By Agnes Shanley, Editor in ChiefWe often hear how corporate mergers lead to slash-and-burn downsizing or culture clash, but mergers can also lead to soul-searching, and change a corporate culture for the better. After the formation of AstraZeneca five years ago — a union between Sweden’s Astra AB and the U.K.’s Zeneca Group — the new company’s leadership took a long, hard look at the way it handled quality and efficiency initiatives.By all indications, the company was doing a good job. Progress had already been made with the corporation’s Site Excellence program. The U.S. Operations’ One Site program had helped eliminate silos and ensure that all plants were on the same wavelength, using the same IT and jargon. On a local level, “continuous improvement” teams were solving specific problems. Still, corporate leaders realized that there was more to do.
“We’d always worked on improvement projects,” says Ron Matthews, vice president of manufacturing and supply chain at the company. “But solutions and improvements weren’t always aligned so that benefits cascaded across the entire organization.”All too frequently, Matthews says, data weren’t measured properly and goals weren’t identified early enough. “Staying power” was another issue. “When we looked at results for some programs,” Matthews says, “we found that, two years later, the benefit and enthusiasm had waned.”Matthews and his team knew that they needed to develop an end-to-end strategy for operational excellence that would address everything from raw material receipt to manufacturing, quality control and distribution. “We didn’t want to end up with a patchwork quilt of efforts, and there had to be a logical sequence or order to what we did,” Matthews says.They opted for a program based on three key, interconnected concepts:
- Pull Manufacturing, a subset of Lean;
- Six Sigma’s DMAIC (for “define, measure, analyze, implement, and control”), which establishes a framework for continuous improvement;
- Overall equipment effectiveness (OEE).
|The Basics of OEE|
Overall Equipment Effectiveness is the product of a production line’s availability, performance and quality percentages. The methodology, key to more pharma operational excellence programs, allows equipment downtime to be readily viewed as a function of total available time. World class OEE is estimated to be around 85%. The pharmaceutical industry has reached close to that figure for some of its packaging lines, but for batch processing, the benchmark is quite a bit lower. For a good primer on OEE, see www.pharmamanufacturing.com.
Keeping Everyone Excited: Secrets to Team Leadership
AstraZeneca typically establishes cross-functional teams with representatives from each “stakeholder” department. Each team has a project leader and sponsor, and begins the process by creating a charter, which outlines the scope, objectives, deliverables, and timeline, explains Westborough team leader Steve Grenier.
A formal Employee Suggestion Program keeps operators involved in continuous improvement, says fellow Westborough team leader Rob Reinfurt. During the program’s first two and one-half years, almost 900 ideas were submitted, $400,000 saved, and over $40,000 awarded. Rewards are made in public and those involving significant savings are publicized. In addition, where appropriate, operators are utilized on project teams.
Communication is ensured by holding regular meetings involving all levels of management. For operators, this includes meetings with Supervisors, Directors, and Senior Directors. Education and training are regularly discussed at these meetings. Product quality is often built in as a measured objective within each employee’s annual performance management plan and cGMP Notebooks are issued as required reading by the Compliance Group. Bulletin boards are utilized throughout the site, posting information on key performance indicators (KPI), both performance and targets.
In addition, Town Halls are held with the Site General Manager. The site newsletter is sometimes used to communicate key information, while posters and displays are used for site events, such as a Site Fair that explained OEE.
At Newark, team meetings are held monthly. These one-hour reviews involve operators, maintenance, engineering, technical services and packaging management, distilling the essence of what they need to know and outlining how each will be accountable.
Since they received training in troubleshooting and rapid changeover, Newark packaging teams demonstrated a real sense of self-direction, says John Callahan, senior packaging manager. In one case, when one packaging team’s two supervisors were out on leave, the team operated independently, achieving 75% OEE without any supervision, and sustaining that level for the three weeks that the supervisors were out.
|PAT Focuses on Development|
In Sweden, AstraZeneca’s development group uses PAT whenever possible to support formulation and process development. “The earlier PAT can be used in drug development, the better,” says Ulrika Henningsson, manager of the Process Analytical Chemistry team for Drug Product Supply in Gartuna, Sweden. Operations gets involved from Phase 3 onwards, and the company uses risk-management tools such as FMEA (Failure Mode and Effects Analysis) to identify raw materials and unit operations that might benefit from PAT and lead to greater product quality. Financial gains from improved yields and Right First Time rate, and reduced cycle times, are also figured into the equation.
Manufacturing is doing some pilot-level PAT work in Newark for antipsychotic therapies. The PAT team at the site is using near-infrared (NIR) spectroscopy to determine the content uniformity of one of the solid oral dosage forms manufactured at the site, says PAT project leader Ziggy Waraszkiewicz. NIR is being used, first, in the QA analytical lab to reduce lab test cycle time, but may later be moved to the manufacturing area to obtain content uniformity data while the product is being made.
AstraZeneca’s strategic use of PAT should also improve technology transfer and “handoffs” in the future. For example, the company’s R&D group in Wilmington, Del., is using PAT to gain information to identify critical process parameters and product attributes for solid oral dosage forms in development, Waraskiewicz explains. With this information, the group will be able to optimize the manufacturing process, and ease the move from development to full-scale production.