(232 days)
No
The summary describes a standard immunoassay with automated processing and analysis based on a calibration function and cut-off values, which are not indicative of AI/ML. There are no mentions of AI, ML, or related concepts like deep learning or neural networks.
No
This device is an in vitro diagnostic (IVD) assay designed to detect antibodies to HSV-1, aiding in the diagnosis of infection. It does not provide any therapeutic benefit or treatment.
Yes
The device is intended for the "qualitative detection of IgG antibodies to herpes simplex virus type 1 (HSV-1)" in human samples "as an aid in the presumptive diagnosis of HSV-1 infection." This direct contribution to diagnosis qualifies it as a diagnostic device.
No
The device is an immunoassay kit that requires the use of the Theranos System, which performs automated sample processing and analysis. This indicates the device includes physical components and relies on a hardware system, not just software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the device is intended for the "qualitative detection of IgG antibodies to herpes simplex virus type 1 (HSV-1) in human serum, in K2-EDTA anticoagulated human plasma from venous blood, and in human fingerstick K2-EDTA anticoagulated whole blood". This indicates that the device is used to examine specimens derived from the human body.
- Purpose: The test is described as an "aid in the presumptive diagnosis of HSV-1 infection". This clearly indicates that the device is used for diagnostic purposes.
- Device Description: The description details a "chemiluminescent immunoassay" which is a laboratory test performed on biological samples.
- Performance Studies: The document includes detailed performance studies (Clinical Performance, Precision, Reproducibility, etc.) which are typical for IVD devices to demonstrate their accuracy and reliability for diagnostic use.
Therefore, based on the provided information, the Theranos™ HSV-1 IgG Assay fits the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The Theranos™ HSV-1 IgG Assay is a chemiluminescent immunoassay intended for the qualitative detection of IgG antibodies to herpes simplex virus type 1 (HSV-1) in human serum, in K2-EDTA anticoagulated human plasma from venous blood, and in human fingerstick K2-EDTA anticoagulated whole blood obtained with the Theranos Capillary Tubes and Nanotainer Tubes. The test is indicated for sexually active individuals and expectant mothers as an aid in the presumptive diagnosis of HSV-1 infection. The predictive value of positive and negative results depends on the population's prevalence and the pretest likelihood of HSV-1.
The test is not FDA cleared for screening blood or plasma donors. The performance of this assay has not been established for use in a pediatric population, neonates and immunocompromised patients.
The Theranos HSV-1 IgG Assay is for use with the Theranos System which performs automated sample processing steps and result analysis.
Product codes
MXJ
Device Description
The Theranos HSV-1 IgG Assay is for use with the Theranos System. The Theranos System performs automated sample processing steps and analysis to produce the test results.
The Theranos HSV-1 IgG Assay is a three-step sandwich immunoassav with an HSV-1 glycoprotein G (gG) recombinant antigen coated surface, an anti-human IgG detection reagent conjugated to alkaline phosphatase (AP) and chemiluminescent substrate. During the first incubation step, the HSV-1 IgG antibodies present in the positive control and sample bind to the gG recombinant antigen on the coated surface. Following the first incubation step, unbound materials are removed with a wash cycle. Then the detection reagent-AP conjugate is added and during the second incubation step, the detection reagent-AP conjugate reacts with the HSV-1 IgG antibodies already bound to the capture surface. Following the second incubation, unbound materials are removed with a wash cycle. The chemiluminescent substrate is added to the capture-analyte-detection complex during the third incubation step to initiate the chemiluminescence reaction. Light generated by this reaction is detected and analyzed by the Theranos System using a calibration function to determine the cut-off index (COI) values for the sample and controls. The results for the Positive and Negative controls must be within specified limits for a run to be considered valid.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
The test is indicated for sexually active individuals and expectant mothers.
The performance of this assay has not been established for use in a pediatric population, neonates and immunocompromised patients.
Study populations included "sexually active adults (18 years and older)" and "pregnant women."
Age range for sexually active adults in the expected values table: 16 to 89 years.
Age range for pregnant women in the expected values table: 18 to 49 years.
Intended User / Care Setting
CLIA Laboratory Model, Theranos Patient Service Centers (TPSCs)
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Precision - CLIA Laboratory Model, Venous Serum
Sample size: 6 serum samples spanning the analytical range [negative (A), high negative (B), equivocal (C), low positive (D), moderate positive (E), and positive (F)].
