CLSI MM09
Human Genetic and Genomic Testing Using Traditional and High-Throughput Nucleic Acid Sequencing Methods
This CLSI guideline provides step-by-step recommendations for designing, validating, and implementing next-generation sequencing (NGS) and Sanger sequencing tests in clinical laboratories. As sequencing technologies expand from single-gene to whole-genome applications, MM09 offers essential guidance for hereditary disorder diagnostics, tumor testing, HLA typing, noninvasive prenatal testing, and circulating tumor DNA sequencing.
MM09 helps laboratories translate regulatory requirements into clinical practice through instructional worksheets and real-world examples, ensuring quality and compliance in sequencing-based testing.
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{{FormatPrice(nonMemberPrice)}} List PriceSequencing-based clinical tests have evolved from single-gene tests to whole-genome tests. Next-generation sequencing (NGS) technologies have largely replaced Sanger sequencing and are firmly established in the medical management of hereditary disorders, as well as in tumor testing. Newer clinical NGS applications include human leukocyte antigen typing, noninvasive prenatal testing, sequencing of circulating tumor DNA in peripheral blood, and RNA sequencing. Although NGS applications have undergone major technical simplifications, clinical implementation continues to be complex. Clinical and Laboratory Standards Institute guideline MM09—Human Genetic and Genomic Testing Using Traditional and High-Throughput Nucleic Acid Sequencing Methods provides recommendations for design, development, validation, results reporting, and continual quality management of NGS-based tests, as well as Sanger sequencing–based tests. In conjunction with instructional worksheets and educational examples, MM09 provides step-by-step guidance to help medical laboratories translate regulatory requirements into clinical practice.
This guideline replaces the previous edition of the approved guideline, MM09-A2, published in 2014. MM09-A2 introduced NGS as a new technology. This edition has been updated beyond an introduction of NGS technology to provide practical use case and implementation guidance, as well as instructions that cover each step of the clinical NGS test development lifecycle. Several changes were made in this edition, including:
• Providing step-by-step recommendations on designing, developing, validating, and implementing a clinical NGS test
• Adding clear and specific instructions on performing steps in the clinical NGS test lifecycle
• Presenting an application-driven approach
• Providing educational use case examples, supplemented by instructional worksheets
• Updating appendixes with additional details on steps in the test development process and specific applications
This guideline covers nucleic acid sequencing applications in clinical use, including hereditary disorders, solid tumor and hematological malignancy testing, HLA typing, noninvasive prenatal testing (NIPT), liquid biopsy, and RNA sequencing (RNAseq). It focuses on next-generation sequencing (NGS) but also includes guidance on Sanger sequencing.
The guideline introduces the computational and bioinformatics aspects of NGS, with detailed bioinformatics guidance to be provided in a future CLSI document. It does not cover microbial or infectious diseases applications (see CLSI document MM24) or validation of confirmatory testing or mitochondrial DNA testing for inherited disorders.
The guideline is intended for developers of sequencing-based clinical tests, including manufacturers of IVD devices and developers of laboratory-developed tests (LDTs). IVD device manufacturers may have additional quality system requirements, such as design controls, which are described in existing literature.
Sequencing-based clinical tests have evolved from single-gene tests to whole-genome tests. Next-generation sequencing (NGS) technologies have largely replaced Sanger sequencing and are firmly established in the medical management of hereditary disorders, as well as in tumor testing. Newer clinical NGS applications include human leukocyte antigen typing, noninvasive prenatal testing, sequencing of circulating tumor DNA in peripheral blood, and RNA sequencing. Although NGS applications have undergone major technical simplifications, clinical implementation continues to be complex. Clinical and Laboratory Standards Institute guideline MM09—Human Genetic and Genomic Testing Using Traditional and High-Throughput Nucleic Acid Sequencing Methods provides recommendations for design, development, validation, results reporting, and continual quality management of NGS-based tests, as well as Sanger sequencing–based tests. In conjunction with instructional worksheets and educational examples, MM09 provides step-by-step guidance to help medical laboratories translate regulatory requirements into clinical practice.
This guideline replaces the previous edition of the approved guideline, MM09-A2, published in 2014. MM09-A2 introduced NGS as a new technology. This edition has been updated beyond an introduction of NGS technology to provide practical use case and implementation guidance, as well as instructions that cover each step of the clinical NGS test development lifecycle. Several changes were made in this edition, including:
• Providing step-by-step recommendations on designing, developing, validating, and implementing a clinical NGS test
• Adding clear and specific instructions on performing steps in the clinical NGS test lifecycle
• Presenting an application-driven approach
• Providing educational use case examples, supplemented by instructional worksheets
• Updating appendixes with additional details on steps in the test development process and specific applications
This guideline covers nucleic acid sequencing applications in clinical use, including hereditary disorders, solid tumor and hematological malignancy testing, HLA typing, noninvasive prenatal testing (NIPT), liquid biopsy, and RNA sequencing (RNAseq). It focuses on next-generation sequencing (NGS) but also includes guidance on Sanger sequencing.
The guideline introduces the computational and bioinformatics aspects of NGS, with detailed bioinformatics guidance to be provided in a future CLSI document. It does not cover microbial or infectious diseases applications (see CLSI document MM24) or validation of confirmatory testing or mitochondrial DNA testing for inherited disorders.
The guideline is intended for developers of sequencing-based clinical tests, including manufacturers of IVD devices and developers of laboratory-developed tests (LDTs). IVD device manufacturers may have additional quality system requirements, such as design controls, which are described in existing literature.