The BD Kiestra IdentifA module is an automated in vitro diagnostic specimen preparation system for use with the BD Kiestra Laboratory Automation Solution to prepare MALDI targets for the Bruker MALDI Biotyper CA System for the qualitative identification and differentiation of microorganisms using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis of colonies grown on plated culture media from human specimens.

The BD Kiestra IdentifA is indicated for use in the clinical laboratory with the BD Kiestra Read Compact and Bruker MALDI Biotyper CA System to aid in the diagnosis of bacterial and fungal infections.

Device Description

The BD Kiestra™ IdentifA is an instrument which automates picking of technologist-selected colonies from plated media and prepares a Bruker MALDI target for identification and differentiation of organisms. The BD Kiestra IdentifA includes the following components (Note: Bruker MALDI targets, Matrix and Bacterial Test Standard (BTS) are required, however, they are obtained directly from Bruker Daltonik GmbH):

. BD Kiestra IdentifA instrument and software with onboard pipetting and nephelometry.
. BD formic acid, deionized water, pipet tips, Matrix and BTS transfer vials.
. BD Kiestra IdentifA nephelometer calibration standards (0.2, 0.5, 1.0 and 3.0 McFarland).
BD Kiestra IdentifA cuvette array.

When a MALDI identification is ordered by a technologist selects the colonies from an image of a plated medium obtained using the BD Kiestra™ ReadA Compact. The coordinates of the colonies and the plated medium are transferred to BD Kiestra IdentifA where the colonies are picked. The colonies are suspended in deionized water and the onboard nephelometer determines the McFarland turbidity. Based on the McFarland, BD Kiestra IdentifA pipets the organism suspension onto a Bruker MALDI target. The BD Kiestra IdentifA uses the Bruker extended Direct Transfer method for preparation of the MALDI target by overlaying formic acid and Bruker Matrix onto the target spot. In addition, BTS spots are prepared on the target slide for quality control. Once dried, the technologist manually removes the target and loads onto the Bruker MALDI Biotyper CA System. The BD Kiestra IdentifA transfers the location of sample and BTS spots to the MALDI Biotyper CA. If requested by the technologist, BD Kiestra IdentifA will also dilute the organism suspension to a target of 0.5 McFarland.

The BD Kiestra IdentifA can be used as a standalone instrument or integrated into the BD Kiestra Laboratory Automation System. The standalone instrument utilizes an input/output module for manual plate loading, which handles de-stacking and stacking of plates. When physically integrated into the BD Kiestra Laboratory Automation System, BD Kiestra IdentifA is connected to a track by way of a connection module for automatic plate transfer. BD Kiestra IdentifA software is responsible for the instrument functionality and a touchscreen is mounted on the instrument for user interface.

AI/ML Overview

Here's an analysis of the acceptance criteria and the studies performed for the BD Kiestra IdentifA device, based on the provided text:

Acceptance Criteria and Reported Device Performance

Criteria	Acceptance Criteria (Explicit or Implied)	Reported Device Performance
Colony Picking Accuracy	100% of colonies successfully selected and picked. 100% of prepared target spots provide the expected identification with Log(score) values ≥ 2.00.	1200 (100%) colonies successfully selected and picked. 400 (100%) target spots provided the expected identification with Log(score) values ≥ 2.00.
Organism Identification Accuracy	BD Kiestra IdentifA processing yields equivalent or better identification accuracy compared to manual sample preparation. Specifically, for samples with positive organism identification (Log(score) ≥ 2.00), the percentage matching the expected identification should be comparable to manual preparation.	Of 397 samples with positive organism identification (Log(score) ≥ 2.00), BD Kiestra IdentifA processing yielded 388 (97.7%) matching the expected identification. Manual eDT method yielded 387 (97.5%). This demonstrates equivalency. Individual species results are detailed in the tables for Gram-negative, Gram-positive, and yeast species, indicating high concordance rates.
Reproducibility	For most strains, Log(score) ≥ 2.00 > 95% of the time across BD Kiestra IdentifA modules, replicates, groups, and lots. (Note: Acknowledged exceptions for strains where the predicate also performs poorly).	13 out of 15 strains showed 100% (or 96%) agreement for Log(score) ≥ 2.00. Corynebacterium jeikeium (37%) and Candida albicans (74%) did not meet the >95% criterion, but this was attributed to the original Bruker system's performance for these strains, as manual preparation also failed to meet the criterion.
Limit of Detection (LoD)	For each organism tested at or above the LoD (0.2 McFarland), at least 6/8 replicates should result in a correct identification. (Implied acceptance based on comparison to manual eDT method's LoD.)	All organisms except Saccharomyces cerevisiae (3/8) achieved 8/8 acceptable MALDI identifications at 0.2-0.3 McFarland. The low performance for S. cerevisiae was noted to be consistent with the original Bruker system's limitations. Demonstrated equivalency to the claimed LoD for the manual eDT method (CFU/target spot).
Cross-contamination	No cross-contamination within and between culture plates, and between spots on the MALDI target. 100% correct results for inoculated and uninoculated samples, with "No peaks" or "No identification" for uninoculated and Log(score) > 2.00 for inoculated. Zero reported cross-contamination events in field use (European data).	For the study, 100% of inoculated and uninoculated samples yielded the correct results (no contamination). Over 58,000 samples processed across 3 BD Kiestra IdentifA instruments in Europe since January 2020 without any reported cross-contamination events.