Data source: Not explicitly stated, implied to be contrived by using a high positive sample and diluting it with pooled negative serum for the interfering substances study.
Annotation protocol: Not explicitly stated beyond testing being performed by 16 operators across 35 TSPU devices and 3 lots of cartridges for 13 days, with samples tested in replicates.
Precision - CLIA Laboratory Model, Fingerstick Whole Blood
Sample size: 3 fingerstick plasma samples spanning the analytical range [high negative (P), equivocal (Q), moderate positive (R)].
Data source: Not explicitly stated, implied to be derived from fingerstick whole blood samples.
Annotation protocol: Not explicitly stated beyond testing being performed by 9 operators across 36 TSPU devices and 3 lots of cartridges for 4 days, with samples tested in replicates.
Reproducibility
Sample size: 30 subjects (10 subjects at each of 3 collection sites). From each subject, 9 Capillary Tubes and Nanotainer Tubes (3 per manufacturing lot) and 2 serum separator tubes (SSTs) were collected.
Data source: Not explicitly stated, implied to be clinical samples collected from subjects.
Annotation protocol: Each of the 9 Capillary Tubes and Nanotainer Tubes was tested for between-Capillary Tubes and Nanotainer Tubes imprecision, between-lot imprecision, and total imprecision. One Nanotainer Tube was tested in duplicate for within-Capillary Tubes and Nanotainer Tubes imprecision. Each of the 2 SSTs was tested for between-SST imprecision.
Assay Cut-off Validation
Sample size: 192 serum samples were used to establish the cut-off and the limits of the equivocal zone, and 120 independent serum samples were used to validate the established cut-off.
Data source: Not explicitly stated, implied to be serum samples.
Annotation protocol: Not explicitly stated.
Fingerstick Plasma - CLIA Laboratory Model
Sample size: 20, 16, and 25 adult subjects at three collection sites (total of 61 subjects). From each subject, fingerstick whole blood samples were collected into a pair of Theranos Capillary Tubes and Nanotainer Tubes, and venous samples were collected into serum tubes.
Data source: Samples were collected at 3 Theranos Patient Service Centers (TPSCs).
Annotation protocol: Samples were shipped refrigerated to Theranos CLIA-certified laboratory, centrifuged, plasma extracted, processed and analyzed on the Theranos System.
Matrix Comparison
Sample size: Matched venous serum, venous K2-EDTA plasma, and fingerstick K2-EDTA plasma samples from 70 donors were used.
Data source: 70 donors.
Annotation protocol: 43 matched sample sets were contrived to have analyte values close to the cut-off. Comparisons were made between different sample types and matrices.
Expected Values
Sample size: 558 total subjects, with 260 sexually active adults and 298 pregnant women. Results reported for 557 subjects.
Data source: Individuals for whom an HSV-1 IgG test was ordered by a physician, including pregnant women.
Annotation protocol: Not explicitly stated beyond data being summarized by age group, gender, and reactive/equivocal/non-reactive results.
Clinical Performance in the Intended Use Populations (CLIA Laboratory Model)
Sample size: Not explicitly stated beyond "prospectively collected, archived venous serum samples". 260 sexually active adults and 298 pregnant women datasets were presented in tables.
Data source: Prospectively collected, archived venous serum samples collected from pregnant women and sexually active adults (18 years and older) who had a prescription for an HSV-1 IgG test. Samples were obtained from multiple specimen sources covering 10 US states and Mexico.
Annotation protocol: Performance was compared to the FOCUS HerpeSelect Immunoblot. Equivocal results on the Focus HerpeSelect Immunoblot were resolved using a validated western blot reference test (University of Washington, Seattle). Invalid results on the Theranos HSV-1 IgG test were rerun.
CDC Panel Testing
Sample size: 100 well characterized serum samples.
Data source: U.S. Centers for Disease Control and Prevention (CDC).
Annotation protocol: The CDC sample panel was tested with the HSV-1 IgG Assay and results sent to the CDC for confirmation.
Low Prevalence Population
Sample size: 82 samples.
