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Selected Publications on Quality Standards and Quality Management Systems for Diagnostic Testing Based on NGS

Hutchins RJ, Phan KL, Saboor A, Batra D, Booth R, Breaker E, Casas ME, Cherney B, Chang HY, Daniels J, Driggers J, Eby M, Gargis A, Gee J, Gregoricus NA, Halpin JL, Khemani R, Korth M, Kulasekarapandian Y, Langley G, Lauer A, Lubin I, Mclean JA, Mercante A, Myrick A, Okoth S, Perry KA, Ramos E, Schmerer M, Sheth M, Turnsek M, Vlachos N, Williams GM, Miller JD, and Muehlenbachs A. (2019). Practical Guidance to Implementing Quality Management Systems in Public Health Laboratories Performing Next Generation Sequencing: Personnel, Equipment, and Process Management (Phase 1). J Clin Microbiol. Jul 26;57(8). pii:e00261-19.

Carey RB, Bhattacharyya S, Kehl SC, Matukas LM, Pentella MA, Salfinger M, and Schuetz AN. (2018). Implementing a Quality Management System in the Medical Microbiology Laboratory. Clin Microbiol Rev. May 2;31(3). pii: e00062-17.

Endrullat C, Glökler J, Franke P, and Frohme M. (2016) Standardization and quality management in next-generation sequencing. Appl Transl Genom. Jul 1;10:2-9.

Peer Reviewed Publications on Guidelines, Standards, and Best Practices for Germline and Somatic Variant Diagnostic Testing Based on NGS

Roy S, Coldren C, Karunamurthy A, Kip NS, Klee EW, Lincoln S, Leon A, Pullambhatla M, Temple-Smolkin RL, Voelkerding KV, Wang C, Carter A. (2018) Standards and guidelines for validating next generation sequencing bioinformatics pipelines: A joint recommendation of the Association for Molecular Pathology and College of American Pathologists. Journal of Molecular Diagnostics. 20(1):4-27.

Merker JD, Devereaux K, Iafrate AJ, Kamel-Reid S, Kim AS, Moncur JT, Montgomery SB, Nagarajan R, Portier BP, Routbort MJ, Smail C, Surrey LF, Vasalos P, Lazar AJ, Lindeman NI. (2018) Proficiency Testing of Standardized Samples Shows Very High Interlaboratory Agreement for Clinical Next-Generation Sequencing-Based Oncology Assays. Arch Pathol Lab Med. 2018 Oct 30.

Santani A, Simen BB, Briggs M, Lebo M, Merker JD, Nikiforova M, Vasalos P, Voelkerding KV, Pfeifer J, Funke B. (2018). Designing and Implementing NGS Tests for Inherited Disorders – a Practical Framework with Step-by-Step Guidance for Clinical Laboratories. Journal of Molecular Diagnostics. Dec 31

Hegde M, Santani A, Mao R, Ferreira-Gonzalez A, Weck K, Voelkerding KV. (2017) Development and validation of clinical whole exome and genome sequencing for the detection of germline variants in inherited disease. Arch Path Lab Med. 141(6):798-805.

Santani A, Murrell J, Funke B, Yu Z, Hegde M, Mao R, Ferreira-Gonzalez A, Voelkerding KV, Weck K. (2017) Development and validation of targeted next generation sequencing panels for detection of germline inherited disease. Arch Path Lab Med. 141(6):787-797.

Lubin IM, Aziz N, Babb LJ, Ballinger D, Bisht H, Church DM, Cordes S, Eilbeck K, Hyland F, Kalman L, Landrum M, Lockhart ER, Maglott D, Marth G, Pfeifer JD, Rehm HL, Roy S, Tezak Z, Truty R, Ullman-Cullere M, Voelkerding KV, Worthy E, Zaranek AW, Zook J. (2017) Principles and recommendations for standardizing the use of next generation sequencing variant file in clinical settings. Journal of Molecular Diagnostics. 19(3):417-426.

