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Too narrow a focus on regulatory compliance may prevent organizations from embracing-and profiting from-quality and operational excellence.
Over the past five years, global regulators have started a dialogue with pharmaceutical manufacturers about how best to measure quality (1). Frank discussions are taking place about management and corporate cultures (2) and whether they advance or impede efforts to establish operational excellence and customer-focused quality.
Efforts to study the relationship between quality and manufacturing performance peaked in the 1950s and 1960s. Inspired by thinkers such as Peter Drucker (3), W. Edwards Deming, and Taiichi Ohno, former chairman of the Toyota Motor Corp. in Japan, corporate leaders in a number of industries began to view quality as a revenue-creating opportunity rather than a cost center, and looked for new ways to empower workers to achieve excellence. The work clearly paid off. In 2014, in a study of 60 corporations, the Harvard Business School found that companies with strong quality cultures saved an average of $350 million per year (4).
The first formal operational excellence programs embracing these concepts took off in the pharmaceutical industry in the late 1980s. In 2014, the Parenteral Drug Association (PDA) surveyed pharmaceutical companies on quality practices and set up a task force to help elucidate current connections between culture, behavior, and quality attributes, and to show how quality culture is reflected in manufacturing and quality performance. PDA then teamed up with the University of St. Gallen, Switzerland, to analyze survey results along with data from the Swiss university’s extensive studies of pharmaceutical manufacturing and quality practices. The research focused on such metrics as communication; transparency; commitment and employee engagement; and standardization of requirements. Mature quality practices were defined as being objective and verifiable and included having formal programs in preventive maintenance, risk management, human error prevention, training, and continuous improvement (5). Results of that study enabled the development of a quality culture assessment tool that PDA has used to train 50 firms and more than 100 regulators in the United States and Europe, according to PDA task force leader Cylia Chen Ooi, director of quality at Amgen.
Observers see the need for pharma to expand its definition of quality. “Compliance, rather than a tradition of operational excellence, remains deep in pharma’s DNA,” says Nuala Calnan, founder and principal of Biopharm Excel and a member of Dublin Institute of Technology’s (DIT) regulatory science team, who worked on the quality culture metrics program with PDA and St. Gallen. “This mindset presents a significant barrier to excellence and must shift if the industry is to move beyond inspection readiness to true patient focus,” she says. The past decade, marked by mergers, downsizing, offshoring, and increased competition, has provided the industry with a number of negative examples of quality culture, for example:
The quality department of one Big Pharma over-the-counter (OTC) drug subsidiary in the US, whose managers allegedly coerced quality control (QC) lab analysts into passing failed batches. The department was unofficially nicknamed “EZ Pass” (6). Senior managers at the company were ultimately sued for failure to fund adequate QC, resulting in a $22.9-million settlement (7).
Two Indian pharmaceutical companies, which fired workers after their facilities received warning letters from FDA (8).
Operators and technicians at a number of Indian and Chinese manufacturing facilities in 2014–2017, who, during FDA site inspections, reacted to auditor requests by shredding documents, pouring samples down the drain, or removing a memory stick from a computer and running away with it (9). FDA has noted document shredding as recently as 2019 in a warning letter citing deficiencies at a facility in India (10).
Observers see the need for more proactive pharmaceutical company managers who actively support and invest in quality efforts and employee training. Toyota’s quality leaders often discussed the need for senior managers to walk the manufacturing, research, and testing laboratory floors (i.e., the gemba, or, in Japanese, the place where truth will be found) to learn directly from employees what the day-to-day problems are, to coach them, and work with them to find solutions. “For gemba to work, managers must talk while they’re out there, not telling but listening, observing, coaching, and enabling employees by removing barriers,” says Calnan.
More pharma companies are encouraging this approach and shifting to peer-review models with leaders being made more accountable and visible. But, as more companies and managers adopt formal gemba walk programs, says Chen Ooi, there is a real need to measure their effectiveness. As she notes, it’s not a straightforward science. “It’s all about behavior and reactions, and you don’t want to blame. You need to build trust with people on the floor so that they feel comfortable raising issues and provide truthful feedback instead of telling you what they believe you want to hear,” she says. Body language and tone of voice are extremely important, she says, and managers need to understand what goes into creating what Harvard professor Amy Edmondson has described as a “safe” environment where people can be honest (11).
It might be beneficial, says Chen Ooi, for executives to have a better understanding of science and engineering concepts in order to communicate more effectively with the people doing the work. But that understanding needs to flow from the bottom up, too. “Leaders in process development, supply chain, and manufacturing also need to be able to translate the very technical aspects of their operations into the more general language of business,” she says.
At the most fundamental level, there is a real need to understand the cost of poor quality in order to weigh potential losses (e.g., of a warning letter or consent decree) against the costs of hiring more quality control staff and investing in more modern analytics or information technology (IT). Georgetown University professor Jeffrey Macher has found that most pharmaceutical companies fail to measure or track the cost of quality within their organizations (12).
To be fair, says Chen Ooi, it can be difficult to quantify the cost of poor quality in dollar values. “It’s really about continuous improvement and preventing issues,” she says. At many pharmaceutical companies today, basic metrics are tracked, such as successful batch release rate, rate of invalid or out-of-specification (OOS) results, and inspection findings. But these are lagging metrics, she says, and only available after something has gone wrong.
