(293 days)
The AccuProbe Group B Streptococcus Culture Identification Test is a rapid DNA probe test which utilizes the technique of nucleic acid hybridization for the identification of Group B Streptococcus isolated from culture.
The new indication for use covered in this 510(k) is for culture identification of Group B Streptococcus from vaginal and/or anorectal swab specimens collected from pregnant women at 35 to 37 weeks gestation, and cultured in Lim broth for 18 to 24 hours.
The ACCUPROBE Group B Streptococcus Culture Identification Test is a rapid DNA probe test which is based on the detection of ribosomal RNA sequences that are unique to Streptococcus agalactiae. Nucleic acid hybridization tests are based on the ability of complementary nucleic acid strands to specifically align and associate to form stable double-stranded complexes. The ACCUPROBE test uses a single-stranded DNA probe with a chemiluminescent label that is complementary to the ribosomal RNA of the target organism. After the ribosomal RNA is released from the organism, the labeled DNA probe combines with the target organism's ribosomal RNA to form a double-stranded DNA:RNA hybrid. The Selection reagent allows for the differentiation of non-hybridized and hybridized probe. The labeled DNA:RNA hybrids are measured in the Gen-Probe luminometer. A positive result is a luminometer reading equal to or greater than the cut-off. A value below this result is a negative result.
Here's a breakdown of the acceptance criteria and study details for the Gen-Probe ACCUPROBE Group B Streptococcus Culture Identification Test, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state quantitative acceptance criteria in terms of minimum sensitivity or specificity values that were required for approval. However, the performance data is presented against the "traditional culture methods" as the reference standard. The "Results Following Resolution of Discrepants" represent the final, most accurate performance after re-examination, and are therefore used for the reported device performance.
| Performance Metric | Acceptance Criteria (Implicit) | Reported Device Performance (Total, Post-Resolution) |
|---|---|---|
| Sensitivity | High (compared to culture) | 97.5% |
| Specificity | High (compared to culture) | 99.8% |
| Percent Agreement | High (compared to culture) | 99.4% |
Note: The phrasing "substantially equivalent to other commercially available products" for the original device (and implicitly for this new indication) suggests that meeting performance levels comparable to predicate devices was the unstated acceptance criterion. The high sensitivity and specificity demonstrated are consistent with such an implicit criterion.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set:
- Initial Determination Total: 1633 specimens (300 Pos/Pos + 18 Pos/Neg + 25 Neg/Pos + 1290 Neg/Neg)
- Post-Resolution Total: 1633 specimens (316 Pos/Pos + 2 Pos/Neg + 8 Neg/Pos + 1307 Neg/Neg) - The total number of samples remains the same, only the classification changed after resolution.
- Data Provenance: The study was conducted across four clinical sites. The country of origin is not explicitly stated, but the submission is to the U.S. FDA, implying the data is likely from the United States. The study appears to be prospective in nature, as it involved developing a "clinical protocol" for specimen collection and processing, and tested against "traditional culture methods."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- Number of Experts: Not specified.
- Qualifications of Experts: Not specified.
- The ground truth was established by "traditional culture methods" which included:
- Culture on sheep blood agar and Lim broth
- Subculture from Lim broth to sheep blood agar
- Colony identification methods: CAMP test, PathoDx test, and the ACCUPROBE Group B Streptococcus test (this is confusing as the device itself is also listed as an identification method to establish ground truth, though it's likely referring to a conventional version or as confirmation).
- While specific expert qualifications (e.g., "microbiologist with X years of experience") are not given, the reliance on established laboratory culture and identification techniques implies that trained laboratory personnel or microbiologists performed these tasks.
- The ground truth was established by "traditional culture methods" which included:
4. Adjudication Method for the Test Set
The study used an adjudication method for discrepant results.
- Method: "ACCUPROBE assays with discrepant results were repeated, and culture was either repeated from the swab pledget or re-examined to determine whether correct identification of Group B colonies had been made."
- This suggests a re-evaluation process for cases where the ACCUPROBE result did not match the initial culture result. It's a form of "resolution of discrepants" rather than a specific n-rater adjudication scheme (like 2+1, 3+1). The re-examination acted as the adjudicator.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not explicitly described.
- This study evaluated the standalone performance of the ACCUPROBE device compared to culture methods. It did not involve comparing human readers' performance with and without AI assistance. The device is an in-vitro diagnostic test, not an AI-assisted diagnostic tool for human interpretation.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
- Yes, a standalone performance study was done.
- The ACCUPROBE Group B Streptococcus Culture Identification Test is a "rapid DNA probe test" that produces a "luminometer reading equal to or greater than the cut-off" for a positive result. This indicates an objective, automated reading by the Gen-Probe luminometer without human interpretation, making it a standalone device performance evaluation. The "Results Following Resolution of Discrepants" table clearly represents the standalone performance of the device against the established ground truth.
7. The Type of Ground Truth Used
- The ground truth used was expert consensus / established laboratory methods (culture and biochemical/immunological tests).
