(58 days)
The DiaSorin Molecular Simplexa™ GBS Direct assay is a real-time polymerase chain reaction (PCR) assay intended for use on the LIAISON® MDX instrument for the in vitro qualitative detection of Group B Streptococcus (GBS) nucleic acid from 18 to 24 hour Lim broth enrichments of vaginal/rectal specimen swabs obtained from antepartum women. Assay results can be used as an aid in determining the colonization status of antepartum women, but are not intended to diagnose or monitor treatment of a GBS infection.
The Simplexa™ GBS Direct assay does not provide susceptibility results. Culture isolates are needed to perform susceptibility testing as recommended for penicillin-allergic women.
Simplexa™ GBS Positive Control Pack
The Simplexa™ GBS Positive Control Pack is intended to be used as a control with the Simplexa™ GBS Direct kit. This control is not intended for use with other assays or systems.
The Simplexa™ GBS Direct assay system is a real-time PCR system that enables the direct amplification and qualitative detection of Group B Strep bacterial DNA from vaginal swabs enriched in Lim Broth for eighteen to twenty-four (18 to 24) hours that have not undergone a nucleic acid extraction. The system consists of the Simplexa™ GBS Direct assay, the LIAISON® MDX (with LIAISON® MDX Studio Software), the Direct Amplification Disc (DAD) and associated accessories.
In the Simplexa™ GBS Direct assay, primers and fluorescent probes are used together to amplify Group B Streptococcus bacterial DNA and the Internal Control (DNA IC). The assay targets a conserved region of the cfb gene to identify Group B Streptococus in the specimen. The DNA IC is used to detect PCR failure and/or inhibition.
The provided document is a 510(k) Summary for a medical device called Simplexa™ GBS Direct. This document primarily focuses on the device's analytical and clinical performance for the qualitative detection of Group B Streptococcus (GBS) nucleic acid in Lim broth enrichments. It is not an AI/ML medical device in the typical sense that would involve human interpretation of images or other data assisted by an AI, but rather a PCR-based diagnostic assay.
Therefore, many of the requested items related to AI/ML device studies (e.g., number of experts, adjudication methods, MRMC studies, human reader improvement) are not applicable to this type of device. The study described focuses on the device's accuracy against a culture reference method and its analytical performance characteristics.
Here’s a breakdown of the information that can be extracted and which requested items are not applicable:
Acceptance Criteria and Study for Simplexa™ GBS Direct
The "acceptance criteria" for this device are implicitly tied to a demonstration of substantial equivalence to a predicate device, which includes showing acceptable clinical and analytical performance. The study described is the clinical performance evaluation.
1. A table of acceptance criteria and the reported device performance
The document does not explicitly state pre-defined "acceptance criteria" in terms of specific sensitivity and specificity thresholds that were set before the study. Instead, it presents the clinical performance results. The implicit acceptance is based on these results being deemed sufficient for substantial equivalence.
| Performance Metric | Acceptance Criteria (Implicit) | Reported Device Performance (Simplexa™ GBS Direct vs. Culture) |
|---|---|---|
| Clinical Performance: | ||
| Sensitivity | N/A (demonstrate acceptable clinical agreement) | 97.0% (97/100) with 95% CI: 91.5% to 99.0% |
| Specificity | N/A (demonstrate acceptable clinical agreement) | 96.1% (319/332) with 95% CI: 93.4% to 97.7% |
| Reproducibility (Overall Agreement with Expected Results): | ||
| GBS (FAM) Signal | N/A (demonstrate high agreement) | 99.6% (538/540) with 95% CI: 98.7% to 99.9% |
| Internal Control (Q670) Signal | N/A (demonstrate high agreement) | 100.0% (540/540) with 95% CI: 99.3% to 100.0% |
| Analytical Sensitivity (LoD): | N/A (establish lowest detectable concentration) | ATCC BAA-22 (serotype III): 80,000 CFU/mL ATCC BAA-1138 (serotype Ia): 30,000 CFU/mL |
| Analytical Reactivity: | N/A (demonstrate detection of various GBS strains) | 100% detection for 18 additional GBS strains tested at 2 x LoD |
| Cross Reactivity (Analytical Specificity): | N/A (demonstrate no detection of non-GBS organisms) | 0% detection for 74 potential cross-reacting organisms |
| Interference: | N/A (demonstrate no interference from common substances) | No interference observed with 26 potentially interfering substances |
| Inhibition by other Microorganisms: | N/A (demonstrate reliable detection in presence of other organisms) | 100% detection for GBS BAA-22, Some false negatives (88.9% or 77.8% detected) for GBS BAA-1138 with 7 specific organisms (e.g., Bacillus cereus, Candida parapsilosis, Clostridium perfringens) |
2. Sample size used for the test set and the data provenance
- Test Set Sample Size: 432 clinical samples were used for the prospective clinical performance study.
- Data Provenance:
- Country of Origin: Not explicitly stated, but the applicant (DiaSorin Molecular LLC) is based in Cypress, California, USA, suggesting the data is likely from the United States.
- Retrospective or Prospective: The clinical study was prospective. Samples were collected from pregnant women at 35-37 weeks of gestation, and Lim broth enrichments were made and tested fresh.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
This is not applicable as this is not an AI/ML device involving human interpretation of data where expert consensus is required for ground truth. The ground truth for the clinical performance study was established by a "GBS culture reference method." This refers to standard microbiological laboratory procedures for culturing and identifying GBS, not to human expert interpretation of an AI's output.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
This is not applicable for the same reason as above. Discrepancies between the device and the culture reference method (ground truth) were investigated by testing with an "alternate FDA cleared NAAT" (Nucleic Acid Amplification Test). For example:
- 3/3 samples where Simplexa™ GBS Direct was negative and Culture was positive, were found negative by alternate NAAT.
- 11/13 samples where Simplexa™ GBS Direct was positive and Culture was negative, were found positive by alternate NAAT.
This indicates a form of discrepant analysis, not human reader adjudication.
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
This is not applicable as this is not an AI/ML device where human readers interact with or are assisted by AI. The device is a standalone diagnostic assay.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done
Yes, the primary clinical performance study (Table 1) represents the standalone performance of the Simplexa™ GBS Direct assay against a culture reference method. The results provided (Sensitivity and Specificity) represent the algorithm's diagnostic accuracy.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The ground truth for the clinical performance study was established by a "GBS culture reference method." This is a laboratory-based microbiological culture and identification process, considered the gold standard for GBS detection in this context.
8. The sample size for the training set
The document describes a 510(k) submission for a diagnostic assay, not an AI/ML model that undergoes a "training" phase with a large dataset. Therefore, the concept of a "training set" for an AI model is not directly applicable here. The device's PCR primers and probes are designed based on biological knowledge (targeting the cfb gene) rather than being learned from data. Extensive analytical studies (LoD, reactivity, cross-reactivity, interference, inhibition) are done during development and validation, but this isn't analogous to training an AI model.
9. How the ground truth for the training set was established
As the concept of a "training set" in the context of AI/ML is not applicable to this diagnostic assay, this question is also not applicable. The underlying assays are developed based on known biological targets and validated through a series of analytical and clinical studies.
