The Applied Biosystems™ 3500 Dx Genetic Analyzer and the Applied Biosystems™ 3500xL Dx Genetic Analyzer are in vitro diagnostic devices intended for detection of fluorescently-labeled human genomic deoxyribonucleic acid (DNA) nucleotides by capillary electrophoresis.

The Applied Biosystems™ 3500 Dx Genetic Analyzer and the Applied Biosystems™ 3500xL Dx Genetic Analyzer are indicated for sequencing and fragment analysis using FDA- cleared or approved assays.

Device Description

The Applied Biosystems™ 3500 Dx Genetic Analyzer and the Applied Biosystems™ 3500xL Dx Genetic Analyzer are fluorescence-based DNA analysis instruments that use capillary electrophoresis technology with 8 and 24 capillaries, respectively.

The 8-capillary system and the 24-capillary system include the following components:

8-capillary or 24-capillary array and POP™ polymer .
. Consumables for system qualification
Computer workstation and monitor
Integrated software for instrument control, data collection, quality control, . basecalling and sizecalling of samples

The following consumables (branded with the Applied Biosystems name) are required to operate the Applied Biosystems™ 3500 Dx Genetic Analyzer and the Applied Biosystems™ 3500xL Dx Genetic Analyzer.

. 50cm Capillary Array: enable the labeled DNA fragments to migrate from the cathode toward the anode for detection
POP-6TM Polymer: used as a separation matrix to separate DNA fragments by size ● during electrophoresis for sequencing
POP-7TM Polymer: used as a separation matrix for separating DNA fragments by size during electrophoresis for fragment analysis
Hi-Di™ Formamide: sample re-suspension solution used for electrokinetic ● injection and denaturing the DNA
Sequencing Standard v1.1: used for spectral calibration of the instrument and instrument performance check
Cathode Buffer Container: pre-filled with running buffer which maintains a source . of ions and the correct pH for electrophoresis
Anode Buffer Container: pre-filled with running buffer which maintains a source ● of ions and the correct pH for electrophoresis
Conditioning Reagent: pre-filled pouch used for priming the polymer pump, ● washing the pump between polymer type changes, and during instrument shutdown
DS-30 Matrix Standard Dx: used for spectral calibration ●
DS-33 Matrix Standard - Dx: used for spectral calibration
DS-33 GeneScan™ Install Kit Dx: used for instrument operational qualification ●
GeneScan™ 600 LIZ® Size Standard v2.0 Dx: used as a ladder for sizing DNA ● fragments
Other accessories (e.g. sample plate holders, plate retainers, septa) .

AI/ML Overview

The provided text describes the Applied Biosystems™ 3500 Dx Genetic Analyzer and Applied Biosystems™ 3500xL Dx Genetic Analyzer, which are in vitro diagnostic devices. It details their intended use, comparison to a predicate device, and supporting performance studies.

Here's an analysis of the acceptance criteria and study information provided:

1. Table of Acceptance Criteria and Reported Device Performance

The document states that for both non-clinical and clinical performance studies, "all pre-established acceptance criteria were met." However, it does not explicitly list the quantitative acceptance criteria themselves.

Performance Metric	Acceptance Criteria	Reported Device Performance
Non-Clinical	Not explicitly stated (e.g., specific thresholds for accuracy, precision, reproducibility)	"The pre-established acceptance criteria were met."
Clinical	Not explicitly stated (e.g., specific thresholds for clinical accuracy, sensitivity, specificity)	"All pre-established performance criteria were met."

2. Sample Size Used for the Test Set and Data Provenance

Non-Clinical Study: "a reproducibility study using a representative fragment analysis assay. The reproducibility study was performed across multiple sites, using different instruments, multiple operators, and across several days."
- Sample Size: Not specified.
- Data Provenance: Implied to be prospective, collected across multiple sites for the study. Country of origin not specified, but the device is manufactured by Life Technologies Holdings Pte Ltd in Singapore and the submission is to the US FDA.
Clinical Study: "Clinical performance studies were conducted across 3 US clinical laboratory sites, with multiple instruments using a representative fragment analysis assay and an appropriate method comparison assay."
- Sample Size: Not specified.
- Data Provenance: Prospective, conducted across 3 US clinical laboratory sites.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

The document does not mention the use of experts to establish ground truth. The studies appear to be focused on the analytical performance of the instrument using "a representative fragment analysis assay and an appropriate method comparison assay," rather than clinical diagnosis by human experts.

4. Adjudication Method for the Test Set

Not applicable, as ground truth was not established by human experts requiring adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance

This section is not applicable. The device described is a genetic analyzer (an instrument for detecting fluorescently-labeled DNA nucleotides). It is not an AI-based diagnostic tool designed to assist human readers or clinicians in interpreting images or other data that typically involve MRMC studies.