- The "traditional culture methods" are considered the reference standard for identifying Group B Streptococcus from culture. These methods included sheep blood agar, Lim broth, CAMP test, and PathoDx test. The re-examination of discrepant results further refined this ground truth.
8. The Sample Size for the Training Set
- The document does not specify a separate training set or its sample size.
- This type of DNA probe test is likely developed and optimized based on known genetic sequences and biochemical properties of the target organism (Streptococcus agalactiae) and non-target organisms. The document describes the "within run" and "between-run precision" studies, which are part of device characterization but not typically a "training set" in the machine learning sense. The clinical studies are presented as performance evaluation, not for training.
9. How the Ground Truth for the Training Set Was Established
- Since no separate "training set" is identified or discussed, the method for establishing its ground truth is not applicable based on the provided text.
- The development of the probe itself would have relied on established scientific knowledge of Streptococcus agalactiae ribosomal RNA sequences, which would have been confirmed through molecular biology techniques and culture in a research and development phase prior to these clinical validation studies.
{0}------------------------------------------------
SEP 2 4 1998
10. 510(k) Summary
Ka74572
A. Name and Address of Submitter
Gen-Probe Incorporated 10210 Genetic Center Drive San Diego, CA 92121
Telephone: 619-410-8749 619-410-8622 FAX:
Contact Person: Gerald H. Schell, Director, Regulatory Affairs
Date 510(k) Summary was prepared: December 4, 1997
B. Device Names
Proprietary Name: Gen-Probe ACCUPROBE Group B Streptococcus Culture Identification Test cDNA probe test for the identification of Group B Common Name: Streptococcus from culture
Classification Name: DNA-Probe, Reagents, Streptococcal
C. Legally Marketed Device
The ACCUPROBE Group B Streptococcus Culture Identification Test has been determined to be substantially equivalent to other commercially available products for the identification of Group B Streptococcus isolated from culture that were in commercial distribution prior to May 28, 1976.
D. Device Description
The ACCUPROBE Group B Streptococcus Culture Identification Test is a rapid DNA probe test which is based on the detection of ribosomal RNA sequences that are unique to Streptococcus agalactiae. Nucleic acid hybridization tests are based on the ability of complementary nucleic acid strands to specifically align and associate to form stable double-stranded complexes. The ACCUPROBE test uses a single-stranded DNA probe with a chemiluminescent label that is complementary to the ribosomal RNA of the target organism. After the ribosomal RNA is released from the organism, the labeled DNA probe combines with the target organism's ribosomal RNA to form a double-stranded DNA:RNA hybrid. The Selection reagent allows for the differentiation of non-hybridized and
T:RA\RADEPT\GRPB\510K\010
{1}------------------------------------------------
hybridized probe. The labeled DNA:RNA hybrids are measured in the Gen-Probe luminometer. A positive result is a luminometer reading equal to or greater than the cut-off. A value below this result is a negative result.
E. Intended Use
As stated in the Package Insert, the ACCUPROBE Group B Streptococcus Culture Identification Test is a rapid DNA probe test which utilizes the technique of nucleic acid hybridization for the identification of Group B Streptococcus isolated from culture.
F. Comparison with Predicate Device
The ACCUPROBE Group B Streptococcus Culture Identification Test has been determined to be substantially equivalent to other commercially available products for the identification of Group B Streptococcus isolated from culture that were in commercial distribution prior to May 28, 1976 (reference: K894711/A, cleared for commercial distribution on November 14, 1989).
The purpose of this 510(k) Premarket Notification is to add a new indication for use for this product. The test kit reagents and procedures for hybridization, selection, detection, and interpretation of results, as well as the test specificity and recovery claims, remain unchanged. The product labeling has been modified to include the new indication for use in prenatal screening, appropriate instructions for collection and handling the vaginal and/or anorectal swab specimens, additional materials required to collect and culture the specimens, expected values, performance characteristics, clarification of current text, and an addition to the bibliography.
G. Performance Data
Non-Clinical Studies
Precision
The within run and between-run precision of the ACCUPROBE Group B Streptococcus test using mixtures of ribosomal RNA to mimic vaginal and anorectal swabs.
Within run precision was calculated by assaying a mixture of ribosomal RNA isolated from Streptococcus agalactiae, Staphylococcus epidermidis, Escherichia coli, and Neisseria gonorrhoeae, using 10 replicates in a single assay, with the following results:
T:RA\RADEPT\GRPB\510K\010
{2}------------------------------------------------
| Number of replicates | 10 |
|---|---|
| Mean Response | 77,612 |
| Standard Deviation | 2,767 |
| Coefficient of Variation | 3.6% |
Between-run precision was calculated by assaying the same mixture culture of ribosomal RNA using single determinations in 12 consecutive assays, with the following results:
| Number of Replicates | 12 |
|---|---|
| Mean Response | 78,676 |
| Standard Deviation | 2,966 |
| Coefficient of Variation | 3.8% |
Clinical Studies
Sensitivity and Specificity
The diagnostic sensitivity and specificity of the ACCUPROBE Group B Streptococcus test as compared to the traditional culture methods are presented below, for each individual clinical site and for all sites combined.
