As a drug manufacturer you are required to ensure the virological safety of the biological therapeutics you have under development. Regulatory guidance advocates virus control at various stages of the drug manufacturing process, directing that you:
Regulators require that an overall safety margin, such as <1 virus particles per 106 doses, be used to demonstrate the virus safety of the manufacturing process. Drug manufacturers are required to qualify the virus “load” in the process.
For biotech products derived from murine cell lines, such as the Chinese hamster ovaries (CHO) and NSO, this typically translates to ~12 – 18 log10 clearance for endogenous retroviruses and ~6 log10 removal for adventitious viruses.
|Composite Summary of Current Regulatory Guidance on Virus Clearance
US Food and Drug Administration: Requires that manufacturers of biotech products that use murine cell lines are to demonstrate clearance capability of their manufacturing processes with one, relevant retrovirus (murine retrovirus) before starting Phase I studies. German and French Regulatory Agencies: Require that manufacturing processes be evaluated to clear non-enveloped parvoviruses in addition to retroviruses. Before marketing authorization: Manufacturers are required to assess clearance of multiple model and relevant viruses in their manufacturing processes.
While customers are responsible for review of and compliance with applicable laws and regulations, Merck monitors regulatory bodies worldwide and can assist customers with the interpretation of guidelines. We strive to ensure that we have the latest information about the current and future regulatory environment.
You also need to determine if your particular process requires retrovirus clearance, or retrovirus and parvovirus removal, or no viral clearance at all. When virus clearance is indicated, you need to select the filter that best fits your needs.
|Select the Filter
Filters are broadly classified into two categories: