(81 days)
The BD ProbeTec™ Herpes Simplex Viruses (HSV 1 & 2) Q* Amplified DNA Assays, when tested with the BD Viper™ System in Extracted Mode, use Strand Displacement Amplification technology for the direct, qualitative detection and differentiation of Herpes Simplex virus type 1 (HSV1) and Herpes Simplex virus type 2 (HSV2) DNA in clinician-collected external anogenital lesion specimens. The assays are indicated for use with symptomatic individuals to aid in the diagnosis of anogenital HSV1 and HSV2 infections.
Warning: The BD ProbeTec™ Herpes Simplex Viruses (HSV 1 & 2) Q* Amplified DNA Assays (HSV Q* Assays) are not FDA cleared for use with cerebrospinal fluid (CSF). The assays are not intended to be used for prenatal screening or for individuals under the age of 17 years.
The BD ProbeTec Herpes Simplex Viruses (HSV 1 & 2) Q* Amplified DNA Assays (HSV Q* Assays) are based on the simultaneous amplification and detection of target DNA using amplification primers and fluorescently-labeled detector probes. The reagents for SDA are dried in two separate disposable microwells for each HSV Q* Assay: the Priming Microwell contains the amplification primers, fluorescently-labeled detector probe, nucleotides and other reagents necessary for amplification, while the Amplification Microwell contains the two enzymes (a necessary for amplification, a restriction endonuclease) that are required for SDA. The BD Viper™ System pipettes a portion of the purified DNA solution from each Extraction Tube into a Priming Microwell to rehydrate the contents. After a brief incubation, the reaction mixture is transferred to a corresponding, pre-warmed Amplification Microwell which is then sealed to prevent contamination and incubated in one of the two thermally-controlled fluorescent readers. The presence or absence of Herpes Simplex virus type 1 (HSV1) or Herpes Simplex virus type 2 (HSV2) DNA is determined by calculating the peak fluorescence (Maximum Relative Fluorescent Units (MaxRFU)) over the course of the amplification process and by comparing this measurement to a predetermined threshold value.
In addition to the fluorescent probe used to detect amplified HSV1 or HSV2 target DNA, a second labeled oligonucleotide is incorporated in each reaction. The Extraction Control (EC) oligonucleotide is labeled with a different dye than that used for detection of the HSV 1 or HSV2 specific target and is used to confirm the validity of the extraction process. The EC is dried in the Extraction Tubes and is rehydrated upon addition of the specimen and extraction reagents. At the end of the extraction process, the EC fluorescence is monitored by the BD Viper System and an automated algorithm is applied to both the EC and target-specific signals to report results as positive, negative, or EC failure.
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:
BD ProbeTec™ Herpes Simplex Viruses (HSV1 & 2) Q* Amplified DNA Assays
The provided document describes the BD ProbeTec™ Herpes Simplex Viruses (HSV1 & 2) Q Amplified DNA Assays*, which are intended for the direct, qualitative detection and differentiation of HSV1 and HSV2 DNA in clinician-collected external anogenital lesion specimens from symptomatic individuals.
1. Acceptance Criteria and Reported Device Performance
The document does not explicitly present a table of predefined acceptance criteria in the format of a requirement with a corresponding target performance. Instead, it reports the device's performance characteristics, particularly diagnostic sensitivity and specificity, against a reference method (viral culture and PCR for discrepants). The performance of the predicate device is not provided, making a direct comparison to explicit acceptance criteria difficult. However, the study aims to demonstrate substantial equivalence.
Based on the clinical performance section, the key performance metrics reported are:
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance (HSV1 Q* Assay) | Reported Device Performance (HSV2 Q* Assay) |
|---|---|---|---|
| Sensitivity (UVT_Qx Swab Diluent) | Sufficient for diagnostic aid | 96.8% (60/62) | 98.4% (186/189) |
| Specificity (UVT_Qx Swab Diluent) | Sufficient for diagnostic aid | 97.6% (244/250) | 83.7% (261/312) |
| Sensitivity (Qx Swab Diluent) | Sufficient for diagnostic aid | 96.7% (59/61) | 98.4% (186/189) |
| Specificity (Qx Swab Diluent) | Sufficient for diagnostic aid | 95.1% (235/247) | 80.6% (249/309) |
| Analytical Sensitivity (LOD) HSV1 | To detect low viral loads | 23 vp/mL (Q Swab Diluent), 85 vp/mL (UVT) | N/A (HSV1 assay) |
| Analytical Sensitivity (LOD) HSV2 | To detect low viral loads | N/A (HSV2 assay) | 84 vp/mL (Q Swab Diluent), 635 vp/mL (UVT) |
| Analytical Specificity | No cross-reactivity with common organisms | No interference observed with 57 organisms (Table 1) | No interference observed with 57 organisms (Table 1) |
| Interfering Substances | No significant interference from common substances | No interference observed with listed substances (Table 2) | No interference observed with listed substances (Table 2) |
| Reproducibility | Consistent results across sites/runs | High agreement with expected results (Tables 7 & 8) | High agreement with expected results (Tables 7 & 8) |
Note: The document states "The analytical and clinical study results ... support the determination of substantial equivalence in accordance with the intended use as stated in the product labeling." This implies that the reported performance metrics met the FDA's criteria for substantial equivalence to a predicate device, even if explicit quantitative targets for each metric are not listed as "acceptance criteria."
