(139 days)
Not Found
No
The device description details a standard immunoassay technique (ELFA) and automated instrument processing. There is no mention of AI or ML in the device description, intended use, or performance studies. The calculations are based on calibration curves and fluorescence thresholds, which are standard analytical methods, not AI/ML.
No
The device is an automated in vitro diagnostic test used to determine the concentration of human procalcitonin, aiding in risk assessment and antibiotic therapy decisions, rather than directly treating a condition.
Yes
This device is intended to aid in risk assessment for severe sepsis and septic shock, aid in assessing the 28-day risk of all-cause mortality, and aid in decision-making for antibiotic therapy and discontinuation. These are all diagnostic or prognostic purposes, helping to inform clinical decisions about a patient's condition and treatment.
No
The device description clearly outlines a hardware-based system involving an instrument (VIDAS® family), Solid Phase Receptacle (SPR®), and reagent strips, utilizing an ELFA technique for sample analysis. This is not a software-only device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states that the device is for the "determination of human procalcitonin in human serum or plasma". This involves testing biological samples in vitro (outside the body).
- Device Description: The description details an "automated test" using the ELFA technique, which is a laboratory method for analyzing biological samples. It describes the use of reagents, a solid phase, and a fluorescent detection system, all characteristic of an in vitro diagnostic assay.
- Performance Studies: The performance studies describe testing of human samples to determine analytical performance (limits of detection, precision, interference) and clinical performance in aiding medical decisions based on the test results. This is consistent with the evaluation of an IVD.
The definition of an In Vitro Diagnostic (IVD) is a medical device that is used to examine specimens, such as blood, tissue, or urine, taken from the human body to help detect infections, diagnose a medical condition, prevent disease, or monitor drug therapies. This device clearly fits this definition.
N/A
Intended Use / Indications for Use
VIDAS® B+R+A+H+M+S PCT™ (PCT) is an automated test for use on the instruments of the VIDAS® family for the determination of human procalcitonin in human serum or plasma (lithium heparinate) using the ELFA (Enzyme-Linked Fluorescent Assay) technique.
Used in conjunction with other laboratory findings and clinical assessments, VIDAS® B•R•A•H•M•S PCT™ is intended for use as follows:
· to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock.
· to aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, using a change in PCT level over time.
· to aid in decision making on antibiotic therapy for patients with suspected or confirmed lower respiratory tract infections (LRTI) - defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) - in an inpatient setting or an emergency department,
· to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis.
Product codes
PRI, PMT, NTM
Device Description
The assay principle combines a one-step immunoassay sandwich method with a final fluorescent detection (ELFA).
The Solid Phase Receptacle (SPR®), serves as the solid phase as well as the pipetting device. Reagents for the assay are ready-to-use and pre-dispensed in the sealed reagent strips.
All of the assay steps are performed automatically by the instrument. The sample is transferred into the wells containing anti-procalcitonin antibodies labeled with alkaline phosphatase (conjugate). The sample/conjugate mixture is cycled in and out of the SPR® several times. This operation enables the antigen to bind with the immunoglobulins fixed to the interior wall of the SPR® and the conjugate to form a sandwich. Unbound compounds are eliminated during washing steps.
Two detection steps are performed successively. During each step, the substrate (4-Methylumbelliferyl phosphate) is cycled in and out of the SPR®. The conjugate enzyme catalyzes the hydrolysis of this substrate into a fluorescent product (4-Methyl-umbelliferone) the fluorescence of which is measured at 450 nm. The intensity of the fluorescence is proportional to the concentration of antigen present in the sample.
At the end of the assay, results are automatically calculated by the instrument in relation to two calibration curves corresponding to the two detection steps. A fluorescence threshold value determines the calibration curve to be used for each sample. The results are then printed out.
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
Not Found
Intended User / Care Setting
ICU, emergency department or other medical wards, inpatient setting or an emergency department.
