New manufacturing concepts and platforms are therefore required to meet commercial expectations for existing and upcoming new drugs. Product yields must be improved and the process must use manufacturing space and resources more efficiently. Reevaluating existing purification schemes and redefining the process may reduce the COGs by as much as 50% (2).
The concept of a generic technology platform for the purification of multiple drug candidates enables faster drug development and earlier definition of the commercial process and facilitates the effective utilization of manufacturing space. A key element to consider for any new biopharmaceutical manufacturing platform is the use of disposable equipment (disposables). This practice, together with the requirement for a viral clearance strategy, has led to the development of disposable nanofiltration technology. Using disposable nanofilters within the downstream process has been proven to reduce capital expenditure for housings and reduce labor, cleaning, and validation costs. Disposable nanofilters are capable of turning fixed costs into variable costs with single-use membrane technology. These costs become relevant as cash-out only when the plant is in operation and the nanofiltration step is up and running.Purification process
For this ovine-based product, the nanofiltration step is the cornerstone of the virus clearance strategy, targeting small nonenveloped viruses. Regulatory expectations are that the nanofiltration step provides robust and efficient removal of small nonenveloped viruses (porcine parvo virus [PPV] is the model virus being used) and achieves a 4-log10 (or greater) reduction.
When developing a manufacturing platform for this product, disposability was a prime consideration to ensure simplification of the process, reduction of labor, increased flexibility, and elimination of cross-contamination. The 20-nm nanofiltration was introduced at the end of the purification process where the purity of the product is the highest and filter blockage due to contaminants is the lowest. Protein concentration at this stage is 2–6 mg/mL, and pH is 7.0–7.8.