6. If a Standalone (i.e. algorithm only without human-in-the loop performance) Was Done

The device itself is a standalone instrument (analyzer) with integrated software for control, data collection, quality control, basecalling, and sizecalling. The performance studies evaluate the instrument's (algorithm's) ability to perform these functions. Therefore, the non-clinical and clinical performance data effectively describe the standalone performance of the instrument.

7. The Type of Ground Truth Used

The ground truth for the non-clinical and clinical studies appears to be based on the analytical results obtained from "a representative fragment analysis assay and an appropriate method comparison assay." This implies that the ground truth is established by the expected results of these assays or comparison to a reference method, rather than pathology, expert consensus, or outcomes data.

8. The Sample Size for the Training Set

The document does not provide information about a separate "training set" in the context of machine learning or AI. This device is an instrument, and its software (Data Collection Software 3 IVD v3.2) controls its operations and processes data. While software development involves testing, the concept of a "training set" as used in machine learning for algorithm development is not addressed here.

9. How the Ground Truth for the Training Set Was Established

Not applicable, as there is no mention of a traditional machine learning "training set" with established ground truth outlined in the document. The device's functionality is based on established principles of capillary electrophoresis and DNA analysis.

Summary

{0}------------------------------------------------

Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in a sans-serif font.

February 21, 2020

Life Technologies Corporation Darcie Baynes Regulatory Affairs Specialist 5781 Van Allen Way Carlsbad, CA 92008

Re: K191030

Trade/Device Name: Applied Biosystems™ 3500 Dx Genetic Analyzer and Applied Biosystems™ 3500xL Dx Genetic Analyzer Regulation Number: 21 CFR 862.2570 Regulation Name: Instrumentation For Clinical Multiplex Test Systems Regulatory Class: Class II exempt, meets the limitation of exemptions 21 CFR 862.9(a) Product Code: PCA Dated: February 3, 2020 Received: February 4, 2020

Dear Darcie Baynes:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

Please note that if you modify your IVD in the future to exceed any of the limitations to the exemption found in 21 CFR 862.9(c), your device will require a new 510(k) prior to marketing this device in the United States and will not be exempt from the premarket notification requirements so long as it exceeds the limitations to the exemption found in 21 CFR 862.9.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of

{1}------------------------------------------------

Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Kellie B. Kelm, Ph.D. Acting Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

{2}------------------------------------------------

Indications for Use

510(k) Number (if known) K191030

Device Name Applied Biosystems™ 3500 Dx Genetic Analyzer and Applied Biosystems™ 3500xL Dx Genetic Analyzer

Indications for Use (Describe)

The Applied Biosystems™ 3500 Dx Genetic Analyzer and the Applied Biosystems™ 3500xL Dx Genetic Analyzer are indicated for sequencing and fragment analysis using FDA- cleared or approved assays.

Type of Use (Select one or both, as applicable)

X Prescription Use (Part 21 CFR 801 Subpart D)

| Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

*DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW."

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{3}------------------------------------------------

510(k) Summary

Submitter Information - 21 CFR 807.92(a)(1):

Submitter:	Life Technologies Corporation5781 Van Allen WayCarlsbad, CA 92008
Manufacturer:	Life Technologies Holdings Pte LtdBlk 33, #07-06, Marsiling Industrial Estate,Road 3 Singapore 739256
Establishment Registration No:	3003673482
510(k) Number	K191030
Contact:	Darcie Baynes, Sr. Regulatory AffairsSpecialist
Phone:	760.918.3148
Fax:	760.603.2804
E-mail:	darcie.baynes@thermofisher.com
Alternate Contact:	Jody Schulz, Senior Manager RegulatoryAffairs
Phone:	262.357.4605
Fax:	414.278.0688
E-mail:	jody.schulz@thermofisher.com
Date Prepared:	February 18, 2020

Device Name - 21 CFR 807.92(a)(2):

Device Name:	Applied Biosystems™ 3500 Dx GeneticAnalyzerandApplied Biosystems™ 3500xL Dx GeneticAnalyzer
Common Name:	DNA Genetic Analyzer
Classification:	Class II, exempt from the premarketnotification requirement subject to thelimitations in 21 CFR 862.9
Product Code:	PCA

{4}------------------------------------------------

Predicate Device 21 CFR 807.92(a)(3)

Predicate	Applied Biosystems 3500 Dx/3500xL DxGenetic Analyzer CS2 and 3500 Dx SeriesSoftware, BK110039
-----------	-------------------------------------------------------------------------------------------------------

Device Description 21 CFR 807.92(a)(4):

The 8-capillary system and the 24-capillary system include the following components:

8-capillary or 24-capillary array and POP™ polymer .
. Consumables for system qualification
Computer workstation and monitor
Integrated software for instrument control, data collection, quality control, . basecalling and sizecalling of samples