Jennings LJ, Arcila ME, Corless C, Kamel-Reid S, Lubin IM, Pfeifer J, Temple-Smolkin RL, Voelkerding KV, Nikiforova MN. (2017) Guidelines for validation of next generation sequencing (NGS) based oncology panels: A joint consensus recommendation of the Association for Molecular Pathology and College of American Pathologists. Journal of Molecular Diagnostics. 19(3):341-365. 11. Li MM, Datto M, Duncavage EJ, Kulkarni S, Lindeman NI, Roy S, Tsimberidou AM, Vnencak-Jones CL, Wolff DJ, Younes A, Nikiforova MN. (2017) Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. Journal of Molecular Diagnostics. 19(1):4-23

Matthijs G, Souche E, Alders M, Corveleyn A, Eck S, Feenstra I, Race V, Sistermans E, Sturm M, Weiss M, Yntema H, Bakker E, Scheffer H, Bauer P. (2016). Guidelines for diagnostic next generation sequencing. Eur J Hum Genet. 24(10):1515

Aziz N, Zhao Q, Bry L, Driscoll DK, Funke B, Gibson JS, Grody WW, Hegde MR, Hoeltge GA, Leonard DG, Merker JD, Nagarajan R, Palicki LA, Robetorye RS, Schrijver I, Weck KE, Voelkerding KV. (2015) College of American Pathologists’ Laboratory Standards for Next Generation Sequencing Clinical Tests. Arch Pathol Lab Med. 139(4): 481-93.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding KV, Rehm HL. (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 17(5):405-24.

Gargis AS, Kalman L, Bick DP, da Silva C, Dimmock DP, Funke BH, Gowrisankar S, Hegde MR, Kulkarni S, Mason CE, Nagarajan R, Voelkerding KV, Worthey EA, Aziz N, Barnes J, Bennett SF, Bisht H, Church DM, Dimitrova Z, Gargis SR, Hafez N, Hambuch T, Hyland FC, Luna RA, MacCannell D, Mann T, McCluskey MR, McDaniel TK, Ganova-Raeva LM, Rehm HL, Reid J, Campo DS, Resnick RB, Ridge PG, Salit ML, Skums P, Wong LJ, Zehnbauer BA, Zook JM, Lubin IM. (2015) Good Laboratory Practice for Clinical Next Generation Sequencing Informatics Pipelines. Nature Biotechnology. 33(7): 689-93.

Rehm HL, Bale SJ, Bayrak-Toydemir P, Berg JS, Brown KK, Deignan JL, Friez MJ, Funke BH, Hegde MR, Lyon E; Working Group of the American College of Medical Genetics and Genomics Laboratory Quality Assurance Commitee. (2013) ACMG clinical laboratory standards for next-generation sequencing. Genet Med. 15(9):733-47

Gargis AS, Kalman L, Berry MW, Bick DP, Dimmock DP, Hambuch T, Lu F, Lyon E, Voelkerding KV, Zehnbauer BA, Agarwala R, Bennett SF, Chen B, Chin EL, Compton JG, Das S, Farkas DH, Ferber MJ, Funke BH, Furtado MR, Ganova-Raeva LM, Geigenmüller U, Gunselman SJ, Hegde MR, Johnson PL, Kasarskis A, Kulkarni S, Lenk T, Liu CS, Manion M, Manolio TA, Mardis ER, Merker JD, Rajeevan MS, Reese MG, Rehm HL, Simen BB, Yeakley JM, Zook JM, Lubin IM. (2012). Assuring the quality of next generation sequencing in clinical laboratory practice. Nature Biotechnology, 30 (11), 1033-6. 2.