Study Details

2. Sample sizes used for the test set and the data provenance

Colony Picking Accuracy: 200 mixed culture plates were used, from which 1200 colonies were selected and picked. The data provenance is not explicitly stated (e.g., country of origin), though it is noted as "internal analytical testing." The study design appears to be prospective (experimental).
Organism Identification Accuracy: A total of 464 isolates of Gram-positive bacteria, Gram-negative bacteria, and yeasts were tested. The data provenance is not explicitly stated (e.g., country of origin), but it is referred to as "internal analytical testing." The study design appears to be prospective (experimental).
Reproducibility: For each of the 15 strains, 27 tests were performed (3 days x 3 replicates x 3 instruments). This totals 15 strains * 27 tests/strain = 405 tests. The data provenance is not explicitly stated. The study design appears to be prospective (experimental).
Limit of Detection: 9 organisms were tested, with 8 MALDI target spots inoculated for each. This totals 9 organisms * 8 spots/organism = 72 tests. The data provenance is not explicitly stated. The study design appears to be prospective (experimental).
Cross-contamination: 100 plates inoculated with Staphylococcus aureus and 100 plates with Klebsiella pneumoniae. These 200 inoculated plates were alternated with 200 uninoculated media, for a total of 400 media processed. An additional field examination included "over 58,000 samples" processed in Europe since January 2020. The study design combined prospective experimental testing with retrospective field data analysis.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

The text does not explicitly state the number of experts or their qualifications for establishing ground truth for the test set. However, for the colony picking accuracy, it mentions "Colonies from both isolates on each plate were selected by a technologist". The "Organism Identification" study implicitly used comparison to an "expected result," which would typically be based on a validated identification method and potentially confirmed by expert review, but this is not detailed. The "Reproducibility" study used "Strains with known identifications."

4. Adjudication method for the test set

The document does not describe a formal adjudication method (like 2+1, 3+1) for disagreements or ambiguous cases in the test set. For the "Organism Identification Accuracy," results from the BD Kiestra IdentifA were "compared to the expected result for each isolate." For colony picking, it was confirmed visually and by the Bruker MALDI Biotyper CA identification.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study focusing on human reader performance improvement with AI assistance was not done. This device is an automated specimen preparation system, not an AI for interpretation that would assist human readers in diagnosing. Its function is to automate the preparation stage for downstream MALDI-TOF MS analysis. The comparison is between automated preparation vs. manual preparation using the predicate device.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, the performance studies (Colony Picking, Organism Identification Accuracy, Reproducibility, LoD, Cross-contamination) evaluate the standalone performance of the BD Kiestra IdentifA in preparing samples. The output of the BD Kiestra IdentifA is a prepared MALDI target, which is then loaded onto the Bruker MALDI Biotyper CA System for organism identification. While a technologist selects colonies from a digital image, the subsequent steps of picking, suspension, turbidity measurement, and spotting are automated without human intervention. The performance metrics are based on the results obtained from the prepared targets by the downstream MALDI-TOF MS system.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The ground truth primarily appears to be "expected identification" or "known identifications" of microorganisms. This implies an established and validated identification for each isolate, likely obtained through standard microbiological methods or a reference MALDI-TOF MS system. For the "Organism Identification Accuracy" study, the comparison was between the BD Kiestra IdentifA prepared samples and "manual sample preparation, i.e. performing the extended Direct Transfer (eDT) Procedure and spotting on a MALDI target according to the previously FDA-cleared Bruker MALDI Biotyper CA user manual." This suggests the "expected result" was either based on prior rigorous identification or the result from the manual predicate method.

8. The sample size for the training set

The document does not explicitly state the sample size for a training set. As an automated specimen preparation system, it's possible its internal algorithms (e.g., for colony picking, turbidity estimation, pipetting precision) were developed and optimized using various datasets, but these "training sets" are not described in terms of size or content. The provided studies focus on validation/test set performance.

9. How the ground truth for the training set was established

Not applicable, as a specific "training set" and its ground truth establishment are not described in the provided text. The device's function is mechanical automation of a known lab procedure, not an AI model that learns from training data in the same way. Any inherent 'intelligence' (e.g., image processing for colony identification) would have been programmed based on established features rather than learned through labeled training data.