2. Sample Size and Data Provenance for the Test Set
- Sample Size (Clinical Performance Study - Test Set):
- Initial Subjects: 564 subjects
- Final Compliant Subjects for Analysis: 508 subjects
- HSV1 Analysis: 501 samples for viral culture typing reference method evaluation.
- UVT in Qx Swab Diluent: n=312 for positive/negative comparison to viral culture.
- Qx Swab Diluent: n=308 for positive/negative comparison to viral culture.
- HSV2 Analysis: 501 total samples for viral culture typing reference method evaluation for UVT in Qx Swab Diluent, and 498 for Qx Swab Diluent.
- Data Provenance: The clinical samples were collected prospectively from nine geographically diverse clinical sites in North America.
3. Number and Qualifications of Experts for Ground Truth (Test Set)
The document does not specify the number or qualifications of experts used to establish the "ground truth" for the test set.
4. Adjudication Method for the Test Set
The primary reference method for the clinical performance study was a commercially available viral culture and typing procedure.
For discrepant results between the ProbeTec HSV Q* Amplified DNA Assays and the reference culture and typing method, a PCR method was used for analysis. The document states, for example, regarding HSV2 specificity that "46 of the 51 HSV2 UVT in Q* Swab Diluent positive and viral culture negative were positive for HSV2 by PCR," indicating that PCR served as a secondary adjudicator for discrepant cases to determine the true positive or negative status when culture results conflicted with the new assay.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No Multi-Reader Multi-Case (MRMC) comparative effectiveness study was done. This device is a diagnostic assay (DNA amplification) and not an imaging or diagnostic support tool for human readers. Therefore, the concept of human readers improving with AI vs. without AI assistance is not applicable.
6. Standalone Performance Study (Algorithm Only)
Yes, a standalone performance study was done. The entire document describes the performance of the BD ProbeTec™ Herpes Simplex Viruses (HSV1 & 2) Q Amplified DNA Assays* as a standalone diagnostic device. The assay determines results (positive, negative, or Extraction Control failure) using an automated algorithm applied to the fluorescent signals.
7. Type of Ground Truth Used
The type of ground truth used for the clinical performance evaluation was:
- Viral Culture and Typing Procedure: This was the primary reference method.
- PCR Testing: Used as an adjudicator for discrepant results between the viral culture and the BD ProbeTec assays.
8. Sample Size for the Training Set
The document does not explicitly define or report a "training set" sample size in the context of machine learning. The study focuses on evaluating the performance of the already developed assay. The analytical performance characteristics (Limit of Detection, Analytical Specificity, Interfering Substances) and reproducibility studies involve controlled experiments with known viral strains and substances, which could be considered part of the assay's development and internal validation, but not a "training set" in the typical ML sense.
9. How the Ground Truth for the Training Set Was Established
As there is no distinct "training set" described in the context of an AI/ML algorithm development, the method for establishing ground truth for such a set is not applicable or detailed in this submission. The assay's "algorithm" described is likely based on fixed thresholds and logic for interpreting fluorescent signals, rather than a machine learning model requiring a training phase with labeled data. The established ground truth for analytical studies involved controlled spiking of known quantities of viral particles and other organisms or substances.
