scope:

This guideline covers nucleic acid sequencing applications currently in clinical use: medical management of hereditary disorders, solid tumor and hematological malignancy testing, human leukocyte antigen (HLA) typing, noninvasive prenatal testing (NIPT), liquid biopsy, and RNA sequencing (RNAseq) applications. Most of the content in this guideline focuses on next-generation sequencing (NGS), which is the predominant platform in current use. Sanger sequencing continues to be used for certain clinical applications, so guidance on Sanger sequencing is also included. This guideline also provides introductory information on the management of computational and/or bioinformatics aspects of NGS, because these concepts are fundamental yet somewhat novel for the clinical testing community. Detailed guidance on bioinformatics will be provided in a forthcoming CLSI document.

MM09 does not cover microbial or infectious diseases applications. Detailed guidance on NGS-based infectious diseases testing is provided in CLSI document MM24.¹ This guideline also does not cover validation of confirmatory testing or mitochondrial DNA testing for inherited disorders.

This guideline is intended for developers of sequencing-based clinical tests (both Sanger sequencing and NGS), including manufacturers of commercially distributed in vitro diagnostic (IVD) devices and developers of laboratory-developed tests (LDTs). IVD device manufacturers might be subject to additional quality system requirements. For example, design controls are not included in this guideline, but they are well described in existing literature.^2,3