Operations Excellence

Many biopharmaceutical companies are transitioning from a strict R&D focus to one that incorporates manufacturing and supply-chain management capabilities, and it is critical they start thinking about operations excellence.

Increased competition, long development and production lead times, a shortage of qualified personnel, challenging compliance requirements, the high cost of quality, and the notion that biogenerics are only a few years away are shaping this industry trend of world-class operations development. Operations excellence will be essential to developing and maintaining a competitive edge and capitalizing on new product opportunities.

Until recently, biopharmaceutical companies concentrated on the consistent manufacture of their difficult products. Now, after proving their capabilities, they are attempting to improve overall performance, mostly as it relates to supply-chain management and quality systems and processes.

One indication of this trend is the formation of the BioPharma Operations Excellence Consortium (www.tefen.com/consortium). This cross-functional group of industry executives and managers, representing manufacturing, the supply chain, quality assurance, and quality control, meets regularly to informally benchmark operational challenges and propose solutions.

Operations Excellence Consortium

The consortium was founded in April 2002 and serves as a forum for addressing the most effective and efficient cross-functional business processes related to product development and delivery. This group's purpose, as stated in its charter, is "to share experiences and surface key challenges facing biotech manufacturing companies and to use the group's collective knowledge to drive each member company, and the industry as a whole, to world-class levels of operational effectiveness and efficiency."

Tefen Ltd., an operations consulting firm specializing in the biopharmaceutical industry, was selected to lead and facilitate the consortium's efforts. The group of representatives from more than 25 different companies meets quarterly for a full-day conference hosted by one of the member companies. To date, Genentech, Amgen, Bayer, Baxter, and Chiron have hosted the consortium.

Each meeting is devoted to a central theme, such as lot release cycle time reduction, contract manufacturing, corrective and preventive actions (CA/PA), and human errors. The forum atmosphere is informal, and the agenda combines case study presentations with brainstorming sessions, panel discussions, and vendor demonstrations. Time is always set aside for networking and open discussions.

Human Errors Reduction

Chiron Corporation hosted the Consortium's most recent meeting (May 2003), during which members addressed the challenge of human errors and their effect on cycle time, manufacturing costs, compliance, and overall company performance.

Consortium members agreed that one category of human errors — document errors — has a significant impact on performance. Reducing such errors and establishing measures to identify nonconformance were a central part of the discussion.

Tefen presented the results of its recently-conducted industry survey on human errors. Different bio/pharmaceutical companies revealed that the most effective efforts in resolving human errors includes:

• increasing the visibility of operator errors
• simplifying operator tasks
• offering more robust and rigorous operator training
• improving the clarity of, or providing additional detail to, batch records and standard operating procedures.

The survey revealed that the most common methods for increasing visibility and publicizing operator errors is by reviewing them in shift and area management meetings and posting quantities and trends in highly visible public places. It also indicated that in most organizations, there is a lack of personal accountability in terms of operator error. Only a small portion of the surveyed companies currently considers errors in the annual employee performance review.

Mistake-proofing. Consortium members extensively discussed mistake-proofing — a process that prevents errors and accidents. Cross-industry experience indicates that the most cost-effective way to prevent human errors and yield quality at the source is to apply advanced quality engineering techniques early in the design process. This allows an organization to proactively mistake-proof its systems and procedures, a concept originally introduced by Toyota, called poka-yoke (1).

Poka-yoke (pronounced POH-kuh YOH-kay) is defined as: "Avoiding [yokeru, in Japanese] inadvertent errors [poka], by designing and implementing mechanisms that either prevent a mistake from being made or make the mistake obvious at a glance" (2). The automotive, aerospace, and high-tech industries already successfully implement poka-yoke.

Biopharmaceutical operations are good candidates for applying poka-yoke principles. The high variability of the manufacturing processes, complex manual activities, extensive and required paperwork, and the high turnover of manufacturing staff make mistake-proofing a cost-effective method that can help the industry shift from focusing its efforts on detection and correction to prevention and perfection.

Failure mode and effect analysis. Tefen's cross-industry experience shows that combining poka-yoke techniques with failure mode and effect analysis (FMEA) yields the best results. FMEA is an inductive engineering technique used at the component level to define, identify, and eliminate known and potential failure modes from the system, process, or service before they reach the customer. When combined with poka-yoke, FMEA can identify and prioritize failures that should be targeted for mistake-proofing through poka-yoke mechanisms. This approach estimates the effect of each potential failure on the product by analyzing its severity and the likelihood of both occurrence and detection.

A recent redesign of a biopharmaceutical media and buffer operation demonstrated the advantages of successful poka-yoke implementation. Formerly, the operation scrapped more than 50 media and buffer runs annually, resulting in a $5,000,000 loss in materials alone. Following the analysis and implementation, media and buffer scraps were reduced 50%, saving the company $2,500,000 in material costs, as well as approximately $300,000 in direct costs related to deviation handling.

A Partnership

The biopharmaceutical industry is in transition, with operations excellence tools and methods becoming valuable components of the industry's day-to-day life. BioPharm International has partnered with Tefen and made a commitment to support this effort and promote operations excellence across the industry by publishing this Operations Excellence column quarterly. Our plan is to summarize the highlights of each consortium meeting, with the goal of promoting the importance of operations excellence to the biopharmaceutical industry and encouraging additional industry representatives to join the forum.

References

(1) Shingo, S.,

A Study of the Toyota Production System from an Industrial Engineering Viewpoint

, A.P. Dillon, Translator (Productivity Press, Portland, OR, revised edition August 1989).

(2) Grout, J.R. and Downs, B.T., A Brief Tutorial on Mistake-Proofing, Poka-Yoke, and ZQC (i Six Sigma website, Mount Berry, GA, visited July 2003). Available at www.isixsigma.com/tt/poka_yoke.

Poka-Yoke Strategies Used Daily

A few examples of poka-yoke mechanisms that we use daily without even noticing are:

• diesel fuel nozzles so they do not fit into the gas tank of vehicles using unleaded fuel
• 3.5-inch floppy disks that can only be inserted into a disk drive one way
• brake-shift interlock devices on automatic transmission cars that prevent car engines from starting unless the brake is engaged and the shift selector is in park or neutral
• automated teller machine (ATM) terminals that dispense requested cash only after the ATM card is removed
• Internet order forms that can only be submitted after all required information is provided.

Poka-Yoke for Biopharmaceutical Operations

Poka-yoke strategies that could easily be designed and implemented within the biopharmaceutical industry include:

• lock mechanisms that require a raw material’s bar code to be scanned before a tank unlocks and material is added; tanks that remain locked if the raw material is expired or quarantined
• color-coded tanks, hoses, wires, electrical plugs, and nonstandard connectors to eliminate incorrect connection setups
• lab-sample freezers in manufacturing areas that lock after the last sample pickup of the day, requiring the hand delivery of time-sensitive samples to the lab
• vision systems or sensors that provide real-time identification of equipment defects, preventing excessive reinspections
• batch records redesigned for simplicity and standardization. BPI