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BD ProbeTec™ Herpes Simplex Viruses (HSV1 & 2) Q* Amplified DNA Assays
| Applicant | BD Diagnostic Systems7 Loveton CircleSparks, MD 21152 | MAR 18 2011 |
|---|---|---|
| Establishment Registration No. | 1119779 | |
| Contact Person | Thalia Charlestel. 410-316-4145fax. 410-316-4499Thalia_E_Charles@bd.com | |
| Summary Date | March 14, 2011 | |
| Proprietary Name | BD ProbeTecTM Herpes Simplex Viruses (HSV 1 & 2) QxAmplified DNA Assays | |
| Generic Name | DNA probe, nucleic acid amplification, Herpes Simplex virus | |
| Classification | Class II | |
| Classification Name | Herpes simplex virus serological assays | |
| Regulation Number | 21 CFR 866.3305 | |
| Product Code | OQO | |
| Predicate Device | ELVIS HSV ID and D3 Typing Test System |
Device Description
The BD ProbeTec Herpes Simplex Viruses (HSV 1 & 2) Q* Amplified DNA Assays (HSV Q* Assays) are based on the simultaneous amplification and detection of target DNA using amplification primers and fluorescently-labeled detector probes. The reagents for SDA are dried in two separate disposable microwells for each HSV Q* Assay: the Priming Microwell contains the amplification primers, fluorescently-labeled detector probe, nucleotides and other reagents necessary for amplification, while the Amplification Microwell contains the two enzymes (a nocessary for anipinioused, intion endonuclease) that are required for SDA. The BD Viper™ System pipettes a portion of the purified DNA solution from each Extraction Tube into a Priming Microwell to rehydrate the contents. After a brief incubation, the reaction mixture is transferred to a corresponding, pre-warmed Amplification Microwell which is then sealed to prevent contamination and incubated in one of the two thermally-controlled fluorescent readers. The presence or absence of Herpes Simplex virus type 1 (HSV1) or Herpes Simplex virus type 2 (HSV2) DNA is determined by calculating the peak fluorescence (Maximum Relative
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Fluorescent Units (MaxRFU)) over the course of the amplification process and by comparing this measurement to a predetermined threshold value.
In addition to the fluorescent probe used to detect amplified HSV1 or HSV2 target DNA, a second labeled oligonucleotide is incorporated in each reaction. The Extraction Control (EC) oligonucleotide is labeled with a different dve than that used for detection of the HSV I or HSV2 specific target and is used to confirm the validity of the extraction process. The EC is dried in the Extraction Tubes and is rehydrated upon addition of the specimen and extraction reagents. At the end of the extraction process, the EC fluorescence is monitored by the BD Viper System and an automated algorithm is applied to both the EC and target-specific signals to report results as positive, negative, or EC failure.
Intended Use
The BD ProbeTec™ Herpes Simplex Viruses (HSV 1 & 2) O* Amplified DNA Assays, when tested with the BD Viper™ System in Extracted Mode. use Strand Displacement Amplification technology for the direct, qualitative detection and differentiation of Herpes Simplex virus type 1 (HSV1) and Herpes Simplex virus type 2 (HSV2) DNA in clinician-collected external anogenital lesion specimens. The assays are indicated for use with symptomatic individuals to aid in the diagnosis of anogenital HSV1 and HSV2 infections.
Warning: The BD ProbeTec™ Herpes Simplex Viruses (HSV 1 & 2) Q Amplified DNA Assays (HSV Of Assays) are not FDA cleared for use with cerebrospinal fluid (CSF). The assays are not intended to be used for prenatal screening or for individuals under the age of 17 years.
Summary and Principles of Operation
When used with the BD Viper System, the BD ProbeTec HSV Q* Amplified DNA Assays involve automated extraction of DNA from clinical specimens through the chemical lysis of cells, followed by binding of DNA to para-magnetic particles, washing of the bound nucleic acid, and elution in an amplification-compatible buffer. When present, HSV1 or HSV2 DNA is then detected by Strand Displacement Amplification (SDA) of either specific target sequence in the presence of a fluorescently-labeled detector probe.
Analytical Performance Characteristics
Limit of Detection (Analytical Sensitivity)
The Limits of Detection (LODs) for the HSV1 Q* Assay with HSV1 ATCC strain VR-539 in model matrix specimens when extracted on the BD Viper System were determined to be 23 viral particles/mL (vp/mL) in the Q Swab Diluent medium, and 85 vp/mL in the Universal Viral Transport medium (UVT). These values correspond to 7 TCID50/mL and 25 TCIDsy/mL,
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BD ProbeTec™ Herpes Simplex Viruses (HSV1 & 2) Q* Amplified DNA Assays
respectively. The Limits of Detection (LODs) for the HSV2 Q* Assay with HSV2 ATCC strain VR-734 in model matrix specimens when extracted on the BD Viper System were determined to be 84 vp/mL (35 TCIDss/mL) in the Q Swab Diluent medium and 635 vp/mL (262 TCIDs6/ml.) in the UVT medium. Evaluation of the HSV1 Q* Assay on the BD Viper System in extracted mode with three additional HSV1 strains gave LoD values between 6 and 14 vp/mL in clean Q* Swab Diluent and between 110 and 185 vp/mL in clean UVT. Evaluation of the HSV2 Q* Assay on the BD Viper System in extracted mode with one additional HSV2 strain gave an LOD of 34 vp/mL in clean Q* Swab Diluent and 380 vp/mL in clean UVT.