Summary

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November 3, 2021

Becton, Dickinson and Company Laura Stewart Senior Manager Regulatory Affairs 7 Loveton Circle, MC 964 Sparks, Maryland 21152

Re: K191964

Trade/Device Name: BD Kiestra IdentifA Regulation Number: 21 CFR 866.3378 Regulation Name: Clinical Mass Spectrometry Microorganism Identification And Differentiation System Regulatory Class: Class II Product Code: QQV, QBN Dated: March 13, 2020 Received: March 16, 2020

Dear Laura Stewart:

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.

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 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

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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 mediation-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,

Ribhi Shawar, Ph.D. (ABMM) Chief General Bacteriology and Antimicrobial Susceptibility Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K191964

Device Name BD Kiestra™ IdentifA

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
☑ Prescription Use (Part 21 CFR 801 Subpart D)	☐ Over-The-Counter Use (21 CFR 801 Subpart C)

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BD Kiestra™ IdentifA

Summary Preparation Date:

10/21/2021

Submitted by:

BD Diagnostic Systems Becton, Dickinson and Company 7 Loveton Circle Sparks, Maryland 21152

Contact: Laura Stewart Senior Manager Regulatory Affairs Tel: 410-316-4435 Fax: 410-316-4188 Email: laura.stewart(@bd.com

Proprietary Names: BD Kiestra™ IdentifA

Common Names: BD Kiestra IdentifA

Regulatory Information

Regulation section: 21 CFR 866.3378 - Clinical mass spectrometry microorganism identification and differentiation device

Classification: Class II

Review Panel: Microbiology

Product Code: QQV, QBN

Predicate Device

Bruker MALDI Biotyper CA

Similarities and Differences of BD Kiestra™ IdentifA to Predicate

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Becton, Dickinson and Company
Similarities
Item	Device:BD Kiestra™ IdentifA	Predicate:Bruker MALDI Biotyper CA System
Sample Type	Bacterial colonies isolated from culture onplated media.	Same
Method of MALDItarget preparation	Extended Direct Transfer SamplePreparation Procedure	Same
Amount of organism ontarget	Meets Bruker Limit of Detection	Same
Quality Controls	US IVD Bacterial Test Standard (BTS)	Same
Matrix	US IVD HCCA matrix	Same
Targets	MBT Biotarget 96 US IVD (96-spotdisposable) and US IVD 48 Spot (48-spotreusable) targets	Same
Loading of target onBruker instrument	Manual	Same
Differences
Item	Device:BD Kiestra™ IdentifA	Predicate:Bruker MALDI Biotyper CA System
Intended Use	The BD Kiestra IdentifA module is anautomated in vitro diagnostic specimenpreparation system for use with the BDKiestra Laboratory Automation Solution toprepare MALDI targets for the BrukerMALDI Biotyper CA System for thequalitative identification and differentiationof microorganisms using matrix-assistedlaser desorption/ionization - time of flightmass spectrometry (MALDI-TOF MS)analysis of colonies grown on platedculture media from human specimens.The BD Kiestra IdentifA is indicated foruse in the clinical laboratory with the BDKiestra ReadA Compact and BrukerMALDI Biotyper CA System to aid in inthe diagnosis of bacterial and fungalinfections.	The MALDI Biotyper CA System is amass spectrometer system using matrix-assisted laser desorption/ionization - timeof flight (MALDI-TOF) for theidentification and differentiation ofmicroorganisms cultured from humanspecimens. The MALDI Biotyper CASystem is a qualitative in vitro diagnosticdevice indicated for use in conjunctionwith other clinical and laboratory findingsto aid in the diagnosis of bacterial andfungal infections.
Colony Visualization	Digital image from the BD ReadACompact	Direct
Organism preparation	Suspension in deionized water fromorganism picked by way of a pipettor	Organism placed directly to target by wayof stick.
Number of Colonies	Up to 9 per suspension or per spot	One per target spot
Alternative methods ofMALDI targetpreparation	None	Direct Transfer (DT) and Extraction (Ext)Sample Preparation Procedure
Sample and reagentapplication	Automated	Manual
Drying of targets	35°C ± 2°C	Ambient temperature
Results Achieved	Prepared MALDI target	Identification of the organism
Result Reported	None	Identification of the organism
Technology	Robotic x-y-z platform using pipettors andonboard nephelometry	Mass spectrometer using matrix-assistedlaser desorption/ionization - time of flight(MALDI-TOF)

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Device Establishment

Becton, Dickinson and Company 7 Loveton Circle Sparks, Maryland 21152 Registration Number: 1119779

Performance Standards

N/A

Intended Use

The BD Kiestra IdentifA module is an automated in vitro diagnostic specimen preparation system for use with the BD Kiestra Laboratory Automation Solution to prepare MALDI targets for the Bruker MALDI Biotyper CA System for the qualitative identification and differentiation of microorganisms using matrixassisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis of colonies grown on plated culture media from human specimens.

