Calculation of Reduction Factors in Studies to Determine Viral Clearance
The virus reduction factor of an individual purification or inactivation step is defined as the log10 of the ratio of the virus load in the pre-purification material and the virus load in the post-purification material which is ready for use in the next step of the process. If the following abbreviations are used:
Starting material: vol v¢; titer 10a¢;
Final material: vol v¢¢; titer 10a¢¢;
virus load: (v¢¢)(10a¢¢),
the individual reduction factors Ri are calculated according to
10Ri = (v¢)(10a¢) / (v¢¢)(10a¢¢)
This formula takes into account both the titers and volumes of the materials before and after the purification step.
Because of the inherent imprecision of some virus titrations, an individual reduction factor used for the calculation of an overall reduction factor should be greater than 1.
The overall reduction factor for a complete production process is the sum logarithm of the reduction factors of the individual steps. It represents the logarithm of the ratio of the virus load at the beginning of the first process clearance step and at the end of the last process clearance step. Reduction factors are normally expressed on a logarithmic scale which implies that, while residual virus infectivity will never be reduced to zero, it may be greatly reduced mathematically.