Data source: Serum samples from individuals who are not sexually active, and without a recent or current sexually transmitted disease. Samples were obtained from multiple specimen sources covering 10 US states and Mexico.
Annotation protocol: Not explicitly stated beyond performance of the assay being summarized.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Precision - CLIA Laboratory Model, Venous Serum
Study type: Precision study.
Sample size: Panel of 6 serum samples, 35 TSPU devices, 3 lots of cartridges, 16 operators, 13 days.
Key results: Precision was in the range of 10.2% to 14.2% (%CV for COI values).
Precision - CLIA Laboratory Model, Fingerstick Whole Blood
Study type: Precision study.
Sample size: Panel of 3 fingerstick plasma samples, 36 TSPU devices, 3 lots of cartridges, 9 operators, 4 days.
Key results: Precision was in the range of 10.9% to 12.2% (%CV for COI values).
Reproducibility
Study type: Reproducibility study (processing multiple fingerstick whole blood samples).
Sample size: 30 subjects (10 at each of 3 collection sites).
Key results:
- Within-Capillary Tubes and Nanotainer Tubes imprecision: %CV=7.5% (COI ≥ 0.5), SD=0.008 (COI
§ 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).
0
Image /page/0/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features the department's emblem, which consists of a stylized representation of human profiles arranged in a cascading manner. The emblem is encircled by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in a circular arrangement.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
July 7, 2015
THERANOS, INC. BRAD ARINGTON ASSOCIATE DIRECTOR, REGULATORY 1701 PAGE MILL ROAD PALO ALTO, CA 94304
Re: K143236
Trade/Device Name: Theranos Herpes Simplex Virus-1 IgG Assav Regulation Number: 21 CFR 866.3305 Regulation Name: Herpes simplex virus serological assays Regulatory Class: II Product Code: MXJ Dated: June 29, 2015 Received: June 30, 2015
Dear Mr. Arington:
This letter corrects our substantially equivalent letter of July 2, 2015.
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. 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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the
1
electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. 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 Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Sally A. Hojvat -S
Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K143236
Device Name Theranos Herpes Simplex Virus-1 IgG Assay
Indications for Use (Describe)
The Theranos™ HSV-1 IgG Assay is a chemiluminescent immunoassay intended for the qualitative detection of IgG antibodies to herpes simplex virus type 1 (HSV-1) in human serum, in K2-EDTA anticoagulated human plasma from venous blood, and in human fingerstick K2-EDTA anticoagulated whole blood obtained with the Theranos Capillary Tubes and Nanotainer Tubes. The test is indicated for sexually active individuals and expectant mothers as an aid in the presumptive diagnosis of HSV-1 infection. The predictive value of positive and negative results depends on the population's prevalence and the pretest likelihood of HSV-1.
The test is not FDA cleared for screening blood or plasma donors. The performance of this assay has not been established for use in a pediatric population, neonates and immunocompromised patients.
The Theranos HSV-1 IgG Assay is for use with the Theranos System which performs automated sample processing steps and result analysis.
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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3
510(k) SUMMARY K143236
I. GENERAL INFORMATION
Submitter: Theranos, Inc. 1701 Page Mill Road Palo Alto, CA 94304 Phone: 650-838-9292 Fax: 650-838-9165
Contact Person: Brad Arington Associate Director, Regulatory Phone: 650-856-7304 650-838-9165 Fax: Email: barington@theranos.com
Date Prepared: June 29, 2015
II. DEVICE INFORMATION
| Trade Name: | Theranos™ Herpes Simplex Virus-1 (HSV-1) IgG Assay |
|---|---|
| Common Name: | HSV-1 IgG assay |
| Regulation Number: | 21 CFR§866.3305 |
| Regulation Name: | Herpes simplex virus serological assays |
| Regulatory Class: | Class II |
| Product Code: | MXJ (Enzyme Linked Immunosorbent Assay, Herpes Simplex Virus, HSV-1) |
| Panel: | Microbiology (83) |
III. PREDICATE DEVICE
HerpeSelect® 1 and 2 Immunoblot IgG (K000238; Focus Diagnostics, Inc.)
4
IV. DEVICE DESCRIPTION
The Theranos HSV-1 IgG Assay is for use with the Theranos System. The Theranos System performs automated sample processing steps and analysis to produce the test results.
