Page 87 - Assurance of Sterility for Sensitive Combination Products and Materials

Aseptic processing 73

EMA proposed revisions to Annex 1 (Manufacture of Sterile Medicinal
Products), prepared by an international PIC/S working group that in-
cluded representatives from Europe, United States, Australia, and Japan.
The 2107 draft revision contains numerous specific recommendations
for risk approaches, with many more implied. This signals the openness
by the regulatory bodies for the industry to propose new approaches.
• Manufacturers are recognizing that traditional approaches may no longer fit
what we need: The future will involve new and more complex delivery sys-
tems as well as sterile ATMP (Advanced Therapy Medicinal Products), Cell
and Gene Therapy products, and personalized medicine. These new thera-
pies require aseptic processing. Traditional aseptic processing approaches do
not adequately address the unique needs of the manufacturing of autolo-
gous sterile products on a very small scale. New (and improved) science and
risk-based approaches are needed. The tight release criteria and the timeline
for these products will provide an opportunity for rapid microbiological
testing, and in-process and real-time release of sterile products.
• Better technology is here and waiting: There is a significant opportunity
to acquire and link data at unprecedented levels. This information and
knowledge can be used to better model, predict, and control aseptic
processes. Simulations along with virtual and augmented reality can be
used to significantly reduce costs and timelines for building facilities and
developing the process by minimizing change requests and proactively
addressing design problems prior to the build-out. Augmented reality
can provide more frequent and effective training and expedite qualifi-
cations with higher levels of worker skill level and awareness. Artificial
intelligence and machine learning can utilize data to optimize processes
and process control minimizing variability and improving quality.
It is important to note that the utilization of technology improve-
ments will require extensive use of automation and knowledge man-
agement. As processes become more automated and continuous, process
validation will shift from a matter of process testing and replicate runs
to qualification of the automated control systems that control process
parameters. As manufacturing intelligence and shared data acquisition
and utilization systems are used more, the notion of computer system
validation based on the US FDA Part 11 and computer software guid-
ance may need to change. Methodologies that have been developed for
the software industry [19, 20] may need to be adopted.
• The technology workforce is changing: It is more difficult to attract,
train, and retain technical resources. The shortage of skilled, qualified