FLOW MAINTENANCE

BioPharm: How can manufacturers maintain product flow g during adjuvant filtration?

Bromm (Sartorius Stedim): For the manufacturer of the adjuvants, it is important to study and understand the process variables involved in making the adjuvant. The process variables identified to have a significant impact on the filterability of the formulation should be controlled carefully and kept within a narrow operating window. This will enable constant performance of the filtration process within established process parameters.

If a specific flow rate is desired over the duration of a filtration operation where the potential for plugging exists, the filtration operation should be performed under constant flow mode using an appropriately sized filtration area. Product flow can be maintained by increasing the inlet pressure as needed. Throughput of complex biological fluids often benefits from operation in his constant flow mode, as opposed to operating at high initial pressure and allowing flux to decay as the filter plugs.

With adjuvanated vaccines, or similar products at risk for reduced bacterial retention efficiency, preliminary filterability trial performed at the initial stages of process developments can identify filters providing the highest level of sterility assurance for further formulation or process optimization, perhaps including limited microbial challenges to confirm initial suitability. Further filterability studies can then focus on optimizing process time and economy under operating parameters known to further increase bacterial retention likelihood with these highest assurance filters. This will maximize both retention and throughput to provide for successful sterilizing filtration, validation, and processing.

Koklitis (3M): As mentioned, the careful management and control of the operating conditions during process filtration is usually advantageous for achieving consistency and robustness. In addition, the choice of filter membrane type can can contribute to maintaining a consistent flow. An asymmetric membrane structure, with a more open upstream zone, can provide a relatively higher initial flux, for example, which results in higher filter capacity for some process streams.

A higher filter surface area can be obtained per cartridge cylinder by selecting products that use advanced pleat technologies, thus enabling higher throughput without increasing filter-system size. This approach may help with filtering highly viscous process streams, such as emulsions.

Powell (Asahi): Large areas of membrane is the brainless solution, but working with filter vendors and doing DOE-based filter screening under the desired, "high stability" API conditions is the better choice.

Just like in horse racing, where some horses perform better than others on different courses, choosing the right filter type or perhaps a cascade of filters can solve the problem and provide a balanced solution to your filtration problem. If your feed contaminant is primarily a slowly precipitating molecule of some sort, a relatively small coarse filter such as a 1 μm or 5 μm might be able to trap it and allow a medium-sized sterile grade filter handle the higher flow rate and process larger volumes.

Depth filters often provide significantly higher capacity than membrane filters so placing them upstream of a sterile grade filter is often a good idea when possible. As with any filter, but especially depth filters, a study of undesired reduction (by binding) in solution components should be considered. Find a balanced approach to this cascade of filters, with each filter sized appropriately to deal with and control the specific contaminant that causes the processing roadblock.

Featured in the roundtable: Holger Bromm, director of marketing and product management filtration technologies at Sartorius Stedim Biotech; Jerold Martin, senior vice-president of Global Scientific Affairs at Pall Life Sciences; Peter Koklitis, a technical filtration specialist at 3M Purification in the United Kingdom; and Jim Powell, business development manager of Asahi Kasei Bioprocess.