The BD Kiestra Identif A is indicated for use in the clinical laboratory with the BD Kiestra Read A Compact and Bruker MALDI Biotyper CA System to aid in the diagnosis of bacterial and fungal infections.

Special Conditions for Use Statement: For in vitro diagnostic use. For prescription use.

Special Instrument Requirements:

Standalone or integrated into the BD Kiestra™ Laboratory Automation System

BD Kiestra™ ReadA Compact, v 1.1

MALDI Biotyper CA (Bruker)

Device Description

. BD Kiestra IdentifA instrument and software with onboard pipetting and nephelometry.
. BD formic acid, deionized water, pipet tips, Matrix and BTS transfer vials.
. BD Kiestra IdentifA nephelometer calibration standards (0.2, 0.5, 1.0 and 3.0 McFarland).
BD Kiestra IdentifA cuvette array.

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of the MALDI target by overlaying formic acid and Bruker Matrix onto the target spot. In addition, BTS spots are prepared on the target slide for quality control. Once dried, the technologist manually removes the target and loads onto the Bruker MALDI Biotyper CA System. The BD Kiestra IdentifA transfers the location of sample and BTS spots to the MALDI Biotyper CA. If requested by the technologist, BD Kiestra IdentifA will also dilute the organism suspension to a target of 0.5 McFarland.

Device Comparison

The BD Kiestra™ IdentifA demonstrated substantially equivalent performance when compared with the FDA cleared Bruker MALDI Biotyper CA with manual extended Direct Transfer method. This premarket notification provides data supporting the use of the BD Kiestra™ IdentifA for automated preparation of a MALDI target.

Summary of Substantial Equivalence1 Testing

The BD Kiestra™ IdentifA has demonstrated substantially equivalent performance when compared to the Bruker MALDI Biotyper CA.

Analytical Performance

Internal analytical testing confirmed the performance of BD Kiestra IdentifA automated sample processing compared to the FDA cleared Bruker MALDI manual sample processing using the extended Direct Transfer (eDT) method.

Accuracy of the BD Kiestra IdentifA:

Colony Picking

The ability of the BD Kiestra IdentifA to pick colonies designated by the operator in the digital image obtained by the BD Kiestra ReadA Compact was evaluated. Two organisms, Escherichia coli and Streptococcus pyogenes, were inoculated on 200 mixed culture plates. Colonies from both isolates on each plate were selected by a technologist and picked by BD Kiestra IdentifA. Picking of each colony was confirmed visually, and prepared target spots were identified on Bruker MALDI Biotyper CA. One thousand two hundred (1,200) colonies (100%) were successfully selected and picked by the BD Kiestra IdentifA, and 400 target spots (100%) provided the expected identification, with Log(score) values ≥ 2.00.

Organism Identification

Accuracy of organism identification with samples prepared by the BD Kiestra IdentifA was evaluated in the Identification Equivalency Study. A total of 464 isolates of Gram-positive bacteria, Gram-negative bacteria and yeasts were tested using 3 BD Kiestra IdentifA instruments and compared to results by manual sample preparation, i.e. performing the extended Direct Transfer (eDT) Procedure and spotting on

The term "substantial equivalence" as used in this 510(k) notification is limited to the definition of substantial equivalence as found in the Federal Food, Drug and Cosmetic Act, as amended and as applied under which a device can be marketed without pre-market approval or reclassification of substantial equivalency under this notification is not intended to have any bearing whatsoever on the resolution of patent infingement suits or any other patent matters. No statements related to, or in support of substantial equivalence herein shall be construed as an admission aganst interest under the US Patent Laws on the courts.

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a MALDI target according to the previously FDA-cleared Bruker MALDI Biotyper CA user manual. Results from both methods of preparation were compared in the table below.

BD Kiestra IdentifA performance compared to the expected result compared to manual sample preparation:
Log(score)

	Log(score)
Method	Concordant		Discordant	No Identification
	≥2.00	1.70-1.99	≥2.00	1.70-1.99	<1.70	No Peaks
BD KiestraIdentifA	388 (83.6)	25 (5.4)	9 (1.9)	2 (0.4)	22 (4.7)	18 (3.9)
Manual	387 (83.4)	28 (6.0)	10 (2.2)	0 (0.0)	21 (4.5)	18 (3.9)

Of the 397 samples with positive organism identification (Log(score) ≥ 2.00), BD Kiestra IdentifA processing yielded 388 (97.7%) of the isolates matching the expected identification. Sample processing with the Bruker manual eDT method yielded 387 (97.5%) of the isolates matching the expected identification. This demonstrates that the BD Kiestra IdentifA performs equivalently to manually prepared samples to provide accurate results on the Bruker MALDI Biotyper CA.

