Liquid Filtration Microbial Control in Biotech and Pharmaceutical Production

Liquid filtration plays a critical role in contaminant removal at many points in the biopharmaceutical and pharmaceutical production process, ultimately ensuring safety and sterility of the final drug product. From upstream growth media through downstream buffer additions to final formulation and filling, correct liquid filter selection and validation drives efficiencies in processing while providing confidence in achieving drug critical quality attributes (CQAs).

Filtration challenges are different for each type of fluid, product and scale of production. The optimal grade of filtration solution required for microbial control (bioburden reduction, sterilizing-grade or enhanced sterility with mycoplasma control) will also depend on the process step and associated risk assessment.

The growing interest in cell-modified gene therapies has highlighted the challenges associated with manufacturing viral vectors at the scales required for these therapeutics to gain regulatory approval. Minimizing loss (improving yield) at each production step of these highly complex molecules is paramount due to the high value of the product.

Lentivirus is increasingly the vector of choice due to its large cargo capacity that can transmit multiple genes. At 200 nm, the size of the lentivirus, compounded with a highly shear-sensitive bilipid envelope layer, and a half-life as low as 8-12 hours, mean specialist consideration is needed for filtration. Our specialists are working closely with cell and gene therapy process developers to better understand these challenges and refine filtration solutions for this emerging technology. 

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Monoclonal antibodies (mAbs) remain the predominant class of recombinant biologic drugs in development. Administration routes are changing with subcutaneous delivery (sub-C) using pre-filled syringes now preferred for patients requiring a frequent dosing regimen. Preparing mAbs at the high concentrations required to be able to administer sub-C doses in these small volumes presents challenges for sterile filtration.

High aggregate content and the high viscosities of concentrated mAbs affect both filter capacity and flux. Both factors are often compensated for by using oversized filters for what would traditionally be considered ‘small’ batch volumes.

Oversizing of sterilizing filters creates operational inefficiencies including excessive fluid hold-up volumes. This fluid is hard to recover, and the cost implications of this loss in yield is greater than for traditional IV drugs. In process development when fluid is scarce, yield loss can limit material availability for clinical trials.

Careful consideration and the right choice of filter can remove potential delays to the commercialization of a drug product and ensure long-term production efficiency.

Liposomes are the first nano drug delivery systems that have been successfully translated into real-time clinical applications, and are also used as adjuvants in vaccines. These nanosuspensions allow diversified routes of administration for both topical oral and injectable drug delivery.

Liposomal drug formulations tend to be hard to filter-sterilize compared with conventional formulations. Due to their large size (100-200 nm), liposomes are more likely to cause premature filter blocking compared to other parenteral drug types. Filter sizing needs to be considered carefully during the development of a liposome filtration process to avoid an oversized choice which may create excessive hold-up volumes and lead to product loss.

Select a sterilizing-grade filter with a high-capacity asymmetric membrane for liposomal fluids. These attributes combined with scalable formats with a high filtration area per standard 254 mm (10 in.) filter can facilitate a more compact filter system at production scale.