Analytical Specificity
The DNA from 57 organisms was extracted on the BD Viper System and tested with the BD ProbeTec HSV Q Amplified DNA Assays. All potential cross-reactive species were tested at approximately 1x108 Colony Forming Units/mL for bacteria and yeast or 1x106 Plaque Forming Units/mL or greater for viruses, except where noted. Results are summarized in Table 1.
| Table 1: Potential Cross-Reactants | |
|---|---|
| Actinomyces israelii | Human papillomavirus 161 |
| Adenovirus | Human papillomavirus 181 |
| Alcaligenes faecalis | Kingella kingae |
| Candida albicans | Klebsiella pneumoniae |
| Chlamydia trachomatis serovar H | Lactobacillus acidophilus |
| Chlamydia trachomatis serovar LGV-2 | Listeria monocytogenes |
| Clostridium perfringens | Mobiluncus mulieris |
| Corynebacterium genitalium | Moraxella lacunata |
| Cryptococcus neoformans | Mycobacterium tuberculosis1 |
| HHV-5 Cytomegalovirus (CMV)1 | Mycoplasma genitalium |
| Enterobacter cloacae | Neisseria gonorrhoeae |
| Enterococcus faecalis | Neisseria meningitidis |
| Enterococcus faecium | Propionibacterium acnes |
| Enterovirus (Echovirus 11)1 | Proteus vulgaris |
| HHV-4 Epstein Barr virus2 | Pseudomonas aeruginosa |
| Escherichia coli (strain K1) | Staphylococcus aureus |
| Gardnerella vaginalis | Staphylococcus epidermidis |
| Gemella haemolysans | Staphylococcus saprophyticus |
| Haemophilus ducreyi | Streptococcus agalactiae |
| Haemophilus influenzae | Streptococcus mitis |
| Hepatitis B Virus1 | Streptococcus pneumoniae |
| HHV-6 (Roseolovirus)1 | Streptococcus pyogenes |
| HHV-6B (Roseolovirus)1 | Treponema pallidum |
| HHV-7 (Roseolovirus)1 | Trichomonas vaginalis |
Table 1: Potential Cross-Reactants
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| HHV-8 (Rhadinovirus)1 | Varicella Zoster Virus (HHV-3)1 |
|---|---|
| Human Immunodeficiency Virus 1 (HIV-1)2 | Veillonella parvula |
| Human Immunodeficiency Virus 2 (HIV-2)2 | Herpes Virus Type 1 (HSV1)2* |
| Human papillomavirus 61 | Herpes Virus Type 2 (HSV2)2** |
| Human papillomavirus 111 |
4 Genomic DNA tested at 1x106 DNA copies/mL
2 Viruses tested at 1x10* viral particles/ml_
- Tested as a cross-reactant in the HSV2 Q* Assay only
** Tested as a cross-reactant in the HSVI Q* Assay only
Interfering Substances
Potentially interfering substances which may be encountered in external anogenital lession specimens were tested in the absence and presence of HSV1 and HSV2 targets (for HSV1 target, 69 vp/mL in Qx Swab Diluent and 255 vp/mL in UVT; for HSV2 target, 252 vp/mL in Qx Swab Diluent and 1905 vp/mL in UVT; these levels are 3 times each LOD) and tested with the BD ProbeTec HSV Q* Amplified DNA Assays on the BD Viper System. Results are summarized in Table 2.
| Interpretation | Q* Swab Diluent | UVT |
|---|---|---|
| Blood (2.5% v/v) | Blood (3.3% v/v) | |
| Seminal fluid (2.5% v/v) | Seminal fluid (3.3% v/v) | |
| Mucus (2.5% v/v) | Mucus (3.3% v/v) | |
| Feces (2.5%) | Feces (3.3%) | |
| Urine (2.5% v/v) | Urine (3.3% v/v) | |
| Cornstarch (2.5%) | Cornstarch (3.3%) | |
| Over the counter vaginal productsand contraceptives (2.5% v/v) | Over the counter vaginal productsand contraceptives (3.3% v/v) | |
| No interference observedat levels listed | Over the counter cold sore products(2.5% v/v) | Over the counter cold sore products(3.3% v/v) |
| Hemorrhoidal cream (2.5% v/v) | Hemorrhoidal cream (3.3% v/v) | |
| Prescription vaginal and anti-viraltreatments (2.5% v/v) | Prescription vaginal and anti-viraltreatments (3.3% v/v) | |
| Leukocytes (1x106 cells/mL) | Leukocytes (1x106 cells/mL) | |
| 1x106 viral particles/mL HSV1(when tested in the HSV2 Q* assay) | 1x106 viral particles/mL HSV1(when tested in the HSV2 Q* assay) | |
| 1x106 viral particles/mL HSV2(when tested in the HSV1 Q* assay) | 1x106 viral particles/mL HSV2(when tested in the HSV1 Q* assay) | |
| May cause extraction control (EC)failures | Not applicable | Not applicable |
| May cause false negative results | Not applicable | Not applicable |
Table 2: Potentially Interfering Substances
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BD ProbeTec™ Herpes Simplex Viruses (HSV1 & 2) Q* Amplified DNA Assays
Clinical Performance Characteristics
Clinician-collected external anogenital lesion swab specimens were collected from 564 compliant male and female subjects attending family planning, OB/GYN, and sexually transmitted disease clinics at nine geographically diverse clinical sites in North America. Subjects were classified as symptomatic if they presented with an external anogenital lesion that met the study inclusion/exclusion criteria and the physician suspected a herpes infection. Fiftysix subjects were excluded from the data analysis due to age requirement violations, antiviral use in the last 21 days, opting to withdraw from the study after initially consenting, transport errors, informed consent issues, failing to meet the inclusion criteria, collection errors, shipping errors, or labeling errors. Therefore, the final data analysis included 508 compliant subjects.