Results from the BD Kiestra IdentifA were compared to the expected result for each isolate to determine agreement in the tables below.

BD Kiestra IdentifA performance compared to the expected result, by species:

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BD Kiestra™ IdentifA K191964 BD Dia gnostic Systems

BD Kiestra IdentifA agreement in comparison to expected identity for Gram-negative bacteria

	N	Log(Score)
Expected Identity		Concordant		Discordant		No Identification
		≥2.00	1.70-1.99	≥2.00	1.70-1.99	<1.70	NoPeaks
Acinetobacter baumannii/nosocomialis group	10	10	0	0	0	0	0
Bacteroides fragilis	2	2	0	0	0	0	0
Campylobacter coli	3	3	0	0	0	0	0
Campylobacter jejuni	3	3	0	0	0	0	0
Campylobacter lari	1	0	0	0	0	1	0
Citrobacter amalonaticus complex	1	1	0	0	0	0	0
Citrobacter freundii complex	4	4	0	0	0	0	0
Citrobacter koseri	9	9	0	0	0	0	0
Eikenella corrodens	2	2	0	0	0	0	0
Enterobacter aerogenes	9	9	0	0	0	0	0
Enterobacter cloacae complex	7	7	0	0	0	0	0
Escherichia coli	37	37	0	0	0	0	0
Gardnerella vaginalis	2	0	1	$1^2$	0	0	0
Haemophilus influenzae	4	4	0	0	0	0	0
Haemophilus parainfluenzae	2	2	0	0	0	0	0
Hafnia alvei	1	1	0	0	0	0	0
Klebsiella oxytoca/Raoultella ornithinolytica	13	12	0	0	0	0	1
Klebsiella pneumoniae	20	19	0	0	0	0	1
Moraxella sg Branhamella catarrhalis	2	2	0	0	0	0	0
Morganella morganii	12	12	0	0	0	0	0
Neisseria gonorrhoeae	1	1	0	0	0	0	0
Pantoea agglomerans	1	0	0	0	$1^6$	0	0
Porphyromonas gingivalis	1	0	0	$1^3$	0	0	0
Prevotella oralis	1	0	0	0	$1^7$	0	0
Proteus mirabilis	9	9	0	0	0	0	0
Proteus vulgaris group	14	11	0	0	0	0	3
Providencia stuartii	10	8	0	$1^4$	0	0	1
Pseudomonas aeruginosa	15	15	0	0	0	0	0
Salmonella sp.	4	4	0	0	0	0	0
Serratia liquefaciens	2	2	0	0	0	0	0
Serratia marcescens	14	13	0	$1^5$	0	0	0
Shigella sonnei	3	3	0	0	0	0	0
Stenotrophomonas maltophilia	5	5	0	0	0	0	0
Total (%)	224	210(93.8)	1(0.4)	4(1.8)	2(0.9)	1(0.4)	6(2.7)
		211(94.2)		6(2.7)		7(3.1)
		BD Kiestra IdentifA agreement in comparison to expected identity for Gram-positive bacteriaLog(Score)
Expected Identity	N	Concordant		Discordant		No Identification
		≥2.00	1.70-1.99	≥2.00	1.70-1.99	<1.70	No Peaks
Corynebacterium jeikeium	3	3	0	0	0	0	0
Corynebacterium urealyticum	1	0	0	0	0	1	0
Enterococcus avium	2	2	0	0	0	0	0
Enterococcus casseliflavus	3	3	0	0	0	0	0
Enterococcus faecalis	12	11	0	0	0	0	1
Enterococcus faecium	19	17	1	12	0	0	0
Enterococcus gallinarum	5	5	0	0	0	0	0
Propionibacterium acnes	2	0	1	0	0	1	0
Rothia dentocariosa	3	1	0	0	0	0	2
Staphylococcus aureus	21	20	0	0	0	0	1
Staphylococcus cohnii	1	0	1	0	0	0	0
Staphylococcus epidermidis	16	15	0	0	0	1	0
Staphylococcus haemolyticus	6	1	4	0	0	1	0
Staphylococcus hominis	3	3	0	0	0	0	0
Staphylococcus lugdunensis	1	1	0	0	0	0	0
Staphylococcus saprophyticus	3	3	0	0	0	0	0
Staphylococcus sciuri	1	0	0	0	0	1	0
Staphylococcus simulans	2	2	0	0	0	0	0
Staphylococcus warneri	1	1	0	0	0	0	0
Staphylococcus xylosus	1	1	0	0	0	0	0
Streptococcus agalactiae	25	24	0	13	0	0	0
Streptococcus anginosus	1	1	0	0	0	0	0
Streptococcus dysgalactiae	8	8	0	0	0	0	0
Streptococcus gordonii	1	0	1	0	0	0	0
Streptococcus infantarius	1	11	0	0	0	0	0
Streptococcus mitis/oralis group	4	2	1	0	0	1	0
Streptococcus parasanguinis	1	1	0	0	0	0	0
Streptococcus pneumoniae	32	19	6	14	0	3	3
Streptococcus pyogenes	10	9	0	15	0	0	0
Total (%)	189	154(81.5)	15(7.9)	4(2.1)	0(0.0)	9(4.8)	7(3.7)
			169(89.4)		4(2.1)		16(8.5)
	N	Log(Score)
Expected Identity		Concordant		Discordant		No Identification
		≥2.00	1.70-1.99	≥2.00	1.70-1.99	<1.70	No Peaks
Candida albicans	8	6	2	0	0	0	0
Candida dubliniensis	2	2	0	0	0	0	0
Candida glabrata	5	3	0	0	0	2	0
Candida guilliermondii	1	1	0	0	0	0	0
Candida kefyr	2	0	2	0	0	0	0
Candida parapsilosis	3	1	2	0	0	0	0
Candida pelliculosa	1	0	1	0	0	0	0
Candida sphaerica	1	0	0	0	0	1	0
Cryptococcus gattii	3	3	0	0	0	0	0
Cryptococcus neoformans var. grubii	2	1	0	0	0	0	1
Cryptococcus neoformans var. neoformans	3	0	0	12	0	1	1
Cryptococcus neoformans var. Not Known	1	11	0	0	0	0	0
Geotrichum candidum	3	0	1	0	0	2	0
Magnusiomyces capitatus	1	0	0	0	0	1	0
Pichia angusta	2	0	0	0	0	1	1
Saccharomyces cerevisiae	2	1	1	0	0	0	0
Trichosporon aquatile	1	0	0	0	0	1	0
Trichosporon asahii	4	3	0	0	0	1	0
Trichosporon inkin	2	2	0	0	0	0	0
Trichosporon mucoides group	2	0	0	0	0	1	1
Ttrichosporon ovoides	1	0	0	0	0	0	1
Trichosporon pullulans	1	0	0	0	0	1	0
Total (%)	51	24	9	1	0	12	5
		(47.1)	(17.6)	(2.0)	(0)	(23.5)	(9.8)
		(64.7)		(2.0)		(33.3)

