Lifetime Studies for Membrane Reuse: Principles and Case Studies - - BioPharm International

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Lifetime Studies for Membrane Reuse: Principles and Case Studies


BioPharm International
Volume 21, Issue 9

In this case study, product pool pH, conductivity, impurity percentage, and recovery percentage were used to assess step performance. As Table 1 shows, the performance of the scale-down model is equivalent to that at large scale with respect to the parameters given, and the performance of the step is comparable across scales. Recovery was primarily used as a consistency indicator and was greater than 100% because different assays were used to measure product concentration in the load and pool samples. Small-scale reuse studies were performed using this scale-down model. NWP and flux-versus-time curves were monitored to assess the cleanability of the membrane. Finally, blank runs were performed after every five runs to assess carryover at small scale and host cell proteins (HCP), and product concentration via ELISA and DNA were monitored.

Figure 2 shows data from the small-scale reuse study. The membrane performance was acceptable based on pool pH, conductivity, impurity percentage, and recovery percentage (Figure 2A). Flux-versus-time curves (Figure 2C) overlapped, and NWP (Figure 2D) was stable over the number of membrane reuses. Carryover for the blank runs (2, 7, 12, 15, and 17) was minimal with respect to HCP, DNA, and product concentration (Figure 2B). Higher values for host cell proteins and ELISA samples for run 15 were attributed to sampling error, as supported by results for run 17. The small-scale data presented here suggested that 10 reuses could be validated at commercial scale, and this was eventually proven.

CONCLUSION

The application should dictate the approach used to establish membrane lifespan. Substantial time and resources are required to create and qualify a scale-down model and perform small-scale reuse studies, but when a strong likelihood of cleaning failure exists, these studies are justifiable. Robust routine in-process testing may be substituted for reuse validation, and it may provide a strong assurance of membrane performance. Because lifetime studies for membrane reuse require sampling and testing between lots, the studies may have an impact—sometimes a significant one—on production schedules. A cost–benefit analysis can often substantiate the benefits of validation.

Anurag S. Rathore, PhD, is director of process development at Amgen, Inc., Thousand Oaks, CA, 805.447.1000,
R. Samavedam, T. Kichefski, and S. Cote are all senior validation engineers at Amgen, Inc., West Greenwich, RI. R. Morrison is a manager at Commissioning Agents, Inc., Stonington, CT.

REFERENCES

1. Rathore AS, Karpen M. Economic analysis as a tool for process development: Harvest of a high cell density fermentation. BioPharm Int. 2006 Nov;19(11)56–63.

2. Parenteral Drug Association. PDA technical report 42: Process validation of protein manufacturing. PDA J Pharm Sci Technol. 2005 Sep–Oct;59 Suppl 4:1–28.

3. Rathore AS, Sofer G. Life span studies for chromatography and filtration media. In: Rathore AS, Sofer G, editors. Process validation in manufacturing of biopharmaceuticals: Guidelines, current practices, and industrial case studies. 2nd ed. Boca Raton: CRC Press; 2005:169–203.


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