For each of the 508 compliant subjects, two swab specimens were collected from the external anogenital lesion. The first specimen collected was always the Universal Viral Transport specimen followed by the BD ProbeTec OF Collection Kit for Endocervical or Lesion Specimens (Q* Swab Diluent specimen). The UVT was aliquotted into a Q* Swab Diluent Tube (UVT in Q* Swab Diluent), and a cryovial (vial suitable for -70 ℃ storage), and the remaining UVT was sent to one of two laboratories for viral culture and typing. The Q Swab Diluent specimen and the UVT in Q Swab Diluent specimen were transported to one of the three BD Viper testing laboratories where they were tested using the BD ProbeTec HSV1 and HSV2 Q* Assays on the BD Viper System. The cryovial containing the UVT aliquot was sent to a laboratory for PCR testing.
All sensitivity and specificity calculations were based on the total number of BD ProbeTec HSV1 and HSV2 Q Assays results for Q Swab Diluent and UVT in Q Swab Diluent specimens, as compared to a commercially available viral culture and typing procedure as the reference method. A PCR method was also used for analysis of discrepant results from the ProbeTec HSV Q* Amplified DNA Assays and the reference culture and typing method.
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D ProbeTec™ Herpes Simplex Viruses (HSV1 & 2) Q* Amplified DNA Assays
Table 3: HSV1 Q* Assay Performance Compared to Viral Culture (by specimen type)
| SpecimenType | n1 | Sensitivity | 95% C.I. | Specificity | 95% C.I. |
|---|---|---|---|---|---|
| UVT inQx SwabDiluent | 312 | 96.8% (60/62)3 | (88.8% - 99.6%) | 97.6%(244/250)4 | (94.8% -99.1%) |
| Qx SwabDiluent | 3082 | 96.7% (59/61)3 | (88.7% - 99.6%) | 95.1%(235/247)5 | (91.7% -97.5%) |
' The reference viral culture used in this study was unable to detect co-infected specimen is negative for 'SV V is it types and The reference the number of samples used for HSV lanalysis equals the number of samples with a reference virtl culture typing result (501) minus the number of samples positive for HSV2 by the reference method (189).
4 A total of four Q Swab Diluent specimens were not included in the HSV1 analysis due to insufficient volume, aliquot error, or extraction error ..
3 Both subjects that were identified as positive for HSV I with viral culture were negative for HSVI with the HSVI Q* Assay and PCR. Both the M HSV Q* Assays and the PCR assay identified the subjects as positive for HSV2.
- There were six UVT in Q Swab Diluent specimens that were identified as negative for HSVI with viral culture but were positive for both the HSV1 Qx Assay and the PCR assay.
110 Y Q Thoughter of Swab Dilvent speciment that were identified as negative for HSVI with viral culture but were positive with the HSVI QV Assay. Seven of these specimens were also positive with the PCR assay.
Table 4: HSV2 Q* Assay Performance Compared to Viral Culture (by specimen type)
| SpecimenType | n | Performance Compared to Viral Culture | |||
|---|---|---|---|---|---|
| Sensitivity | 95% C.I. | Specificity | 95% C.I. | ||
| UVT inQxSwabDiluent | 501 | 98.4% (186/189)6 | (95.4% -99.7%) | 83.7%(261/312)7,9 | (79.1% -87.6%) |
| Qx SwabDiluent | 498 | 98.4% (186/189)6 | (95.4% -99.7%) | 80.6%(249/309)8,9 | (75.7% -84.8%) |
6 All three subjects that were identified as positive for HSV2 with viral culture were negative for USV1 All three subjects that were neemned as possions for ree subjects as positive for HSVI.