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
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Nonclinical Tests:
Limits of detection and quantitation:
Limit of Blank (LoB): 0.01 ng/mL
Limit of Detection (LoD): 0.03 ng/mL
Limit of Quantitation (LoQ): 0.05 ng/mL (with bias ≤ 10%, %CV ≤ 20% and Total Error ≤ 50%.)
Precision:
Study performed according to CLSI® document EP5-A3.
Sample Size: 11 human samples covering the measuring range, tested in duplicate in 2 runs per day, over 20 days. N=240 values for each sample.
Data Source: 3 VIDAS® and 3 VIDAS® 3 instruments at 3 sites (one instrument per site).
Results in tables (refer to original document for full tables): Repeatability, Between-Day precision, Within-Laboratory precision, and Reproducibility / Total precision were estimated for each sample.
Study of drugs and other potentially interfering substances:
Study performed following CLSI® document EP7-A2.
Results: No interference was observed at the concentration tested for various drugs and substances (e.g., Acetominophen, Alcohol, Hemoglobin, Bilirubin).
Clinical performance data:
Decision making on antibiotic therapy for patients with suspected or confirmed LRTI:
Study Type: Two systematic literature reviews along with study and patient-level meta-analyses.
Sample Size:
Study-level meta-analysis: 11 randomized control trials (RCTs) (published 2004-2016), 4090 patients.
Patient-level meta-analysis: 13 RCTs (published 2004-2011), 3142 patients.
Key results: PCT guided antibiotic therapy resulted in:
- 19.2% reduction in relative antibiotic initiation for all patients
- 38% reduction in overall antibiotic exposure (i.e. total days of antibiotic therapy) for inpatients
- 51% reduction in overall antibiotic exposure (i.e. total days of antibiotic therapy) for patients in emergency departments
- 2.9 day reduction in antibiotic duration [1.25 day reduction in study-level]
- 3.6 day reduction in total antibiotic exposure [2.79 day reduction in study-level]
- No negative effects in regards to mortality, complications, or length of stay.
Additionally, a modified DOOR/RADAR analysis found that PCT-guided management had a statistically significant improvement in ranked patient outcomes compared to standard management.
Decision making on antibiotic discontinuation for septic patients:
Study Type: Two systematic literature reviews along with study and patient-level meta-analyses.
Sample Size:
Study-level meta-analysis: 10 RCTs (published 2008-2016), 3489 patients.
Patient-level meta-analysis: 5 RCTs (published 2008-2010), 598 patients.
Key results: PCT guided antibiotic therapy resulted in:
- 1.5 day reduction in antibiotic duration
- 3.2 day reduction in total antibiotic exposure
- 23% reduction in overall antibiotic exposure (i.e. total days of antibiotic therapy)
- No negative effects in regards to mortality, hospital length of stay, or ICU length of stay.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found. (Quantitative results for reduction in antibiotic use and duration are provided in the performance study summary.)
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 866.3215 Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis.
(a)
Identification. A device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis is identified as an in vitro device intended for the detection and qualitative and/or quantitative measurement of one or more non-microbial analytes in human clinical specimens to aid in the assessment of patients with suspected sepsis when used in conjunction with clinical signs and symptoms and other clinical and laboratory findings.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include the device's detailed Indications for Use statement describing what the device detects and measures, the results provided to the user, whether the measure is qualitative and/or quantitative, the clinical indications for which the test is to be used, and the specific population(s) for which the device use is intended.
(2) Premarket notification submissions must include detailed documentation of the device description, including (as applicable), all device components, software, ancillary reagents required but not provided, explanation of the device principle and methodology, and for molecular devices include detailed documentation of the primer/probe sequence, design, and rationale for sequence selection.
(3) Premarket notification submissions must include detailed documentation of applicable analytical studies, such as, analytical sensitivity (Limit of Detection, Limit of Blank, and Limit of Quantitation), precision, reproducibility, analytical measuring range, interference, cross-reactivity, and specimen stability.
