From a recruitment perspective we have seen an increase in companies in the UK looking for lean and six sigma skills and experience from their candidates, with a view to driving improvements in quality. Many more senior managers within manufacturing come to us looking for the challenge of driving change in these facilities, and implementing these changes successfully to add increasing value in the long term to companies.
The article below explores the progress within pharmaceutical manufacturing industry.
The Pulse of Pharmaceutical Manufacturing
During the past decade, pharmaceutical manufacturing and quality functions were thrust into an unaccustomed spotlight. After an extended spate of consent decrees, noncompliance and drug quality problems, FDA began to look for root causes and to consider lessons in manufacturing science that regulators and manufacturers might learn from other industries.
At FDA’s Center for Drug Evaluation and Research, the Office of Pharmaceutical Sciences held a series of meetings to analyze these issues. In quick succession the Process Analytical Technology (PAT) team was formed in 2002, the 21st Century cGMP’s were published, outlining a risk-based approach to regulation and compliance, and the PAT Guidance appeared in 2004. During this period, a challenge was issued to drug companies by then-Commissioner Mark McClellan, who was quoted by The Wall Street Journal as saying that the science of drug manufacturing was “behind that of potato chip and soap making.”
Today, drug companies still face quality and compliance problems ranging from supply shortages to consent decrees and warning letters. We asked a number of expert industry observers, including some who had led the call for change last decade, to share their thoughts on how pharmaceutical manufacturing has progressed, and whether anything had actually changed. This is a brief summary of some of what they had to say.
Examining the big picture, experts agree that the “sea change” predicted for drug manufacturing still hasn’t occurred. “McClellan’s quote still resonates today,” says Bikash Chatterjee, President and CTO of Pharmatech Associates, Inc. “Our processes have not demanded the level of sophistication required in other market segments where margins are much tighter, so it’s natural to expect them to evolve at a different rate.”
Although some companies have implemented processes that run at 6 Sigma, the industry overall still operates at the same Sigma level of 2.5 to 3 that it did last decade, says G.K. Raju, Executive Director of the Pharmaceutical Manufacturing Initiative at MIT, and President of Light Pharma, Inc. At FDA’s Science Advisory Board meetings last decade, Mr. Raju documented the high cost of traditional QC and its contributions to pharma’s unusually high cycle times.
“Progress seems to be slow when one looks at reports on shortages, recalls and other quality issues,” says Ajaz Hussain, CSO at Philip Morris International, and former Deputy Director of OPS and head of the PAT Team at FDA. FDA had launched PAT and the 21st Century initiatives, in part, to prevent just these types of problems from recurring. “Efforts towards developing guidelines have been laudable,” he says, “but additional emphasis is needed on certain fundamental aspects of quality such as effective QMS, training, root-cause investigations and setting of specifications based on an analysis of variance.”
However, there are bright spots. More people seem to realize that changing operations is not simply doing some Lean Sigma training, but changing mindsets, says Thomas Friedli, professor at the University of St. Gallen, whose research group has been closely tracking pharmaceutical operational excellence progress for a number of years. “The complexity that drug plants have to master has increased, so a plant that maintains operational performance over the years has in fact improved,” he says. Traditional pharma leads in Lean and Six Sigma efforts, but biopharma is now devoting more resources to operational excellence in manufacturing, and to consolidating isolated improvement activities, Friedli says. Currently, the University of California Berkeley and NSF have launched the Initiative for Research in Biopharmaceutical Operations to study this issue, while, funded by the Sloan Foundation, MIT and Georgetown are exploring related issues and the impact of globalization on regulation and innovation.
· Increased Use of Modern Manufacturing Tools
· Benefits of New Process Validation Guidance
· Clueless on the Cost of Poor Quality?
· Right First Time
· Regulatory Uncertainty
Companies need to understand that manufacturing skills and understanding are an essential component of the mix in a boardroom. Until that happens, decisions will continue to be made which look sensible on the balance sheet, but are disastrous on the factory floor,” says Mahboubian-Jones. The future of drug manufacturing belongs, he says, to small, flexible, forward-looking companies which create a base by filling niches deemed “uncompetitive” by Big Pharma. “Once this base is established, they will progressively out-compete the current generation of companies. There are clear signs that this process has started, and it seems to be most vibrant away from the conventional manufacturing centers in the Western world,” he says.
Overall, there is reason for optimism, he says. “Today’s positive examples suggest that pharma is capable of transforming its manufacturing and the quality of its products. The future has great potential. The question is: Will that potential be realized by the current generation of companies, or will it be a new generation of more flexible, more responsive, less autocratic companies which take up the gauntlet and bring about the transformation which is required?”