Life Sciences Biopharmaceuticals> Scale-up Direct Flow Filtration Technology

Scale-up Direct Flow Filtration Technology

Direct flow filtration (DFF) is an efficient separation method that is widely used in all industrial sectors to remove contaminants from liquids and gases. It plays a key role in the quality and the safety of all the solutions utilized and produced by the biopharmaceutical industry. Direct flow filtration can be used for the removal of solid or gel contaminants from a wide range of fluids, and in the biopharmaceutical industry, it is the technology of choice for the sterilization of heat-sensitive biological, intermediate and final products, particularly those within an aseptic process. Advanced membrane technologies now available are also being applied to the removal of viruses and prions from biological processes and have contributed to the overall viral safety of products.

What Types of Direct Flow Filters are Available?

Direct flow filters are usually divided into several categories:

Depth Filters

Depth filters are available for large scale applications, depending on the filtration media, in the following formats:

Plate-and-Frames
Lenticular modules
Cartridge elements

Membrane Filters

For large-scale operations, the membrane is pleated within a cartridge element to maximize available area. Pall® filters with patented Ultipleat® construction have a crescent-shaped pleat geometry that offer as much as a 30% increase in effective filtration area (EFA)over traditional pleated filters.

Formats

Most filter elements can be inserted into stainless steel housings, or are available in ready-to-use capsule formats that eliminate the need for cleaning and cleaning validation. It is an especially attractive format for product development. It offers maximum flexibility in terms of equipment use until a process is totally defined and validated.

Capsule filters can also be supplied pre-sterilized or can be assembled in more complex systems with several prefiltration stages to enhance ease-of-use and reduce the time and cost of labor.

Direct Flow Filtration Scale-Up Strategy

How to Scale-up

Direct flow filtration processes are scaled up from a given surface area using a scaleup factor, (the ratio of process scale to test scale filter area). This scale-up factor is applied to the flow-rate and throughput. As part of a scale-up assessment, it will be necessary to ensure that a filtration process has been carefully optimized. This should be done by carefully evaluating system sizing and filtrate quality for prefiltration, final sterile filtration and any virus removal steps. For certain applications, particularly sterile filtration and virus removal, once the filtration process has been defined, the end user will need to validate the filtration process to ensure that even under worst-case process conditions, acceptable filtrate quality is obtained. As part of Pall's Total Fluid Management program, we can provide you with support services which will help you to size direct flow systems and fully comply with regulatory requirements.

Approaches to Scale-up

Additional area can be added at process-scale to ensure performance
Intermediate scale tests can be performed to ensure scale-up to process volumes
If there is a difference in process system scale based on flow-rate throughput, worst case conditions are used to size the system
Prefilters are often used as an economical way to protect the final filter

Filterability or Scale-up Trials

Filterability or scale-up trials will usually be run at small-scale. The size of the filter used will most often be dictated by the volume available for testing.

The trial can be run at a constant flow-rate or a constant pressure.

During the trial, it is important to monitor appropriate parameters, such as differential pressures, filtrate flow-rate, volume, temperature and effluent quality. Effluent quality can be determined by turbidity, product analysis or other appropriate method.