(4) Premarket notification submissions must include detailed documentation of a prospective clinical study or, if appropriate, results from an equivalent sample set. This detailed documentation must include the following information:
(i) Results must demonstrate adequate device performance relative to a well-accepted comparator.
(ii) Clinical sample results must demonstrate consistency of device output throughout the device measuring range likely to be encountered in the Intended Use population.
(iii) Clinical study documentation must include the original study protocol (including predefined statistical analysis plan), study report documenting support for the Indications for Use(s), and results of all statistical analyses.
(5) Premarket notification submissions must include evaluation of the level of the non-microbial analyte in asymptomatic patients with demographic characteristics (
e.g., age, racial, ethnic, and gender distribution) similar to the Intended Use population.(6) As part of the risk management activities performed under 21 CFR 820.30 design controls, you must document an appropriate end user device training program that will be offered as part of your efforts to mitigate the risk of failure to correctly operate the instrument.
(7) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling, and a detailed explanation of the interpretation of the limitations of the samples (
e.g., collected on day of diagnosis) must be included in the device's 21 CFR 809.10(b)(10) compliant labeling.
0
Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized caduceus symbol, which is a staff with two snakes entwined around it. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged around the symbol in a circular fashion. The logo is black and white.
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
May 22, 2017
bioMérieux, Inc. John Albright Regulatory Affairs Manager 595 Anglum Rd., Hazelwood, MO 63042 US
Re: K162827 Trade/Device Name: VIDAS B.R.A.H.M.S. PCT (PCT) Regulation Number: 21 CFR 866.3215 Regulation Name: Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis Regulatory Class: Class II Product Code: PRI, PMT, NTM Dated: January 25, 2017 Received: January 25, 2017
Dear Mr. Albright:
This letter corrects our substantially equivalent letter of February 23, 2017.
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
1
CFR Part 807); labeling 21 CFR Parts 801 and 809; medical device 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 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 regulation 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/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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.
Steven R. Gitterman -S for
Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiological Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Form Approved: OMB No. 0910-0120
Expiration Date: January 31, 2017
See PRA Statement below.
DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
510(k) Number (if known) K162827
Device Name
VIDAS B.R.A.H.M.S PCT (PCT)
Indications for Use (Describe)
VIDAS® B+R+A+H+M+S PCT™ (PCT) is an automated test for use on the instruments of the VIDAS® family for the determination of human procalcitonin in human serum or plasma (lithium heparinate) using the ELFA (Enzyme-Linked Fluorescent Assay) technique.
Used in conjunction with other laboratory findings and clinical assessments, VIDAS® B•R•A•H•M•S PCT™ is intended for use as follows:
· to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock.
· to aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission, using a change in PCT level over time.
· to aid in decision making on antibiotic therapy for patients with suspected or confirmed lower respiratory tract infections (LRTI) - defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic
obstructive pulmonary disease (AECOPD) - in an inpatient setting or an emergency department,
· to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis.
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)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
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Image /page/3/Picture/0 description: The image shows the logo for bioMérieux. The logo features the company name in gray, block letters. Above the name is a blue and white globe-like design with a green curved line extending upwards from it. Below the name is a horizontal bar that transitions from yellow to green.
510(K) SUMMARY
This 510(k) summary of safety and effectiveness information is being submitted in accordance with the requirement of Safe Medical Devices Act of 1990 and 21 CFR 807.92.
VIDAS® B-R-A-H-M-S PCT™
A. Submitter Information
| Submitter's Name: | bioMérieux, Inc. |
|---|---|
| Address: | 595 Anglum Road |
| Hazelwood, MO 63042 | |
| Contact Person: | John Albright |
| Phone Number: | 314-731-8546 |
| Fax Number: | 314-731-8689 |
| Date of Preparation: | October 6, 2016 |
B. Device Name
| Trade Name: | VIDAS® B·R·A·H·M·S PCT™ (PCT) |
|---|---|
| Common Name: | Endotoxin Assay |
| Classification Names: | Device to detect and measure procalcitonin (pct) in human clinical |
| specimens (21 CFR 866.3215, Product Code PMT) | |
| Procalcitonin assay (21 CFR 866.3215, Product Code PRI) |
C. Predicate Devices
VIDAS® B·R·A·H·M·S PCT™ (K160911)
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Image /page/4/Picture/0 description: The image features the logo of bioMérieux, a company specializing in in-vitro diagnostics. The logo consists of the company name in a sans-serif font, with the "bio" part in a darker shade and the "Mérieux" part in a lighter shade. Above the name is a stylized graphic that resembles a globe with vertical lines, topped by a curved green line that looks like a sprout or a blade of grass. Below the name is a gradient bar that transitions from yellow to green, adding a visual element to the logo.
