IDI-Strep B™ assay is a qualitative in vitro diagnostic test for the rapid detection of Group B streptococcus (GBS) DNA in vaginal/rectal specimens from prepartum or intrapartum women. The test performed on the Smart Cycler® automated analyzer utilizes polymerase chain reaction (PCR) for the amplification of a cfb gene sequence of GBS recovered from clinical samples and fluorogenic target-specific hybridization for the detection of the amplified DNA.

IDI-Strep B™ assay can be used to establish GBS colonisation status of prepartum and intrapartum women.

Device Description

IDI-Strep B™ assay is a qualitative in vitro diagnostic test for the rapid detection of Group B streptococcus (GBS) in vaginal/rectal specimens from intrapartum maternity patients. The test performed on the Smart Cycler® automated analyzer utilizes polymerase chain reaction (PCR) for the amplification of GBS DNA recovered from clinical samples and fluorogenic target-specific hybridization for the detection of the amplified GBS DNA.

IDI-Strep B™ assay can be used as the sole diagnostic information at the time of delivery for establishing GBS colonisation status of intrapartum maternity patients.

Test Description: GBS collected from a vaginal/rectal swab is resuspended in sample preparation buffer. A sample is added to the lysing tube containing glass beads. The proprietary procedure is based on a combination of chemical and physical (glass beads) action and takes less than 10 minutes. A sample of the lysate solution is then added to the tube containing the PCR master mix which has the GBS-specific primers used to amplify the GBS ofb gene, if present, and the internal control (IC) template. Finally, 25 µi is transferred to the reaction tube which is placed in the Smart Cycler® assay.

Amplified target DNA is detected with hybridization probes labeled with quenched fluorophores, i.e. molecular beacons. Different fluorophores are used for the GBS amplicon and for the detection of the IC amplicon. Their detection is independent of one another. Amplification of the internal control monitors for inhibitors potentially introduced with the clinical specimen and, in negative specimens, confirms the integrity of assay reagents. The interpretation of the data collected by the Smart Cycler® is made entirely by the diagnostic software of the Smart Cycler® instrument.

The amount of fluorescence at any given cycle, or following cycling, depends on the amount of specific amplicon present at that time. The Smart Cvcler® instrument monitors simultaneously the fluorescence emitted by each beacon, interprets all data and at the end of the cycling program provides a final result. The operation of the Smart Cycler® instrument is based on the proprietary microprocessor-controlled I-CORE® (Intelligent Cooling/Heating Optical Reaction) module. Each Smart Cycler® processing block contains 16 independently controlled, programmable I-Core® modules, each with one reaction site. Thermally optimized proprietary reaction tubes combined with the design of the I-CORE® modules allow very rapid temperature cycling and rapid amplification. Up to 6 Smart Cycler® processing blocks can be daisy-chained together, allowing simultaneous analysis of 96 discrete samples.

AI/ML Overview

Here's an analysis of the provided text regarding the IDI-Strep B™ assay, addressing the requested information:

Acceptance Criteria and Device Performance Study for IDI-Strep B™ Assay

The IDI-Strep B™ assay is a qualitative in vitro diagnostic test for the rapid detection of Group B streptococcus (GBS) DNA in vaginal/rectal specimens from intrapartum maternity patients. Its performance was evaluated against a broth culture technique in a multi-center study.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria. However, for diagnostic tests, performance metrics like sensitivity, specificity, and predictive values are typically assessed for substantial equivalence. The reported overall study results demonstrate the device's performance against the reference method.

Performance Metric	Reported Device Performance (95% CI)
Clinical Sensitivity	94% (89.0% - 97.2%)
Clinical Specificity	95.9% (94.0% - 97.3%)
% Unresolved Specimens	1.2%
% Invalid Runs	2.6%
Negative Predictive Value	98.6% (97.3% - 99.3%)
Positive Predictive Value	83.8% (77.4% - 89.1%)

Note: While specific "acceptance criteria" for these percentages are not explicitly listed, the FDA's decision to grant substantial equivalence implies that these results were deemed acceptable for the intended use and in comparison to the predicate device.

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

Sample Size for Test Set: 803 vaginal/rectal swab specimens.
Data Provenance: The study was a multi-center study with samples collected from intrapartum maternity patients. The locations of the investigational sites are mentioned as JGH, Montreal; MWH, Pittsburgh; ACH, Calgary; WCH, Milwaukee; and WHT, Houston. This indicates data from both Canada and the United States. The study was likely prospective, as samples were "collected from intrapartum maternity patients" and then evaluated.

