Peer-Reviewed Technical Note: Quality by Design in Freeze-Drying - Pharmaceutical Technology

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Peer-Reviewed Technical Note: Quality by Design in Freeze-Drying
Cycle design and robustness testing using advanced process analytical technology.


Pharmaceutical Technology
Volume 32, Issue 10, pp. 88-93

Conclusion

The study indicates that safety margins for shelf temperature and chamber pressure for a given product can be pre-evaluated in a laboratory using advanced PAT tools and therefore may allow for a rational QbD approach in the future. In addition, product resistance data obtained from MTM may provide valuable information about microcollapse in the product ("benchmark" properties). This information can be very useful in interpreting the effect of temperature or pressure deviations on a product.

Henning Gieseler, PhD,* and Stefan Schneid work in the Division of Pharmaceutics at the University of Erlangen, Erlangen, Germany 91058, tel. +49 9131 85 29545,
Tony Kramer works at the Ecolab Research Center in Eagan, Michigan.

*To whom all correspondence should be addressed. Submitted: Jan. 23, 2008. Accepted. Apr. 23, 2008.




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References

1. J. Wechsler, "Modernizing Pharmaceutical Manufacturing," Pharm. Technol. 26 (2002).

2. FDA/ORA, "Compliance Policy Guide, Sub Chapter 490.100," Process Validation Requirements for Drug Products and Active Pharmaceutical Ingredients Subject to Pre-Market Approval (CPG 7132c.08).

3. M.J. Pikal and H.R. Costatino, "Lyophilization of Biopharmaceuticals" in Biotechnology: Pharmaceutical Aspects, R.T. Borchard and C. R. Middaught, Eds. (AAPS Press, Arlington, VA, Vol. II, 2004).

4. X. Tang, S.L. Nail, and M.J. Pikal, "Freeze-Drying Process Design by Manometric Temperature Measurement: Design of a Smart Freeze-Dryer," Pharm. Res. 22 (4) 685–700 (2005).

5. H. Gieseler H, T. Kramer, and M.J. Pikal, "Use of Manometric Temperature Measurement (MTM) and SMART Freeze Dryer Technology for Development of an Optimized Freeze-Drying Cycle," J. Pharm. Sci. 96 (12), 3402–3418 (2007).

6. H. Gieseler, "Process Analytical Technology for Freeze-Drying: Cycle Optimization in the Laboratory," Eur. Pharm. Rev., 1, 2007.

7. F. Fonseca et al., "Collapse Temperature of Freeze-Dried Lactobacillus bulgaricus Suspensions and Protective Media," Biotechnol. Prog. 20, 229-238 (2004).

8. E. Meister and H. Gieseler, "Evaluation of Collapse Temperatures by Freeze-Dry Microscopy: Impact of Excipient Concentration on Measured Transition and the Overall Dependence on Measurement Methodology," in Proceedings of Fifth World Meeting on Pharmaceutics and Pharmaceutical Technology (Geneva, Switzerland, March 2006).

9. S. Rambhatla et al., "Cake Shrinkage During Freeze Drying: A Combined Experimental and Theoretical Study," Pharm. Dev. Technol, 1, 33–40 (2005).

10. S. Tchessalov, "Principles of Lyophilization Cycle Scale Up" in Processing CPPR Freeze Drying of Pharmaceuticals and Biologicals Conference (Garmisch-Patenkirchen, October 2006).

11. M.J. Pikal, "Use of Laboratory Data in Freeze Drying Process Design: Heat and Mass Transfer Coefficients and the Computer Simulation of Freeze Drying," J. Parent. Sci. Technol. 39 (3), 115–138 (1985).

12. J.P Dolan, "Use of Volumetric Heating to Improve Heat Transfer During Vial Freeze Drying" in Mechanical Engineering (PhD Thesis, Virginia Polytechnic Institute, Blacksburg, VA, 1998).

13. M.J. Pikal and S. Shah, "The Collapse Temperature in Freeze Drying: Dependence on Measurement Methodology and Rate of Water Removal from the Glassy Phase," Int. J. Pharm. 62, 165–186 (1990).


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