Abstract
The filtration of protein solutions, especially in the manufacture of biologically derived proteins, is a large and increasingly important step in the production of protein pharmaceuticals. The focus of this chapter is on the use of membrane filters for purification and sterilization of protein pharmaceuticals. However, we also review other important uses of membranes and nonmembrane filters in the production of protein pharmaceuticals. The reader is directed to several useful reference books that describe in more detail both the theory and the practice of filtration in the biopharmaceutical industry (Cheryan, 1986; Ho and Sirkar, 1992; Johnston, 1992a; Meltzer, 1987; Meltzer and Jornitz, 1998). Additional discussion of interactions between filters and protein formulations can be found in Chapters 2 and 3. The appendix to this chapter contains definitions of terms for those readers unfamiliar with terminology of membrane filtration.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Belter, P. A., Cussler, E. L., and Hu, W.-S., 1988, Bioseparations:Downstream Processing for Biotechnology, Wiley, New York.
Blatt, W. F., Dravid, A., Michaels, A. S., and Nelsen, L., 1971, Solute polarization and cake formation in membrane ultrafilters: Causes, consequences, and control techniques, in: Membrane Processes in Industry and Biomedicine (M. Beir, ed.), Plenum Press, New York, pp. 65–68.
Brose, D. J., and Henricksen, G., 1994, A quantitative analysis of preservative adsorption on microfiltration membranes, Pharm. Technol. 18:64–72.
Brose, D. J., and Waibel, P., 1996, Adsorption of proteins in commercial microfiltration capsules, Pharm. Technol. 20:48–52.
Brose, D. J., Cates, S., and Hutchison, F. A., 1994, Studies on the scale-up of microfiltration membrane devices, J. Parenteral Sci. Technol. 48:184–188.
Brown, S., and Fuller, A. C., 1993, Depyrogenation of pharmaceutical solutions using submicron and ultrafilters, J. Parenteral Sci. Technol. 47:285–288.
Cheryan, M., 1986, Ultrafiltration Handbook, Technomic, Lancaster, PA.
Datar, R., Martin, J. M., and Manteuffel, R. L., 1992, Dynamics of protein recovery from process filtration systems using microporous membranes, J. Parenteral Sci. Technol 46:35–42.
Devereaux, N, and Hoare, M., 1986, Membrane separation of protein precipitates: Studies with crossflow in hollow fibers, Biotechnol. Bioeng. 28(3):422–431.
Green, L., and Duwez, P., 1951, Fluid flow through porous metals, J. Appi. Mech. 18:39–45.
Hermia, J., 1982, Constant pressure blocking filtration laws—Application to power-law non-Newtonian fluids, Trans. IChemE 60:183–187.
Ho, W. S. W., and Sirkar, K. K., 1992, Membrane Handbook, Van Nostrand Reinhold, New York.
Hu, H., Camilleri, J., and Tamashiro, W., 1993, A new membrane for biopharmaceutical filtration, Pharm. Technol. 17:30–44.
Johnston, P. R., 1992a, Fluid Sterilization by Filtration: The Filter Integrity Test and Other Topics, 1st ed., Interpharm Press, Buffalo Grove, IL.
Johnston, P. R., 1992b, Fluids flow through filter medium: A tutorial Pharm. Technol, 16(9): 136–146.
Jornitz, M. W., Brose, D. J., and Meltzer, T. H., 1998, Experimental evaluations of diffusive airflow integrity testing, J.Pharm. Sci. Technol. 52:46–49.
Resting, R. E., 1985, Synthetic Polymeric Membranes: A Structural Perspective, 2nd ed. J Wiley, New York.
Kim, M., Kojima, J., Saito, K., Furusaki, S., and Sugo, T., 1994, Reduction of nonselective adsorption of proteins by hydrophilization of microfiltration membranes by radiation-induced grafting, Biotechnol. Prog. 10:114–120.
Kirsch, L. E., Riggin, R., Gearhart, D. A., Lefber, D. F., and Lytle, D. I., 1993, In-process protein degradation by exposure to trace amounts of sanitizing agents, J. Parenteral. Sci. Technol. 47:155–160.
Levy, P., and Shehan, J., 1991, Performance characteristics of polysulfone and cellulose membranes for the ultrafiltration of biological process streams, BioPharm, 14:24–33.
Loeb, S., 1981, The Loeb-Sourirajan membrane: How it came about, in: Synthetic Membranes (A. Turbak, ed.), American Chemical Society, Washington, DC, Vol. 1, pp. 1–9.
Marshall, A. D., Munro, P. A., and Tragardh, G., 1993, Effect of protein fouling in microfiltration and ultrafiltration on permeate flux, protein retention, and selectivity: A literature review, Desalination 91:65–108.
Martin, J. M., and Manteuffel, R. L., 1988, Protein recovery from effluent of microporous membranes, BioPharm 1:20–27.
McDonogh, R. M., Bauser, H., Stroh, N., and Chmiel, H., 1990, Concentration polarization and adsorption effects in cross-flow ultrafiltration of proteins, Desalination 79:217–231.