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

The ground truth was established using a "broth culture technique." The document does not specify the number of experts involved in performing or interpreting the broth culture results, nor does it specify their qualifications. It simply refers to "broth culture" as the comparator method.

4. Adjudication Method for the Test Set

The document does not describe an explicit adjudication method for the test set. The comparison is made directly between the IDI-Strep B™ assay results and the broth culture results. Discrepancies were investigated post-hoc (e.g., initial culture negatives found to be positive upon investigation, retesting of invalid controls), but a formal, pre-defined adjudication process for conflicting results between the two methods is not detailed.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. This study evaluates the performance of a diagnostic assay (IDI-Strep B™) compared to a laboratory reference method (broth culture) to detect the presence of GBS. It does not involve human readers interpreting images or data alongside and without AI assistance.

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

The IDI-Strep B™ assay, being a PCR-based diagnostic test, inherently operates in a standalone mode (algorithm-only). The text states: "The interpretation of the data collected by the Smart Cycler® is made entirely by the diagnostic software of the Smart Cycler® instrument." This confirms that the device's performance is independent of human interpretation for the final result.

7. The Type of Ground Truth Used

The ground truth used was broth culture, which is a laboratory-based method for identifying and growing microorganisms. In this context, it serves as the reference standard for confirming the presence or absence of GBS.

8. The Sample Size for the Training Set

The document does not specify a separate training set size or methodology. The provided study describes the clinical validation of the device, implying that the 803 specimens were used as a test set against the reference standard. For a molecular diagnostic assay like this, "training" often refers to the internal development and optimization process, which is not typically detailed in 510(k) summaries in terms of distinct sample sizes. The Smart Cycler® software's interpretation is based on predefined algorithms rather than a machine learning model that would require an external training set from this specific clinical trial data.

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

As no specific "training set" is described in the context of this regulatory submission (which focuses on clinical validation), the ground truth establishment method for a training set is not applicable from the provided text. The device's internal algorithms would have been developed using known positive and negative controls and characterized samples during its engineering phase, but this is not the subject of this clinical performance study.

Summary

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K022504

510(k) Summary

NOV 1 8 2002

July 26, 2002

Infectio Diagnostic Inc. IDI-Strep B™ assay

Submitted by:	Infectio Diagnostic Inc.2050, boul. René-Lévesque O, 4ᵉ étageSainte-Foy, QuébecCanadaG1V 2K8
Contact:	Christian Choquet, PhD.
Name of Device:
Trade Name:	IDL-Strep B™ Assay

Trade Name:	IDI-Strep B™ Assay
Common Name:	Group B streptococcus detection assay
Classification Name:	Streptococcus spp. Serological reagents

Predicate Device:

Thermo BioStar™ STREP B OIA®

Device Description:

Intended Use: IDI-Strep B™ assay is a qualitative in vitro diagnostic test for the rapid detection of Group B streptococcus (GBS) in vaginal/rectal specimens from intrapartum maternity patients. The test performed on the Smart Cycler® automated analyzer utilizes polymerase chain reaction (PCR) for the amplification of GBS DNA recovered from clinical samples and fluorogenic target-specific hybridization for the detection of the amplified GBS DNA.

IDI-Strep B™ assay can be used as the sole diagnostic information at the time of delivery for establishing GBS colonisation status of intrapartum maternity patients.

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Smart Cycler® processing block contains 16 independently controlled, programmable I-Core® modules, each with one reaction site. Thermally optimized proprietary reaction tubes combined with the design of the I-CORE® modules allow very rapid temperature cycling and rapid amplification. Up to 6 Smart Cycler® processing blocks can be daisy-chained together, allowing simultaneous analysis of 96 discrete samples.

Substantial Equivalence:

The Infectio Diagnostic Inc. IDI-Strep B™ assay has been found to be substantially equivalent to the Thermo BioStar™ STREP B OIA® (K991828) and to broth culture. All assays detect GBS; the IDI-Strep B™ assay determines the presence of GBS through PCR amplification and fluorogenic target-specific hybridization detection; BioStar STREP B OIA® assay uses optical immunoassay technology for the detection of GBS antigen; broth culture uses culture characteristics for identification.

A multi-center study was conducted on 803 vaginal/rectal swab specimens collected from intrapatum maternity patients. The samples were evaluated with the IDI-Strep B™ assay and broth culture.

The results of the studies are summarized in the following table.