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
November 7, 2018
DiaSorin Molecular LLC Sharon Young Principal Regulatory Affairs Specialist 11331 Vallev View Street Cypress, California 90630
Re: K182467
Trade/Device Name: Simplexa GBS Direct, Simplexa GBS Positive Control Pack Regulation Number: 21 CFR 866.3740 Regulation Name: Streptococcus spp. Serological Reagents Regulatory Class: Class I Product Code: NJR, OOI Dated: September 5, 2018 Received: September 10, 2018
Dear Sharon Young:
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/cdrl/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 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR
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- for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Steven R. Gitterman -S for
Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K182467
Device Name Simplexa™ GBS Direct Simplexa™ GBS Positive Control Pack
Indications for Use (Describe)
Simplexa™ GBS Direct
The DiaSorin Molecular Simplexa™ GBS Direct assay is a real-time polymerase chain reaction (PCR) assay intended for use on the LIAISON® MDX instrument for the in vitro qualitative detection of Group B Streptococcus (GBS) nucleic acid from 18 to 24 hour Lim broth enrichments of vaginal/rectal specimen swabs obtained from antepartum women. Assay results can be used as an aid in determining the colonization status of antepartum women, but are not intended to diagnose or monitor treatment of a GBS infection.
The Simplexa™ GBS Direct assay does not provide susceptibility results. Culture isolates are needed to perform susceptibility testing as recommended for penicillin-allergic women.
Simplexa™ GBS Positive Control Pack
The Simplexa™ GBS Positive Control Pack is intended to be used as a control with the Simplexa™ GBS Direct kit. This control is not intended for use with other assays or systems.
| 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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Image /page/3/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo features a stylized DNA double helix in shades of green and blue on the left. To the right of the helix are the words "DiaSorin" in dark blue, with "Molecular" underneath in green. The logo is clean and modern, representing the company's focus on molecular diagnostics.
510(k) Summary
Simplexa™ GBS Direct Catalog No. MOL3550 Simplexa™ GBS Positive Control Pack Catalog No. MOL3560 October 25, 2018 Page 1 of 19
| Applicant | DiaSorin Molecular LLC.11331 Valley View StreetCypress, California 90630USA |
|---|---|
| Establishment Registration No. | 2023365 |
| Contact Person | Sharon YoungPrincipal Regulatory Affairs Specialisttel 562.240.6680fax 562.240.6529Sharon.Young@DiaSorin.com |
| Summary Date | October 25 2018 |
| Proprietary Name | Simplexa™ GBS Direct and Simplexa™ GBS Positive Control Pack |
| Generic Name | Nucleic Acid Amplifications System, Group B Streptococcus, DirectSpecimen Testing |
| Classification | Class I |
| Predicate Devices | GenePOC GBS LB Assay K170557 |
Intended Use
Simplexa™ GBS Direct
The DiaSorin Molecular Simplexa™ GBS Direct assay is a real-time polymerase chain reaction (PCR) assay intended for use on the LIAISON® MDX instrument for the in vitro qualitative detection of Group B Streptococcus (GBS) nucleic acid from 18 to 24 hour Lim broth enrichments of vaginal/rectal specimen swabs obtained from antepartum women. Assay results can aid in determining the colonization status of antepartum women, but are not intended to diagnose or monitor treatment of a GBS infection.
The Simplexa™ GBS Direct assay does not provide susceptibility results. Culture isolates are needed to perform susceptibility testing as recommended for penicillin-allergic women.
Simplexa™ GBS Positive Control Pack
The Simplexa™ GBS Positive Control Pack is intended to be used as a control with the Simplexa™ GBS Direct kit. This control is not intended for use with other assays or systems.
Device Description
The Simplexa™ GBS Direct assay system is a real-time PCR system that enables the direct amplification and qualitative detection of Group B Strep bacterial DNA from vaginal swabs enriched in Lim Broth for eighteen to twenty-four (18 to 24) hours that have not undergone a nucleic acid extraction. The system consists of the Simplexa™ GBS Direct assay, the LIAISON® MDX (with LIAISON® MDX Studio Software), the Direct Amplification Disc (DAD) and associated accessories.
In the Simplexa™ GBS Direct assay, primers and fluorescent probes are used together to amplify Group B Streptococcus bacterial DNA and the Internal Control (DNA IC). The assay targets a conserved region of the cfb gene to identify Group B Streptococus in the specimen. The DNA IC is used to detect PCR failure and/or inhibition.
| Component Name | REF | EC SYMBOLON LABEL | AbbreviatedName | CapColor | Number ofVials | ReactionsperVial/Kit | Volumeper Vial |
|---|---|---|---|---|---|---|---|
| Simplexa™ GBSDirectReaction Mix | MOL3551 | REAGC | RM | Orange | 24 | 1/24 | 50 μL |
Kit Description
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Image /page/4/Picture/0 description: The image contains the logo for DiaSorin Molecular. The logo features a stylized DNA double helix in shades of green and blue on the left. To the right of the helix are the words "DiaSorin" in a dark blue, sans-serif font, stacked above the word "Molecular" in a lighter green, sans-serif font.
510(k) Summary
Simplexa™ GBS Direct Catalog No. MOL3550 Simplexa™ GBS Positive Control Pack Catalog No. MOL3560 October 25, 2018 Page 2 of 19
Component Description
| Kit Component | Contents | ||||
|---|---|---|---|---|---|
| Simplexa™ GBSDirect ReactionMix (RM) | DNA polymerase, buffers, dNTPs, Internal Control DNA Template, dye-labeled fluorescentprimers and probes specific for detection of Group B Strep and for the DNA Internal Control | ||||
| Target | ProbeFluorophore(Dye) | Excitation | Emission | Targeted Gene | |
| GBS | CFR610 | 590 | 610 | cfb | |
| InternalControlDNA (IC) | Q670 | 644 | 670 | NA | |
| Simplexa™ GBSDirect BarcodeCard | Assay specific parameters, lot number, expiration date. |
MATERIALS SUPPLIED SEPARATELY
Direct Amplification Disc Kit (REF) MOL1455) Direct Amplification Discs for use on the LIAISON® MDX
Predicate Device Information
| Similarities | ||
|---|---|---|
| Comparison toPredicate Device | Predicate Device:GenePOC GBS LB Assay K170557 | Candidate Device:Simplexa™ GBS Direct andSimplexa™ GBS Positive Control Pack |
| Product Code | NJR and OOI21 CFR 866.3740 - Streptococcal spp.serological reagents21 CFR 862.2570 - Instrumentation forclinical multiplex test systems | Same |
| OrganismDetected | Group B Streptococcus | Same |
| Measurand | Target DNA sequence in cfb gene ofStreptococcus agalactiae (Group BStreptococcus, GBS) | Conserved region of the cfb gene ofStreptococcus agalactiae (Group BStreptococcus, GBS) |
| Intended Use | The GenePOC GBS LB assayperformed on the revogene instrumentis a qualitative in vitro diagnostic testdesigned to detect Group BStreptococcus (GBS) DNA from 18-24hour LIM broth enrichments ofvaginal/rectal specimen swabs | The DiaSorin Molecular Simplexa™ GBSDirect assay is a real-time polymerasechain reaction (PCR) assay intended foruse on the LIAISON® MDX instrumentfor the in vitro qualitative detection ofGroup B Streptococcus (GBS) nucleicacid from 18 to 24 hour Lim broth |
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Image /page/5/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo consists of a stylized DNA double helix in shades of green on the left. To the right of the DNA helix are the words "DiaSorin" in dark blue on the top line and "Molecular" in light green on the bottom line.
