Biotechnology (Biotech) is recognised as the technology by which the worlds next generation of medicines and vaccines will be produced.
The applications encountered demand filtration products that are scalable allowing users to screen products at the earliest stages of drug development and continue to use the same functional media in formats of increasing size up to and including the final production stages of manufacturing.
High productivity and flexibility are essential requirements which has driven the trend to single use technologies.
For all your depth, membrane and sterile filtration requirements 3M Purification offers cost-effective and robust solutions which help optimize your drug development, RD&E and Industrial Production.
3M Purification can draw upon over 45 in house technology platforms to deliver the solutions that you need today and to partner with you on the development of new products to address your needs of tomorrow.
3M™ Zeta Plus series filters provide a solution for an efficient and economic purification of biotechnological products. Initially developed for the fractionation of plasma products they have been continually developed to address the needs of the Biotechnology Industry, providing cost effective solutions for cell harvesting with the capability of handling large levels of cell debris and biomass. The latest grades of ZA Formulation also have the capability to significantly reduce levels of DNA and HCP providing increased levels of protection for the more sensitive downstream processes such as chromatography.
In addition to final filling the 3M™ LifeASSURE™ PDA sterilizing grade of filters are used for the protection of chromatography columns and membrane crossflow systems. Incorporating PES filtration media they are benchmarked to be low protein binding and assembled in cartridge formats which offer increased surface area for longer life and smaller systems.
Housings applicable for this solution are 3M™ IP Housings, 3M™ IP 8" Housings and 3M™ IW Housings.
In a biotechnology process cells or cell constituents are used for the production of therapeutic proteins.
Cell lines can be complex mammalian cell lines or bacterial / yeast or plant extract systems.
Upstream the development of production cells, the preparation of media, fermenters and inoculants as well as the fermentation of cell systems take place.
A classical manufacture process for the production of biopharmaceuticals consists of various upstream and downstream systems. Upstream the development of production cells, the preparation of media, fermenters and inoculants as well as the fermentation of cell systems take place.
In biotech companies 3M™ Zeta Plus™ EXT filters are successfully used downstream for the clarification and purification of biomass during cell harvest. This partly happens through separators or, in case of single use production systems, directly through a 3M™ Zeta Plus™ EZP system. For further elimination of particles and biomass after a sterile filtration with 3M™ LifeASSURE™ PDA product isolation takes place through different chromatography steps.
Proteins of non-human species can lead to immune reactions when parenterally administered and therefore need to be reduced. The main source of contamination when manufacturing therapeutic proteins is the cell line used. Amongst other things, host cell proteins rank as process-related contaminations. The World Health Organization (WHO) provides miscellaneous specifications of ppm/rh protein per therapeutic dose as contamination limit.
Different studies on the filtration of cell solutions with 3M™ Zeta Plus™ EXT ZA have shown that HCP can be successfully reduced through depth filtration with positively charged 3M™ Zeta Plus™ ZA material during cell harvest. This also applies to later process steps, e.g. after protein A columns.
During the production of therapeutic proteins with transformed cell lines the risk of a transfer of host cell DNA fragments exists. Amongst other things double-stranded DNA of host cell organisms is a key source for contamination in the biotechnological manufacturing process and has to maximally amount to a quantity between 0,1 ng (Wolter and Richter, 2005) and 10 ng (WHO, 1998) per therapeutic dose.
In filtration studies on 3M™ Zeta Plus™ EXT ZA a 300-fold DNA reduction during cell harvest could be achieved with a depth filtration of cell suspensions through the charged 3M™ Zeta Plus™ EXT ZA. These results are confirmed by depth filtration of protein A eluate.
Endotoxins (pyrogenes) are lipopolysaccharides (LPS) from the cell membrane outer layers of gram-negative bacteria, like e.g. E.coli. Endotoxins can cause fever reactions in humans when parenterally administered and therefore have to be removed from the processes.
These contaminations naturally occur during e.g. bacterial fermentation processes, but are also partially transferred by humans or by polluted water systems at manufacturing.
Endotoxins are very resistant to temperature and pH fluctuations. That is why adsorptive removal processes have proven to be successful in endotoxin reductions.
Endotoxins exhibit a negative charge in aqueous or protein solutions as of pH 2. Thus the endotoxins can be adsorbed with positively charged filter media.
For this purpose 3M Purification offers positively charged nylon membranes, e.g. the 3M™ LifeASSURE™ 020SP series, which can either act as a particle or sterile filter. In addition the positively charged 3M™ Zeta Plus™ EXT ZA depth filters with their comparatively thick filter layers are able to remove by far the most endotoxins thanks to its large charge and multitude of binding sites. Also activated carbon media like 3M™ ZetaCarbon™ are ideal for endotoxins removal.
Pre-Filtration / Particle Filtration
A so-called pre- or particle filtration is often used in the pharmaceutics and biotechnology industry for clarification and/or particle reduction.
Reasons for this are the need for:
maintaining the product quality, e.g. through elimination of precipitates after bottling
making further process stages easier, e.g. purification in subsequent biological/biotechnological manufacturing processes
timely removal of contaminants for the protection of further processes
greater efficiency during the overall process.
Filter media guarantee consistent quality of service media, such as water, alkalis, acids, buffers, growth media, gases and air.
For this purpose 3M Purification offers a variety of products:
To discuss any of these applications with one of our trained technicians please contact us