PDA Letter Article

Industry Experts: Quality Requires Proactive Approach

by Rebecca Stauffer, PDA

Quality is not something listed in the packaging insert that accompanies a drug product. Yet the US FDA (and the public at large) expects high quality to be inherent to drug products on the market, stated Sarah Pope Miksinski, Director, Office of New Drug Products, OPQ, CDER, FDA, at the start of the “Quality Risk Management” track, Feb. 28–March 1, at the 2017 IFPAC Annual Meeting, in Bethesda, Md.

The track offered a look at how quality factors into new manufacturing technologies, such as continuous manufacturing, in today’s environment. The overall consensus of the speakers? Ensuring quality requires a proactive approach that enables communication and collaboration.

After all, as Miksinski emphasized, quality is “a shared responsibility of all of us.” And when it comes to managing quality, “leadership is not management. It does not apply only to office directors or to division directors,” she explained. “It applies to the people who are leading these conversations, who are essentially responsible for having the right conversation at the right time.”

And great leaders understand that communication is critical, she added.


Sonja Sekulic, SPECTech Group Lead, Pfizer, agreed with Miksinski on the importance of communication, especially when it comes to sharing expertise about a system. Her group is accountable for the analytical aspects of Pfizer’s Portable, Continuous, Miniature, and Modular (PCMM) setup at its Groton, Conn. site. Here, the company is using movable pods for continuous manufacturing of oral solid doses (1). Sekulic views the switch from batch to continuous manufacturing as an opportunity to review all facets of an operation from every level (small-scale clinical production to larger clinical production and, finally, to large-scale commercial production). The data gained from this review should then be delivered to senior management.

“One way to communicate your knowledge is to be able to demonstrate, via models and predictive capability, your level of understanding,” she said. “That takes work, but I think that is a great communication vessel.”

Complexity: Another Potential Risk

Naturally, working with technology that can be adjusted for small-scale and largescale manufacturing presents challenges when it comes to quality risk management (QRM). For each of these levels, the risks must be reestablished and evaluated—an inherently complex task. And this is why developing a knowledge base is so important with continuous manufacturing.

“I believe that if I can fully understand a product and a process, then I should be able to manage my risks more effectively, more knowledgeably, and more agilely,” Sekulic explained. “We want to understand all the individual components of the platform.”

This understanding should also extend to the raw materials used in continuous manufacturing. According to Brian Carlin, Chair of the IPEC QbD/Excipient Composition Committee, as complex raw materials enter complex systems, there is potential for special cause variation in the finished product.

Carlin, whose area of interest is complexity, explained “when there are too many moving parts, you’re going to get emerging behaviors.” He added, “If you don’t know the risk is there, you can’t quantify it...uncertainty can destroy your products just as effectively as risks that are known.”

He is especially concerned about special cause variations, or “new, unanticipated, emergent” behaviors within a system. While some may argue that the answer is to tighten specifications for incoming materials, Carlin cautions that this cannot wholly prevent special cause variations, likening it to the legend of an English king who tried to order the tides to stop.

“There’s no such thing as a noncritical excipient; they all contribute to product quality,” Carlin said. A key risk assessment for excipients should be a comprehensive “continuous monitoring of your control strategy.”

He pointed out that proactive monitoring reduces risks significantly. This was echoed by Teva’s Director of Manufacturing Science and Technology Tate Edwards who discussed the quality concerns of legacy products. When Teva developed a QbD strategy for legacy products, the company’s approach “was to form a product risk assessment and then document a control strategy.”

Risk assessments, of course, are documented in large, resource intensive documents, he added.

“Importantly, at the outcome of the CPP [critical process parameter], you really build a foundation for the CPP program so that you can detect some of the uncertainties and variations that may crop up,” Edwards explained. This serves as an “early warning detection system to really meet the goal of modernizing your legacy products.”

In a panel discussion, CDER’S Rick Friedman emphasized that no matter the manufacturing technology or type of product, quality should be innate to the process.

“The best situation for compliance is when you rarely have to say ‘regulatory compliance’ in your company because you’re so focused on quality and maintaining a state of control and assuring quality…that the words ‘regulatory compliance’ really don’t have to come out of people’s mouths…because you will be de facto compliant,” he said.


  1. Stauffer, R. “Portable Pods Part of New Strategy for Pfizer.” PDA Letter 51 (May 2015): 32–34.