510(k) Summary
Simplexa™ GBS Direct Catalog No. MOL3550 Simplexa™ GBS Positive Control Pack Catalog No. MOL3560 October 25, 2018 Page 3 of 19
| Similarities | ||
|---|---|---|
| Comparison toPredicate Device | Predicate Device:GenePOC GBS LB Assay K170557 | Candidate Device:Simplexa™ GBS Direct andSimplexa™ GBS Positive Control Pack |
| obtained from pregnant women. TheGenePOC GBS LB assay utilizesautomated sample processing andreal-time polymerase chain reaction(PCR) to detect a cfb gene sequencespecific to the Streptococcusagalactiae genome. The GenePOCGBS LB assay is indicated for theidentification of antepartum GBScolonization and does not providesusceptibility results. It is not intendedto diagnose or monitor treatment ofGBS infection. Culture isolates areneeded for performing susceptibilitytesting as recommended for penicillin-allergic women. | enrichments of vaginal/rectal specimenswabs obtained from antepartumwomen. Assay results can be used as anaid in determining the colonization statusof antepartum women, but are notintended to diagnose or monitortreatment of a GBS infection.The Simplexa™ GBS Direct assay doesnot provide susceptibility results. Cultureisolates are needed to performsusceptibility testing as recommended forpenicillin-allergic women.Simplexa™ GBS Positive Control PackThe Simplexa™ GBS Positive ControlPack is intended to be used as a controlwith the Simplexa™ GBS Direct kit.This control is not intended for use withother assays or systems. | |
| AutomatedSystem (Sampleto Answer) | Yes | Yes |
| Differences | ||
|---|---|---|
| Comparison toPredicateDevice | GenePOC GBS LB Assay K170557 | Simplexa™ GBS Direct andSimplexa™ GBS Positive ControlPack |
| Instrumentation | Revogene instrument | LIAISON® MDX |
| Single Use | Yes Cartridge (PIE) can be used once. | No. Consumable disc can be used untilall eight (8) wedges have been used. |
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Image /page/6/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo consists of a stylized DNA double helix in shades of green and blue on the left. To the right of the helix are the words "DiaSorin" in dark blue on the top line and "Molecular" in green on the bottom line. The text is aligned to the right of the DNA helix.
510(k) Summary
Simplexa™ GBS Direct Catalog No. MOL3550 Simplexa™ GBS Positive Control Pack Catalog No. MOL3560 October 25, 2018 Page 4 of 19
CLINICAL PERFORMANCE
The performance of the Simplexa™ GBS Direct assay was evaluated in a prospective study that was conducted with residual de-identified Lim broth enrichment cultures of vaginal/rectal swabs obtained from pregnant women at thirty-five to thirty-seven (35-37) weeks of gestation. The specimens were collected and enriched according to established CDC guidelines. Lim Broth cultures were incubated for eighteen to twenty-four (18-24) hours at 35-37 °C. Four hundred and thirty-two (432) samples that met the prescribed inclusion criteria were used to evaluate the performance of the Simplexa™ GBS Direct assay in comparison to those obtained with a GBS culture reference method. All samples were tested fresh upon completion of the enrichment process. Aliquots were made from each freshly enriched Lim Broth sample; the first aliquot was held at 2-8 °C and tested on the Simplexa™ GBS Direct at the collection site, and the second aliquot was kept at 2-8 °C and sent on cold packs to a central laboratory for GBS culture.
For the GBS culture reference method, enriched Lim Broth samples were sub-cultured to selective and non-selective blood agar for twenty-four (24) hours. If GBS was not observed, the plates were reincubated for an additional twenty-four (24) hours and deemed negative if GBS was not identified. Colonies with an appearance that was suggestive of GBS were further processed to confirm the presence of GBS using general laboratory methods, which included: gram stain, catalase testing, and latex agglutination.
The testing of samples with Lim broth incubation periods per CDC guidelines included eighty-four (84) total runs with thirty-one (31) control pairs, all of which produced the expected positive/negative results. The invalid rate of the clinical prospective study samples with Lim broth incubation periods per CDC guidelines was 0.0%, zero out of four hundred and thirty-two (0/432). The results of the study are shown in Table 1.
| Simplexa™™ GBSDirect Results | Culture Comparator Method | ||
|---|---|---|---|
| Detected | Not Detected | Total | |
| Detected | 97 | 13b | 110 |
| Not Detected | 3a | 319 | 322 |
| Total | 100 | 332 | 432 |
| Sensitivity97.0%(97/100)95% CI: 91.5% to 99.0% | Specificity96.1%(319/332)95% CI: 93.4% to 97.7% |
Table 1. Clinical Agreement Summary Results - Prospective Clinical Agreement Results Simplexa™ GBS Direct vs. Culture
ª 3/3 samples with discrepant results were negative when tested with an alternate FDA cleared NAAT.
b 11/13 samples with discrepant results were positive when tested with an alternate FDA cleared NAAT.
REPRODUCIBILITY
Three (3) investigative sites assessed the device's inter-day and inter/intra-assay reproducibility. Each of the laboratories tested Simplexa™ GBS Direct Positive Control, No Template Control (Lim Broth), and four (4) contrived samples in negative matrix. Two (2) strains of GBS were used in the study, BAA-22 and BAA-1138. The four (4) contrived samples consisted of a low positive (LP) at approximately 1.5 x LoD and a medium positive (MP) at approximately 3.5 x LoD for each GBS strain. The assays were performed in triplicate on five (5) different days. Each site had two (2) operators who each assayed the entire sample panel and Positive Control once per day, for a total of two (2) sets of data per day on a total of six (6) LIAISON® MDX instruments. The combined results for all sites are presented in Tables 2 and 3.
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Image /page/7/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo consists of a stylized DNA double helix in shades of green and blue on the left. To the right of the helix are the words "DiaSorin" in a bold, dark blue font, with the word "Molecular" underneath in a lighter green font. The logo is clean and modern, suggesting a company involved in molecular diagnostics or biotechnology.
