Vertellus shares insight on Hollow Fibre Membranes (HFM) in biopharmaceuticals and how it became a crucial part of the biotech industry’s value chain in recent years.
The Role of Hollow Fibre Membranes in the Biopharmaceutical Value-Chain
The use of hollow fibre membranes (HFM) in the continuous production of biologics has long been established. However, it was not until the pandemic afforded a rapid increase in investment and accelerated regulatory support that hollow fibre technology became a crucial part of the biotech industry’s value chain, particularly for vaccine and viral vector manufacturing. The fast-evolving bio-manufacturing landscape has created an opening for continuous bioprocessing, which is widely recognised as a next generation technology for reducing manufacturing cost, while providing more flexibility and scalability with improved product quality.
In the upstream operation of bioprocessing, where bio-technologists are constantly challenged to produce more cells and cell products, HFM bioreactors have increasingly become popular compared to conventional methods, such as T-flasks, roller bottles and micro carriers. HFM Bioreactors offer many advantages such as the ability to produce high-density cells due to higher surface area-to-volume ratio, better cell viability due to a more in-vivo like culture environment, continuous harvesting and significantly smaller operational footprint.
In the downstream operation, continuous perfusion, tangential-flow HFM filter technology is commonly used to optimise filtration, maximise yield and achieve the desired critical quality attributes.
Potting Adhesive – A Critical Component of a Hollow Fibre Membrane Module
In a typical HFM bio-manufacturing operation, the membrane helps separate and purify the cell concentrate, or acts as nucleation sites for culture growth. While much has been written about the membrane materials and selection criteria, a critical component often overlooked, is the potting material that helps seal the membrane bundle together.
Though multiple materials have been investigated, including silicone elastomers and epoxy resins, today 2-part polyurethane remains the material of choice for medical and biomedical applications. Other than providing the vital, reliable barrier between the retentate and permeate sides, this potting material must also survive the many stressors of the HFM operation for an optimised, efficient operation and a high-quality output:
• Biocompatibility to ensure safe interaction with system components and cell concentrate
• Broad pH compatibility to accommodate exposure to buffer solutions with pH ranges of 2-14 without experiencing changes in physical properties or leeching into the cell concentrate
• Chemical resistance to survive the multiple cleaning cycles, typically using NaOH solution, between batches to prevent fouling due to pore blockage
• Compatibility with various sterilisation methods deployed to necessitate reuse of the filter, most commonly autoclave and gamma sterilisation.
Vertellus Biothane Polyurethane Systems provide a wide range of process and performance advantages to offer the right sealant for any bio-filter application.
Biothane Systems – A Biocompatible Solution for Biopharmaceutical Filters
Each Biothane System consists of two liquid components – the Vorite prepolymer and the Polycin polyol, which when mixed together cure at room temperature to yield a cross-linked polyurethane. Once combined, adhesive viscosity begins to increase as the chemical reaction develops a cross-linked network. As time progresses, the potting adhesive cures into a solid.
In the design of an HFM bioreactor and perfusion filter module, selection of a suitable filter cartridge potting adhesive starts with consideration of the type of membrane fibre being potted, primarily defined by the filtration requirements (micro- , ultra-, or nano-) and corresponding pore size. Full permeation of the membrane is achieved by leveraging the relationship between pore size and mix viscosity. The viscosity must be low enough for the adhesive to completely penetrate the spaces between fibres during the potting process, however excessively low viscosity can lead to clogging of pores.
Centrifugal and static potting processes require different potting adhesive viscosity profiles to set the membrane in the cartridge housing. An adhesive that increases in viscosity too quickly may result in defects such as bubbles or incomplete fill. Similarly, the rate of hardness development as the adhesive cures is an important factor in optimisation of the cutting process. Filter cartridge cutting efficiency is guided by potting hardness and the rate at which it develops, relying on a tight window of hardness to enable clean cuts that properly open the membrane lumen while producing the necessary strength and adhesion for cartridge integrity.
The modular technology of these two-part Biothane systems enables Vertellus to offer a broad spectrum of adhesive performance and physical properties required for a variety of upstream and downstream processes. Viscosity profiles in the figure below represent the spectrum of reactivity that can be achieved with various combinations of Polycin polyol and Vorite prepolymer components.