D. Device Description
The assay principle combines a one-step immunoassay sandwich method with a final fluorescent detection (ELFA).
The Solid Phase Receptacle (SPR®), serves as the solid phase as well as the pipetting device. Reagents for the assay are ready-to-use and pre-dispensed in the sealed reagent strips.
All of the assay steps are performed automatically by the instrument. The sample is transferred into the wells containing anti-procalcitonin antibodies labeled with alkaline phosphatase (conjugate). The sample/conjugate mixture is cycled in and out of the SPR® several times. This operation enables the antigen to bind with the immunoglobulins fixed to the interior wall of the SPR® and the conjugate to form a sandwich. Unbound compounds are eliminated during washing steps.
Two detection steps are performed successively. During each step, the substrate (4-Methylumbelliferyl phosphate) is cycled in and out of the SPR®. The conjugate enzyme catalyzes the hydrolysis of this substrate into a fluorescent product (4-Methyl-umbelliferone) the fluorescence of which is measured at 450 nm. The intensity of the fluorescence is proportional to the concentration of antigen present in the sample.
At the end of the assay, results are automatically calculated by the instrument in relation to two calibration curves corresponding to the two detection steps. A fluorescence threshold value determines the calibration curve to be used for each sample. The results are then printed out.
E. Intended Use
VIDAS® B·R·A·H·M·S PCT™ (PCT) is an automated test for use on the instruments of the VIDAS® family for the determination of human procalcitonin in human serum or plasma (lithium heparinate) using the ELFA (Enzyme-Linked Fluorescent Assay) technique.
Used in conjunction with other laboratory findings and clinical assessments, VIDAS® B+R+A+H+M+S PCT™ is intended for use as follows:
- to aid in the risk assessment of critically ill patients on their first day of ICU admission for . progression to severe sepsis and septic shock,
- . to aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission. using a change in PCT level over time.
- . to aid in decision making on antibiotic therapy for patients with suspected or confirmed lower respiratory tract infections (LRTI) - defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) - in an inpatient setting or an emergency department,
- . to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis.
F. Technological Characteristics Summary
A general comparison of the similarities and differences of the assay with the predicates is presented in the following table.
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Image /page/5/Picture/0 description: The image shows the logo for bioMérieux. The logo consists of the company name in a sans-serif font, with the "BIO" portion in a darker gray and the "MÉ RIEUX" portion in a lighter gray. Above the name is a stylized graphic of a globe with blue lines and a green sprout emerging from the top. The logo is set against a background that transitions from yellow to green.
| Item | Proposed Device:
VIDAS® B-R-A-H-M-STM PCT | Predicate device:
VIDAS® B-R-A-H-M-S PCTTM (K160911) |
|-----------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended
Use and
indications
for use | VIDAS® B-R-A-H-M-S PCTTM (PCT) is an
automated test for use on the instruments of the
VIDAS® family for the determination of human
procalcitonin in human serum or plasma (lithium
heparinate) using the ELFA (Enzyme-Linked
Fluorescent Assay) technique.