1 46 of the 51 HSV2 UVT in Q* Swab Diluent positive and viral culture negative were positive for HSV2 by PCR.
40 of the 60 HSV2 Q Swab Diluent positive specimens and viral culture negatives were positive for HSV2 by PCR.
49 to the of to Y L Q S Nat Diness: peach Assay in samples that were culture negative could indicate detection of nonviable viral particles.
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Frequency distributions of the initial MaxRFU values for the HSV1 Q Assay with an assay cutoff of 125 MaxRFU for specimens in each media type are shown in Figures A and B.
Image /page/6/Figure/4 description: The image is titled "Figure A: Frequency Distribution of MaxRFU for the HSV1 Q Assay, UVT in Q Swab Diluent". The title describes the contents of the figure, which is a frequency distribution of MaxRFU values for the HSV1 Q assay. The assay was performed using UVT in Q swab diluent.
Image /page/6/Figure/5 description: The image is a bar graph showing the frequency of MaxRFU values. The x-axis represents the MaxRFU ranges, and the y-axis represents the frequency. The bar graph shows that the highest frequency is in the 0-49 range, with a value of 246. There is also a notable frequency in the >=800 range, with a value of 60.
Figure B: Frequency Distribution of MaxRFU for the HSV1 Q* Assay, Q* Swab Diluent
Image /page/6/Figure/7 description: This bar graph shows the frequency of MaxRFU values. The x-axis represents the MaxRFU ranges, while the y-axis represents the frequency. The highest frequency is observed in the 0-49 range, with a value of 236. The frequency for the range >=800 is 60.
Frequency distributions of the initial MaxRFU values for the HSV2 Q Assay with an assay cutoff of 125 MaxRFU for specimens in each media type are shown in Figures C and D.
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Figure C: Frequency Distribution of MaxRFU for the HSV2 O' Assay, UVT in O* Swab Diluent
Image /page/7/Figure/4 description: The image is a bar graph showing frequency on the y-axis and MaxRFU on the x-axis. The x-axis is divided into categories: 0-49, 50-99, 100-124, 125-149, 150-199, 200-249, 250-349, 350-499, 500-799, and >=800. The frequencies for each category are 260, 4, 0, 0, 1, 0, 1, 1, 2, and 232 respectively.
Figure D: Frequency Distribution of MaxRFU for the HSV2 Q Assay, Q* Swab Diluent
Image /page/7/Figure/6 description: This bar graph shows the frequency of MaxRFU. The x-axis shows the MaxRFU ranges, and the y-axis shows the frequency. The bar graph shows that the frequency is highest for the 0-49 range, with a value of 251, and the >=800 range, with a value of 238.
Reproducibility
Reproducibility of the BD Viper System using the BD ProbeTec HSV1 and HSV2 Q* Assays was evaluated at three test sites (two external and one internal) on one BD Viper System per site. Two panels of simulated specimens were tested that were comprised of HSV (strain VR-539) and/or HSV2 (strain VR-734) viral particles seeded into either Q* Swab Diluent containing a swab (simulated Q* Swab Diluent) or UVT in Q* Swab Diluent (simulated UVT in Q* Swab Diluent specimen type). Viral particles were spiked into the simulated samples at 2-fold or 5-fold LOD. Uninoculated Q* Swab Diluent or UVT in Q* Swab Diluent was used for the negative samples. Six replicates of each panel member were tested every day for five days on each BD Viper System. A summary of the reproducibility data for the HSV1 and HSV2 Q Assays is presented in Tables 7 and 8.
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Table 7: Summary of Reproducibility Data on the BD Viper System for the HSV1 Q* Assay.