. 50cm Capillary Array: enable the labeled DNA fragments to migrate from the cathode toward the anode for detection
POP-6TM Polymer: used as a separation matrix to separate DNA fragments by size ● during electrophoresis for sequencing
POP-7TM Polymer: used as a separation matrix for separating DNA fragments by size during electrophoresis for fragment analysis
Hi-Di™ Formamide: sample re-suspension solution used for electrokinetic ● injection and denaturing the DNA
Sequencing Standard v1.1: used for spectral calibration of the instrument and instrument performance check
Cathode Buffer Container: pre-filled with running buffer which maintains a source . of ions and the correct pH for electrophoresis
Anode Buffer Container: pre-filled with running buffer which maintains a source ● of ions and the correct pH for electrophoresis
Conditioning Reagent: pre-filled pouch used for priming the polymer pump, ● washing the pump between polymer type changes, and during instrument shutdown
DS-30 Matrix Standard Dx: used for spectral calibration ●
DS-33 Matrix Standard - Dx: used for spectral calibration
DS-33 GeneScan™ Install Kit Dx: used for instrument operational qualification ●
GeneScan™ 600 LIZ® Size Standard v2.0 Dx: used as a ladder for sizing DNA ● fragments
Other accessories (e.g. sample plate holders, plate retainers, septa) .

{5}------------------------------------------------

Intended Use 21 CFR 807.95(a)(5):

The Applied Biosystems™ 3500 Dx Genetic Analyzer and the Applied Biosystems™ 3500xL Dx Genetic Analyzer are indicated for sequencing and fragment analysis using FDA- cleared or approved assays.

Predicate Device Comparison 21 CFR 807.92(a)(6):

A summary of the technological characteristics of the device compared to the predicate device is provided. The Applied Biosystems™ 3500 Dx Genetic Analyzer and the Applied Biosystems™ 3500xL Dx Genetic Analyzer and the legally marketed device the Applied Biosystems 3500 Dx/3500xL Dx Genetic Analyzer CS2 and 3500 Dx Series Software are compared in the table below.

Feature	AppliedBiosystems 3500Dx/3500xL Dx CS2and 3500 Dx SeriesSoftware(BK110039)	AppliedBiosystems™ 3500Dx GeneticAnalyzer and theAppliedBiosystems™3500xL Dx GeneticAnalyzer (withFragmentAnalysis)	Comparison
510k number	BK110039	K191030	N/A
Regulation	862.2570	862.2570	Same
Product Code	PCA	PCA	Same
Device Class	Class II	Class II	Same
Intended Use	The AppliedBiosystems® 3500Dx / 3500xL DxGenetic AnalyzerCS2 and 3500 DxSeries Software arein vitro diagnosticdevices intended forthe sequencing(detection andidentification) offluorescently-labeleddeoxyribonucleic	The AppliedBiosystems™ 3500Dx GeneticAnalyzer and theAppliedBiosystems™3500xL Dx GeneticAnalyzer are in vitrodiagnostic devicesintended fordetection offluorescently-labeled humangenomic	Software upgrade toData CollectionSoftware (DCS) 3IVD v3.2 andenablement ofFragment Analysisin Diagnostic mode.
Feature	AppliedBiosystems 3500Dx/3500xL Dx CS2and 3500 Dx SeriesSoftware(BK110039)	AppliedBiosystems™ 3500Dx GeneticAnalyzer and theAppliedBiosystems™3500xL Dx GeneticAnalyzer (withFragmentAnalysis)	Comparison
	acid (DNA) bycapillaryelectrophoresis.The AppliedBiosystems® 3500Dx / 3500xL DxGenetic AnalyzerCS2 with 3500 DxSeries Software2011 (v1) areindicated for usewith FDA-clearedor approvedsequencing assaysspecifying their useand only bytechnologiststrained in laboratorytechniques,procedures, and useof the analyzer.	deoxyribonucleicacid (DNA)nucleotides bycapillaryelectrophoresis.The AppliedBiosystems™ 3500Dx GeneticAnalyzer and theAppliedBiosystems™3500xL Dx GeneticAnalyzer areindicated forsequencing andfragment analysisusing FDA- clearedor approved assays.
Data CollectionSoftware	3500 Dx DataCollection Software2011 v1.01	AppliedBiosystems™ 3500Dx Series DataCollection Software3 IVD v3.2	Upgrade to DataCollection Software3 IVD v3.2
Firmware	6228001-05	6228001-05	Same
Computer	Dell OptiPlex XE	Dell OptiPlex XE2	Upgrade to newmodel.
Windows	Windows® 7	Windows® 7	Same
Laser	Single-line 505 nm,solid-state	Single-line 505 nm,solid-state	Same
Feature	AppliedBiosystems 3500Dx/3500xL Dx CS2and 3500 Dx SeriesSoftware(BK110039)	AppliedBiosystems™ 3500Dx GeneticAnalyzer and theAppliedBiosystems™3500xL Dx GeneticAnalyzer (withFragmentAnalysis)	Comparison
ElectrophoresisVoltage	Up to 20Kv	Up to 20Kv	Same
Oven Temperature	18°C to 70°C	18°C to 70°C	Same
OperatingEnvironment	Temperature: 15°C-30°C	Temperature: 15°C-30°C	Same
	Humidity: 20-80%(non-condensing)	Humidity: 20-80%(non-condensing)	Same
Main PowerVoltage	100-240 V ±10%;50–60 Hz	100–240 V ±10%;50–60 Hz	Same
PowerConsumption	320 VA	320VA	Same
Dimensions(Width x Depth xHeight)	61cm(122cm) x61cm x 72cm	61cm(122cm) x61cm x 72cm	Same
Weight	82Kg	82Kg	Same
Polymer Use	POP-6TM Dx	POP-6TM Dx andPOP-7TM Dx	Inclusion of POP-7for FragmentAnalysis applicationin IVD mode ofproposed device.
Capillary Array	50 cm lengthavailable in 8-capillary and 24capillaryconfiguration	50 cm lengthavailable in 8-capillary and 24capillaryconfiguration	Same, however the50 cm array will beused for fragmentanalysis workflowin IVD mode.
Applications	Sequencing andFragment Analysisin RUO mode,Sequencing in IVDmode	Sequencing andFragment Analysisin RUO mode,Sequencing andFragment Analysisin IVD mode	Inclusion ofFragment Analysisapplication in IVDmode of proposeddevice.
Feature	AppliedBiosystems 3500Dx/3500xL Dx CS2and 3500 Dx SeriesSoftware(BK110039)	AppliedBiosystems™ 3500Dx GeneticAnalyzer and theAppliedBiosystems™3500xL Dx GeneticAnalyzer (withFragmentAnalysis)	Comparison
Input Sample	DNA	DNA	Same

