Next Generation Sequencing Quality · – For NGS, such issues include but are not limited to,...

Next Generation Sequencing Quality

Collette Fitzgerald, PhDDeputy Director for Science

Division of Laboratory SystemsNovember 6, 2019

Excellent Laboratories, Outstanding Health

Topics to be Covered

1)Update on activities following the CLIAC April 2019 NGS recommendations

https://www.cdc.gov/cliac/docs/summary/cliac0419_summary.pdf

2) CDC-APHL NGS Quality Initiativehttps://www.cdc.gov/labquality/ngs-quality-initiative

Division of Laboratory Systems 2

https://www.cdc.gov/cliac/docs/summary/cliac0419_summary.pdf

https://www.cdc.gov/labquality/ngs-quality-initiative


CLIAC NGS Activities

• NGS agenda topic at the CLIAC Spring 2018 meeting: “Implementation of Next-Generation Sequencing (NGS) in clinical and public health laboratories”

CLIAC recommendation: Form an NGS workgroup

• CLIAC NGS workgroup formed in Fall 2018Charge: Provide input to CLIAC for consideration in developing recommendations to CDC, CMS, and FDA for assuring the quality of next generation sequencing based testing in clinical laboratory settings.

– Face-to-Face Meeting January 16-17, 2019 in Atlanta, GA– Report presented to CLIAC at April 2019 meeting

https://www.cdc.gov/cliac/docs/addenda/cliac0419/10a_NGS_Workgroup_Report.pdf

Outcome: 8 NGS CLIAC recommendations


https://www.cdc.gov/cliac/docs/addenda/cliac0419/10a_NGS_Workgroup_Report.pdf


CLIAC April 2019 NGS Recommendation #1

• CLIAC recommends that HHS thoroughly update CLIA regulations to address issues related to new biomarker testing and other new technologies.

– This update may include a new section, revising existing sections, or other alternatives. This update should take account of the reports by the Personnel Regulations, Non-Traditional Workflow Models, and NGS workgroups presented to CLIAC.

– For NGS, such issues include but are not limited to, e.g., the definition, role, and responsibilities of bioinformaticists; quality control, e.g. moving from a simple requirement for positives and negatives to controls more appropriate for NGS; establishment and verification of performance specifications, including the availability and sharing of samples; proficiency testing; reporting; delivery of data to patients, e.g. FASTQ vs. BAM vs. VCF-formatted NGS files; measurement, e.g. of NGS testing volumes; and data sharing, e.g. repositories and incentives and/or requirements for contribution to them.


Presenter

Presentation Notes



• CLIAC recommends creation of a new CLIAC workgroup to advise on how CLIA might specifically be updated, integrating and reflecting the reports by the Personnel Regulations, Non-Traditional Workflow Models, and NGS workgroups presented to CLIAC, ideally incorporating members from each of these groups (for continuity).



New CLIAC Workgroup Formation

• Form a new CLIAC Workgroup– CLIAC Member(s) as Chair(s)– 2-3 CLIAC Members – Representation from the Personnel Regulations, Non-

Traditional Workflow Models, and NGS workgroups– 20-25 additional members with representation from clinical

and anatomic pathology laboratories, public health laboratories, laboratory accreditation organizations, CLIA-exempt states, and industry

– CDC, CMS, FDA Ex Officios

• Submit potential workgroup candidates to [email protected]


mailto:[email protected]


CLIAC April 2019 NGS Recommendation #3• CLIAC recommends that CMS, CDC, and FDA encourage

professional societies and others (e.g. CLSI) to develop and/or update NGS guidelines. Specific fields of interest include, but are not limited to, oncology, inherited testing, and microbiology applications of NGS. Recommended topics for guidelines include, but are not limited to:1) Revalidation of:

a. analytical targets (e.g. additional genes or additional variant types)b. the bioinformatics pipeline (e.g. sequencing software updates,

updates/changes in software in pipeline etc.)2) Data retention (e.g. file types, duration, intent)3) Data sharing (e.g. to patients, between organizations,

between providers)




• CLIAC recommends that CMS, CDC and FDA create guidelines or best practices related to clinical and public-health NGS. These could be based on or in partnership with guidelines already established by the government, professional societies, or other groups (e.g. CLSI).



NGS Guidelines/Standards

• Emerging Technologies/NGS Guidance Organization Forum coming soon– American College of Medical Genetics and Genomics,

Association for Molecular Pathology, American Society of Clinical Oncology, American Society for Histocompatibility, American Society for Microbiology, College of American Pathologists, Clinical and Laboratory Standards Institute, New York State Department of Health, CDC and FDA

– Other organizations who would like to participate should contact [email protected]


Presenter

Presentation Notes




• CLIAC recommends expanding the CDC GeT-RM program with regards to scope and type (e.g. wet samples and data files). Focus should be on the three major categories of oncology, inherited testing, and microbiological applications. Expansion could also include the creation/curation of NGS data sets to be used by laboratories while validating/revalidating bioinformatic pipelines.



Genetic Testing Reference Materials program (GeT-RM)

• Based on CLIAC recommendations, GeT-RM has initiated a new reference material project for hereditary cancer

• The feasibility of developing commutable NGS data sets is also being explored

• An update on the GeT-RM program will be provided at the April 2020 CLIAC meeting



NGS Quality Initiative Project

A collaborative effort between CDC, APHL, and state and local public health laboratories.

GOAL: Develop an NGS-focused quality management system to address challenges PHLs encounter when they develop and implement NGS-based tests by providing deliverables of customizable ready-to-implement guidance docs, SOPs, and forms.



Next Generation Sequencing (NGS) Quality Initiative

Quality System Essentials* focus in year 1

* https://clsi.org/Division of Laboratory Systems 13


In-person Meeting – May 8, 2019

Purpose: Convene stakeholders from CDC, APHL, and state public health laboratories to inform the

deliverables and priorities for this project.



In-person Meeting – Important Takeaways

Priority QSE’s in Year 1- Information Management- Process Management- Assessments- Equipment- Personnel

Agreement to form technical coordinating committee



NGS Quality Initiative Technical Coordinating Committee’s (TCC) Current Activities

*Hutchins RJ, et al. 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. 57:(8) e00261-19



QSE Status Update – Needs Summary



NGS Quality Initiative Website Published

www.cdc.gov/labquality/ngs-quality-initiative/



Goals for Year 2• Needs assessment COMING SOON!

- Comprehensive assessment of sequencing total test process from sample prep to bioinformatic analysis to communication to end users.

All questions are mapped to corresponding QSEs.Audience for this include all state PHLs, large local PHLs, and CDC laboratories.

• Continue development of consensus ready-to-implementdocuments

For more information on the NGS Quality Initiative, contact us at: [email protected]




For more information, contact CDC1-800-CDC-INFO (232-4636)TTY: 1-888-232-6348 www.cdc.gov

Images used in accordance with fair use terms under the federal copyright law, not for distribution.

Use of trade names is for identification only and does not imply endorsement by U.S. Centers for Disease Control and Prevention.

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of Centers for Disease Control and Prevention.


http://www.cdc.gov/

Next Generation Sequencing Quality · – For NGS, such issues include but are not limited to,...

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