Chromatography Optimization Strategy - Robust packing procedures can improve process performance and increase resin lifetime. - BioPharm International

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Chromatography Optimization Strategy
Robust packing procedures can improve process performance and increase resin lifetime.


BioPharm International
Volume 22, Issue 3


Figure 10. Overlay of previous 1.09 compression and current 1.18 compression elution profiles
Large-scale results matched the experimental data from laboratory and pilot runs for this project with improved resolution at the beginning of the elution profile (Figure 10).

The bench-scale approach to evaluate end-of-collection was applied to pilot and large scales to evaluate the impact of the shift in retention. A new elution collection set up was developed to handle the retention shift and generate data necessary for a filing change. For each run with the proposed elution collection set up, the elute pool was well within historical results and met all acceptance criteria. In fact, product purity improved.

Reproducibility between purity and recovery results between bench and large scales demonstrated that the process was scalable and reproducible at both scales. This paved the way to qualify a bench-scale method to assist manufacturing events.

The overall chromatography process showed that it is receptive to the amount of resin or compression factor. A higher compression sharpened the prepeak elution profiles. Specifying the compression factor as a process characterization variable is critical in maintaining a scaled-down model.

LARGE-SCALE BLANK ELUTION RUN

The large-scale run was followed with a blank elution run to evaluate cleaning capability at a higher compression. The pool was analyzed with molecule concentration of below maximum limits. The results indicated that the regeneration is sufficient to mitigate concerns of product carry-over. Additional characterization efforts based on packing stability promoted the increase in pack re-uses from 10 to 30 cycles. Significant improvement was seen on yield recovery and the performance was more stabilized. The 30-cycle lifetime extension has been achieved at scale.

CONCLUSION

A scalable and consistent performance was demonstrated at large scale by an increase in both chromatographic step recovery and product purity. Asymmetry and HETP results were improved in both average results and consistency. The stability of the new pack procedure allowed for a lifetime extension for the chromatography step. The work culminated in the successful completion of three validation lots in the facility. The filings were submitted and approved and the facility now runs with this new large process.

Overall, the project had an impact of drug substance yield improvement by 7%, reduced recovery variability by 50%, reduced impurity levels by 12%, and zero nonconformance events post implementation. The resin determination by centrifuge and changes to packing procedure dramatically reduced cycle time.

AKNOWLEDGEMENTS

The authors are grateful to the cross-functional team of engineers and scientists for their dedication and support throughout all stages of the project.

Javier O. Tapia is a process engineer, Carlos Escobar is a principal engineer, and James Weidner is a director, all at bulk process development, Amgen Manufacturing, Ltd., Juncos, PR, 787.916.6871,

REFERENCES

1. Escobar C, Keener N. Chromatography unit operation optimization plan, process development study. PD-008-06, Amgen; 2006.

2. Rivera O. Determination resin percent for resin slurry by centrifuge method. Technical report 070072TR. Amgen; 2007.

3. Stickel J, Fotopoulos A. Pressure-flow relationships for packed beds of compressible chromatography media at laboratory and production scale. Biotechnol Prog. 2001;17:744-751.

4. Tapia J. Pressure flow correlation for resin. Technical report 070002TR. Amgen; 2007.

5. Keener N. Column packing study. Technical report 060409TR. Amgen; 2007.

6. Britton D. Pilot plant campaign summary. Technical report 060408TR. Amgen; 2007.


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