Used in conjunction with other laboratory
findings and clinical assessments, VIDAS®
B·R·A·H·M·S PCTTM is intended for use as
follows:
to aid in the risk assessment of critically ill
patients on their first day of ICU admission
for progression to severe sepsis and
septic shock, to aid in assessing the cumulative 28-day
risk of all-cause mortality for patients
diagnosed with severe sepsis or septic
shock in the ICU or when obtained in the
emergency department or other medical
wards prior to ICU admission, using a
change in PCT level over time, to aid in decision making on antibiotic
therapy for patients with suspected or
confirmed lower respiratory tract infections
(LRTI) - defined as community-acquired
pneumonia (CAP), acute bronchitis, and
acute exacerbation of chronic obstructive
pulmonary disease (AECOPD) – in an
inpatient setting or an emergency
department, to aid in decision making on antibiotic
discontinuation for patients with suspected
or confirmed sepsis. | VIDAS® B-R-A-H-M-S PCTTM (PCT) is an
automated test for use on the instruments of the
VIDAS® family for the determination of human
procalcitonin in human serum or plasma (lithium
heparinate) using the ELFA (Enzyme-Linked
Fluorescent Assay) technique.
VIDAS® B-R-A-H-M-S PCTTM (PCT) is intended for
use in conjunction with other laboratory findings
and clinical assessments to aid in the risk
assessment of critically ill patients on their first day
of ICU admission for progression to severe sepsis
and septic shock.
VIDAS® B-R-A-H-M-S PCTTM (PCT) is also
intended for use to determine the change in PCT
level over time as an aid in assessing the
cumulative 28-day risk of all-cause mortality in
conjunction with other laboratory findings and
clinical assessments for patients diagnosed with
severe sepsis or septic shock in the ICU or when
obtained in the emergency department or other
medical wards prior to ICU admission.
Procalcitonin (PCT) is a biomarker associated with
the inflammatory response to bacterial infection that
aids in the risk assessment of critically ill patients
on their first day of Intensive Care Unit (ICU)
admission for progression to severe sepsis and
septic shock. The percent change in PCT level over
time also aids in the prediction of cumulative 28-day
mortality in patients with severe sepsis and septic
shock.
PCT levels on the first day of ICU admission above
2.0 ng/mL are associated with a higher risk for
progression to severe sepsis and/or septic shock
than PCT levels below 0.5 ng/mL.
A PCT level that declines ≤ 80% from the day that
severe sepsis or septic shock was clinically
diagnosed (Day 0) to four days after clinical
diagnosis (Day 4) is associated with higher
cumulative 28-day risk of all-cause mortality than a
decline > 80%.
The combination of the first PCT level (≤ 2.0 ng/mL
or > 2.0 ng/mL) at initial diagnosis of severe sepsis
or septic shock with the patient's clinical course and
the change in PCT level over time until Day 4
provides important additional information about the
mortality risk.
The PCT level on Day 1 (the day after severe
sepsis or septic shock is first clinically diagnosed)
can be used to calculate the percent change in PCT
level at Day 4 if the Day 0 measurement is
unavailable. |
| Specimen | Human serum or plasma (lithium heparinate). | Same as the proposed device |
| Analyte | Procalcitonin (PCT) | Same as the proposed device |
| Item | Proposed Device:
VIDAS® B-R-A-H-M-S™ PCT | Predicate device:
VIDAS® B-R-A-H-M-S PCT™ (K160911) |
| Automated | Automated assay | Same as the proposed device |
| Assay
Technique | ELFA (Enzyme-Linked Fluorescent Assay)
technique. | Same as the proposed device |
| Assay
principle | Immunoassay based on sandwich principle | Same as the proposed device |
| Detection
method | Fluorescence (ELFA) of 4-methyl-umbelliferyl
measured at 450 nm | Same as the proposed device |
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Image /page/6/Picture/0 description: The image shows the logo for bioMerieux. The logo features the company name in a sans-serif font, with the word "BIO" in a darker shade of gray and "MERIEUX" in a lighter shade of gray. Above the name is a stylized graphic of a globe with vertical lines on the left side and a green curved line running vertically through the center.
G. Nonclinical Tests
A summary of the non-clinical (analytical) results is presented below.
