Drug Makers Take Aim at Variability

By Angelo De Palma, Ph.D., Contributing Editor

Reducing human error has been a goal of manufacturing since tools were made from mammoth tusk. Best implemented as an ongoing process rather than a one-time event, successful error-reduction programs incorporate science, art, psychology, and a big dose of common sense.

Human error extends up and down the pharmaceutical supply chain. The United States Pharmacopeia reported in October, 2003, that healthcare workers often interchange medications with similar names--for example Visicol, used for bowel prep before colonoscopy, and Vicodin, the narcotic painkiller. Serious mistakes occur, even though two different words are staring someone in the face. It's no stretch to assume that errors can occur at every stage in the fuzzy world of manufacturing.

Production managers tend to fall into two camps with respect to human error: Fatalists believe errors are inevitable, while optimists hold that mistakes can and should be reduced. "We subscribe to the second philosophy," says Bonnie Smith, managing director of Lean Sigma Process at TBM Consulting, Durham, N.C.

For Smith, error-laden processes manifest themselves in wasted time, which percolates venomously through everything an organization does, ultimately showing up in the product. Conversely, "when you reduce the time needed to get things done you improve quality and become more competitive by reducing lead time and/or increasing capacity."

Smith cites a biotech company that took thirteen days for fermenter changeover, an operation that adds no value to manufacturing and, necessary as it is, "takes time away from productivity." Smith convinced management to develop new protocols, locate all supplies on a tool trolley before the changeover, and revise the spare parts list so that everything was ready to go. The very next changeover took just four days.

What was management thinking, you might ask, as it squandered nine productive days several times a year? Smith explains the psychology of wasting time by analogy to a simple home improvement job. "Only a fraction of the time it takes to hang a picture in your living room is actually spent hanging the picture," she observes. "You first have to find the hammer, the nail that fits into the hanger, and maybe some wire. Before you know it a five-minute job takes an hour. In pharm and biotech, where production is king, value-added operations are scrutinized, but companies don't spend much time trying to improve the other stuff."

Wisdom from the Orient

Taiichi Ohno, credited with saving Toyota from oblivion in the 1940s, identified seven "wastes" of production: overproduction, non-value-added transportation of goods, non-value-added movement of people, idle time (unprepared workers or operations), non-value-added processing, excess inventory, and defects. Like Bonnie Smith fifty years later, Ohno recognized that value is realized not only by optimizing core activities, but through streamlining day-to-day operations.

During their rise to pre-eminence in manufacturing, the Japanese perfected several techniques for error-proofing and quality management. Kaizen, or continuous improvement, seeks to eliminate operational waste by incorporating the best concepts of lean manufacturing and six-sigma quality practices. Kaizen literally means "school of wisdom" (kai = "school", zen = "wisdom"). Related is poka yoke, literally "error to avoid" which is usually translated as "mistake-proofing."

Kaizen goes hand-in-hand with six-sigma variability reduction--the elimination, as much as is humanly possible, of inconsistencies in processes and in the finished product. Six sigma is not the same as quality control, Smith points out. QC detects substandard product after it comes off line, whereas six sigma seeks to prevent defects from occurring in the first place.

In her practice, Smith comes across companies at every conceivable level of competence and ineptitude. No matter where she finds them, she strives to make them better at what they do.

"That's why it's called continuous improvement. It doesn't matter where you are --you can always get better. Maybe your changeover on a packaging line is "just" one hour. We view that as one hour of wasted time. We've achieved our goal of reducing that time by fifty percent again and again."

Many pharm/biotech companies, says Smith, have been converted to lean manufacturing and six sigma, but the industry still has a long way to go. "Some are using one or the other, but in reality they should be using both because the goal should not be only to eliminate waste, but to reduce variability as well."

Missionary Work

If lean and six sigma are so effective, why doesn't everyone employ them? More and more companies do, says Smith, but even after managers agree to such programs, they must then commit to the discipline of putting them into action. "Implementation is the killer. Management is usually receptive to these ideas but doesn't execute them well. Without management commitment you might as well forget it."

A kaizen program's logic and potential benefits often clash with big egos, one or two of which have been known to reside in pharmaceutical establishments. Smith recalls one manager whom she thought she could challenge with her standard promise to improve throughput by 50%. His response, "Are you telling me I've been doing this wrong all this time?" is not easily countered, especially when the answer is "yes" and you want the guy's business. Another hurdle is the "Ph.D. syndrome," which goes something like this: "We have so many Ph.D.s running around here " why can't we figure it out?" A corollary to the Ph.D. excuse is that kaizen and related methods couldn't possibly work because they're too simple.

Pharmaceutical manufacturing carries enough inefficiency, says Smith, that startling improvements are possible without even touching regulated, value-added operations. Companies can work within Good Manufacturing Practices (GMPs), for example, focusing only on preparation, mechanics, and other day-to-day activities, and still garner many of the benefits of lean manufacturing and six sigma.