510(k) Summary
Simplexa™ GBS Direct Catalog No. MOL3550 Simplexa™ GBS Positive Control Pack Catalog No. MOL3560 October 25, 2018 Page 5 of 19
| GBS(FAM) | Site 1 | Site 2 | Site 4 | Total %AgreementwithExpectedResults | 95% CI | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| %AgreementwithExpectedResults | AvgCt | Total%CV | %AgreementwithExpectedResults | AvgCt | Total%CV | %AgreementwithExpectedResults | AvgCt | Total%CV | |||
| BAA-22 -LP | 100.0%(30/30) | 33.2 | 1.2 | 100.0%(30/30) | 33.7 | 1.7 | 100.0%(30/30) | 32.1 | 0.9 | 100.0%(90/90) | 95.9% to100.0% |
| BAA-22 -MP | 100.0%(30/30) | 32.6 | 1.1 | 100.0%(30/30) | 31.6 | 1.3 | 100.0%(30/30) | 31.9 | 1.1 | 100.0%(90/90) | 95.9% to100.0% |
| BAA-1138 -LP | 100.0%(30/30) | 34.1 | 1.6 | 93.3%(28/30) | 34.6 | 3.1 | 100.0%(30/30) | 33.1 | 2.3 | 97.8%(88/90) | 92.3% to99.4% |
| BAA-1138 -MP | 100.0%(30/30) | 32.7 | 1.2 | 100.0%(30/30) | 33.1 | 1.4 | 100.0%(30/30) | 31.9 | 1.5 | 100.0%(90/90) | 95.9% to100.0% |
| PC | 100.0%(30/30) | 30.2 | 0.6 | 100.0%(30/30) | 28.7 | 0.7 | 100.0%(30/30) | 29.1 | 0.7 | 100.0%(90/90) | 95.9% to100.0% |
| NTC | 100.0%(30/30) | NA | NA | 100.0%(30/30) | NA | NA | 100.0%(30/30) | NA | NA | 100.0%(90/90) | 95.9% to100.0% |
| TotalAgreement | 100.0% (180/180)95% Cl: 97.9% to 100.0% | 98.9% (178/180)95% Cl: 96.0% to 99.7% | 100.0% (180/180)95% CI: 97.9% to 100.0% | 99.6% (538/540)95% Cl: 98.7% to 99.9% |
Table 2. Simplexa™ GBS Direct Reproducibility (FAM)
Table 3. Simplexa™ GBS Direct Internal Control Reproducibility (Q670)
| Site 1 | Site 2 | Site 4 | Total % | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| SampleDNA IC(Q670) | %AgreementwithExpectedResults | AvgCt | Total%CV | %AgreementwithExpectedResults | AvgCt | Total%CV | %AgreementwithExpectedResults | AvgCt | Total%CV | AgreementwithExpectedResults | 95% Cl |
| BAA-22 -LP | 100.0%(30/30) | 31.1 | 0.9 | 100.0%(30/30) | 31.1 | 0.7 | 100.0%(30/30) | 29.8 | 0.6 | 100.0%(90/90) | 95.9% to100.0% |
| BAA-22 -MP | 100.0%(30/30) | 31.0 | 0.4 | 100.0%(30/30) | 30.3 | 0.6 | 100.0%(30/30) | 30.6 | 0.7 | 100.0%(90/90) | 95.9% to100.0% |
| BAA-1138 -LP | 100.0%(30/30) | 31.0 | 0.8 | 100.0%(30/30) | 31.1 | 0.4 | 100.0%(30/30) | 29.9 | 1.6 | 100.0%(90/90) | 95.9% to100.0% |
| BAA-1138 -MP | 100.0%(30/30) | 31.0 | 0.7 | 100.0%(30/30) | 31.1 | 0.5 | 100.0%(30/30) | 29.8 | 0.7 | 100.0%(90/90) | 95.9% to100.0% |
| РС | 100.0%(30/30) | 30.9 | 0.7 | 100.0%(30/30) | 30.2 | 0.4 | 100.0%(30/30) | 30.4 | 0.6 | 100.0%(90/90) | 95.9% to100.0% |
| NTC | 100.0%(30/30) | 31.0 | 0.5 | 100.0%(30/30) | 31.1 | 0.5 | 100.0%(30/30) | 30.0 | 0.9 | 100.0%(90/90) | 95.9% to100.0% |
| TotalAgreement | 100.0% (180/180)95% Cl: 97.9% to 100.0% | 100.0% (180/180)95% Cl: 97.9% to 100.0% | 100.0% (180/180)95% Cl: 97.9% to 100.0% | 100.0% (540/540)95% Cl: 99.3% to100.0% |
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Image /page/8/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo features a stylized DNA helix in shades of green and blue on the left. To the right of the helix, the word "DiaSorin" is written in a bold, dark blue font. Below "DiaSorin", the word "Molecular" is written in a lighter green font.
510(k) Summary
Simplexa™ GBS Direct Catalog No. MOL3550 Simplexa™ GBS Positive Control Pack Catalog No. MOL3560 October 25, 2018 Page 6 of 19
ANALYTICAL SENSITIVITY/LIMIT OF DETECTION
The Limit of Detection (LoD) was determined for the Simplexa™ GBS Direct assay using quantified stocks of two (2) GBS strains (BAA-22 and BAA-1138) serially diluted into negative eighteen to twentyfour (18 to 24) hour Lim broth enrichments of vaginal/rectal specimen swabs obtained from antepartum women. The LoD was determined to be the lowest concentration that could be detected positive ≥ 95% of the time. The results are shown in Table 4.
Table 4. Simplexa™ GBS Direct Summary of Limit of Detection (LoD)
| GBS strain | LoD Concentration (CFU/mL) |
|---|---|
| ATCC BAA-22(serotype III) | 80,000 |
| ATCC BAA-1138(serotype la) | 30,000 |
ANALYTICAL REACTIVITY/CROSS REACTIVITY
Analytical Reactivity
The Simplexa™ GBS Direct assay was evaluated for analytical reactivity to an additional eighteen (18) GBS strains spiked at 2 x LoD into eighteen to twenty-four (18 to 24) Lim broth enrichments of vaginal/rectal specimen swabs obtained from antepartum women. The results are shown in Table 5. All eighteen (18) strains were detected.
