Viral clearance studies are mandated as part of the viral safety evaluation of products derived from human or other mammalian cell lines. When acceptable ranges of process parameters are known, the ICH and EMA recommend that scale-down models are evaluated under worst-case conditions for viral clearance.
To identify operating parameters that are commonly considered to present worst-case conditions for viral clearance, our Development Group Viral Clearance Workstream performed a benchmarking survey. We assessed whether companies evaluated process parameters differently for clinical trial stages (e.g., investigational new drug applications) and commercialization (e.g., biologics license applications).
The results are documented in an article called Worst-Case Conditions for Viral Clearance, which has been published in BioProcess International.
In the paper, we discuss how worst-case conditions for a viral clearance step differ depending on its stage in a manufacturing process. Our aim is not to provide an exhaustive list of conditions or offer specific recommendations but to show what parameters are studied and controlled most frequently at worst-case for several common viral clearance steps. The survey also shows which parameters are not controlled for worst-case studies.
We recommend that a case-by-case assessment using process knowledge and available literature should be carried out for each method when determining worst-case conditions for any process.
We include detailed figures that use qualitative values (e.g., high, low) to indicate worst-case directionality for parameters considered by most survey respondents. The virus inactivation methods included in the survey were low-pH incubation, solvent-detergent incubation, and UV exposure.
The piece includes lots of detail on worst-case conditions for chromatography steps, such as Protein A Affinity Chromatography, Bind–Elute Chromatography, and CEX Bind–Elute Chromatography. We also discuss virus-retentive filtration and process parameters for virus activation and removal. The full list of survey responses is included in a supporting information file alongside the article.
Need to know more about the worst-case conditions for viral clearance? Then read the article here..