FAQS

To ensure that the column efficiency of the scale-down model is consistent with the manufacturing process, the client is required to ship the pre-packed chromatography columns to us before conducting viral clearance validation for the chromatography process. In addition, if the client is unable to perform the operations on-site, our laboratory personnel may be entrusted to carry out the validation experiments. The client shall submit a PM (Project Management) entrustment application for chromatography and provide a detailed process parameter sheet. Our laboratory personnel will then set up the running method for the chromatography validation, draft an operation record, and submit it to the client for confirmation. Our company will conduct a Mock Run in advance, and the client's technical personnel will confirm that the chromatograms and peak shapes from the Mock Run are consistent with the manufacturing process. Only after confirmation will our laboratory personnel proceed with the formal validation experiments. The resulting records and chromatograms will be provided together to the client's technical personnel for final review.

The maximum fouling conditions and the maximum process interruption conditions. The maximum fouling conditions are determined based on the selection of loading capacity, filtration pressure, sample pH, conductivity, and other relevant parameters.

For IND application, at least two batches or one batch with duplicate runs are required, and the panel of indicator viruses used is relatively limited. Generally, for low pH inactivation, at least MVM (Mouse Minute Virus) is required; for nanofiltration and chromatography, at least MVM and MVM (Mouse Parvovirus) are required.

For BLA application, first, at least two batches or one batch with duplicate runs are required. In addition, a full virus panel must be tested, including: for low pH inactivation - X-MuLV (Xenotropic Murine Leukemia Virus) and PRV (Pseudorabies Virus); for nanofiltration and chromatography - X-MuLV/PRV/Reo-3/MVM.

 

 

 

 

 

 

 

 

 

There are generally two principles for chromatography process scale-down. The most common one is the linear scale-down principle, where column bed height and linear flow rate are kept consistent, resulting in the same residence time. The other is the constant residence time principle, which is applicable to bind-and-elute modes such as affinity chromatography, hydrophobic interaction chromatography (HIC), and ion exchange chromatography. Under this principle, even if column bed height and linear flow rate differ, maintaining the same residence time can still achieve equivalency. However, this approach has limitations and is not applicable to chromatography processes dominated by convection-diffusion that rely on theoretical plate numbers, such as gel filtration chromatography and flow-through mode of ion exchange chromatography. It is also not applicable to mixed-mode chromatography.