(156 days)
The cassette COBAS INTEGRA Acid / Prostatic Phosphatase contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the catalytic activity of total and prostatic acid phosphatase in serum.
The cassette Roche COBAS INTEGRA Benzodiazepines contains an in vitro diagnostic reagent system intended for use on the COBAS INTEGRA for the semi-quantitative detection of benzodiazepines in human urine using the enzyme ß-glucuronidase.
The COBAS INTEGRA Analyzer and COBAS INTEGRA Reagent cassettes together provide an integrated system for in vitro diagnostic testing. The COBAS INTEGRA Analyzer utilizes three measuring principles, i.e., absorbance, fluorescence polarization and ion-selective electrodes. The analyzer has a throughput of up to 600 tests per hour with STAT samples prioritized and tested immediately. Random sample access, robotics and a user interface optimize time management and streamline workflow. The COBAS INTEGRA can store up to 68 COBAS INTEGRA Reagent Cassettes on board, 24 hours a day at 2-8°C. The COBAS INTEGRA Reagent Cassettes are compact and preparation-free with the added convenience of long term on-board stability. Barcode readers are used to identify newly loaded reagent cassettes, samples for patient identification, and rack inserts and to read calibration and control data from the cassette label. COBAS INTEGRA tests include chemistry, drugs of abuse, immunology, ion selective electrodes, therapeutic drug monitoring, and hematology reagents.
The provided text describes two in vitro diagnostic reagent systems: COBAS INTEGRA Acid/Prostatic Phosphatase (ACPP) and COBAS INTEGRA Benzodiazepines with β-glucuronidase (BNZGL). The 510(k) summary focuses on demonstrating their substantial equivalence to previously marketed devices rather than establishing novel acceptance criteria or performing a comparative effectiveness study in the typical sense of AI/human reader studies.
Here's an analysis of the provided information against your requested categories, acknowledging that some categories may not be directly applicable to this type of device and submission:
1. A table of acceptance criteria and the reported device performance
The document presents performance characteristics for the new devices and compares them to their predicate devices, implying these are the "acceptance criteria" for demonstrating substantial equivalence. Exact numerical acceptance criteria (e.g., "CV must be < X%") are not explicitly stated, but rather the performance is shown to be comparable.
COBAS INTEGRA Acid/Prostatic Phosphatase (ACPP)
| Performance Characteristic | Acceptance Criteria (Implied by Predicate) | Reported Device Performance (COBAS INTEGRA ACPP) |
|---|---|---|
| Total Acid Phosphatase | ||
| Assay range | Linear to 40 U/L | 0 - 100 U/L (Improved range) |
| Precision: Level 1 Mean | 3.1 U/L | 4 U/L |
| Precision: Level 1 CV (within-run) | 2.7 % | 4.5 % |
| Precision: Level 2 Mean | 22.6 U/L | 11 U/L |
| Precision: Level 2 CV (within-run) | 0.51 % | 2.5 % |
| Precision: CV (total) | NA | Level 1: 5.7 %, Level 2: 4.6 % |
| Accuracy: Corr. Coefficient | 0.990 | 0.978 |
| Accuracy: Linear regression | 1.02x + 0.43 U/L | 1.54x - 0.1 U/L |
| Prostatic Acid Phosphatase | ||
| Precision: Level 1 Mean | Not specified | 1 U/L |
| Precision: Level 1 CV (within-run) | Not specified | 23 % |
| Precision: Level 2 Mean | Not specified | 3 U/L |
| Precision: Level 2 CV (within-run) | Not specified | 9.4 % |
| Precision: CV (total) | Not specified | Level 1: 25 %, Level 2: 15 % |
| Accuracy: Corr. Coefficient | 0.997 | 0.996 |
| Accuracy: Linear regression | 1.00x - 0.07 U/L | 1.83x + 0.5 U/L |
COBAS INTEGRA Benzodiazepines with β-glucuronidase (BNZGL)
| Performance Characteristic | Acceptance Criteria (Implied by Predicate) | Reported Device Performance (COBAS INTEGRA BNZGL) |
|---|---|---|
| Assay range | 0 - 300 ng/mL | 0 - 200 ng/mL |
| Cutoff | 100, 200 and 300 ng/mL | 100 ng/mL |
| Precision: Level 1 Mean | 49 ng/mL | 52 ng/mL |
| Precision: Level 1 % CV (within-run) | 7.1 % | 5.1 % |
| Precision: Level 2 Mean | 80 ng/mL | 86 ng/mL |
| Precision: Level 2 % CV (within-run) | 4.3 % | 3.0 % |
| Precision: Level 3 Mean | 101 ng/mL | 108 ng/mL |
| Precision: Level 3 % CV (within-run) | 4.4 % | 5.2 % |
| Precision: Level 4 Mean | 126 ng/mL | 139 ng/mL (Corresponds to L4 of 126 ng/mL for predicate) |
| Precision: Level 4 % CV (within-run) | 4.4 % | 4.4 % |
| Precision: Level 5 Mean | NA | 171 ng/mL |
| Precision: Level 5 % CV (within-run) | NA | 3.4 % |
| Sensitivity | 5.0 ng/mL of nordiazepam at > 95% confidence | 5.0 ng/mL of nordiazepam at > 95% confidence |
| Accuracy: Positive Samples (INTEGRA vs GC/MS) | 50 (INTEGRA +)/50 (GC/MS +) ; 0 (INTEGRA -)/0 (GC/MS -) from table | 50 (INTEGRA +)/50 (GC/MS +) ; 0 (INTEGRA -)/0 (GC/MS -) from table; i.e., 100% agreement when positive |
2. Sample sizes used for the test set and the data provenance
- ACPP Accuracy Test Set:
- Total Acid Phosphatase: n = 260 samples.