{6}------------------------------------------------

{7}------------------------------------------------

{8}------------------------------------------------

{9}------------------------------------------------

Non-Clinical Performance Data 21 CFR 807.92(b)(1)

Non-clinical performance of the instrument was evaluated in a reproducibility study using a representative fragment analysis assay. The reproducibility study was performed across multiple sites, using different instruments, multiple operators, and across several days. The pre-established acceptance criteria were met.

Clinical Performance Data 21 CFR 807.92(b)(2)

Clinical performance studies were conducted across 3 US clinical laboratory sites, with multiple instruments using a representative fragment analysis assay and an appropriate method comparison assay. All pre-established performance criteria were met.

Conclusion 21 CFR 807.92(b)(3)

The proposed Applied Biosystems™ 3500 Dx Genetic Analyzer and the Applied Biosystems™ 3500xL Dx Genetic Analyzer with fragment analysis and sequencing, and the legally marketed Applied Biosystems 3500 Dx/3500xL Dx Genetic Analyzer and 3500 Dx Series Data Collection Software with sequencing use the same capillary electrophoresis technology and are the same instrument. The Applied Biosystems™ 3500 Dx Genetic Analyzer and the Applied Biosystems™ 3500xL Dx Genetic Analyzer did not require changes to the instrument hardware or firmware to expand the intended use to include fragment analysis. The change was made in the Applied Biosystems™ 3500 Dx Series Data Collection Software to enable the fragment analysis workflow in the Diagnostic mode.

Therefore, the Applied Biosystems™ 3500 Dx Genetic Analyzer and the Applied Biosystems™ 3500xL Dx Genetic Analyzer and the legally marketed device, the Applied Biosystems 3500 Dx/3500xL Dx Genetic Analyzer CS2 and 3500 Dx Series Software. are substantially equivalent based on the study data provided in this 510(k). In addition, the performance of the fragment analysis application has been demonstrated by Clinical and Non-Clinical performance studies using a representative assay.

Regulation Number and Section

§ 862.2570 Instrumentation for clinical multiplex test systems.

(a)
Identification. Instrumentation for clinical multiplex test systems is a device intended to measure and sort multiple signals generated by an assay from a clinical sample. This instrumentation is used with a specific assay to measure multiple similar analytes that establish a single indicator to aid in diagnosis. Such instrumentation may be compatible with more than one specific assay. The device includes a signal reader unit, and may also integrate reagent handling, hybridization, washing, dedicated instrument control, and other hardware components, as well as raw data storage mechanisms, data acquisition software, and software to process detected signals.(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9. The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Instrumentation for Clinical Multiplex Test Systems.” See § 862.1(d) for the availability of this guidance document.