Applying Process Analytical Technology to Biotech Unit Operations - - BioPharm International


Applying Process Analytical Technology to Biotech Unit Operations

BioPharm International
Volume 19, Issue 8

Figure 7. Testing the JMP model for cation exchange chromatography against the actual data. The central point is at 96.4%.
In this case study, we wanted to design a PAT-based control strategy that would ensure that the column pools had the desired purity. Cation-exchange chromatography was carried out in an XK 16 column packed with Sepharose Fast Flow resin (GE Healthcare, Piscataway, NJ). Chromatog-raphy runs were carried out on an AKTA Explorer 100 (GE Healthcare). Samples from the column were analyzed by reversed phase HPLC (RP-HPLC) for product purity and percent impurity. A design of experiments study consisting of 17 experiments was conducted with purity of the load material, start point of pooling (start collect), and end point of pooling (stop collect) as the variables. Pool purity and step yield were monitored for each experiment.

Table 2. Estimations of start collect and stop collect from the JMP model for a given load purity and to get a targeted pool purity (mAU = milli absorbance unit).
The results were analyzed using JMP software (SAS Institute, Cary, NC) and are presented in Figure 6. It is seen that load purity and stop collect have significant impact on pool purity, while start collect does not. We tested the JMP model by calculating the pool purity for all experiments. Figure 7 is a plot of measured purity vs. calculated purity. The correlation is good (R 2 = 0.87), supporting feasibility of this scheme.

In production, this JMP model could be used to estimate start collect and stop collect for a known load purity to yield a targeted pool purity. Four cases of this calculation are presented in Table 2. It is seen that for feed material with different purities, targeted pool purity can be achieved by changing the stop collect.

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