| Site #1 | Site #2 | Site #3 | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SimulatedSpecimenType | TargetsHSV1/HSV2(xLOD)** | AgreementwithExpectedResults | MaxRFUMean | MaxRFUStdDev | %CV | AgreementwithExpectedResults | MaxRFUMean | MaxRFUStdDev | %CV | AgreementwithExpectedResults | MaxRFUMean | MaxRFUStdDev | %CV | TotalAgreementwithExpectedResults(%) | 95%ConfidenceInterval |
| UVT inQ' SwabDiluent | 0/0 | 30/30 | 2.2 | 6.7 | N/A* | 30/30 | 4.3 | 12.9 | N/A* | 30/30 | 0.7 | 2.2 | N/A* | 90/90(100%) | 96% -100% |
| 2x/0 | 29/30 | 1432.6 | 447.6 | 31.2 | 30/30 | 1375.4 | 326.2 | 23.7 | 30/30 | 1474.5 | 307.9 | 20.9 | 89/90(98.9%) | 94% -100% | |
| 0/2x | 30/30 | 3.8 | 10.9 | N/A* | 30/30 | 7.8 | 27.6 | N/A* | 30/30 | 7.3 | 10.7 | N/A* | 90/90(100%) | 96% -100% | |
| 2x/5x | 29/30 | 1123.1 | 622.9 | 55.5 | 30/30 | 1144.9 | 397.7 | 34.7 | 30/30 | 1441.4 | 205.8 | 14.3 | 89/90(98.9%) | 94% -100% | |
| 5x/2x | 30/30 | 1586.2 | 346.8 | 21.9 | 30/30 | 1531.5 | 165.4 | 10.8 | 30/30 | 1619.7 | 175.7 | 10.8 | 90/90(100%) | 96% -100% | |
| Q' SwabDiluent | 0/0 | 29/30 | 24.9 | 39.0 | N/A* | 29/30 | 15.5 | 84.7 | N/A* | 30/30 | 0.9 | 3.8 | N/A* | 88/90(97.8%) | 92.2% -99.7% |
| 2x/0 | 30/30 | 1477.2 | 392.3 | 26.6 | 28/30 | 999.2 | 482.9 | 48.3 | 30/30 | 1276.7 | 396.0 | 31.0 | 88/90(97.8%) | 92.2%-99.7% | |
| 0/2x | 30/30 | 12.3 | 23.7 | N/A* | 30/30 | 0.0 | 0.0 | N/A* | 30/30 | 0.3 | 0.8 | N/A* | 90/90(100%) | 96% -100% | |
| 2x/5x | 30/30 | 1551.0 | 369.1 | 23.8 | 30/30 | 1395.1 | 144.3 | 10.3 | 30/30 | 1320.5 | 349.9 | 26.5 | 90/90(100%) | 96% -100% | |
| 5x/2x | 30/30 | 1751.5 | 174.0 | 9.9 | 30/30 | 1441.8 | 214.8 | 14.9 | 30/30 | 1535.1 | 244.1 | 15.9 | 90/90(100%) | 96% -100% |
*The coefficient of variation (CV) is not a useful mean approaches 0, as the CV is very sensitive to small changes in the mean. ** HSV1 and HSV2 were spiked at either 2-fold (2x) or 5-fold (5x) the LOD.
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Table 8: Summary of Reproducibility Data on the BD Viper System for the HSV2 QF Assay.
| Site #1 | Site #2 | Site #3 | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SimulatedSpecimenType | TargetsHSV1/HSV2(xLOD)** | AgreementwithExpectedResults | MaxRFUMean | MaxRFUStdDev | %CV | AgreementwithExpectedResults | MaxRFUMean | MaxRFUStdDev | %CV | AgreementwithExpectedResults | MaxRFUMean | MaxRFUStdDev | %CV | TotalAgreementwithExpectedResults(%) | 95%ConfidenceInterval |
| UVT inQ' SwabDiluent | 0/0 | 29/29*** | 6.5 | 9.2 | N/A* | 30/30 | 5.2 | 16.4 | N/A* | 30/30 | 7.4 | 8.1 | N/A* | 89/89(100%) | 95.9% -100% |
| 2x/0 | 30/30 | 6.8 | 9.8 | N/A* | 30/30 | 3.9 | 12.2 | N/A* | 30/30 | 14.4 | 13.5 | N/A* | 90/90(100%) | 96% -100% | |
| 0/2x | 30/30 | 1768.6 | 390.0 | 22.0 | 30/30 | 1806.1 | 263.6 | 14.6 | 30/30 | 1910.6 | 236.5 | 12.4 | 90/90(100%) | 96% -100% | |
| 2x/5x | 30/30 | 1946.5 | 246.8 | 12.7 | 30/30 | 1800.1 | 267.6 | 14.9 | 30/30 | 1965.1 | 171.7 | 8.7 | 90/90(100%) | 96% -100% | |
| 5x/2x | 30/30 | 1866.1 | 319.9 | 17.1 | 30/30 | 1823.8 | 250.8 | 13.8 | 30/30 | 1861.2 | 224.8 | 12.1 | 90/90(100%) | 96% -100% | |
| Q' SwabDiluent | 0/0 | 29/29*** | 8.2 | 19.1 | N/A* | 30/30 | 0.4 | 2.2 | N/A* | 30/30 | 2.9 | 11.9 | N/A* | 89/89(100%) | 95.9%-100% |
| 2x/0 | 30/30 | 11.2 | 23.6 | N/A* | 30/30 | 0.2 | 1.3 | N/A* | 30/30 | 2.2 | 4.0 | N/A* | 90/90(100%) | 96% -100% | |
| 0/2x | 29/29*** | 2007.1 | 219.4 | 10.9 | 30/30 | 1679.5 | 331.1 | 19.7 | 30/30 | 1757.3 | 289.2 | 16.5 | 89/89(100%) | 95.9%-100% | |
| 2x/5x | 29/29*** | 2028.3 | 230.6 | 11.4 | 30/30 | 1787.5 | 327.9 | 18.3 | 30/30 | 1882.7 | 342.1 | 18.2 | 89/89(100%) | 95.9%-100% | |
| 5x/2x | 29/29*** | 1960.7 | 254.7 | 13.0 | 30/30 | 1756.2 | 286.7 | 16.3 | 30/30 | 1762.7 | 350.3 | 19.9 | 89/89(100%) | 95.9% -100% |
*The coefficient of variation (CV) is not a useful measure when the mean approaches 0, as the CV is very sensitive to small changes in the mean. ** HSV1 and HSV2 were spiked at either 2-fold (2x) or 5-fold (5x) the LOD.
