“The virus safety industry is reactive,” notes Andy Bailey, Ph.D., CEO of Virusure. “It tends not to address an issue until it really presents itself.” As examples, Dr. Bailey mentions experience at Genentech during the 1990s with a minute virus of mice (MVM), a parvovirus that has become arguably the number-one suspect for CHO-based processes.
Parvovirus, a nonenveloped single-stranded rodent virus discovered in 1975, represents the gold standard for removal/inactivation. Parvoviruses are among the smallest viruses known and withstand harsh pH, high temperature, and solvent treatment. Removal is typically achieved using nanofiltration. Several companies manufacture nanofiltration products suitable for parvovirus removal, including Millipore (Viresolve PRO) and Sartorius Stedim Biotech (Virosart CPV).
Despite the retrospective status quo with respect to virus safety, biomanufacturers have, in recent years, begun to shift toward a more risk-based approach to virus safety. To some degree this has reduced the regulatory burdens with respect to viral clearance. “In the past there wasn’t too much thought devoted to whether virus safety tests made sense or not,” says Dr. Bailey. “Now the authorities are much more open to discuss options if you can make a valid argument for replacing one test with another.”
New European guidelines for virus safety make it easier for manufacturers to reduce the number of virus-safety tests required for commencing human testing. “The basis for that new guideline was risk management,” Dr. Bailey observes. “The question was, does it make sense to conduct all these tests, and do they actually enhance product safety, when drugs are still at the developmental stage?”
Previously, EMEA required that companies about to enter Phase III submit clearance data on up to four viruses. This has been reduced to two viruses (typically murine leukemia virus and MVM) whose removal is orthogonal or complementary. “If you can remove those viruses, your process will also remove other model viruses that previously would have been mandated for testing,” Dr. Bailey says.
Harmonization of regulations between the U.S. FDA and Europe’s EMEA with respect to virus safety have also been a positive step, notes Franz Nothelfer, associate director of purification development at Boehringer Ingelheim.