Limits of detection and quantitation
The Limit of Blank (LoB), the Limit of Detection (LoD) and the Limit of Quantitation (LoQ) were
determined on the VIDAS® and VIDAS® instruments according to the CLSI® EEP17-A recommendations. The limits reported below apply for all the instruments of the VIDAS family:
| Limit of Blank (LoB) | 0.01 ng/mL |
|---|---|
| Limit of Detection (LoD) | 0.03 ng/mL |
| Limit of Quantitation (LoQ) | 0.05 ng/mL |
The LoQ was determined to be 0.05 ng/mL (with bias ≤ 10%, %CV ≤ 20% and Total Error ≤ 50%.)
Precision
The study was performed according to the recommendations of CLSI® document EP5-A3. A panel of 11 human samples covering the measuring range were tested in duplicate in 2 runs per day, over 20 days using 3 VIDAS® and 3 VIDAS® 3 instruments (N=240 values for each sample) at 3 sites (one instrument per site). Two reagent lots were used: 10 days of tests and 6 calibrations were performed for each lot. The repeatability, between-day precision, within-laboratory precision and reproducibility/total precision (between-laboratory precision) were estimated for each sample and are reported in the following tables:
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Image /page/7/Picture/0 description: The image shows the logo for bioMérieux. The logo features the company name in a sans-serif font, with the "BIO" portion in a darker shade of gray and the "MÉ RIEUX" portion in a lighter shade. Above the company name is a stylized graphic consisting of a blue globe-like shape with curved lines and a green sprout extending upwards through the center.
| VIDAS® | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Sample | N | Mean | ||||||||
| concentration | ||||||||||
| (ng/mL) | Repeatability | Between-Day | ||||||||
| precision | Within-Laboratory | |||||||||
| precision | Reproducibility / | |||||||||
| Total precision | ||||||||||
| Standard | ||||||||||
| Deviation | ||||||||||
| (ng/mL) | CV | |||||||||
| (%) | Standard | |||||||||
| Deviation | ||||||||||
| (ng/mL) | CV | |||||||||
| (%) | Standard | |||||||||
| Deviation | ||||||||||
| (ng/mL) | CV | |||||||||
| (%) | Standard | |||||||||
| Deviation | ||||||||||
| (ng/mL) | CV | |||||||||
| (%) | ||||||||||
| PP12 | 240 | 0.08 | 0.011 | 14.6% | 0.012 | 15.9% | 0.015 | 20.2% | 0.015 | 20.2% |
| PP16 | 240 | 0.10 | 0.009 | 9.0% | 0.011 | 10.4% | 0.016 | 15.9% | 0.016 | 15.9% |
| PS01 | 240 | 0.12 | 0.011 | 8.9% | 0.013 | 10.8% | 0.017 | 14.2% | 0.017 | 14.2% |
| PS02 | 240 | 0.15 | 0.010 | 6.5% | 0.014 | 8.9% | 0.019 | 12.3% | 0.019 | 12.3% |
| PP14 | 240 | 0.23 | 0.009 | 4.0% | 0.011 | 4.9% | 0.016 | 7.1% | 0.016 | 7.1% |
| PS04 | 240 | 0.53 | 0.013 | 2.4% | 0.021 | 4.0% | 0.023 | 4.2% | 0.023 | 4.2% |