*** Non-reportable results due to a BD Viper Instrument error which caused a reduction in the full number of replicates.
Conclusions:
The analytical and clinical study results for the BD ProbeTec Herpes Simplex Viruses (HSV) Q* Amplified DNA Assays support the determination of substantial equivalence in accordance with the intended use as stated in the product labeling.
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Image /page/10/Picture/0 description: The image shows the logo for the Department of Health & Human Services USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. Inside the circle is an image of a stylized bird.
Food and Drug Administration 10903 New Hampshire Avenue Document Mail Cemer - WO66-0609 Silver Spring, MD 20993-0002
BD Diagnostic Systems c/o Thalia Charles Regulatory Affairs Specialist 7 Loveton Circle Sparks, MD 21152
MAR 1 8 201
Re: K103798
| Trade/Device Name: | BD ProbeTec™ Herpes Simplex Viruses (HSV 1 & 2) Qˣ Amplified DNA Assays |
|---|---|
| Regulation Number: | 21 CFR §866.3305 |
| Regulation Name: | Herpes Simplex Virus Nucleic Acid Amplification Assay |
| Regulatory Class: | Class II |
| Product Code: | OQO |
| Dated: | December 22, 2010 |
| Received: | December 27, 2010 |
Dear Ms. Charles:
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 class II (Special Controls), 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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket
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Page 2 - Thalia Charles
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 Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. 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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
TaqcAtyms
Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known): K103798
BD ProbeTec™ Herpes Simplex Viruses (HSV 1 & 2) Q* Amplified DNA Assays Device Name:
Indications For Use:
The BD ProbeTec™ Herpes Simplex Viruses (HSV 1 & 2) Q* Amplified DNA Assays, when tested with the BD Viper™ System in Extracted Mode, use Strand Displacement Amplification technology for the direct, qualitative detection and differentiation of Herpes Simplex virus type 1 (HSV1) and Herpes Simplex virus type 2 (HSV2) DNA in clinician-collected external anogenital lesion specimens. The assays are indicated for use with symptomatic individuals to aid in the diagnosis of anogenital HSV1 and HSV2 infections.
Warning: The BD ProbeTec™ Herpes Simplex Viruses (HSV 1 & 2) Q* Amplified DNA Assays (HSV Q* Assays) are not FDA cleared for use with cerebrospinal fluid (CSF). The assays are not intended to be used for prenatal screening or for individuals under the age of 17 years.
Prescription Use V (Part 21 CFR 801 Subpart D)
AND/OR (21 CFR 807 Subpart C)
Over-The-Counter Use
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Uwe Schif
Division Sign-Off
Division Sign-Off
Page 1 of 1
Office of In Vitro Diagnostic Device Evaluation and Safety
k to3798 510(k)_
§ 866.3305 Herpes simplex virus serological assays.
(a)
Identification. Herpes simplex virus serological assays are devices that consist of antigens and antisera used in various serological tests to identify antibodies to herpes simplex virus in serum. Additionally, some of the assays consist of herpes simplex virus antisera conjugated with a fluorescent dye (immunofluorescent assays) used to identify herpes simplex virus directly from clinical specimens or tissue culture isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by herpes simplex viruses and provides epidemiological information on these diseases. Herpes simplex viral infections range from common and mild lesions of the skin and mucous membranes to a severe form of encephalitis (inflammation of the brain). Neonatal herpes virus infections range from a mild infection to a severe generalized disease with a fatal outcome.(b)
Classification. Class II (special controls). The device is classified as class II (special controls). The special control for the device is FDA's revised guidance document entitled “Class II Special Controls Guidance Document: Herpes Simplex Virus Types 1 and 2 Serological Assays.” For availability of the guidance revised document, see § 866.1(e).