Filtration equipment for the biopharmaceutical industry

Based on the separation and retention mechanism normal flow filters are divided into two types: membrane filters and depth filters. Membrane filters are based on the separation based on size, therefore choosing an appropriate membrane can ensure that 99,99999% filtration efficiency is achieved, i.e. sterile filtration achieved with a 0.2 µm pore-sized filter. Whereas depth filtration is based on adsorption, conductivity or simply on the internal pore structure, as a result of which the retention qualities may vary one filter to another, but 99% retention efficiency can be achieved.

Filtration is an obligatory step of the utmost importance in the biopharmaceutical and biotechnological manufacturing processes. Membrane filters find successful applications in feedstock preparation for production, disinfection between manufacturing phases, elimination of sediment or solid particles of another nature, or achieving a sterile final/commercial product formulation. It is important to choose a right membrane for fluid and gas filtration. The membrane is chosen based on the chemical and physical parameters of the filtered product. Hydrophobic filters are best suited for gas filtration and organic solvents and would also serve as a venting duct. These filters maintain a similar to ambient pressure in the reservoir and simultaneously ensure sterility of the product. When using external gas, the reservoir vent filter removes the microorganisms from the gas. Hydrophilic filters are used for aqueous solutions.

In view of advancement in biopharmaceutical and biotechnological processes and time-to-market deadlines, biopharmaceutical manufacturer's range of membrane filters, as well as required additional equipment and components becomes the deciding factor. As official representatives of Merck, the company that has over 50-years' experience in the area of sterile filtration, we offer their products of exceptional quality, such as Aervent®, Durapore®, Merck Express®. All membrane filters are offered as disposable sterile Opticap XL capsules or multiple-use autoclavable cartridge filters to be used together with stainless steel holders.

Mobius® FlexReady system for buffer and media preparation featuring an optimised single-use flow-path. Designed to deliver optimal operational flexibility in the process of buffer and media preparation. The system features a choice of Millipore Express® PES or Durapore® filters and single-use Flexware™ assemblies, as well as an innovative process setup software. Mobius FlexReady can be used for clinical production to small-scale commercial manufacturing. The self-contained and disposable nature of the system eliminates maintenance as well as cleaning validation requirements.

The main objective of depth filtration is to separate impurities of higher molecular weight or bigger size fast, effectively and at low cost. Depth pre-filter increases the effectiveness of membrane filters, prolongs their useful life and reduces the operational cost. 

Merck Millistak+® Pod is one of the fastest growing depth filters. These filters are ideal for a wide variety of primary and secondary clarification applications, including cell cultures, yeast and E. coli lysates post centrifuge, E. coli refolds, media, vaccines, plasma proteins and sera. Usually used for separation of protein aggregates and other visible macromolecular structures from solutions in between the production stages in various biotechnological and biopharmaceutical processes.

Benefits of Millistak+® Pod: low hold-up volume for greater product yield; as many as 23 media types offered in single and multilayer products; Millistak+® HC dual-action media improves pre-filtration and compresses clarification; flexible, modular format offers scalability from 5 to 12,000 litres or more; patented disposable design eliminates need for housing, CIP or cleaning validation; self-contained Pod filters protect operators from exposure to biohazards; robust construction is easy to use and set up; smaller footprint facilitates use in tight spaces.

Biotecha team is trained and certified to carry out both depth and membrane filtering experiments in order to choose the membrane and porosity based on the chemical composition and complexity of the solution, as well as a process-optimal filter size according to the Pmax and Vmax sizing methods.

Tangential flow filtration is essentially a cross-filtration method, which, based on the membrane pore size, is divided into micro-filtration and ultra-filtration. In manufacturing processes micro-filtration replaces centrifugation and is successfully applied for removal of cell wall debris, protein aggregates and other larger components from solvents. Whereas the application of ultra-filtration is substantially wider: it can be used to desalinate protein solutions, differentiate protein by molecular weight (assumed the size differs at least thrice), prepare final protein formulation, concentrate protein, etc. For all tangential flow filtration applications we offer arguably the most popular in the world Merck Pellicon® cassettes. Compared to the competing hollow fibre and spiral wound module formats, these cassettes stand out because of their beneficial configuration. The integrated grids allow for the tangential sweeping all along the membrane's surface at low pumping rates. As a result, the TFF equipment (pumps, pipeline diameter, and similar) does not require large investment. Pellicon® cassettes are linearly scalable; the holders can be mounted to achieve a wider filtration surface for a wider-scale operation. No complex pipeline engineering design is needed to connect the increase amount of membranes, normally used for alternative membrane configurations.

Older generation Pellicon® 2 tangential flow filtration cassettes, whether with a cellulose (Ultracel), PES (Biomax) or PVDF (Durapore) membrane, are used for concentration, diafiltration, purification and cell harvest (cell solution clarification). Choose your screens to best match your process requirements: A screen (tight screen), C screen (coarse screen), D screen (coarse screen for high viscosity). 

As TFF application in biopharmaceutical processes increases, Pellicon®  2 cassettes are being replaced by the new generation Pellicon® 3 cassettes. The new generation cassettes benefit from the integrated silicone gasket to speed up the cassette installation into the holder. Manufacturing of Pellicon® 3 cassettes is fully robotised, this way ensuring that the production quality is not compromised by human factors. Pellicon® 3 cassette family has introduced D screen membranes, designed for processing of highly concentrated (250 mg/mL) antibody solutions.  Thanks to perfected production methods Pellicon® 3 are much more resistant to the traditional chemical substances used for their cleaning.

All cassettes can be purchased in a small format: Pellicon 3 (88 cm2 cassettes) or Pellicon XL 50. Used for process research, optimisation or comparison. Biotecha offers TFF experiments with equipment suitable for process development and optimisation.

The main component of TFF is the membrane, however, the system used is equally important. Merck offers Cogent® half-automated or fully automated TFF systems, designed to be used together with, but not limited to, Pellicon cassettes.

Cogent® μScale is a semi-automated bench top TFF system, ideal for both micro-scale process development and everyday low-volume ultrafiltration/diafiltration work in biopharmaceutical research. The system features a low minimum working volume (16 mL*), the ability to operate at feed pressures (up to 80 psi/ 5.5 bar), and low pulsation rates (≤3 psi). Ideal for purifying and concentrating monoclonal antibodies, recombinant proteins, vaccines, gene therapy constructs, blood serum products, and other cell-derived components.

Cogent® M1 TMP Control is a bench top tangential flow filtrations system, equipped with a 10 liter tank with embedded balance for process automation. This system can run in fed-batch or diafiltration mode using an optional transfer pump, which enables the system to process up to 100 litres or more based on product and membrane filter characteristics. In addition, the proprietary membrane filter holder is designed with integrated sensors and sanitary connections, greatly contributing to a low minimum working volume.

Cogent® Process Scale is a fully-automated TFF system designed to separate and purify monoclonal antibodies, vaccines, plasma, and therapeutic proteins. It is ideally suited for both pilot and production scale applications, thereby supporting rapid scale up from small to large scale operations. Configured to client's process needs and adaptable to suit the most complex biopharmaceutical processes.