To determine bacterial antimicrobial agent susceptibility. The MicroScan ® MICroSTREP plus ™ Panel is used to determine quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of aerobic streptococci, including Streptococcus pneumoniae. After inoculation, panels are incubated for 20 - 24 hours at 35°C +/- 1°C in a non-CO2 incubator, and read visually according to the Package Insert. This particular submission is for the addition of the antimicrobial Chloramphenicol at concentrations of 1 to 32 mcg/ml to the test panel. The organisms which may be used for Chloramphenicol susceptibility testing in this panel are: Susceptible streptococci, including Streptococcus pneumoniae.

Device Description

The MicroScan® MICroSTREP plus™ Panel is used to determine quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of aerobic streptococci, including Streptococcus pneumoniae. After inoculation, panels are incubated for 20-24 hours at 35°C +/- 1°C in a non-CO2 incubator, and read visually according to the Package Insert. The antimicrobial susceptibility tests are miniaturizations of the broth dilution susceptibility test. Various antimicrobial agents are diluted in water, buffer or minute concentrations of broth to concentrations bridging the range of clinical interest. Panels are rehydrated with 115 ul Mueller-Hinton broth supplemented with 2-5% lysed horse blood (LHB) and buffered with 50 mM HEPES, after inoculation of the broth with a standardized suspension of the organism in saline. After incubation in a non-CO2 incubator for 20-24 hours, the minimum inhibitory concentration (MC) for the test organism is manually read by observing the lowest antimicrobial concentration showing inhibition of growth.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the MicroScan® MICroSTREP plus™ Panel, based on the provided text:

1. Acceptance Criteria and Reported Device Performance

Acceptance Criteria Category	Reported Device Performance
Overall Essential Agreement	100% for Chloramphenicol when compared with the NCCLS frozen Reference panel.
Reproducibility	Acceptable reproducibility and precision with Chloramphenicol.
Quality Control	Acceptable results for Chloramphenicol.

Note: The document explicitly states the acceptance criteria were "as defined in the FDA DRAFT document 'Guidance on Review Criteria for Assessment of Antimicrobial Susceptibility Devices', dated March 8, 2000." However, the specific numerical thresholds for "acceptable reproducibility" and "acceptable results for Quality Control" are not detailed in the provided text. The only specific quantitative criterion mentioned is for "Essential Agreement."

2. Sample Size and Data Provenance

Test Set Sample Size: Not explicitly stated as a number. The external evaluation was conducted with "fresh and stock Efficacy isolates and stock Challenge strains." The specific number of isolates for each category is not provided.
Data Provenance: Not explicitly stated by country of origin. The study was an "external evaluation" and compared performance against an "NCCLS frozen Reference Panel." NCCLS (National Committee for Clinical Laboratory Standards) is a US-based organization (now CLSI), suggesting the data is likely US-centric or from facilities following US standards. The study appears to be retrospective as it uses existing "stock" isolates and a reference panel.

3. Number and Qualifications of Experts for Ground Truth

The document does not specify the number of experts or their qualifications used to establish the ground truth for the test set.
The ground truth reference method was the "NCCLS frozen Reference Panel," which implies that the reference panel itself's values (likely MICs) were established through a standardized, expert-validated process at the time of its creation, but details are not provided here.

4. Adjudication Method for the Test Set

The document does not specify an adjudication method like 2+1 or 3+1. The comparison was described as direct, "comparing its performance with an NCCLS frozen Reference panel."

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, an MRMC comparative effectiveness study was not done. This device is a test panel for determining antibiotic susceptibility, not an imaging device that involves human readers interpreting results in a comparative study with and without AI assistance. The panel results are visually read by a human, but the study focuses on the accuracy of the panel itself against a reference method, rather than the improvement of human interpretation with AI.

6. Standalone (Algorithm Only) Performance Study

Yes, in essence, a standalone performance study was done. The MicroScan® MICroSTREP plus™ Panel's performance was evaluated by directly comparing its results (after manual visual reading) against the "NCCLS frozen Reference panel." While a human reads the final MIC, the "device" in question (the panel and its methodology) is evaluated on its ability to produce accurate MIC values independently of specific human reader variability beyond what is inherent in visual reading. The study aimed to show the panel's inherent performance.

7. Type of Ground Truth Used

The ground truth used was established by an NCCLS frozen Reference Panel. This type of ground truth represents a reference standard method that is widely accepted in microbiology for determining minimum inhibitory concentrations (MICs). It is typically established through rigorous, standardized procedures, often reflecting expert consensus on the methodologies.

8. Sample Size for the Training Set

The document does not explicitly mention a separate "training set" or its sample size. The information provided focuses on the evaluation of the device against a reference. For a device like this (which appears to be a chemical assay system rather than an AI/ML algorithm that requires explicit machine learning training), the concept of a "training set" in the context of AI is not directly applicable. The development of the panel itself would have involved extensive R&D and optimization, but not in the sense of a machine learning training set described here.