Identified as Escherichia coli in accordance with a known Limitation of the Bruker MALDI Biotyper CA

2 Identified as Lactobacillus rhamnosus; concordant with the result obtained with manual sample preparation

3 Identified as Veillonella parvula; concordant with the result obtained with manual sample preparation

4 Identified as Citrobacter freundii complex; concordant with the result obtained with manual sample preparation

5 Identified as Enterobacter cloacae complex; concordant with the result obtained with manual sample preparation

6 Identified as Escherichia species; manual result provided Escherichia vulneris (log score of 2.03)

7 Identified as Bacteroides species; manual result provided unspecified (log score of 1.6)

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BD Kiestra Identif A agreement in comparison to expected identity for Gram-positive bacteria

1 Identified as Streptococcus lutetiensis in accordance with a known Limitation of the Bruker MALDI Biotyper CA

2 Identified as Enterococcus faecalis; concordant with the result obtained with manual sample preparation

3 Identified as Streptococcus pyogenes; concordant with the result obtained with manual sample preparation

4 Identified as Streptococcus mitis/oralis group; concordant with the result obtained with manual sample preparation

5 Identified as Streptococcus agalactiae; concordant with the result obtained with manual sample preparation

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October21,2021

BD Kiestra™ IdentifA K191964 BD Dia gnostic Systems

Becton, Dickinson and Company

BD Kiestra IdentifA agreement in comparison to expected identity for yeast

1 Identified as Cryptococcus neoformans var. grubii

2 Identified as Candida lusitaniae; concordant with the result obtained with manual sample preparation

A substantially lower proportion of concordant results for yeast species than for either Gram-positive or Gram-negative bacteria was noted. Consistent with the original Bruker's system, the BD Kiestra IdentifA User's Manual will recommend that yeast species or any samples that produce a Low Confidence Identification or No Identification Result should be manually prepared using the Bruker's Extraction (Ext) Test Procedure and/or an alternative method of organism identification.

Twenty-five (25) isolates included in the study represented species that were not listed in the Bruker MALDI Biotyper CA Reference Library. Both the BD Kiestra IdentifA and Bruker manual eDT method processing accurately yielded no peaks/no identification for these strains not in the Bruker US IVD database on the Bruker MALDI Biotyper CA.

The results of the accuracy study demonstrate that the BD Kiestra IdentifA performs acceptably compared to manually prepared samples to provide accurate results on the Bruker MALDI Biotyper CA.

