3Rs

NGS VS ANIMAL TESTING

The 3Rs model (Replacement, Reduction and Refinement) to ensure the ethical treatment of animals has seen a significant move away from both direct and indirect animal testing models. An alternative testing strategy is long overdue with a legacy of no known in vivo testing positives despite a history of known contamination events in biologics.

In collaboration with Charles River Laboratories (CRL), PathoQuest is the first contract research organization (CRO) to conclusively show the superiority of next-generation sequencing (NGS) over conventional in vivo biosafety testing methods on cells. The ability of our RNA sequencing based strategy to detect more broadly and deeply biological contaminants in biologics than in vivo testing is clear.

Replacement

Reduction

Refinement

3Rs PRINCIPLE

Developed in 1959, the 3Rs is the ethical approach applied to animal experimentation in Europe and North America which recommends reducing the number of animals in experiments, refining the methodology used, and replacing animal models.

A major advantage of NGS has been highlighted by recent regulatory changes driving the reduction in the use of animals for viral safety tests. To comply with the ‘3Rs’ principle on animal experimentation, the regulatory bodies are indeed pushing to limit the use of animal models only when there are no other alternatives.

REGULATIONS ARE CHANGING

The biomanufacturing industry has entered a new phase and regulatory authorities have recognized the potential of NGS with regulations now being revised to take advantage of this method. The International Conference on Harmonisation (ICH) proposed updates to the guideline Q5A for the viral safety evaluation of biotechnology products derived from cell lines of human or animal origin. This revision 2 (R2) was published for consultation in October 2022 and it is anticipated to be adopted in late 2023.

Critically, the first sentence for the section on in vivo assays for viral detection (Chapter 3.2.3), ICH Q5A(R2) guidelines state:

NGS is encouraged as a replacement for in vivo assays because of the breadth of viruses it detects and because its use promotes the global objective to replace, reduce, and refine the use of animal testing.

BENEFITS OF NGS VS ANIMAL TESTING

NGS combines the advantages of classical in vivo testing methods while overcoming many of the drawbacks and challenges associated with in vivo including specificity, sensitivity, and speed.