- Prostatic Acid Phosphatase: n = 264 samples.
- Data Provenance: Not explicitly stated (e.g., country of origin). The studies appear to be retrospective comparisons to predicate devices' performance claims.
- BNZGL Accuracy Test Set:
- Positive Samples: n = 50 samples for INTEGRABNZGL vs GC/MS comparison.
- The table indicates accuracy for positive samples where both INTEGRA with and without β-glucuronidase, and GC/MS all show 50 positive samples and 0 negative samples. This implies 50 positive samples were tested, and perhaps an additional number of negative samples that are not detailed in this specific comparison row, but rather in "overall agreement" data that is not fully presented.
- Data Provenance: Not explicitly stated (e.g., country of origin). Appears to be retrospective.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This information is not provided in the document. For in vitro diagnostic devices, ground truth for quantitative measurements (like acid phosphatase levels) typically comes from reference methods or established laboratory procedures, not from human experts adjudicating images or other subjective interpretations. For benzodiazepine detection, GC/MS is treated as the reference ground truth, which is an analytical method.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set
Not Applicable for these types of in vitro diagnostic tests, which rely on quantitative measurements compared to reference methods (e.g., GC/MS) or predicate biochemical assays. There is no human adjudication process described.
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
Not Applicable. This document describes in vitro diagnostic assays, not AI-powered medical image analysis tools or other devices that involve human readers/interpreters. Therefore, no MRMC study or AI assistance effect size is discussed.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
This refers to the performance of the device without human intervention. In the context of these IVD devices, the stated performance characteristics (e.g., precision, accuracy, sensitivity, assay range) are the standalone performance of the reagent system on the COBAS INTEGRA Analyzer. There is no human-in-the-loop component for the analytical part of these tests.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
- COBAS INTEGRA Acid/Prostatic Phosphatase:
- Ground truth for accuracy was established by comparison to the predicate device, "Roche Reagent for Acid Phosphatase" (K831834). This is a method comparison study where the predicate acts as the reference or "ground truth."
- COBAS INTEGRA Benzodiazepines with β-glucuronidase:
- Ground truth for accuracy was established by comparison to Gas Chromatography/Mass Spectrometry (GC/MS) (as indicated in the "Accuracy Positive Samples" table for the predicate device, which is then compared for the new device). GC/MS is a widely accepted confirmatory method for drug detection and serves as the gold standard ground truth in this context.
8. The sample size for the training set
The document does not explicitly identify or specify a "training set" in the context of machine learning. For these diagnostic assays, the development and optimization of the reagent formulation and instrument parameters are analogous to "training" in a broader sense, but there's no data given for this phase. The presented performance data are from validation/verification studies, which would be considered test sets.
9. How the ground truth for the training set was established
As there is no explicitly defined "training set" in the machine learning sense, this question is not applicable. The ground truth for the performance evaluations (test sets) is described in point 7.
{0}------------------------------------------------
MAY 2 | 1998
510(k) Summary
Roche COBAS® INTEGRA Reagent Cassettes
In accordance with the Safe Medical Devices Act of 1990, a 510(k) summary is provided as outlined in 21 CFR 807.92.