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Reproducibility of the BD Kiestra IdentifA

Reproducibility of organism identification when performed using the BD Kiestra IdentifA for preparation of samples was evaluated. Strains with known identifications were processed on three BD Kiestra Identif A modules by three groups of technologists using three lots of reagents in triplicate for three days (3 days × 3 replicates × 3 instruments = 27 data points per strain). The inoculated MALDI targets were loaded onto the Bruker MALDI Biotyper CA System for identification. The table below provides the reproducibility data by organism.

Organism Name	Strain#	No. TestsPerformed	No. LogScore≥2.00	% Agreement
Escherichia coli	25922	27	27	100%
Escherichia coli	35218	27	27	100%
Enterobacter (Klebsiella)aerogenes	13048	27	27	100%
Pseudomonas aeruginosa	27853	27	27	100%
Proteus mirabilis	10070	27	27	100%
Alcaligenes faecalis	9139	27	26	96%
Staphylococcus aureus	29213	27	27	100%
Staphylococcus aureus (MRSA)	43300	27	27	100%
Staphylococcus epidermidis	274	27	27	100%
Enterococcus faecalis	29212	27	27	100%
Streptococcus agalactiae	9812	27	27	100%
Streptococcus pyogenes	2979	27	26	96%
Bacillus cereus	1059	27	27	100%
Corynebacterium jeikeium	11246	27	10	37%
Candida albicans	18804	27	20	74%

BD Kiestra IdentifA Reproducibility by Organism

All except two strains had a Log(score) ≥ 2.00 > 95% of the time between BD Kiestra IdentifA modules, replicates, groups, and lots. Corynebacterium jeikeium and Candida albicans reproducibility were evaluated by manual preparation using the eDT method and also did not meet the acceptance criteria of > 95%. Due to the results of the Bruker manual eDT method, the failure to meet acceptance criteria was not attributed to performance of the BD Kiestra Identif A because this low confidence identification is a property of the original Bruker's system and not the BD Kiestra IdentifA.

The results of the reproducibility study demonstrate that the BD Kiestra Identif A performs equivalently to manually prepared samples to provide reproducible results on the Bruker MALDI Biotyper CA. The results of the Reproducibility Study were determined to be acceptable.

Limit of Detection of the BD Kiestra IdentifA

The ability of the BD Kiestra IdentifA to obtain the expected organism identification with microbial suspensions at or above the limit of detection as defined for the BD Kiestra IdentifA (0.2 McFarland) was evaluated. Organism suspensions of at least 0.2 McFarland (0.2 - 0.3 McFarland) were inoculated onto eight MALDI target spots and processed on BD Kiestra IdentifA. The MALDI targets were analyzed by the Bruker MALDI Biotyper CA to obtain a log(score).

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BD Kiestra IdentifA Limit of Detection

MALDI Identification Performance
		Result
	Staphylococcus aureus 25923	8/8
ram positiy	Enterococcus faecium 19434	8/8
	Enterococcus faecalis 29212	8/8
ram negativ	Enterobacter cloacae 13047	8/8
	Klebsiella pneumoniae 13883	8/8
	Proteus vulgaris 13315	8/8
	Pseudomonas aeruginosa 27853	8/8
	Escherichia coli 25922	8/8
	Acinetobacter baumannii 19606	8/8
east	Saccharomyces cerevisiae 1125A	3/8

For each organism, 6/8 replicates should result in a correct identification. All of the organisms obtained 8/8 acceptable MALDI identifications except Saccharomyces cerevisiae. For S. cerevisiae, 3/8 replicates produced the expected result and 5/8 were reported as "No Peaks." There were no incorrect identifications for any organism. The inability to obtain a High Confidence Identification when the concentration of yeast in a sample is at the low end of the specified range for turbidity is noted. Consistent with the original Bruker's system, the BD Kiestra IdentifA User's Manual recommends that yeast species or any samples that produce a Low Confidence Identification or No Identification Result should be manually prepared using the Bruker's Extraction (Ext) Test Procedure and/or use an alternative method of organism identification. The concentration of organisms present near the LoD for the BD Kiestra IdentifA (0.2 to 0.3 McFarland) was shown to be equivalent to the claimed LoD for the manual extended Direct Transfer (eDT) method of sample preparation for the Bruker MALDI Biotyper CA (CFU/target spot).

Cross-contamination of BD Kiestra IdentifA

A cross-contamination study was performed in support of the original 510(k) submission. Since the original submission, multiple software updates were made including a modification to remove a delay in pipette tip retraction during target spotting, and further validations were performed. A final crosscontamination study was performed on the most updated software version for the candidate device and is described below.

A cross-contamination study was conducted to evaluate the potential for cross-contamination using the BD Kiestra IdentifA within and between culture plates and between spots on the MALDI target. One hundred plated media were inoculated with a strain of Staphylococcus aureus and one hundred plated media were inoculated with a strain of Klebsiella pneumoniae. The inoculated media were processed on

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BD Kiestra IdentifA, alternating the two hundred inoculated media with two hundred uninoculated media. The inoculated and uninoculated samples yielded the correct results 100% of the time; "No peaks" or "No identification" on Bruker MALDI from all uninoculated samples and the correct identification on Bruker MALDI with a log score >2.00 from all inoculated samples.