McGregor, W. C., 1990, Advances in primary separations with membranes, in Biologicals from Recombinant Microorganisms and Animal Cells: Production and Recovery (M. D. White, S. Reuveny, and A. Shafferman eds.), VCH, Mannheim, Germany, pp. 457–463.
Meltzer, T. H., 1987, Filtration in the Pharmaceutical Industry, Marcel Dekker, New York.
Meltzer, T. H. and Jornitz, M. W., eds., 1998, Filtration in the Biopharmaceutical Industry, Marcel Dekker, New York.
Michaels, A. S., 1986, Forward, in: Ultrafiltration Handbook, by Munir Cheryan, Technomic, Lancaster, PA.
Palecek, S. P., and Zydney, A. L., 1994, Intermolecular electrostatic interactions and their effect on flux and protein deposition during protein filtration, Biotechnol. Prog. 10:207–213.
Parenteral Drug Association, 1992, Industrial Perspective on Validation of Tangential Flow Filtration in Biopharmaceutical Applications, Technical Report No. 15, PDA, Bethesda, MD.
Parenteral Drug Association, 1998, Sterilizing Filtration of Liquids, Technical Report No. 26, PDA, Bethesda, MD.
Pitt, A. M., 1987, The nonspecific protein binding of polymeric microporous membranes, J. Parenteral Sci. Technol. 41:110–113.
Porter, M. C., 1981, The effect of fluid management on membrane filtration, in: Synthetic Membranes (A. Turbak, ed.), Vol. 1, ACS Symp. Ser. 153, American Chemical Society, Washington, DC, pp. 407–448.
Reif, O. W., 1998, Extractables and compatibilities of filters, in: Filtration in the Biopharmaceutical Industry, (T. H. Meltzer and M. W. Jornitz, eds.), Marcel Dekker, New York, pp. 204–206.
Romero, C. A., and Davis, R. H., 1988, Global model of crossflow microfiltrati on based on hydrodynamic particle diffusion, J. Membrane Sci. 39:157–185.
Sarry, C., and Sucker, H., 1992, Adsorption of proteins on microporous membrane filters: Part I, Pharm. Technol. 16:72–82.
Sarry, C., and Sucker, H., 1993, Adsorption of proteins on microporous membrane filters: Part II, Pharm. Technol. 17:60–70.
Soelkner, P., and Rupp, J., 1998, Cartridge filters, in: Filtration in the Biopharmaceutical Industry, (T. H. Meltzer, and M. W. Jornitz, eds.), Marcel Dekker, New York, pp. 147–156.
Strathman, H., 1986, Synthetic membranes and their preparation, in: Synthetic Membranes: Science, Engineering, and Applications (P. M. Bungay, H. K. Lonsdale, and M. N. de Pinho, eds.), Reidel, Boston, pp. 8–34.
Tarry, S. W., 1998, Filter housings for biotechnology and pharmaceutical applications, in: Filtration in the Biopharmaceutical Industry (T. H. Meltzer and M. W. Jornitz, eds.), Marcel Dekker, New York, pp. 435–451.
Truskey, G. A., Gabler, R., Dileo, A., and Manter, T., 1987, The effect of membrane filtration upon protein conformation, J. Parent. Sci. Technol. 41(6):180–193.
U.S. Food and Drug Administration, 1987, Guideline on General Principles of Process Validation, U.S. FDA, Center for Drugs and Biologies and Center for Devices and Radiological Health, Rockville, MD.
U.S. Food and Drug Administration, 1991, Guidance for Large Volume Parenterals, U.S. FDA, Rockville, MD.
USP, 1995, United States Pharmacopeia, 23rd rev., United States Pharmacopeial Convention, Rock ville, MD.
Vertenstein, M., and Ronis, D., 1984, Microscopic theory of membrane transport. II. Darcy-Brinkman flow, J. Chem. Phys. 80:5754–5763.
Visvanathan, C., and Ben Aim, R., 1989, Studies on colloidal membrane fouling mechanisms in crossflow microfiltration, J. Membrane Sci. 45:3–15.
Waibel, P. J., Jornitz, M., and Meltzer, T. H., 1996, Diffusive airflow integrity testing, J. Pharm. Sci. Technol. 50:311–316.
Wolber, P., Dosmar, M., and Banks, J., 1988, Cell harvesting scale-up: Parallel-leaf crossflow microfiltration methods, Bio Pharm 1:38–45.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2002 Springer Science+Business Media New York
About this chapter
Cite this chapter
Brose, D.J., Dosmar, M., Jornitz, M.W. (2002). Membrane Filtration. In: Nail, S.L., Akers, M.J. (eds) Development and Manufacture of Protein Pharmaceuticals. Pharmaceutical Biotechnology, vol 14. Springer, New York, NY. https://doi.org/10.1007/978-1-4615-0549-5_5
Download citation
DOI: https://doi.org/10.1007/978-1-4615-0549-5_5
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4613-5127-6
Online ISBN: 978-1-4615-0549-5
eBook Packages: Springer Book Archive