A Review of Tangential Flow Filtration: Process Development and Applications in the Pharmaceutical Industry

Abstract

Tangential flow filtration is an efficient membrane separation technology utilized across a wide range of industries for separation and purification applications. The requirement of telescoped manufacturing to produce high-volume drugs in the pharmaceutical industry has led to increased adoption of membrane separation for drug substance synthesis. Particularly, for noncrystalline molecules with limited product stability and significant thermal liabilities, TFF is a powerful alternative to traditional isolation techniques. This Review discusses the various considerations during the development of a TFF process and highlights applications of TFF to produce pharmaceutically relevant molecules such as proteins, peptides, monoclonal antibodies, and so on. Finally, a future perspective on the technology is shared for improved performance.

Organic Solvent Nanofiltration in Pharmaceutical Applications

“…Rejection ( R ) is normally calculated as a function of the solute concentration in the permeate ( C p ) and retentate ( C r ) by equation , R = ( 1 − C p C r ) × 100 % There are many factors affecting the membrane flux and rejection, including the membrane type, solvent system, solute type and concentration, and process parameters (operating temperature, pressure, cross-flow velocity, pH, etc.) . For example, solution concentration is a critical yet often neglected factor in membrane studies.…”

Toward microfluidic continuous-flow and intelligent downstream processing of biopharmaceuticals

“…79 In several studies, TFF was demonstrated as an alternative to dead-end filtration, facilitating the sustained maintenance of high flux by minimizing concentration polarization and cake formation. 80 In a study, a modular reactor and in-line TFF microscale system has demonstrated complete substrate conversion, complete enzyme retention and prevention of macromolecule buildup on the membrane. 81 A highly efficient size dependent capturing of circulating tumor cells from a blood sample was demonstrated using an integrated microfluidic system equipped with microfilters of conical-shaped holes, as presented in Fig.…”

Impact of Excipient Extraction and Buffer Exchange on Recombinant Monoclonal Antibody Stability

“…During downstream purification (DSP), the purified protein product or drug substance (DS) is transferred from the chromatography elution buffer into the chosen formulation buffer to form the final DP. This is achieved through a combination of buffer exchange and concentration technology consisting of ultrafiltration–diafiltration (UF–DF) steps . The UF–DF technology is highly efficient at low protein concentrations.…”