In Vivo Replacement

What is in vivo replacement and why is it important?

The use of animal models in the characterization and biosafety testing of biologic medicines has been a staple for decades. Despite their limitations, in vivo testing has remained essential in biologic cell line and viral vector characterization due to the need for prior knowledge of contaminants when using PCR or ELISA. Agnostic cell culture-based methods also fall short as they detect a narrow range of adventitious pathogens. Consequently, animal models, despite their limited sensitivity in detecting a broad range of viruses, have continued as a crucial complementary method.

However, the landscape is changing with the advent of alternatives to animal testing, such as in vitro testing . These in vitro assay methods align with the 3Rs of animal research (Replacement, Reduction, and Refinement), aiming to minimize animal use in scientific research. In vitro testing methods are increasingly recognized for their potential to provide reliable and sensitive detection of contaminants without the ethical and practical issues of animal models.

Next-generation sequencing (NGS) has been used for agnostic detection of unknown pathogens in clinical settings and commercial biopharmaceutical manufacturing, especially for contamination investigations. Moreover the ICHQ5A (R2) and European Pharmacopoeia encourages the replacement of in vivo testing with NGS. “

In collaboration with Charles River Laboratories, PathoQuest has become the first GMP Contract Research Organization (CRO) to demonstrate conclusively that iDTECT® NGS assays are superior to conventional in vivo biosafety testing and characterization methods. This breakthrough, along with regulatory bodies’ commitment to eliminate animal models in most submissions, signals that now is the ideal time to transition from in vivo testing and embrace NGS testing methods as the new standard for biosafety and characterization in biologics.