Additional Guidelines and Documents for Next Generation Sequencing

Lincoln SE, Truty R, Lin C-F, Zook J, Paul J, Ramey V, Salit M, Rehm H, Nussbaum R, Lebo M. Rigorous Interlaboratory Examination of the Need to Confirm Next-Generation Sequencing-Detected Variants with an Orthogonal Method in Clinical Genetic Testing. (2019). Journal of Molecular Diagnostics. Mar;21(2):318-329.

Guidelines on Next Generation Sequencing from the American Society for Histocompatibility and Immunogenetics (ASHI): Standards for Accredited Laboratories Next Generation Sequencing Guidance. Section D.5.2.11 (January 2018).

National Academies of Sciences, Engineering, and Medicine. 2018. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. Washington, DC: The National Academies Press.

Guidelines on Next Generation Sequencing from the Clinical Laboratory Standards Institute: MM09-A2 Nucleic Acid Sequencing Methods in Diagnostic Laboratory Medicine (February 2014).

Guidelines on Next Generation Sequencing from New York State and FDA

Next Generation Sequencing (NGS) Guidelines for Somatic Genetic Variant Detection, New York State Department of Health (January 2018).

Validation of Next Generation Sequencing (NGS)-Based Methods for Identification and/or Characterization of Infectious Agents (Isolates only) (January 2016)

Guidelines for Validation Submissions of Next Generation Sequencing (NGS) Assays under the NYS Testing Category of Genetic Testing – Molecular, New York State Department of Health (July 2015).

Documents on Next Generation Sequencing from FDA

Considerations for Design, Development, and Analytical Validation of Next Generation Sequencing (NGS) – Based In Vitro Diagnostics (IVDs) Intended to Aid in the Diagnosis of Suspected Germline Diseases Guidance for Stakeholders and Food and Drug Administration Staff Document issued on April 13, 2018.

Use of Public Human Genetic Variant Databases to Support Clinical Validity for Genetic and Genomic-Based In Vitro Diagnostics Guidance for Stakeholders and Food and Drug Administration Staff Document issued on April 13, 2018.

Documents on Next Generation Sequencing from FDA

Background material from CLIAC Spring 2023 presentation

Find the presentation, here.

As many of you are aware, the CDC, the Association for Public Health Laboratories, State and local Public Health Laboratory partners are collaborating on the Next Generation Sequencing Quality Initiative.

The NGS Quality Initiative is moving forward a coordinated and comprehensive plan to develop and implement an NGS-focused quality management system to ensure high quality, reliable data for nationwide disease surveillance systems, diagnostic or reference laboratory testing and other public health actions which improves patient care and public health outcomes.

The Initiative is working to harmonize quality standards for Next Generation Sequencing across public health and provide laboratories with confidence in reported results.

The Initiative is working to create a toolkit of resources that NGS testing sites can use as a starting point to prevent duplication of efforts, increase efficiency, and save costs.

The initiative supports NGS activities to meet multiple requirements, including CLIA as a prerequisite for use of this transformative technology in public health laboratory diagnostic and surveillance activities.

The Next Generation Sequencing (NGS) Quality Initiative is happy to announce the completion of an NGS-focused quality management system (QMS) to address the many challenges public health and clinical laboratories encounter when they develop and implement NGS-based tests, by providing ready-to-implement guidance documents, customizable standard operating procedures, and other tools. 

The NGS Quality Initiative’s quality management system is organized and prioritized using the 12 Quality System Essentials, or QSEs, within the Clinical & Laboratory Standards Institute or CLSI quality framework. 

The Initiative has published 105 free customizable tools and resources to our webpage, including resources for wet and dry bench personnel and leadership and have over 20 in development. 

The Initiative will continue to update and add products to each QSE to support training of personnel, choose appropriate protocols and analytic options, and implement effective management and process controls. 

Such tools are especially beneficial to laboratories performing NGS-based tests that are subject to meeting CLIA regulations and other laboratory accreditation standards. Products from this project can serve as a foundational QMS or complement existing resources and support the development of a laboratory’s current QMS.