The Theranos HSV-1 IgG Assay is a three-step sandwich immunoassav with an HSV-1 glycoprotein G (gG) recombinant antigen coated surface, an anti-human IgG detection reagent conjugated to alkaline phosphatase (AP) and chemiluminescent substrate. During the first incubation step, the HSV-1 IgG antibodies present in the positive control and sample bind to the gG recombinant antigen on the coated surface. Following the first incubation step, unbound materials are removed with a wash cycle. Then the detection reagent-AP conjugate is added and during the second incubation step, the detection reagent-AP conjugate reacts with the HSV-1 IgG antibodies already bound to the capture surface. Following the second incubation, unbound materials are removed with a wash cycle. The chemiluminescent substrate is added to the capture-analyte-detection complex during the third incubation step to initiate the chemiluminescence reaction. Light generated by this reaction is detected and analyzed by the Theranos System using a calibration function to determine the cut-off index (COI) values for the sample and controls. The results for the Positive and Negative controls must be within specified limits for a run to be considered valid.
V. INDICATIONS FOR USE
The Theranos™ HSV-1 IgG Assay is a chemiluminescent immunoassay intended for the qualitative detection of IgG antibodies to herpes simplex virus type 1 (HSV-1) in human serum, in K2-EDTA anticoagulated human plasma from venous blood, and in human fingerstick K2-EDTA anticoagulated whole blood obtained with the Theranos Capillary Tubes and Nanotainer Tubes. The test is indicated for sexually active individuals and expectant mothers as an aid in the presumptive diagnosis of HSV-1 infection. The predictive value of positive and negative results depends on the population's prevalence and the pretest likelihood of HSV-1.
The test is not FDA cleared for screening blood or plasma donors. The performance of this assay has not been established for use in a pediatric population, neonates and immunocompromised patients.
The Theranos HSV-1 IgG Assay is for use with the Theranos System which performs automated sample processing steps and result analysis.
5
COMPARISON OF TECHNOLOGICAL CHARACTERISTICS WITH THE PREDICATE DEVICE VI.
Table 1: Similarities between the Theranos HSV-1 IgG Assay and the Predicate
| Characteristic | Theranos™ HSV-1 IgG Assay
(K143236) | Focus HerpeSelect® 1 and 2
Immunoblot IgG
(K000238) |
|----------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended use | Qualitative test to detect presence or
absence of IgG antibodies to HSV-1
in human serum, in K2-EDTA
anticoagulated human plasma from
venous blood, and in human
fingerstick K2-EDTA anticoagulated
whole blood obtained with the
Theranos Capillary Tubes and
Nanotainer Tubes. Indicated for
testing sexually active individuals and
expectant mothers as an aid in
presumptive diagnosis of HSV-1
infection. The predictive value of
positive or negative results depends
on the population's prevalence and the
pretest likelihood of HSV-1 infection. | Qualitative test to detect presence or
absence of IgG antibodies to HSV-1 and
HSV-2 in human sera. Indicated for
testing sexually active adults or expectant
mothers as an aid in presumptive
diagnosis of HSV-1 and HSV-2 infection.
The predictive value of positive or
negative results depends on the
population's prevalence and the pretest
likelihood of HSV-1 and HSV-2 infection. |
Table 2: Differences between the Theranos HSV-1 IgG Assay and the Predicate
| Characteristic | Theranos™ HSV-1 IgG Assay
(K143236) | Focus HerpeSelect® 1 and 2
Immunoblot IgG
(K000238) |
|--------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------|
| Specimen
Types | Venous serum, K2-EDTA anticoagulated human plasma from venous blood, Human fingerstick K2-EDTA anticoagulated whole blood obtained with the Theranos Capillary Tubes and Nanotainer Tubes | Venous Serum |
| Type of Assay | Chemiluminescent immunoassay | Nitrocellulose Immunoblot |
| Sample
Handling | Automated sample handling/processing | Manual sample handling/processing |
| Capture
Reagent | HSV-1 recombinant antigen (gG1) | HSV-1/HSV-2 antigen immobilized on nitrocellulose membrane |
VII. PERFORMANCE
To characterize performance of the Theranos HSV-1 IgG immunoassay the following studies were conducted:
Precision - CLIA Laboratory Model, Venous Serum
6
A study for estimating the precision of the Theranos HSV-1 IgG Assay for venous serum samples in a CLIA Laboratory model was performed by testing a panel of 6 serum samples spanning the analytical range [negative (A), high negative (B), equivocal (C), low positive (D), moderate positive (E), and positive (F)]. The precision study was conducted at one site with thirty five (35) TSPU devices, three (3) lots of cartridges and sixteen (16) operators in total. The study duration was 13 days in total. Details of the study design for different samples are presented in Table 3 below.