An examination of instruments in the field was also conducted. Over 58,000 samples have been processed across the 3 BD Kiestra IdentifA instruments running in Europe since January 2020, without any crosscontamination events reported.

Conclusions Drawn from Substantial Equivalence Studies

The data collected from the substantial equivalence studies demonstrate that specimen and MALDI target preparation on the BD Kiestra™ IdentifA is substantially equivalent to the predicate, Bruker MALDI Biotyper CA, DEN 170081 April 20, 2018.

Regulation Number and Section

§ 866.3378 Clinical mass spectrometry microorganism identification and differentiation system.

(a)
Identification. A clinical mass spectrometry microorganism identification and differentiation system is a qualitative in vitro diagnostic device intended for the identification and differentiation of microorganisms from processed human specimens. The system acquires, processes, and analyzes spectra to generate data specific to a microorganism(s). The device is indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial and fungal infection.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The intended use statement must include a detailed description of what the device detects, the type of results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended, when applicable.
(2) Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt with an indication for in vitro diagnostic use.
(3) The labeling required under § 809.10(b) of this chapter must include:
(i) A detailed device description, including all device components, control elements incorporated into the test procedure, instrument requirements, ancillary reagents required but not provided, and a detailed explanation of the methodology and all pre-analytical methods for processing of specimens, and algorithm used to generate a final result. This must include a description of validated inactivation procedure(s) that are confirmed through a viability testing protocol, as applicable.
(ii) Performance characteristics for all claimed sample types from clinical studies with clinical specimens that include prospective samples and/or, if appropriate, characterized samples.
(iii) Performance characteristics of the device for all claimed sample types based on analytical studies, including limit of detection, inclusivity, reproducibility, interference, cross-reactivity, interfering substances, carryover/cross-contamination, sample stability, and additional studies regarding processed specimen type and intended use claims, as applicable.
(iv) A detailed explanation of the interpretation of test results for clinical specimens and acceptance criteria for any quality control testing.
(4) The device's labeling must include a prominent hyperlink to the manufacturer's website where the manufacturer must make available their most recent version of the device's labeling required under § 809.10(b) of this chapter, which must reflect any changes in the performance characteristics of the device. FDA must have unrestricted access to this website, or manufacturers must provide this information to FDA through an alternative method that is considered and determined by FDA to be acceptable and appropriate.
(5) Design verification and validation must include:
(i) Any clinical studies must be performed with samples representative of the intended use population and compare the device performance to results obtained from an FDA-accepted reference method and/or FDA-accepted comparator method, as appropriate. Documentation from the clinical studies must include the clinical study protocol (including predefined statistical analysis plan, if applicable), clinical study report, and results of all statistical analyses.
(ii) Performance characteristics for analytical and clinical studies for specific identification processes for the following, as appropriate:
(A) Bacteria,
(B) Yeasts,
(C) Molds,
(D) Mycobacteria,
(E) Nocardia,
(F) Direct sample testing (
e.g., blood culture),(G) Antibiotic resistance markers, and
(H) Select agents (
e.g., pathogens of high consequence).(iii) Documentation that the manufacturer's risk mitigation strategy ensures that their device does not prevent any device(s) with which it is indicated for use, including incorporated device(s), from achieving their intended use (
e.g., safety and effectiveness of the functions of the indicated device(s) remain unaffected).(iv) A detailed device description, including the following:
(A) Overall device design, including all device components and all control elements incorporated into the testing procedure.
(B) Algorithm used to generate a final result from raw data (
e.g., how raw signals are converted into a reported result).(C) A detailed description of device software, including validation activities and outcomes.
(D) Acquisition parameters (
e.g., mass range, laser power, laser profile and number of laser shots per profile, raster scan, signal-to-noise threshold) used to generate data specific to a microorganism.(E) Implementation methodology, construction parameters, and quality assurance protocols, including the standard operating protocol for generation of reference entries for the device.
(F) For each claimed microorganism characteristic, a minimum of five reference entries for each organism (including the type strain for microorganism identification), or, if there are fewer reference entries, a clinical and/or technical justification, determined by FDA to be acceptable and appropriate, for why five reference entries are not needed.
(G) DNA sequence analysis characterizing all type strains and at least 20 percent of the non-type strains of a species detected by the device, or, if there are fewer strain sequences, then a clinical and/or technical justification, determined by FDA to be acceptable and appropriate, must be provided for the reduced number of strains sequenced.
(H) As part of the risk management activities, an appropriate end user device training program, which must be offered as an effort to mitigate the risk of failure from user error.