Amgen is shifting to a “predict-and-prevent” focus and using artificial intelligence and data visualization to leverage more of the data gathered within the current good manufacturing practice (cGMP) environment that typically remains unused, says Chen Ooi. Using open-source code, available at very low cost, the company has developed a tool for deviation trending inhouse that can be used to uncover systemic problems, she says. The alternative until now was to have people review hundreds of issues, a painstakingly slow process.
If the industry is to sharpen its focus on quality metrics and culture, university training should include more industrial engineering-type courses to prepare students to understand and take charge of quality initiatives, says Chen Ooi. “There’s a need to educate students on the concept of quality beyond compliance so that they realize the value and business benefits of quality,” she says. “In pharma, every mistake or OOS situation requires a full-blown investigation, which requires significant time and resources,” she says.
Forward thinking universities are transforming traditional curricula. “We try to inculcate experiential learning into educational programs,” says Ajaz Hussain, director of the National Institute for Pharmaceutical Technology and Education (NIPTE), a consortium of 17 universities that include Rutgers, Purdue, Duquesne, and the University of Puerto Rico. NIPTE members have been moving toward integrated multidisciplinary courses that emphasize problem solving and critical thinking and include real-world problems, says Hussain, while also including certification to track continuous learning and improvement.
Corporate training programs can also be an obstacle to building a quality culture. “In organizations with a lower level of quality culture maturity, we often see the ‘shame, blame, and retrain’ approach being used. This is no longer acceptable to regulators,” says Calnan.
“The onus is on companies to create good onboarding and training processes to address the gap between university training and required on-the-job knowledge,” Calnan says. “But many organizations still use traditional onboarding, where success is often based on how many people signed up to train on whatever the topic is, rather than how well they mastered the material,” she says. Instead, she says, companies need to look at how tacit knowledge can be transferred between teams and coaches and mentors.
Technologies such as augmented and virtual reality can be useful because they allow the subject matter expert and the trainee to confer directly. Calnan notes a course that one company uses to train employees on column packing for chromatographic skids. “This is a very specific activity that can cause major problems if done wrong, but, for orphan drugs, operators may only be making two batches a year. Virtual reality refreshes their knowledge and lets them walk through the procedure the day before,” she says.
Hussain sees professional development as crucial to corporate training programs. “Deming emphasized appreciation for systems and the psychology of change. That’s where emotional intelligence comes in and where we use the term ‘culture of quality’,” he says.“You need a critical mass of leaders who are self-authored and self-transforming in order to achieve what Harvard education professor Robert Kegan called ‘orders of consciousness’” (13), he says. Those leaders must bring the rest of the staff up to support continuing education and continuous professional development.
Quality will ultimately depend on understanding the customer. When she visits companies, Calnan says, operators and technicians usually can’t tell her who the patient is that they are manufacturing products for. But even companies that cannot afford “patient engagement days” can bring the patient into their manufacturing and quality efforts, says Calnan.
“Why not have a lunch-and-learn session on corrective and preventive action (CAPA)? Take the last three complaints, get the team together and talk about them and how they might have been avoided,” she advises.
More advanced technology such as PAT, modeling, and AI can play a significant role in improving quality. However, many smaller companies often complain that they cannot invest in new technologies. Chen Ooi disagrees, because the potential savings and benefits of using the tools can far surpass the cost of investment. “People need to think about creative ways of stimulating the use of new tools (e.g., by creating small pilot projects to demonstrate the benefit of a specific technology). With artificial intelligence, for instance, a lot of the coding needed to build solutions is open source and doesn’t cost a lot,” she says.
Overall, training will be crucial to building a culture of quality. “People come to work wanting to do the right thing. It is all how managers send the message down and how they create an environment of trust. That is really the bottom line,” she says.
1. FDA, “Quality Metrics for Drug Manufacturing,” fda.gov, October 7, 2018.
2. A. Harrison and S. Schniepp, PharmTech39(9) pp. 22-25 (2015).
3. S. Caramela, “The Management Theory of Peter Drucker,” business.com, Feb. 27, 2018.
4. T. Friedli et al., PDA Journal72(5), pp. 531–542, September 2018.
5. A. Srinavasan and B. Karey, “Creating a Culture of Quality,” hbr.org, April 2014.
6. M. Kimes, “Why J&J’s Headache Won’t Go Away,” fortune.com, August 19, 2010.
7. W. Adis, “McNeil, a J&J Subsidiary FDA Case Study,” Communications of the International Information Management Association (IIMA), 14 (3), Article 2, 2014.
8. E. Palmer, “Mylan Fired Workers at Agila Plant,” fiercepharma.com, June 27, 2016.
9. FDA, “Warning Letter, Strides Pharma Science Ltd.,” fda.gov, July 1, 2019.
10. A. Shanley, Pharmaceutical Technology Outsourcing Resources SupplementVol. 2016, Issue2, s40-s44.
11. Harvard Business Review ideacast, “Creating Psychological Safety in the Workplace,” Interview with Amy Edmonson, hbr.org, Jan. 22, 2019.
12. J. Macher, “Business Case for Quality, a presentation at the Pharma Quality Systems,” ICH Q10 Conference, October 4–6, 2011.
13. R. Kegan, In Over Our Heads: The Mental Demands of Modern Life(Harvard University Press, Cambridge, MA, 1994).
Vol. 32, No. 8
When referring to this article, please cite it as A. Shanley, “Moving From Compliance to Quality," BioPharm International 32 (8) 26–28 (2019).