| Panel | Valid Replicates | No. of | No. of | No. of | No. of Invalid | |||
|---|---|---|---|---|---|---|---|---|
| Member | Total | Lot 1 | Lot 2 | Lot 3 | Devices | Days | Operators | Replicates |
| A | ||||||||
| (Neg.) | 91 | 26 | 38 | 27 | 35 | 7 | 14 | 3 |
| B | ||||||||
| (High Neg.) | 88 | 24 | 37 | 27 | 28 | 7 | 14 | 2 |
| C | ||||||||
| (Equivocal) | 78 | 27 | 44 | 8* | 35 | 8 | 16 | 3 |
| D | ||||||||
| (Low Pos.) | 80 | 25 | 27 | 28 | 11 | 2 | 4 | 4 |
| E | ||||||||
| (Mod. Pos.) | 64 | 25 | 13 | 26 | 13 | 2 | 6 | 1 |
| F | ||||||||
| (Pos.) | 69 | 25 | 19 | 25 | 15 | 2 | 4 | 3 |
Table 3: Design of Precision Study: Numbers of Replicates, Devices, Days and Onerators
*Sufficient cartridges from reagent lot #3 were not available.
Results of the precision study are presented in Table 4.
| Panel
Member | Mean
(COI) | | Repeatability
(same device,
same lot) | Between-
device | Between-
lot | Precision
(same
device,
different
lot) | Precision
(different
device, same
lot) | Precision
(different
device,
different
lot) |
|------------------|---------------|-----|---------------------------------------------|--------------------|-----------------|----------------------------------------------------|-------------------------------------------------|---------------------------------------------------------|
| A
(Neg.) | 0.425 | SD | 0.049 | 0.007 | 0.000 | 0.049 | 0.049 | 0.049 |
| | | %CV | 11.5% | 1.6% | 0% | 11.5% | 11.6% | 11.6% |
| B
High Neg.) | 0.648 | SD | 0.086 | 0.011 | 0.029 | 0.091 | 0.087 | 0.092 |
| | | %CV | 13.3% | 1.7% | 4.5% | 14.1% | 13.4% | 14.2% |
| C
Equivocal) | 1.016 | SD | 0.093 | 0.062 | 0.065 | 0.113 | 0.112 | 0.129 |
| | | %CV | 9.1% | 6.1% | 6.4% | 11.1% | 11.0% | 12.7% |
| D
(Low Pos. | 1.727 | SD | 0.208 | 0.098 | 0.013 | 0.208 | 0.230 | 0.230 |
| | | %CV | 12.0% | 5.7% | 0.8% | 12.0% | 13.3% | 13.3% |
| E
(Mod. Pos.) | 3.809 | SD | 0.305 | 0.276 | 0.108 | 0.324 | 0.411 | 0.425 |
| | | %CV | 8.0% | 7.3% | 2.8% | 8.5% | 10.8% | 11.2% |
| F
(Pos.) | 8.996 | SD | 0.807 | 0.437 | 0.000 | 0.807 | 0.918 | 0.918 |
| | | %CV | 9.0% | 4.9% | 0.0% | 9.0% | 10.2% | 10.2% |
Table 4: Summary of Precision Study Results
7
Table 5 presents percent of invalid results and percents of negative, equivocal and positive among valid results for each sample.
