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    Membrane Filtration: Daniel J. Brose, Michael Dosmar, and Maik W. Jornitz

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    Aura Urrego
    This document discusses membrane filtration techniques used in the production of protein pharmaceuticals. It describes how membrane filters are used for clarification, fractionation, concentration, diafiltration, and sterilization of protein solutions. The two main modes of membrane filtration are dead-end filtration and crossflow filtration. Dead-end filtration is used for microfiltration to remove particles over 0.1 μm from relatively clean solutions, while crossflow filtration is better for more concentrated or dirty solutions as it reduces fouling of the membrane.

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    Membrane Filtration: Daniel J. Brose, Michael Dosmar, and Maik W. Jornitz

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    Aura Urrego
    75 views2 pages
    This document discusses membrane filtration techniques used in the production of protein pharmaceuticals. It describes how membrane filters are used for clarification, fractionation, concentration, diafiltration, and sterilization of protein solutions. The two main modes of membrane filtration are dead-end filtration and crossflow filtration. Dead-end filtration is used for microfiltration to remove particles over 0.1 μm from relatively clean solutions, while crossflow filtration is better for more concentrated or dirty solutions as it reduces fouling of the membrane.

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    This document discusses membrane filtration techniques used in the production of protein pharmaceuticals. It describes how membrane filters are used for clarification, fractionation, concentration, diafiltration, and sterilization of protein solutions. The two main modes of membrane filtration are dead-end filtration and crossflow filtration. Dead-end filtration is used for microfiltration to remove particles over 0.1 μm from relatively clean solutions, while crossflow filtration is better for more concentrated or dirty solutions as it reduces fouling of the membrane.

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    © All Rights Reserved
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    75 views2 pages

    Membrane Filtration: Daniel J. Brose, Michael Dosmar, and Maik W. Jornitz

    Uploaded by

    Aura Urrego
    This document discusses membrane filtration techniques used in the production of protein pharmaceuticals. It describes how membrane filters are used for clarification, fractionation, concentration, diafiltration, and sterilization of protein solutions. The two main modes of membrane filtration are dead-end filtration and crossflow filtration. Dead-end filtration is used for microfiltration to remove particles over 0.1 μm from relatively clean solutions, while crossflow filtration is better for more concentrated or dirty solutions as it reduces fouling of the membrane.

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    5

    Membrane Filtration

    Daniel J. Brose, Michael Dosmar,


    and Maik W. Jornitz

    1. INTRODUCTION

    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 mem-
    branes and nonmembrane filters in the production of protein pharmaceu-
    ticals. 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.

    Daniel J. Brose • Chemica Technologies, Inc., Bend, Oregon 97701. Michael


    Dosmar • Separations Division, Sartorius Corp., Edgewood, New York 11717. Maik
    W. Jornitz • Product Management, Sartorius AG, D-37075 Goettingen, Germany.
    Development and Manufacture oj Protein Pharmaceuticals, edited by Nail and Akers. Kluwer Academic!
    Plenum Publishers, New York, 2002.

    213
    214 Daniel J. Brose et al.

    1.1. Applications of Membrane Filters in the Production of Protein


    Pharmaceuticals

    Protein biopharmaceuticals are typically produced by fermentation, cell


    culture, or extraction from tissue. Regardless of the origin of the biopharma-
    ceutical protein, many steps are involved in purification of the protein
    before it is ready for pharmaceutical sale and use. The physical processes
    used to purify biopharmaceutical proteins may include filtration, adsorp-
    tion, centrifugation, and chromatography. These processing methods are
    typically used to take a protein through the following sequence of steps in
    the purification scheme:

    • Clarification: removal of cell mass from supernatant liquid


    • Fractionation: isolation of desired protein from other solutes
    • Concentration: concentration of desired protein in solution
    • Diafiltration: removal or exhange of small solutes by sequential
    dilution and concentration steps
    • Sterilization: removal of bacterial cells

    Microfiltration (MF) and ultrafiltration (UF) membrane processes can


    be used to perform the above processing steps. Microporous filtration is
    sometimes used for clarification; UF is used for fractionation, concentra-
    tion, and diafiltration; and MF is used for sterilization. In the sterilization of
    protein pharmaceuticals, MF is the method of choice, because proteins are
    denatured by thermal sterilization processes.
    Membrane filtration processes can be divided into two distinct modes
    of operation. The first is a single-pass dead-end or static mode and the
    second is a multiple-pass crossflow or tangential-flow mode. Crossflow
    filtration is distinguished from dead-end filtration in that the flow path
    of the fluid being filtered is parallel to the membrane surface rather than
    perpendicular to the membrane surface, as shown in Fig. 1. In crossflow
    filtration, the flow parallel to the membrane surface generates shear, which
    limits the thickness of the filter cake or gel layer. In dead-end filtration, the
    filter-cake thickness increases with time, resulting in the eventual cessation
    of flow.

    1.1.1. DEAD-END FILTRATION

    Dead-end filtration is used primarily in micro filtration applications


    where the goal of the filtration is to remove particles greater than 0.1 11m,
    where the feed solution is relatively "clean," and where the filtrate (or solute

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