CRISPR/Cas9 gene editing has evolved into a rapid and efficient model generation method for an array of genetic modifications. However, the potential for unwanted mutations at off-target sites in the genome when using this technology, which may lead to confounding experimental results, remains a concern for study design. Consequently, the uncertainty of obtaining a suitable genetic model using the CRISPR/Cas9 system can diminish its speed advantage over other traditional methods. With the ExpressMODEL® CRISPR platform, we address off-target risks early, utilizing NGS to provide robust characterization of both on- and off-target loci and an assessment of genetic mosaicism in founder mice. These analyses inform the selection of the most suitable founder mouse for germline transmission, which de-risks inheritance of the correct genetic modification and enables simultaneous IVF expansion of the genetic line. Germline transmission by IVF not only provides scalability of the number of heterozygous mice produced, but also assignment of a Taconic International Health Monitoring System (IHMS) health standard. By delivering an appropriately sized cohort of age-matched, off-target analyzed mice with a defined health standard, Taconic's ExpressMODEL® CRISPR platform can accelerate downstream breeding programs and shorten the time to a homozygous study cohort by at least 3 months compared to a standard CRISPR/Cas9-based model development program. And by monitoring parameters critical to success throughout the model generation process, the ExpressMODEL® CRISPR option can save time and money through allowing researchers to make project and program decisions earlier.