| PS05 | 240 | 2.14 | 0.027 | 1.3% | 0.063 | 3.0% | 0.083 | 3.9% | 0.083 | 3.9% |
| PS06 | 240 | 23.12 | 0.504 | 2.2% | 0.882 | 3.8% | 1.020 | 4.4% | 1.020 | 4.4% |
| PS07 | 240 | 92.30 | 3.113 | 3.4% | 5.972 | 6.5% | 6.423 | 7.0% | 6.423 | 7.0% |
| PS08 | 240 | 128.56 | 5.275 | 4.1% | 9.562 | 7.4% | 11.087 | 8.6% | 11.087 | 8.6% |
| PS11 | 240 | 162.99 | 7.308 | 4.5% | 11.377 | 7.0% | 16.082 | 9.9% | 16.082 | 9.9% |
VIDAS® 3
| Sample | N | Mean
concentration
(ng/mL) | Repeatability | | Between-Day
precision | | Within-Laboratory
precision | | Reproducibility /
Total precision | |
|--------|-----|----------------------------------|----------------------------------|-----------|----------------------------------|-----------|----------------------------------|-----------|--------------------------------------|-----------|
| | | | Standard
Deviation
(ng/mL) | CV
(%) | Standard
Deviation
(ng/mL) | CV
(%) | Standard
Deviation
(ng/mL) | CV
(%) | Standard
Deviation
(ng/mL) | CV
(%) |
| PP13 | 240 | 0.08 | 0.008 | 9.4% | 0.009 | 10.4% | 0.015 | 18.2% | 0.015 | 18.2% |
| PP16 | 240 | 0.10 | 0.009 | 9.7% | 0.010 | 10.9% | 0.015 | 15.9% | 0.015 | 15.9% |
| PS01 | 240 | 0.12 | 0.010 | 8.7% | 0.011 | 9.4% | 0.015 | 12.5% | 0.015 | 12.5% |
| PS02 | 239 | 0.15 | 0.013 | 8.3% | 0.014 | 9.3% | 0.017 | 11.2% | 0.017 | 11.2% |
| PP14 | 240 | 0.22 | 0.010 | 4.3% | 0.011 | 4.9% | 0.015 | 6.8% | 0.015 | 6.8% |
| PS04 | 239 | 0.52 | 0.020 | 3.8% | 0.024 | 4.6% | 0.026 | 5.0% | 0.032 | 6.1% |
| PS05 | 240 | 2.06 | 0.041 | 2.0% | 0.073 | 3.5% | 0.098 | 4.8% | 0.102 | 5.0% |
| PS06 | 240 | 21.85 | 0.583 | 2.7% | 0.814 | 3.7% | 0.860 | 3.9% | 0.946 | 4.3% |
| PS07 | 240 | 83.60 | 3.372 | 4.0% | 4.445 | 5.3% | 4.895 | 5.9% | 5.785 | 6.9% |
| PS08 | 240 | 110.83 | 5.495 | 5.0% | 7.091 | 6.4% | 7.927 | 7.2% | 8.525 | 7.7% |
| PS11 | 240 | 140.34 | 6.450 | 4.6% | 10.611 | 7.6% | 11.253 | 8.0% | 12.596 | 9.0% |
8
Image /page/8/Picture/0 description: The image shows the logo for bioMérieux. The logo features the company name in a sans-serif font, with the "BIOMÉ" portion in a darker gray and the "RIEUX" portion in a lighter gray. Above the company name is a stylized graphic consisting of a blue semi-circle with vertical lines, and a curved green line extending from the bottom of the semi-circle. A green and yellow gradient bar is located below the company name.
Study of drugs and other potentially interfering substances
Following the recommendations of CLSI® document EP7-A2, the potential interferences with the following drugs and potentially interfering substances were studied. No interference was observed at the concentration tested.