| Panel
Member | Mean
(COI) | Number of
Replicates | Percent of
Invalid | Percent of
Negative
among
Valid | Percent of
Equivocal
among
Valid | Percent of
Positive
among
Valid |
|------------------|---------------|-------------------------|-----------------------|------------------------------------------|-------------------------------------------|------------------------------------------|
| A
(Neg.) | 0.425 | 94 | 3.2%
(3/94) | 100%
(91/91) | | |
| B
(High Neg.) | 0.648 | 90 | 2.2%
(2/90) | 100%
(88/88) | | |
| C
(Equivocal) | 1.016 | 81 | 3.7%
(3/81) | 17.9%
(14/78) | 60.3%
(47/78) | 21.8%
(17/78) |
| D
(Low Pos.) | 1.727 | 84 | 4.8%
(4/84) | | | 100%
(80/80) |
| E
(Mod. Pos.) | 3.809 | 65 | 1.5%
(1/65) | | | 100%
(64/64) |
| F
(Pos.) | 8.996 | 72 | 4.2%
(3/72) | | | 100%
(69/69) |
Table 5: Percent of Invalid Results and Percents of Negative, Equivocal and Positive among Valid Results
The results of the study demonstrate that the precision of the Theranos HSV-1 IgG Assay (including different TSPU devices, different lots of cartridges, and different operators) when performed in a CLIA Laboratory was in the range 10.2% to 14.2%.
Precision - CLIA Laboratory Model, Fingerstick Whole Blood
A study for estimating the precision of the Theranos HSV-1 IgG Assay for fingerstick whole blood samples in a CLIA Laboratory model was performed by testing a panel of 3 fingerstick plasma samples spanning the analytical range [high negative (P), equivocal (Q), moderate positive (R)]. The precision study was conducted at one site with thirty six (36) TSPU devices, three (3) lots of cartridges and nine (9) operators in total. The study duration was 4 days in total. Details of the study design for different samples are presented in Table 6 below.
Table 6: Design of Precision Study: Numbers of Replicates, Devices, Days and Operators
| Panel
Member | Valid Replicates | | | | No. of
Devices | No. of
Days | No. of
Operators | No. of Invalid
Replicates |
|------------------|------------------|-------|-------|-------|-------------------|----------------|---------------------|------------------------------|
| | Total | Lot 1 | Lot 2 | Lot 3 | | | | |
| P
(High Neg.) | 168 | 56 | 56 | 56 | 30 | 4 | 9 | 3* |
| Q
(Equivocal) | 168 | 56 | 56 | 56 | 29 | 4 | 9 | 2* |
| R
(Mod. Pos.) | 168 | 56 | 56 | 56 | 27 | 4 | 9 | 2* |
*All invalid replicates were repeated
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| Table 7: Summary of Precision Study Results | ||||||||
|---|---|---|---|---|---|---|---|---|
| Panel | ||||||||
| Member | Mean | |||||||
| (COI) | Repeatability | |||||||
| (same device, | ||||||||
| same lot) | Between- | |||||||
| device | Between- | |||||||
| lot | Precision | |||||||
| (same | ||||||||
| device, | ||||||||
| different | ||||||||
| lot) | Precision | |||||||
| (different | ||||||||
| device, | ||||||||
| same lot) | Precision | |||||||
| (different | ||||||||
| device, | ||||||||
| different | ||||||||
| lot) | ||||||||
| P | ||||||||
| (High Neg.) | 0.888 | SD | 0.083 | 0.006 | 0.050 | 0.096 | 0.083 | 0.097 |
| %CV | 9.3% | 0.7% | 5.6% | 10.9% | 9.3% | 10.9% | ||
| Q | ||||||||
| (Equivocal) | 1.047 | SD | 0.094 | 0.025 | 0.069 | 0.117 | 0.098 | 0.119 |
| %CV | 9.0% | 2.4% | 6.6% | 11.1% | 9.3% | 11.4% | ||
| R | ||||||||
| (Mod. Pos.) | 3.241 | SD | 0.342 | 0.122 | 0.157 | 0.377 | 0.363 | 0.396 |
| %CV | 10.6% | 3.8% | 4.9% | 11.6% | 11.2% | 12.2% |
Results of the precision study are presented in Table 7.