ACCUPROBE/CULTURE IDENTIFICATION (CULTURED VAGINAL AND/OR ANORECTAL SWAB SPECIMENS)
Results of Initial Determination:
| ACCUPROBECulture | PosPos | PosNeg | NegPos | NegNeg | Sensitivity/Specificity | PercentAgreement |
|---|---|---|---|---|---|---|
| Site 1 | 84 | 7 | 6 | 401 | 93.3%/98.3% | 97.4% |
| Site 2 | 26 | 0 | 1 | 151 | 96.3%/100% | 99.4% |
| Site 3 | 81 | 6 | 16 | 315 | 83.5%/98.1% | 94.7% |
| Site 4 | 109 | 5 | 2 | 423 | 98.2%/98.8% | 98.7% |
| Total | 300 | 18 | 25 | 1290 | 92.3%/98.6% | 97.4% |
ACCUPROBE assays with discrepant results were repeated, and culture was either repeated from the swab pledget or re-examined to determine whether correct identification of Group B colonies had been made. The results following resolution of the discrepant results are presented below.
T:RA\RADEPT\GRPB\510K\010
{3}------------------------------------------------
Results Following Resolution of Discrepants:
| ACCUPROBECulture | PosPos | PosNeg | NegPos | NegNeg | Sensitivity/Specificity | PercentAgreement |
|---|---|---|---|---|---|---|
| Site 1 | 90 | 2 | 2 | 405 | 97.8%/99.8% | 99.2% |
| Site 2 | 26 | 0 | 1 | 151 | 96.3%/100% | 99.4% |
| Site 3 | 86 | 1 | 3 | 328 | 96.6%/99.7% | 99.0% |
| Site 4 | 114 | 0 | 2 | 423 | 98.3%/100% | 99.6% |
| Total | 316 | 2 | 8 | 1307 | 97.5%/99.8% | 99.4% |
Conventional methods included culture on sheep blood agar and Lim broth (Todd-Hewitt with nalidixic acid and colistin) for 18 to 24 hours, followed by subculture from the Lim broth to another sheep blood agar plate. Colony identification methods included the CAMP test, the PathoDx test (Diagnostic Products Corp., Los Angeles, CA), and the ACCUPROBE Group B Streptococcus test.
The clinical protocol was developed to immerse swabs in Lim broth for at least one minute, and then express against the side of the tube. The tube was then vortexed, incubated at 35° to 37°C for 18 to 24 hours, and vortexed prior to use. The ACCUPROBE Group B Streptococcus test procedure was then performed exactly as recommended in the current Package Insert, using a 50 ul aliquot of the resulting broth culture. The results were interpreted according to the Package Insert recommendations.
{4}------------------------------------------------
Image /page/4/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus symbol, which is a staff with two snakes coiled around it. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" are arranged in a circular pattern around the caduceus symbol. The logo is black and white.
SEP 2 4 1998
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Rhonda A. Moe Regulatory Affairs Specialist Gen-Probe Inc. 10210 Genetic Center Drive San Diego, CA 92121-4362
Re: K974572
Trade Name: Gen-Probe® Accuprobe Group B Streptococcus Culture Identification Test Regulatory Class: I Product Code: MDK Dated: August 14, 1998 Received: August 17, 1998
Dear Ms. Moe:
We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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 (Premarket Approval), 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 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.
{5}------------------------------------------------
Page 2
Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770)488-7655.
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 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" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll free number (800) 638-2041 or at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"
Sincerely yours,
Steven Autman
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
{6}------------------------------------------------
| INDICATIONS FOR USE STATEMENT | |
|---|---|
| 510(k) Number (if known): | K974572 |
| Device Name: | Gen-Probe AccuProbe Group B StreptococcusCulture Identification Test |
| Indications For Use: |
The AccuProbe Group B Streptococcus Culture Identification
Test is a rapid DNA probe test which utilizes the technique
of nucleic acid hybridization for the identification of
Group B Streptococcus isolated from culture.
The new indication for use covered in this 510(k) is for
culture identification of Group B Streptococcus from
vaginal and/or anorectal swab specimens collected from
pregnant women at 35 to 37 weeks gestation, and cultured
in Lim broth for 18 to 24 hours.
(PLEASE DO NOT WRITE BELOW THIS LINE -
CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Woody Dubois
(Division Sign-Off)
Division of Clinical Laboratory Devices
| 510(k) Number | K974572 |
|---|---|
| --------------- | --------- |
| Prescription Use | X (Per 21 CFR 801.109) | OR | Over-the-Counter Use |
|---|---|---|---|
| ------------------ | ----------------------------------------------------------------- | ---- | ---------------------- |
(Optional Format 1-2-96)
। ਉ
§ 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.