responded either have a PAT program in place or are planning to initiate such a program during 2005. The survey also revealed the three most valuable PAT features industry professionals seek to initiate are: real-time product release based on in-process testing, improved characterization of process variation leading to reduced regulatory scrutiny, and improved product quality assurance through proactive design for manufacturing. When surveying the expected time frame for such functionalities, about one-half answered they expect those solutions to be common in the industry in only four to ten years, while twenty to thirty percent estimated a much quicker adoption of one to three years.

A key speaker at Genzyme's session, Glen Williams, general manager of Biogen-Idec's facility in the Research Triangle Park, NC, presented a session on process data management using a system that collects data from a variety of sources such as LIMS, DCS, document management, and manual entry. The system supports statistical process control (SPC) analysis, process monitoring, and raw materials evaluation. Combined with the use of a multivariate analysis tool, the facility is able to identify and highlight key causes of variation from batch to batch and works to eliminate them. The system implementation is a key step to adopting PAT at Biogen-Idec.

Genzyme's Manoj Menon, process engineering manager, provided a presentation on the use of process data statistical analysis for efficient scheduling of manufacturing operations. Through detailed data capture of production information in the filling area on average filling yields and lyophilizer load sizes, optimal campaign sizes were determined for various formulations to minimize lost lyophilizer capacity and scrapped product. Menon explained that without the ability to collect and present valuable data, this project would have been impossible to complete.

Lisa Miller, director of manufacturing, and Regina Grochowski, senior manager of compliance, Human Genome Sciences (HGS), offered a presentation at the west coast meeting summarizing HGS' implementation of a variety of advanced IT solutions. From CAPA to ERP, HGS put a number of critical systems in place. This effort required significant, dedicated IT and implementation resources, but because the company views technology as a priority, it was able to meet its ramp- up targets.

Peter Bland, senior manager at Global Change Control at Genentech, presented a company project that transitioned an object-oriented document model for batch records. Based on a company assessment, one of the causes for a slow new product introduction process was the difficulty in creating documents — people were spending a significant amount of time creating new documents from scratch, while numerous versions of documents for similar processes already existed, resulting in confusion on the part of the operators using the documentation. Through a Six-Sigma project, Genentech identified a potential 50 percent reduction in labor time invested in document creation by designing standard templates, or objects, that are reused to create process documentation. A key project requirement was that the developed object model could integrate nicely with a future manufacturing execution system (MES) solution, currently in the planning stages at Genentech.

At the European meeting, Christian Woelbeling, a guest speaker from Werum Software & Systems AG, demonstrated compliance and productivity benefits achieved through MES implementation. Woelbeling described the system's core functionalities such as electronic batch records, deviation tracking, events correlation, user guidance, material flow control, equipment logbook management, and production planning and scheduling. With a number of successful biopharma MES implementations already in place and more in the planning or initial design phase, the industry is moving to a new process automation and operations control era, following the direction of other highly advanced industries such as the semiconductor industry.

The other key session at the European meeting was dedicated to a discussion of the industry's acceptance of Six-Sigma as a key platform for operations excellence (Figure 1). The objective of Six-Sigma quality is to reduce process output variance so that +/- six standard deviations lie between the process specification upper and lower limits.

The objective of Six-Sigma quality is to reduce process output variation so that ± six standard deviations lie between the process specification upper and lower limits.

At the meeting, Tefen discussed its industry experience, highlighting the fact that almost all biopharma manufacturing companies are engaged in some type of formal operations/process excellence effort, which is most commonly structured around the Six-Sigma approach. The industry preference for Six-Sigma could be explained by the statistical theory behind the program methodology, and the biopharmaceutical industry is by nature a science-based, methodical arena. Also, its preference could be attributed to the method's demonstrated success during recent years by leading companies such as GE, Motorola, etc. Tefen also indicated that a typical program structure consists of dedicated "core team" resources ("black belts") plus part-time operations staff involved in improvement projects parallel to their on-going duties. On average ,three percent of the total full-time operations staff is engaged in operations excellence activities.

The consortium members brainstormed on different applications for the Six-Sigma methodology, and although most people agreed that the approach could be applied to almost any business process or system practiced by biopharma companies including administrative activities, they currently are using the methodology primarily for production and quality related projects. The discussion ended with an understanding that the most common benefits of using Six-Sigma include:

• Reduced rate of de-viations and out of specs (OOS)

• Increased unit oper-ations yield and overall productivity

• Reduced lot release time

• Improved equipment reliability

• Reduced changeover times between campaigns

• Documentation and workflow simplification

• Improved change control business process

• Reduced time/cost of supplier qualification

• Improved tech transfer practices

• Reduced cost and improved productivity of R&D processes

FUTURE ACTIVITY

The three local chapters of the BioPharma Consortium conducted their first meetings of 2005. Abbott Bioresearch Center hosted the east coast meeting; Cell Genesys, the west coast forum; and Wyeth BioPharma Grange Castle Ireland, the European meeting. All meetings will be covered in the next Operations Excellence column. For additional information, please visit the consortium section on Tefen's website (

www.tefen.com

) or send an e-mail to

excellence@tefen.com

.

ACKNOWLEDGMENT

The author wishes to thank Marc Puich, director at Tefen, for his contribution to this column.

Amir London is a partner at Tefen Ltd., 1065 East Hillsdale Boulevard, Suite 112, Foster City, CA 94404-1615, 650.357.1120, ext. 115, fax 650.372.1120 alondon@tefen.com.