| No. | Group BStreptococcus Strain | Serotype | ConcentrationCFU/mL(2 x LoD) | SimplexaTM GBSDirect %Detection# Detected / # Tested |
|---|---|---|---|---|
| 1 | ATCC BAA-1177 | Ia | 110,000 | 100% (3/3) |
| 2 | ATCC 51487 | Ib | 110,000 | 100% (3/3) |
| 3 | ATCC 27591 | Ic | 110,000 | 100% (3/3) |
| 4 | ATCC 12973 | II | 110,000 | 100% (3/3) |
| 5 | ATCC BAA-2675 | II | 110,000 | 100% (3/3) |
| 6 | ATCC BAA-1176 | III | 110,000 | 100% (3/3) |
| 7 | ATCC BAA-2674 | III | 110,000 | 100% (3/3) |
| 8 | ATCC 12403 | III | 110,000 | 100% (3/3) |
| 9 | ATCC 49446 | IV | 110,000 | 100% (3/3) |
| 10 | ATCC BAA-2673 | IV | 110,000 | 100% (3/3) |
| 11 | ATCC BAA-2672 | V | 110,000 | 100% (3/3) |
| 12 | ATCC BAA-611 | V | 110,000 | 100% (3/3) |
| 13 | ATCC BAA-2671 | VI | 110,000 | 100% (3/3) |
| 14 | ATCC BAA-2670 | VII | 110,000 | 100% (3/3) |
| 15 | ATCC BAA-2669 | VIII | 110,000 | 100% (3/3) |
Table 5. Simplexa™ GBS Direct Analytical Reactivity
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510(k) Summary
Simplexa™ GBS Direct Catalog No. MOL3550 Simplexa™ GBS Positive Control Pack Catalog No. MOL3560 October 25, 2018 Page 7 of 19
| No. | Group BStreptococcus Strain | Serotype | ConcentrationCFU/mL(2 x LoD) | Simplexa™ GBSDirect %Detection# Detected / # Tested |
|---|---|---|---|---|
| 16 | ATCC BAA-2668 | IX 1 | 110,000 | 100% (3/3) |
| 17 | ATCC 13813 | Non-Hemolytic | 110,000 | 100% (3/3) |
| 18 | ATCC BAA-2666 | Non-Hemolytic | 110,000 | 100% (3/3) |
Cross Reactivity (Analytical Specificity)
The Simplexa™ GBS Direct assay's analytical specificity was evaluated by testing the ability of the assay to exclusively identify GBS without any cross-reactivity to organisms that are closely related, or cause similar clinical symptoms or may be present in eighteen to twenty-four (18 to 24) hour Lim broth enrichments of vaginal/rectal specimen swabs obtained from antepartum women. Seventy-four (74) potential cross-reacting organisms were spiked into GBS negative enriched Lim broth and tested in triplicate. Four (4) organisms with low concentration stocks were additionally tested in silico. No cross reactivity was observed demonstrating the specificity of the Simplexa™ GBS Direct assay. The results are presented in Table 7.
| No. | Cross Reactant | Tested Concentration | Expected Negative Results% Detection(# Detected/ # Tested) |
|---|---|---|---|
| 1 | Acinetobacter baumannii | 1 x 106 CFU/mL | 0% (0/3) |
| 2 | Actinomyces israelii | 1 x 106 CFU/mL | 0% (0/3) |
| 3 | Aerococcus viridans | 1 x 106 CFU/mL | 0% (0/3) |
| 4 | Aeromonas hydrophila | 1 x 106 CFU/mL | 0% (0/3) |
| 5 | Atopobium vaginae | 1 x 106 CFU/mL | 0% (0/3) |
| 6 | Bacillus cereus | 1 x 106 CFU/mL | 0% (0/3) |
| 7 | Bacteroides fragilis | 1 x 106 CFU/mL | 0% (0/3) |
| 8 | Bifidobacterium adolescentis | 1 x 106 CFU/mL | 0% (0/3) |
| 9 | Bifidobacterium breve | 1 x 106 CFU/mL | 0% (0/3) |
| 10 | Blastocystis hominis | 1 x 106 cells/mL | 0% (0/3) |
| 11 | Brevibacterium linens | 1 x 106 CFU/mL | 0% (0/3) |
| 12 | Campylobacter jejuni | 1 x 106 CFU/mL | 0% (0/3) |
| 13 | Candida albicans | 1 x 106 CFU/mL | 0% (0/3) |
| 14 | Candida glabrata | 1 x 106 CFU/mL | 0% (0/3) |
| 15 | Candida parapsilosis | 1 x 106 CFU/mL | 0% (0/3) |
| 16 | Candida tropicalis | 1 x 106 CFU/mL | 0% (0/3) |
| 17 | Chlamydia trachomatis | 1 x 106 IFU/mL | 0% (0/3) |
| 18 | Chromobacterium violaceum | 1 x 106 CFU/mL | 0% (0/3) |
| 19 | Clostridium difficile | 1 x 106 CFU/mL | 0% (0/3) |
| 20 | Clostridium perfringens | 1 x 106 CFU/mL | 0% (0/3) |
| No. | Cross Reactant | Tested Concentration | Expected Negative Results% Detection(# Detected/ # Tested) |
| 21 | Corynebacterium genitalium | 1 x 106 CFU/mL | 0% (0/3) |
| 22 | Cryptococcus neoformans | 1 x 106 CFU/mL | 0% (0/3) |
| 23 | Enterobacter cloacae | 1 x 106 CFU/mL | 0% (0/3) |
| 24 | Enterococcus avium | 1 x 106 CFU/mL | 0% (0/3) |
| 25 | Enterococcus faecalis | 1 x 106 CFU/mL | 0% (0/3) |
| 26 | Enterococcus faecium | 1 x 106 CFU/mL | 0% (0/3) |
| 27 | Escherichia coli | 1 x 106 CFU/mL | 0% (0/3) |
| 28 | Fusobacterium nucleatum | 1 x 106 CFU/mL | 0% (0/3) |
| 29 | Gardnerella vaginalis* | NA | NA |
| 30 | Giardia lamblia | 1 x 106 cells/mL | 0% (0/3) |
| 31 | HSV-1 | 1 x 105 TCID50/mL | 0% (0/3) |
| 32 | HSV-2 | 1 x 105 TCID50/mL | 0% (0/3) |
| 33 | HIV-1 | 5 x 104 TCID50/mL * | 0% (0/3) |
| 34 | HPV Genotype 18 | 1 x 105 IU/mL | 0% (0/3) |
| 35 | White Blood Cells (Human genomicDNA) | 1 x 106 cells/mL | 0% (0/3) |
| 36 | Human rotavirus | 1 x 104 TCID50/mL * | 0% (0/3) |
| 37 | Klebsiella oxytoca | 1 x 106 CFU/mL | 0% (0/3) |
| 38 | Klebsiella pneumoniae | 1 x 106 CFU/mL | 0% (0/3) |
| 39 | Lactobacillus acidophilus | 1 x 106 CFU/mL | 0% (0/3) |
| 40 | Lactobacillus crispatus | 1 x 106 CFU/mL | 0% (0/3) |
| 41 | Lactobacillus delbrueckii subsp. lactis | 1 x 106 CFU/mL | 0% (0/3) |
| 42 | Lactobacillus iners | 1 x 106 CFU/mL | 0% (0/3) |
| 43 | Lactobacillus jensensii | 1 x 106 CFU/mL | 0% (0/3) |
| 44 | Mobiluncus curtisii | 1 x 106 CFU/mL | 0% (0/3) |
| 45 | Mobiluncus mulieris | 1 x 106 CFU/mL | 0% (0/3) |
| 46 | Mycoplasma genitalium | 5 x 105 CCU/mL* | 0% (0/5)** |
| 47 | Mycoplasma hominis | 1 x 106 CCU/mL | 0% (0/3) |
| 48 | Norovirus Genogroup GI* | NA | NA |
| 49 | Norovirus Genogroup GII* | NA | NA |
| 50 | Neisseria gonorrhoeae | 1 x 106 CFU/mL | 0% (0/3) |
| 51 | Peptostreptococcus anaerobius | 1 x 106 CFU/mL | 0% (0/3) |
| 52 | Porphyromonas asaccharolytica | 1 x 106 CFU/mL | 0% (0/3) |
| 53 | Prevotella melaninogenica | 1 x 106 CFU/mL | 0% (0/3) |
| No. | Cross Reactant | Tested Concentration | Expected Negative Results% Detection(# Detected/ # Tested) |
| 54 | Propionibacterium acnes | 1 x 106 CFU/mL | 0% (0/3) |
| 55 | Proteus mirabilis | 1 x 106 CFU/mL | 0% (0/3) |
| 56 | Pseudomonas aeruginosa | 1 x 106 CFU/mL | 0% (0/3) |
| 57 | Salmonella enterica subsp enterica | 1 x 106 CFU/mL | 0% (0/3) |
| 58 | Serratia marcescens | 1 x 106 CFU/mL | 0% (0/3) |
| 59 | Shigella sonnei | 1 x 106 CFU/mL | 0% (0/3) |
| 60 | Staphylococcus aureus | 1 x 106 CFU/mL | 0% (0/3) |
| 61 | Staphylococcus epidermidis | 1 x 106 CFU/mL | 0% (0/3) |
| 62 | Staphylococcus saprophyticus | 1 x 106 CFU/mL | 0% (0/3) |
| 63 | Streptococcus anginosus | 1 x 106 CFU/mL | 0% (0/3) |
| 64 | Streptococcus bovis | 1 x 106 CFU/mL | 0% (0/3) |
| 65 | Streptococcus dysgalactiae | 1 x 106 CFU/mL | 0% (0/3) |
