Figure 2a. The key steps in process characterization. First, a risk analysis is performed, often using the failure modes
and effects analysis (FMEA) method, to identify parameters for process characterization. Second, studies are designed using
design of experiments (DOE). Third, the studies are executed and the results are analyzed to make decisions about the criticality
of the parameters and to establish the design space.
As shown in Figures 2a and 2b, once acceptable critical quality attributes have been established, process characterization
studies can be used to define the acceptable range of process parameters. Operating within these acceptable ranges—the interaction
of which will ultimately define the design space—ensures quality. Those acceptable ranges are documented in the regulatory
Figure 2b. Illustration of the design space and its relationship to the characterized and operating ranges. The operating
range denotes the range in manufacturing procedures; the characterization range is the range examined during process characterization;
and the acceptable range (AR) is the output of the characterization studies. The AR defines the design space and is documented
in the regulatory filing. Adapted from reference 7.
The overall approach to process characterization involves three key steps.6,8 First, a risk analysis is performed to identify parameters for process characterization. Second, studies are designed using
design of experiments (DOE) so that the resulting data will be amenable for use in understanding and defining the design space.
Third, the studies are executed and the results analyzed for decisions about the criticality of the parameters and about establishing
the design space.
Anurag S. Rathore, PhD, is a consultant, Biotech CMC Issues, and a member of the faculty in the department of chemical engineering at the Indian Institute of Technology. Rathore is also a member of BioPharm International's Editorial Advisory Board.
Articles by Anurag S. Rathore, PhD