9. How Ground Truth for the Training Set Was Established

As there's no explicitly mentioned "training set" in the AI/ML context, there's no information on how its ground truth was established. The development process for a chemical assay panel would rely on established microbiological principles and validated experimental results to optimize the concentrations and reagents, not on a machine learning training process.

Summary

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

JUN 11 2002

510(k) Summary Information:

Device Manufacturer:	Dade MicroScan Inc.
Contact name:	Cynthia Van Duker, Regulatory Affairs Manager
Fax:	916-374-3144
Date prepared:	March 26, 2002
Product Name:	Microdilution Minimum Inhibitory Concentration (MIC) Panels
Trade Name:	MicroScan® MICroSTREP plus™ Panel
Intended Use:	To determine bacterial susceptibility to Chloramphenicol
Indication for Use:	For determining antimicrobic susceptibility with aerobic streptococci, including
	Streptococcus pneumoniae
Predicate device:	MicroScan® Streptococcus MIC Panel (K963641).

510(k) Summary:

The antimicrobial susceptibility tests are miniaturizations of the broth dilution susceptibility test. Various antimicrobial agents are diluted in water, buffer or minute concentrations of broth to concentrations bridging the range of clinical interest. Panels are rehydrated with 115 ul Mueller-Hinton broth supplemented with 2-5% lysed horse blood (LHB) and buffered with 50 mM HEPES, after inoculation of the broth with a standardized suspension of the organism in saline. After incubation in a non-CO2 incubator for 20-24 hours, the minimum inhibitory concentration (MC) for the test organism is manually read by observing the lowest antimicrobial concentration showing inhibition of growth.

The proposed MicroScan® MICroSTREP plus™ Panel demonstrated substantially equivalent performance with streptococcal isolates when compared with an NCCLS frozen Reference Panel, as defined in the FDA DRAFT document "Guidance on Review Criteria for Assessment of Antimicrobial Susceptibility Devices", dated March 8, 2000.

The Premarket Notification (510[k]) presents data in support of the new MICroSTREP plus™ Panel with Chloramphenicol.

The external evaluation was conducted with fresh and stock Efficacy isolates and stock Challenge strains. The external evaluations were designed to confirm the acceptability of the proposed MICroSTREP plus™ Panel by comparing its performance with an NCCLS frozen Reference panel. The MCroSTREP plus™ Panel demonstrated acceptable performance with an overall Essential Agreement of 100% for Chloramphenicol when compared with the frozen Reference panel.

Reproducibility testing demonstrated acceptable reproducibility and precision with Chloramphenicol.

Quality Control testing demonstrated acceptable results for Chloramphenicol.

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

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/1/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized human figure with three wavy lines representing the body and head. The figure is positioned to the right of a circular border containing the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged around the circumference.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUN 1 1 2002

Ms. Cynthia Van Duker Regulatory Affairs Manager Dade Behring Inc. 1584 Enterprise Boulevard West Sacramento, CA 95691

Re: K021018

Trade/Device Name: MicroScan® MICroSTREP plus™ Panels For Chloramphenicol Regulation Number: 21 CFR 866.1640 Regulation Name: Antimicrobial Susceptibility Test System Regulatory Class: Class II Product Code: JWY Dated: March 26, 2002 Received: March 29, 2002

Dear Ms. Van Duker:

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. 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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such 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 dctermination 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); good manufacturing practice requirements as set

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

Page 2 -

This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and 1 additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely vours.

Steven Sutman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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

Indication for Use Statement

・

510(k) No.:	KOZ1018(To be assigned by FDA)
Device Name:	MicroScan ® MICroSTREP plus ™ Panel
Intended Use	To determine bacterial antimicrobial agent susceptibility
Indications for Use:	The MicroScan ® MICroSTREP plus ™ Panel is used to determine quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of aerobic streptococci, including Streptococcus pneumoniae . After inoculation, panels are incubated for 20 - 24 hours at 35°C +/- 1°C in a non-CO2 incubator, and read visually according to the Package Insert.

This particular submission is for the addition of the antimicrobial Chloramphenicol at concentrations of 1 to 32 mcg/ml to the test panel

The organisms which may be used for Chloramphenicol susceptibility testing in this panel are:

Susceptible streptococci, including Streptococcus pneumoniae

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number	K021018
Prescription Use(Per 21 CFR 801.109)	OR	Over-The-Counter Use

(Optional Format 1-2-96)

Regulation Number and Section

§ 866.1640 Antimicrobial susceptibility test powder.

(a)
Identification. An antimicrobial susceptibility test powder is a device that consists of an antimicrobial drug powder packaged in vials in specified amounts and intended for use in clinical laboratories for determining in vitro susceptibility of bacterial pathogens to these therapeutic agents. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.(b)
Classification. Class II (performance standards).