Biomedical Engineering Reference
In-Depth Information
Prior knowledge,
scientific insight
“Process
Parameters”
Pressure
Flow rate
Hold-Time
Filter material
Filter size
Temperature
Fill Speed …
Impact on
Process
performance,
product
quality attributes
Machinability
filterability
sorption
consistency
Product or process
risk assessment
“Material
Attributes”
pH, Rheology/
Viscosity
Density
Surface -
tension …
Figure
10.2. Application of the QbD concept to process development.
10.2 RISK ASSESSMENT PROCESS
To align with ICH Q8, Q9, and Q10, a comprehensive risk assessment process was
developed in Pfizer: “Right First Time for Co-Development” (RFT). The objective of the
work process is to apply risk-based approaches to generate process understanding and
process control that will create
(1) regulatory flexibility and (2) the foundation for continuous
improvement (life cycle).
The work process is intended to be continually improved for
efficiency and effectiveness. The implementation of such a process should lead to
decrease variability in manufacturing, faster change implementation, scientific knowl-
edge at hand to support quality investigations, reduce cost of goods, and create innovation.
10.2.1 Process Understanding
Inputs to the process control variability of the output. The inputs (x) are process
parameters such as people, equipment, measurements, process, materials environment,
and so on while the outputs (y) are protein content, aggregates, host-cell protein,
biopotency, endotoxins, sterility, peptide map, contaminants, and product degradants.
The objective is to establish the functional relationship between quality attribute (y) and
process parameter(s) (x), that is, y
¼
f (x
1
, x
2
, x
3
...
).
10.2.2 Objectives
The objective of the process is to gain agreement on process scope, decide what is
important to evaluate, prioritize parameters based on risk, gain agreement on high-level
experimental strategy, and identify and prioritize process analytical technology (PAT)
applications.
