infectious disease next generation sequencing based ... · pdf filecontains nonbinding...

Contains Nonbinding Recommendations

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Infectious Disease Next Generation 1Sequencing Based Diagnostic Devices: 2Microbial Identification and Detection 3

of Antimicrobial Resistance and 4Virulence Markers 5

6

Draft Guidance for Industry and 7Food and Drug Administration Staff 8

9DRAFT GUIDANCE 10

11This draft guidance document is being distributed for comment purposes 12

only. 1314

Document issued on: May 13, 2016 1516

You should submit comments and suggestions regarding this draft document within 90 days of 17publication in the Federal Register of the notice announcing the availability of the draft guidance. 18Submit electronic comments to http://www.regulations.gov. Submit written comments to the 19Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 20rm. 1061, Rockville, MD 20852. Identify all comments with the docket number listed in the 21notice of availability that publishes in the Federal Register. 22

23For questions about this document, contact Heike Sichtig Ph.D., Division of Microbiology Devices 24at 301-796-4574 or by email at [email protected] 25

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U.S. Department of Health and Human Services 28 Food and Drug Administration 29

Center for Devices and Radiological Health 30 Office of In Vitro Diagnostics and Radiological Health 31

Division of Microbiology Devices 32 33

http://www.regulations.gov/mailto:[email protected]

Contains Nonbinding Recommendations

Draft - Not for Implementation

Preface 3435

Additional Copies 3637

Additional copies are available from the Internet. You may also send an e-mail request to [email protected] to receive a copy of the guidance. Please use the document number 391500016 to identify the guidance you are requesting. 40

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mailto:[email protected]:[email protected]

Contains Nonbinding Recommendations

Draft - Not for Implementation

Table of Contents 4344

I. Introduction .................................................................................................................... 145

II. Background .................................................................................................................... 246

A. Systems Approach for Infectious Disease NGS Dx Devices ................................... 347

B. FDA-ARGOS: FDA dAtabase for Regulatory Grade micrObial Sequences ........... 448

III. Scope .............................................................................................................................. 449

IV. Benefit-Risk Analysis ..................................................................................................... 750

V. Device Description ......................................................................................................... 851

A. Intended Use ............................................................................................................. 852

B. Test Methodology .................................................................................................... 953

C. Ancillary Reagents ................................................................................................. 1054

D. Controls .................................................................................................................. 1155

(1) Negative Controls .................................................................................................. 1256

(2) Positive Controls ................................................................................................... 1357

(3) Internal Controls .................................................................................................... 1458

E. Interpreting Test Results and Reports ....................................................................... 1459

VI. Device Validation ......................................................................................................... 1560

A. Pre-analytical Factors ............................................................................................. 1661

(1) Specimen Collection and Handling ....................................................................... 1662

(2) Specimen Preparation for Sequencing ................................................................... 1763

(3) Sequencing, Chemistry and Data Collection ......................................................... 1864

(4) Data Storage .......................................................................................................... 1865

(5) Clinical Call Determination ................................................................................... 1966

B. Infectious Disease NGS Dx Device Performance Metrics .................................... 2067

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(1) Infectious Disease NGS Dx Device Data Sets ...................................................... 2068

(2) Sequencing Strategy .............................................................................................. 2069

(3) Selected Targets and Reference Sequences Used for Target Identification .......... 2070

(4) Clinical Call Informatics Pipeline ......................................................................... 2171

(5) Subtraction Rationale ............................................................................................ 2172

(6) Quality Controls .................................................................................................... 2173

(7) Sequencing and Read Mapping ............................................................................. 2274

(8) Contaminant Analysis ........................................................................................... 2275

(9) Sample to Result Turn-Around Time (TAT) ......................................................... 2276

(10) Data Storage .......................................................................................................... 2377

C. Analytical Performance .......................................................................................... 2478

(1) Limit of Detection ................................................................................................. 2579

(2) Inclusivity .............................................................................................................. 2680

(3) Interfering Substances ........................................................................................... 2781

(4) Precision (Reproducibility and Repeatability) ...................................................... 2882

(5) Carryover and Cross-contamination ...................................................................... 2883

(6) Stability .................................................................................................................. 2884

(7) Additional Analytical Studies ................................................................................ 2985

D. Instrumentation and Software ................................................................................ 2986

E. Clinical Evaluation .................................................................................................... 3187

(1) Evaluation of Negative Percent Agreement .......................................................... 3188

(2) Evaluation of Positive Percent Agreement ............................................................ 3389

(3) Data Presentation ................................................................................................... 3490

(4) Study Specimens and Specimen Types ................................................................. 3591

Contains Nonbinding Recommendations

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VII. Device Modification ..................................................................................................... 3592

VIII. Appendix: Comparator Database Quality Criteria for Regulatory-Grade Genomic 93Sequence Entries ..................................................................................................................... 3794

A. Extracted Genomic DNA (gDNA) ......................................................................... 3795

B. BioSample Metadata .............................................................................................. 3896

(1) Clinical Sample ..................................................................................................... 3897

(2) Environmental Sample (for clinical next neighbor evaluation and rule out) ........ 3898

(3) Clinical Public Health Need Sample ..................................................................... 3999

C. Sequencing Data ..................................................................................................... 39100

D. Sequencing Metadata ............................................................................................. 40101

E. Suggested Phenotypic Metadata ................................................................................ 40102

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Contains Nonbinding Recommendations

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Infectious Disease Next Generation

1

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Sequencing Based Diagnostic 105Devices: Microbial Identification and 106

Detection of Antimicrobial 107Resistance and Virulence Markers 108

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Draft Guidance for Industry and 1