Considerations for Scaling-up Depth Filtration of Harvested Cell Culture Fluid - Data on the performance and variability of different formats. - BioPharm International

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Considerations for Scaling-up Depth Filtration of Harvested Cell Culture Fluid
Data on the performance and variability of different formats.


BioPharm International
Volume 22, Issue 3

CONCLUSIONS AND RECOMMENDATIONS

All the filters appeared to plug by similar mechanisms. The LSP, Pod, and Stack depth filter formats can be applied to the clarification of harvested cell culture centrate with <10% difference in capacity for sizes ranging from 270 cm2 up to 1.8 m2. These different filter formats also show comparable filtrate quality by NTU and Vmax filterability. No significant averaging effect of area was seen on variability. The variability among these devices was roughly constant.

The 270 cm2 LSP and larger devices are also recommended for accurate scaling. They are useful to assess filter capacity, filtrate quality, and expected variability at scale. The equivalent performance of the Pod and Stack formats indicate that they can be used interchangeably without affecting sizing or filtrate quality. A safety factor of 1.4 for sizing is expected to allow a filtration system to compensate for random batch-to-batch variations in feed, filters, and operating conditions. Other applications with larger variability in capacity because of centrifuge operation or harvest quality may require larger safety factors.

The 23.5 cm2 filters showed capacities that differed from the pod and lenticular formats by an average of 25%. The 23.5 cm2 filter device is useful for rough screening of different filter matrices, rough sizing (within +/- 50%), and filtrate quality evaluation.

This article does not represent an Amgen endorsement of any filters described herein and is not meant to imply that Amgen uses any of these filters for clinical or commercial manufacturing.

ACKNOWLEDGEMENTS

The authors would like to acknowledge the assistance of Karin Stephens from Amgen and Anne-Marie Braun, Matthew Daley, Jeffrey Shumway, and Ben Cacace from Millipore in the planning, execution, and analysis of this study. The significant assistance of Jonathan Royce, formerly with Millipore, is also acknowledged.

APPENDIX: PLUGGING MODELS


Table 4. Constant flux plugging models
Table 4 summarizes different plugging models that describe how pressure varies with L/m2 throughput or normalized volume at constant flux (Badmington, Bolton, Hermans, Hermia, Zeman). The polynomial models are strictly empirical. The other models are associated with different mechanisms of filter plugging. These models can be fit to data to obtain values of the plugging parameters and a statistical measure of goodness of fit. The parameter values obtained have physical meaning based on the associated model.

Herb Lutz is principal engineer and Mark Blanchard is principal research scientist, both at Millipore Corporation, Billerica, MA, 310.309.0984,
Ian Abbott is senior engineer, Ananth Parampalli is engineer, George Setiabudi is senior engineer, Vijay Chiruvolu is director, Megumi Noguchi is senior engineer, all at Amgen, Fremont, CA.

REFERENCES

1. Badmington F, et al. Pharm Techn. 1995;64–76(1995).

2. Bolton, GR, et al, J Memb Sci. 2006;279:625–634.

3. Hermans PH, et al. J Soc Chem Ind. 1936;55T: 1–4.

4. Hermia J, Trans IChemE. 1982;60:183–187.

5. Lutz H. Recovery of biological products XIII Conference, poster;2006 Apr.

6. Zeman LJ, et al. Microfiltration and Ultrafiltration, Marcel Dekker, New York, NY;1996.


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