For years now, FDA has exhorted manufacturers to apply modern techniques to quality assurance and control, drug development and manufacturing. Some companies are taking on the challenges posed by such voluntary FDA guidances as process analytical technologies (PAT) and Quality by Design (QbD).
Many openly admit that FDA’s support for these initiatives was the tipping point that made them embrace PAT and QbD.
As drug manufacturing moves into the “nichebuster” age, others in the industry are still at some stage of the blockbuster grieving cycle—denial, anger, or bargaining—in their response to the call for change. After all, nobody says manufacturing has to be smart, if basic product quality standards are met.
Now that FDA leadership has changed, some may wonder whether these initiatives can survive.
Concerns on that front may have been laid to rest by FDA Commissioner Margaret Hamburg last month, when she emphasized the importance of QbD and better science in a speech at the Regulatory Affairs Professionals annual meeting. (Can you recall when an Agency leader above the level of Dr. Woodcock has specifically mentioned QbD?) It’s safe to assume that FDA will continue to back, and promote, these programs.[pullquote]
But why should one need FDA to embrace methods that, together with properly implemented Lean Six Sigma, are saving money, and have the potential to save corporate reputations, jobs, and even patients’ lives?
Despite high standards for quality, there is still plenty of quality variability, and generics (now almost 70% of all U.S. prescriptions) present a new frontier for applying PAT and the concept of design for manufacturability. Consider the fact, for example, that people are splitting their pills . . . in some cases, one half of the tablet contains no active ingredient and the other, twice the recommended dose. There can also be great variability in excipient quality, with potential risk to patients. Cases abound of generic product recalls due to manufacturing issues—deadly doses of active ingredient, for instance, or problems with asthma inhalants that could have been stopped by PAT and use of QbD concepts.
Customers and shareholders are already demanding that you work smarter. Last Summer, for instance, shareholders filed a lawsuit against Genzyme charging that it withheld information about cGMP issues at its Allston, Mass. facility. Its stock prices fell 35% and product shortages ensued, and then a competitor launched an alternative product.
But let’s forget about science and technology for a moment and consider human issues and management style, and two case studies in pharma crisis response at Bayer Healthcare in Berkeley, California and Wyeth in Pearl River, N.Y.
Bayer’s facility was due to close, and manufacturing was to be outsourced. Could the company’s strong new OpEx program and use of innovative technology have convinced local officials to give the plant $100 million to keep the facility, and its 1,400 jobs, in Berkeley?
Wyeth went into crisis-response mode a year and a half ago, when a generic version of one of its drugs was approved. An immediate decision was made to trim global operating expenses by 25%, a move that many did not think would be possible. After all, the company had already implemented an OpEx program.
After 18 months, the company has met its goals and on its way to exceeding some of them, and saved an additional $23 million by “insourcing” production that would otherwise have been sent to a contract manufacturer.
In both cases, success depended not only on the implementation of Lean tools like OEE and SMED, but also on a foundation of continuous training and improvement and servant leadership. Required was constant management interest, and presence (of the right kind—not the “I don’t trust you so I’m checking on what you’re doing” variety) in the workplace. “Go out and Gemba,” is the new management mantra.
As one operator put it when I recently visited Wyeth’s biotech line at Pearl River, “Once we understood the need for change and the tools, we wondered why we hadn’t started all this a whole lot sooner.” Enough said.
These same crises are playing out, or will soon, at a facility near you—or at yours. Are you prepared? (We’ll have more specifics on what Wyeth and Bayer did in our November/December issue.)
*with apologies to Tennessee Williams