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