Summary of Clinical Trial Results

		IDI-Strep B™
		Positive	Negative	Total
Culture technique	Positive	140A	9	149
	Negative	27B	626C	653
	Total	167	635	802

Overall Study

A Fourteen (14) specimens were initially culture negative but upon investigation were found to be culture positive; 1 of the 14 (specimen #898) had initially tested unresolved but upon re-testing gave a positive result; 3 specimens that were initially IDI-Strep B™ positive were retested because of invalid controls (positive and negative) and tested positive
B One (1) specimen that was initially positive with IDI-Strep B™ was retested because of an invalid control and re-tested positive
C Twelve (12) specimens that were initially negative with IDI-Strep B™ were refested because of an invalid control and all tested negative; 8 specimens that initially gave an unresolved result gave a negative result upon retesting

One specimen that gave an initially unresolved result remained unresolved upon retesting and was not included in the table above. Overall, 192 runs were conducted during the study. There were 5 invalid runs due to invalid controls. A total of 16 specimens were included in those runs.

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Investigational site	Clinical sensitivity(95% CI) A	Clinical specificity(95% CI) A	% unresolvedspecimens	% invalidruns
JGH, Montreal	93% (68%-100%)	93% (87%-96%)	3,0%	3,6%
MWH, Pittsburgh	88% (69%-97%)	100% (97%-100%)	0%	0%
ACH, Calgary	99% (93-100%)	97% (94%-98%)	0.2%	1.8%
WCH, Milwaukee	85% (54%-98%)	100% (98%-100%)	2.0%	4.7%
WHT, Houston	89% (67%-99%)	93% (82%-98%)	4.0%	4.2%
Overall study	94,%(89.0%- 97.2%)	95.9%(94.0% - 97.3%)	1.2%	2.6%

Performances obtained for each investigational site and for the overall study

^ Binomial 95% confidence intervals

The overall prevalence of the study population was 18.6 %, with the highest prevalence being observed in Pittsburgh (28.7%) and the lowest one in Montreal (9.1%). For the population tested in this study, this results in a negative predictive value of 98.6% (Cl. 97.3% - 99.3%) and a positive predictive value of 83.8% (Cl. 77.4% - 89.1%).

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three curved lines representing its wings. The eagle's head is facing to the left, and its body is formed by a negative space silhouette of a human profile. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the eagle.

Food and Drug Administration 098 Gaither Road Rockville MD 20850

Infectio Diagnostic (I.D.I.) Inc. c/o Ms. Judi Smith Principal Sienna Partners, L.L.C. P.O. Box 103 Baldwin, MD 21013

Re: K022504

Trade/Device Name: IDI- Strep BTM Assay Regulation Number: 21 CFR 866.3740 Regulation Name: Streptococcus Spp. Serological Reagents Regulatory Class: Class I Product Code: NJR Dated: October 23, 2002 Received: October 24, 2002

Dear Ms. Smith:

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 Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820).

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Page 2 –

This letter will allow you to begin marketing your device as described in your Section 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 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 yours.

Steven Sutman

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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INDICATIONS FOR USE STATEMENT

510(k) Number (if known): K02250 Y

Device Name: _______IDI Strep B

Indications For Use:

Intended Use: IDI-Strep B™ assay is a qualitative in vitro diagnostic test for the rapid detection of Group B streptococcus (GBS) DNA in vaginal/rectal specimens from prepartum or intrapartum women. The test performed on the Smart Cycler® automated analyzer utilizes polymerase chain reaction (PCR) for the amplification of a cfb gene sequence of GBS recovered from clinical samples and fluorogenic target-specific hybridization for the detection of the amplified DNA.

IDI-Strep B™ assay can be used to establish GBS colonisation status of prepartum and intrapartum women.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Luddi L. Poole

on Sion-Off Division of Clinical Laboratory Devices

510(k) Number K022504

Prescription Use
(Per 21 CFR 801.109)

Over-The-Counter Use (Optional Format 1-2-96)

Regulation Number and Section

§ 866.3740

Streptococcus spp. serological reagents.(a)
Identification. Streptococcus spp. serological reagents are devices that consist of antigens and antisera (excluding streptococcal exoenzyme reagents made from enzymes secreted by streptococci) used in serological tests to identifyStreptococcus spp. from cultured isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by bacteria belonging to the genusStreptococcus and provides epidemiological information on these diseases. Pathogenic streptococci are associated with infections, such as sore throat, impetigo (an infection characterized by small pustules on the skin), urinary tract infections, rheumatic fever, and kidney disease.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.