Table 8 presents percent of invalid results and percents of negative, equivocal and positive among valid results for each sample.
| Panel
Member | Mean
(COI) | Number of
Replicates | Percent of
Invalid | Percent of
Negative
among Valid | Percent of
Equivocal
among Valid | Percent of
Positive
among
Valid |
|------------------|---------------|-------------------------|-----------------------|---------------------------------------|----------------------------------------|------------------------------------------|
| P
(High Neg.) | 0.888 | 171 | 1.8%
(3/171) | 58.3%
(98/168) | 40.5%
(68/168) | 1.2%
(2/168) |
| Q
(Equivocal) | 1.047 | 170 | 1.2%
(2/170) | 6.5% (11/168) | 63.1%
(106/168) | 30.4%
(51/168) |
| R
(Mod. Pos.) | 1.016 | 170 | 1.2%
(2/170) | | | 100%
(168/168) |
Table 8: Percents of Positive. Equivocal. Negative and Invalid Results
The results of the study demonstrate that precision of the Theranos HSV-1 IgG Assay (including different TSPU devices, different lots of cartridges, and different operators) when performed in a CLIA Laboratory was in the range from 10.9% to 12.2%.
Reproducibility
A study designed to process multiple fingerstick whole blood samples from individual subjects was performed to evaluate the reproducibility of the Theranos HSV-1 IgG Assay when used with Theranos Capillary Tubes and Nanotainer Tubes. The study was conducted at 3 collection sites with 10 subjects at each site. From each of 30 subjects, 9 Capillary Tubes and Nanotainer Tubes from 3 manufacturing lots (i.e. 3 Capillary Tubes and Nanotainer Tubes per lot) and 2 serum separator tubes (SSTs) were collected. Each subject had the following measurements:
- Each of the 9 Capillary Tubes and Nanotainer Tubes was tested. These data were . used for evaluation of between-Capillary Tubes and Nanotainer Tubes imprecision, between-lot imprecision and total imprecision that includes between-Capillary Tubes and Nanotainer Tubes and between-lot imprecisions.
- One Nanotainer Tube (from one of the 3rd lot of Capillary Tubes and Nanotainer Tubes for each subject) was tested in duplicate via recovering a sample from one
9
Capillary Tubes and Nanotainer Tubes and transferring a sample to another Capillary Tubes and Nanotainer Tubes. These data were used for evaluation of within-Capillary Tubes and Nanotainer Tubes imprecision.
- . Each of the 2 SSTs was tested. These data were used for evaluation of between-SST imprecision.
For samples with mean COI value at the baseline ≥0.5, percent differences were calculated and for samples with mean COI value at the baseline 0.5 | |
| | | Difference averaged over all samples | The largest observed difference among samples | Percent difference averaged over all samples | The largest observed percent difference among samples |
| Stored at 2-8C, 48 hrs | Venous serum | 0.006 | 0.006 | 1.0% | 13.6% |
| | Venous K2-EDTA plasma | -0.007 | -0.007 | 2.3% | 13.3% |
| | Fingerstick K2-EDTA plasma from whole blood | 0.003 | 0.003 | -0.4% | 13.9% |
| Stored at -20, 1 week | Venous serum | 0.008 | 0.015 | 0.8% | 13.3% |
| | Venous K2-EDTA plasma | 0.003 | 0.005 | -1.0% | 12.7% |
| | Fingerstick K2-EDTA plasma from whole blood | 0.001 | 0.008 | 1.8% | -13.9% |
| Freeze thaw cycles, n=3 | Venous serum | 0.007 | 0.021 | -0.1% | 13.6% |
| | Venous K2-EDTA plasma | 0.021 | 0.037 | -1.7% | -13.4% |
| | Fingerstick K2-EDTA plasma from whole blood | 0.006 | 0.022 | -1.0% | 13.6% |
| Stored at room temp, 6 hrs | Venous serum | -0.001 | -0.011 | -3.2% | -11.9% |
| | Venous K2-EDTA plasma | 0.002 | 0.022 | 0.1% | 13.7% |
| | Fingerstick K2-EDTA plasma from whole blood | -0.004 | -0.026 | 1.1% | 13.9% |
Within 2 hours after collection, one aliquot of each sample type or matrix was tested with the Theranos HSV-1 IgG Assay in duplicate, to establish the value at baseline. The samples were stored in Nanotainer Tubes under the appropriate conditions. Comparison of an average of two replicates at the predetermined time points with the average of two replicates at baseline was performed. For samples with a mean COI value at the baseline ≥0.5, percent differences were calculated and for samples with a mean COI value at the baseline 0.5 must be less than ±10% and a difference averaged over all samples with baseline COI mean 0.5 and must be less than 0.08 for the samples with baseline mean COI value