| 66 | Streptococcus intermedius | 1 x 106 CFU/mL | 0% (0/3) |
| 67 | Streptococcus mitis | 1 x 106 CFU/mL | 0% (0/3) |
| 68 | Streptococcus oralis | 1 x 106 CFU/mL | 0% (0/3) |
| 69 | Streptococcus pneumoniae | 1 x 106 CFU/mL | 0% (0/3) |
| 70 | Streptococcus pyogenes | 1 x 106 CFU/mL | 0% (0/3) |
| 71 | Streptococcus salivarius | 1 x 106 CFU/mL | 0% (0/3) |
| 72 | Streptococcus sanguinis | 1 x 106 CFU/mL | 0% (0/3) |
| 73 | Streptococcus suis | 1 x 106 CFU/mL | 0% (0/3) |
| 74 | Streptococcus uberis | 1 x 106 CFU/mL | 0% (0/3) |
| 75 | Trichomonas vaginalis* | NA | NA |
| 76 | Ureaplasma urealyticum | 1 x 106 CCU/mL | 0% (0/3) |
| 77 | VZV | 1 x 105 copies/mL | 0% (0/3) |
| 78 | Yersinia enterocolitica | 1 x 106 CFU/mL | 0% (0/3) |
Table 7. Simplexa™ GBS Direct Cross Reactivity (Analytical Specificity)
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510(k) Summary
Simplexa™ GBS Direct Catalog No. MOL3550 Simplexa™ GBS Positive Control Pack Catalog No. MOL3560 October 25, 2018 Page 8 of 19
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Image /page/11/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo features a stylized DNA helix in shades of green and blue on the left. To the right of the helix are the words "DiaSorin" in dark blue on the top line and "Molecular" in green on the bottom line. The text is clean and professional.
510(k) Summary
Simplexa™ GBS Direct Catalog No. MOL3550 Simplexa™ GBS Positive Control Pack Catalog No. MOL3560 October 25, 2018 Page 9 of 19
- Tested in silico and no potential for cross-reaction with the Simplexa™ GBS Direct primers and probe observed. ** Tested in quintuplicate due to assay set up error.
NA = not available
INTERFERENCE
The performance of the Simplexa™ GBS Direct assay was evaluated with twenty-six (26) potentially interfering endogenous and exogenous substances that may be present in eighteen to twenty-four (18 to 24) hour Lim broth enrichments of vaginal/rectal specimen swabs obtained from antepartum women. All samples were prepared by spiking each potentially interfering substance into a baseline consisting of either the ATCC BAA-1138 or ATCC BAA-22 strain of GBS at a concentration of 2 x LoD in eighteen to twenty-four (18 to 24) hour Lim broth enrichments of vaginal/rectal specimen swabs obtained from antepartum women. Each interferent was spiked into the baseline sample and tested at the concentrations listed in Table 8. The results are presented in Table 8. No interference was observed at the concentrations indicated in Table 8.
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Image /page/12/Picture/0 description: The image contains the logo for DiaSorin Molecular. The logo features a stylized DNA double helix in shades of green and blue on the left. To the right of the helix are the words "DiaSorin" in a dark blue, sans-serif font, stacked above the word "Molecular" in a lighter green, sans-serif font.
510(k) Summary
Simplexa™ GBS Direct Catalog No. MOL3550 Simplexa™ GBS Positive Control Pack Catalog No. MOL3560 October 25, 2018 Page 10 of 19
| Potentially Interfering Substance | Active Ingredient | Interferent Concentration | |
|---|---|---|---|
| 1 | Amniotic Fluid | NA | 10% v/v |
| 2 | Antacids (Gaviscon) | Aluminum Hydroxide /Magnesium Hydroxide | 5 % v/v* |
| 3 | Antacids/Gastritis Medication | Calcium Carbonate | 10 mg/mL |
| 4 | Anti-Diarrheal Medication(Imodium) | Loperamide Hydrochloride | 10% v/v |
| 5 | Anti-Diarrheal Medication (PeptoBismol) | Bismuth Subsalicylate | 10% v/v |
| 6 | Anti-Fungal /Anti-Itch Vaginal | Nystatin | 10 mg/mL** |
| 7 | Anti-HemorrhoidCreams/Ointments | Hydrocortisone | 10 mg/mL |
| 8 | Anti-HemorrhoidCreams/Ointments | Phenylephrine HCl | 10 mg/mL |
| 9 | Antimicrobials | Clotrimazole | 10% w/v |
| 10 | Fecal Fat | Palmitic Acid | 5 mg/mL* |
| 11 | Gastritis Medications (Nexium) | Esomeprazole Magnesium | 0.31 mg/mL* |
| 12 | Laxatives | Sennosides | 5 mg/mL* |
| 13 | Meconium | NA | 0.31% w/v * |
| 14 | Mesalazine enema | Mesalazine | 5 mg/mL* |
| 15 | Mineral Oil enema | Mineral Oil | 10% v/v |
| 16 | Moist Towelettes | Benzalkonium Chloride | 10% v/v |
| 17 | Moist Towelettes | Ethanol | 10% v/v |
| 18 | Mucus | Immunoglobulin, Lysozyme,Polymers | 10% v/v |
| 19 | Non-Steroidal Anti-InflammatoryMedications | Naproxen Sodium | 3 mg/mL* |
| 20 | Radiology Oral Compounds | Barium Sulfate | 5 mg/mL* |
| 21 | Seminal Fluid | NA | 5% v/v* |
| Potentially Interfering Substance | Active Ingredient | Interferent Concentration | |
| 22 | Spermicidal Lubricant | Nonoxynol-9 | 10 mg/mL |
| 23 | Stool | NA | 0.31% w/v* |
| 24 | Topical Products | Baby Powder | 10 mg/mL |
| 25 | Topical Products | KY Jelly | 10% w/v* |
| 26 | Whole Blood | Glucose, Hormones, Enzymes, Ions, Iron, etc. | 10% v/v |
Table 8. Simplexa™ GBS Direct Interference
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510(k) Summary
Simplexa™ GBS Direct Catalog No. MOL3550 Simplexa™ GBS Positive Control Pack Catalog No. MOL3560 October 25, 2018 Page 11 of 19
False negative and/or Invalid results were obtained at higher concentrations
On initial testing 1 sample produced an EC505 error due to insufficient information to determine whether amplification occurred; the retest result was acceptable
INHIBITION BY OTHER MICROORGANISMS
The Simplexa™ GBS Direct assay was evaluated by testing the ability to identify GBS when other potentially inhibitory organisms were present at high concentrations. The panel of seventy-four (74) potentially inhibitory organisms were individually spiked into a pool with a low concentration of GBS BAA-22 or BAA-1138 strains at approximately 2 x LoD in Lim broth enrichments eighteen to twenty-four (18 to 24) hour of vaginal/rectal specimen swabs obtained from antepartum women. No false negative results were observed with GBS BAA-22 in the presence of any of the potentially interfering organisms or viruses. However, with GBS BAA-1138, at least one false negative result was obtained in the presence of each of the following species: Bacillus cereus, Candida parapsilosis, Clostridium perfringens, Peptostreptococcus anaerobius, Staphylococcus saprophyticus, Streptococcus pyogenes and Ureaplasma urealyticum (Table 9). Additional in silico analysis demonstrated no potential for crossreaction or interference with the Simplexa™ GBS Direct primers and probe by Norovirus genogroups I and II or Trichomonas vaginalis.