| Tested drug | Tested concentration |
|---|---|
| Acetominophen | 20 mg/dL |
| Acetylsalicylic Acid | 65.2 mg/dL |
| Alcohol | 400 mg/dL |
| Amoxicillin | 7.53 mg/dL |
| Ampicillin | 5.31 mg/dL |
| Azithromycin | 1.15 mg/dL |
| Beclometasone dipropionate | 0.1 mg/dL |
| Caffeine | 5.98 mg/dL |
| Cefotaxime | 32.13 mg/dL |
| Ceftriaxone | 93.7 mg/dL |
| Celecoxib | 24 mg/dL |
| Cetirizine HCI | 0.36 mg/dL |
| Cromolyn | 2.4 mg/dL |
| Dextromethorphan | 0.14 mg/dL |
| Dobutamine | 0.15 mg/dL |
| Dopamine | 0.11 mg/dL |
| Epinephrine (adrenaline) | 0.18 mg/dL |
| Fluticasone | 0.03 mg/dL |
| Tested drug | Tested concentration |
| Formoterol | 0.0029 mg/dL |
| Furosemide | 5.98 mg/dL |
| Heparin sodium | 3000 UI/L |
| Ibuprofen | 50 mg/dL |
| Imipenem | 18 mg/dL |
| Levoflaxacin | 1.75 mg/dL |
| Linezolid | 48 mg/dL |
| Loratadine | 0.03 mg/dL |
| Naproxen | 50 mg/dL |
| Nicotine | 0.1 mg/dL |
| Noradrenaline | 0.00021 mg/dL |
| Oxymetazoline HCl | 0.009 mg/dL |
| Phenylephrine | 0.018 mg/dL |
| Prednisolone | 0.3 mg/dL |
| Salmeterol | 0.006 mg/dL |
| Theophylline | 4 mg/dL |
| Tiotropium | 0.0022 mg/dL |
| Vancomycin | 10.25 mg/dL |
| Tested Substances | Tested concentrations |
|---|---|
| Protein (albumin) | 6.5 g/dL |
| Hemoglobin | 600 mg/dL |
| Triglycerides | 3000 mg/dL |
| Bilirubin | 33 mg/dL |
9
Image /page/9/Picture/0 description: The image shows the logo for bioMérieux. The logo features a stylized globe with blue and green lines, with a green curved line extending upwards from the globe. Below the globe, the text "BIOMÉRIEUX" is written in a sans-serif font, with the letters in a light gray color. The background transitions from green to yellow.
H. Clinical performance data
A summary of the clinical performance data is presented below.
Decision making on antibiotic therapy for patients with suspected or confirmed LRTI
Two systematic literature reviews were performed along with study and patient-level meta-analyses, which are studies that combine and contrast data from multiple sources to identify patterns among study results. The study-level meta-analysis encompassed 11 randomized control trials (RCTs) which were published between 2004-2016, and included 4090 patient-level meta-analysis encompassed 13 RCTs which were published between 2004-2011, and included 3142 patients.
These meta-analyses concluded that PCT quided antibiotic therapy resulted in:
- 19.2% reduction in relative antibiotic initiation for all patients
- 38% reduction in overall antibiotic exposure (i.e. total days of antibiotic therapy) for inpatients
- . 51% reduction in overall antibiotic exposure (i.e. total days of antibiotic therapy) for patients in emergency departments*
- 2.9 day reduction in antibiotic duration [1.25 day reduction in study-level]
- 3.6 day reduction in total antibiotic exposure [2.79 day reduction in study-level]
- No negative effects in regards to mortality, complications, or length of stay.
*Patients who presented to the Emergency Department and other associated clinics, but were not admitted.
Additionally, a modified DOOR/RADAR analysis, in which patient outcomes were ranked by clinical severity, was conducted on the patient level data, and found that PCT-guided management had a statistically significant improvement in ranked patient outcomes compared to standard management.
Decision making on antibiotic discontinuation for septic patients
Two systematic literature reviews were performed along with study and patient-level meta-analyses, which are studies that combine and contrast data from multiple sources to identify patterns among study results. The study-level meta-analysis encompassed 10 RCTs which were published between 2008-2016, and included 3489 patients. The patient-level meta-analysis encompassed 5 RCTs which were published between 2008-2010, and included 598 patients.
These meta-analyses concluded that PCT guided antibiotic therapy resulted in:
- . 1.5 day reduction in antibiotic duration
- 3.2 day reduction in total antibiotic exposure ●
- 23% reduction in overall antibiotic exposure (i.e. total days of antibiotic therapy) ●
- No negative effects in reqards to mortality, hospital length of stay, or ICU length of stay.
. Conclusion
The results from the non-clinical performance data submitted in this premarket notification are complete and demonstrate that the VIDAS® B·R·A·H·M·S PCT assay is substantially equivalent to the predicate device.