| No. | Organism | GBS Strain | Tested Concentration | % Detection(# Detected/ # Tested) |
|---|---|---|---|---|
| 1 | Acinetobacter baumannii | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 2 | Actinomyces israelii | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 3 | Aerococcus viridans | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 4 | Aeromonas hydrophila | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| No. | Organism | GBS Strain | Tested Concentration | % Detection(# Detected/ # Tested) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 5 | Atopobium vaginae | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 6 | Bacillus cereus | BAA-1138 | 1 x 106 CFU/mL | 88.9 %(8/9) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 7 | Bacteroides fragilis | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 8 | Bifidobacterium adolescentis | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 9 | Bifidobacterium breve | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 10 | Blastocystis hominis | BAA-1138 | 1 x 106 cells/mL | 100% (3/3) |
| BAA-22 | 1 x 106 cells/mL | 100% (3/3) | ||
| 11 | Brevibacterium linens | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 12 | Campylobacter jejuni | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 13 | Candida albicans | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 14 | Candida glabrata | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 15 | Candida parapsilosis | BAA-1138 | 1 x 106 CFU/mL | 77.8% (7/9) |
| No. | Organism | GBS Strain | Tested Concentration | % Detection(# Detected/ # Tested) |
| 16 | Candida tropicalis | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 17 | Chlamydia trachomatis | BAA-1138 | 1 x 106 IFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 IFU/mL | 100% (3/3) | ||
| 18 | Chromobacterium violaceum | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 19 | Clostridium difficile | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 20 | Clostridium perfringens | BAA-1138 | 1 x 106 CFU/mL | 88.9% (8/9) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 21 | Corynebacterium genitalium | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 22 | Cryptococcus neoformans | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 23 | Enterobacter cloacae | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 24 | Enterococcus avium | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 25 | Enterococcus faecalis | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 26 | Enterococcus faecium | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| No. | Organism | GBS Strain | Tested Concentration | % Detection(# Detected/ # Tested) |
| 27 | Escherichia coli | BAA-22 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 28 | Fusobacterium nucleatum | BAA-22 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 29 | Giardia lamblia | BAA-22 | 1 x 106 cells/mL | 100% (3/3) |
| BAA-1138 | 1 x 106 cells/mL | 100% (3/3) | ||
| 30 | HIV-1 | BAA-22 | 5 x 104 TCID50/mL | 100% (3/3) |
| BAA-1138 | 5 x 104 TCID50/mL | 100% (3/3) | ||
| 31 | HPV Genotype 18 | BAA-22 | 1 x 105 IU/mL | 100% (3/3) |
| BAA-1138 | 1 x 105 IU/mL | 100% (3/3) | ||
| 32 | HSV-1 | BAA-22 | 1 x 105 TCID50/mL | 100% (3/3) |
| BAA-1138 | 1 x 105 TCID50/mL | 100% (3/3) | ||
| 33 | HSV-2 | BAA-22 | 1 x 105 TCID50/mL | 100% (3/3) |
| BAA-1138 | 1 x 105 TCID50/mL | 100% (3/3) | ||
| 34 | Human DNA (White BloodCells) | BAA-22 | 1 x 106 WBC/mL | 100% (3/3) |
| BAA-1138 | 1 x 106 WBC/mL | 100% (3/3) | ||
| 35 | Human rotavirus | BAA-22 | 1 x 104 TCID50/mL | 100% (3/3) |
| BAA-1138 | 1 x 104 TCID50/mL | 100% (3/3) | ||
| 36 | Klebsiella oxytoca | BAA-22 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) | ||
| No. | Organism | GBS Strain | Tested Concentration | % Detection(# Detected/ # Tested) |
| 37 | Klebsiella pneumoniae | BAA-1138 | $1 x 10^6$ CFU/mL | 100% (3/3) |
| BAA-22 | $1 x 10^6$ CFU/mL | 100% (3/3) | ||
| 38 | Lactobacillus acidophilus | BAA-1138 | $1 x 10^6$ CFU/mL | 100% (3/3) |
| BAA-22 | $1 x 10^6$ CFU/mL | 100% (3/3) | ||
| 39 | Lactobacillus crispatus | BAA-1138 | $1 x 10^6$ CFU/mL | 100% (3/3) |
| BAA-22 | $1 x 10^6$ CFU/mL | 100% (3/3) | ||
| 40 | Lactobacillus delbrueckiisubsp. lactis | BAA-1138 | $1 x 10^6$ CFU/mL | 100% (3/3) |
| BAA-22 | $1 x 10^6$ CFU/mL | 100% (3/3) | ||
| 41 | Lactobacillus iners | BAA-1138 | $1 x 10^6$ CFU/mL | 100% (3/3) |
| BAA-22 | $1 x 10^6$ CFU/mL | 100% (3/3) | ||
| 42 | Lactobacillus jensensii | BAA-1138 | $1 x 10^6$ CFU/mL | 100% (3/3) |
| BAA-22 | $1 x 10^6$ CFU/mL | 100% (3/3) | ||
| 43 | Mobiluncus curtisii | BAA-1138 | $1 x 10^6$ CFU/mL | 100% (3/3) |
| BAA-22 | $1 x 10^6$ CFU/mL | 100% (3/3) | ||
| 44 | Mobiluncus mulieris | BAA-1138 | $1 x 10^6$ CFU/mL | 100% (3/3) |
| BAA-22 | $1 x 10^6$ CFU/mL | 100% (3/3) | ||
| 45 | Mycoplasma genitalium | BAA-1138 | $5 x 10^5$ CCU/mL | 100% (3/3) |
| BAA-22 | $5 x 10^5$ CCU/mL | 100% (3/3) | ||
| 46 | Mycoplasma hominis | BAA-1138 | $1 x 10^6$ CCU/mL | 100% (3/3) |
| BAA-22 | $1 x 10^6$ CCU/mL | 100% (3/3) | ||
| 47 | Neisseria gonorrhoeae | BAA-1138 | $1 x 10^6$ CFU/mL | 100% (3/3) |
| BAA-22 | $1 x 10^6$ CFU/mL | 100% (3/3) | ||
| No. | Organism | GBS Strain | Tested Concentration | % Detection(# Detected/ # Tested) |
| 48 | Norovirus genogroup I* | NA | NA | NA |
| 49 | Norovirus genogroup II* | NA | NA | NA |
| 50 | Peptostreptococcusanaerobius | BAA-1138 | 1 x 106 CFU/mL | 88.9% (8/9) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 51 | Porphyromonasasaccharolytica | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 52 | Prevotella melaninogenica | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 53 | Propionibacterium acnes | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 54 | Proteus mirabilis | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 55 | Pseudomonas aeruginosa | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 56 | Salmonella enterica subspenterica | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 57 | Serratia marcescens | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 58 | Shigella sonnei | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 59 | Staphylococcus aureus | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| No. | Organism | GBS Strain | Tested Concentration | % Detection(# Detected/ # Tested) |
| 60 | Staphylococcus epidermidis | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 61 | Staphylococcus saprophyticus | BAA-1138 | 1 x 106 CFU/mL | 77.8% (7/9) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 62 | Streptococcus anginosus | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 63 | Streptococcus bovis | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 64 | Streptococcus dysgalactiae | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 65 | Streptococcus intermedius | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 66 | Streptococcus mitis | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 67 | Streptococcus oralis | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 68 | Streptococcus pneumoniae | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 69 | Streptococcus pyogenes | BAA-1138 | 1 x 106 CFU/mL | 88.9% (8/9) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 70 | Streptococcus salivarius** | BAA-1138 | 1 x 106 CFU/mL | 100% (6/6) |
| BAA-22 | 1 x 106 CFU/mL | 100% (6/6) | ||
| No. | Organism | GBS Strain | Tested Concentration | % Detection(# Detected/ # Tested) |
| 71 | Streptococcus sanguinis | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 72 | Streptococcus suis | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 73 | Streptococcus uberis | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) | ||
| 74 | Trichomonas vaginalis* | NA | NA | NA |
| 75 | Ureaplasma urealyticum | BAA-1138 | 1 x 106 CCU/mL | 77.8% (7/9) |
| BAA-22 | 1 x 106 CCU/mL | 100% (3/3) | ||
| 76 | VZV | BAA-1138 | 1 x 105 copies/mL | 100% (3/3) |
| BAA-22 | 1 x 105 copies/mL | 100% (3/3) | ||
| 77 | Yersinia enterocolitica | BAA-1138 | 1 x 106 CFU/mL | 100% (3/3) |
| BAA-22 | 1 x 106 CFU/mL | 100% (3/3) |
Table 9. Simplexa™ GBS Direct Microbial Inhibition
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Image /page/14/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo features a stylized DNA double helix in shades of green and blue on the left. To the right of the helix, the word "DiaSorin" is written in dark blue, and below that, the word "Molecular" is written in light green.
510(k) Summary
Simplexa™ GBS Direct Catalog No. MOL3550 Simplexa™ GBS Positive Control Pack Catalog No. MOL3560 October 25, 2018 Page 12 of 19
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510(k) Summary
Simplexa™ GBS Direct Catalog No. MOL3550 Simplexa™ GBS Positive Control Pack Catalog No. MOL3560 October 25, 2018 Page 13 of 19
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510(k) Summary
Simplexa™ GBS Direct Catalog No. MOL3550 Simplexa™ GBS Positive Control Pack Catalog No. MOL3560 October 25, 2018 Page 14 of 19
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Image /page/17/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo features a stylized DNA double helix in shades of green and blue on the left. To the right of the helix, the word "DiaSorin" is written in dark blue, and below that, the word "Molecular" is written in light green.
510(k) Summary
Simplexa™ GBS Direct Catalog No. MOL3550 Simplexa™ GBS Positive Control Pack Catalog No. MOL3560 October 25, 2018 Page 15 of 19
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510(k) Summary
Simplexa™ GBS Direct Catalog No. MOL3550 Simplexa™ GBS Positive Control Pack Catalog No. MOL3560 October 25, 2018 Page 16 of 19
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Image /page/19/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo consists of a stylized DNA double helix in shades of green and blue on the left. To the right of the helix are the words "DiaSorin" in dark blue on the top line and "Molecular" in light green on the bottom line.
510(k) Summary
Simplexa™ GBS Direct Catalog No. MOL3550 Simplexa™ GBS Positive Control Pack Catalog No. MOL3560 October 25, 2018 Page 17 of 19
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Image /page/20/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo consists of a stylized DNA double helix in shades of green and blue on the left. To the right of the helix are the words "DiaSorin" in dark blue, with the word "Molecular" underneath in a lighter green color. The logo is clean and modern, suggesting a company involved in molecular diagnostics or biotechnology.
510(k) Summary
Simplexa™ GBS Direct Catalog No. MOL3550 Simplexa™ GBS Positive Control Pack Catalog No. MOL3560 October 25, 2018 Page 18 of 19
- Tested in silico and no potential for cross-reaction or interference with the Simplexa™ GBS Direct primers and probe observed
** Streptococcus salivarius was inadvertently tested twice.
NA = not available
CARRY-OVER CONTAMINATION
Amplification carry-over for the Simplexa™ assays has been assessed. The study was performed by testing alternating high positive and negative samples on each disc. No evidence of carry-over contamination was observed.
EXPECTED VALUES
The prevalence of GBS as determined by the Simplexa™ GBS Direct assay in a multi-site clinical study with prospectively collected specimens is shown in Table 10.
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Image /page/21/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo features a stylized DNA helix in shades of green and blue on the left. To the right of the helix are the words "DiaSorin" in dark blue on the top line and "Molecular" in light green on the bottom line.
510(k) Summary Simplexa™ GBS Direct Catalog No. MOL3550 Simplexa™ GBS Positive Control Pack Catalog No. MOL3560 October 25, 2018 Page 19 of 19
| Site ID | Total | Simplexa™ GBS DirectPositive | GBS Prevalence |
|---|---|---|---|
| 01 | 168 | 49 | 29.2% |
| 05 | 208 | 44 | 21.2% |
| 06 | 56 | 17 | 30.4% |
| All | 432 | 110 | 25.5% |
Table 10. Expected Values per Site
The expected values for GBS per site varied between 21.2% and 30.4%. The overall prevalence for all sites was 25.5% one hundred and ten of four hundred and thirty-two (110/432) by the Simplexa™ GBS Direct assay and 23.1% one hundred of four hundred and thirty-two (100/432) as determined by a culture reference method.
CONCLUSION
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
§ 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.