The assigned 510(k) number is:________________________________________________________________________________________________________________________________________________
I. Identification of 510(k) Sponsor:
Roche Diagnostic Systems, Inc. a subsidiary of Hoffmann-La Roche, Inc. Branchburg Township 1080 U.S. Highway 202 Somerville, New Jersey 08876-3771
510(k) Submission dated December 12, 1997
James W. Haynes Contact: Regulatory Affairs Associate Phone: (908) 253-7569 (908) 253-7547 Fax:
{1}------------------------------------------------
Device Name: II.
The device name, including both the trade/proprietary name and the classification name are provided in the table below.
| Table | 1 |
|---|---|
| -------------- | ---------- |
| Proprietary Name | Classification Name | Product Code | Regulation Number |
|---|---|---|---|
| COBAS INTEGRA Acid/ ProstaticPhosphatase (ACPP) | Acid phosphatase (total orprostatic) test system | CKB | 862.1020 |
| COBAS INTEGRABenzodiazepines with β-glucuronidase (BNZGL) | Benzodiazepine test system | JXM | 862.3170 |
{2}------------------------------------------------
III. Identification of the legally marketed device to which the 510(k) sponsor claims equivalence:
The following table identifies the legally marketed devices to which Roche Diagnostic Systems, Inc. claims equivalence.
| ableCC | 1 |
|---|---|
| ---------------- | --- |
| Product Name | Predicate Product Name | K number | Date of substantialequivalence |
|---|---|---|---|
| COBAS INTEGRA Acid/ ProstaticPhosphatase (ACPP) | Roche Reagent for Acid Phosphatase(OEM from Reagents Applications, Inc.) | K831834 | 8/26/83 |
| COBAS INTEGRA Benzodiazepineswith β-glucuronidase (BNZGL) | COBAS INTEGRA Benzodiazepines(BENZ) | K951595 | 9/8/95 |
IV. Description of the Device/Statement of Intended Use:
The COBAS INTEGRA test applications contained in this submission are intended for use with the COBAS INTEGRA Analyzer. The COBAS INTEGRA Analyzer and COBAS INTEGRA Reagent cassettes together provide an integrated system for in vitro diagnostic testing. The COBAS INTEGRA Analyzer along with 107 other Roche COBAS INTEGRA Reagent Cassettes were previously cleared on September 8, 1995 (K951595); January 25, 1996 (K954992); July 23, 1996 (K961824); October 31,1996 (K963292); January 21, 1997 (K964457), and August 12, 1997 (K972250). COBAS INTEGRA Benzodiazepines was previously cleared on September 8, 1995.
The COBAS INTEGRA Analyzer utilizes three measuring principles, i.e., absorbance, fluorescence polarization and ion-selective electrodes. The analyzer has a throughput of up to 600 tests per hour with STAT samples prioritized and tested immediately. Random sample access, robotics and a user interface optimize time management and streamline workflow. The COBAS INTEGRA can store up to 68 COBAS INTEGRA Reagent Cassettes on board, 24 hours a day at 2-8°C. The COBAS INTEGRA Reagent Cassettes are compact and preparation-free with the added convenience of long term on-board stability. Barcode readers are used to identify newly loaded reagent cassettes, samples for patient identification, and rack inserts and to read calibration and control data from the cassette label. COBAS INTEGRA tests include chemistry, drugs of abuse, immunology, ion selective electrodes, therapeutic drug monitoring, and hematology reagents. For additional information on the COBAS INTEGRA Analyzer and its constituent modules, please refer to the Operator's Manual in Volumes 1 through 2, pages 92-703, of the original 510(k) submission (K951595).
{3}------------------------------------------------
Through this submission, it is the intention of Roche to gain clearance for one additional COBAS Reagent Cassette and one optional application for a previously approved COBAS Reagent These are the COBAS INTEGRA Acid / Prostatic Phosphatase and the COBAS Cassette. INTEGRA Benzodiazepines with ß-glucuronidase, respectively.
COBAS INTEGRA Acid / Prostatic Phosphatase:
The cassette COBAS INTEGRA Acid / Prostatic Phosphatase contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the catalytic activity of the total and prostatic acid phosphatase in serum.
COBAS INTEGRA Benzodiazepines with ß-glucuronidase:
The cassette COBAS INTEGRA Benzodiazepines contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the semi-quantitative detection of benzodiazepines in human urine using the enzyme ß-glucuronidase. B-glucuronidase is added automatically as a diluent for sample pre-treatment enabling enhanced detection of metabolites of certain low-dose, short-acting benzodiazepines.
The intended use, clinical utility and methodology of each reagent cassette are further described in the test specific COBAS INTEGRA Method Manual sheets, contained in the test specific sections of this submission.
V. Summary of the technological characteristics of the new device in comparison to those of the predicate.
Tables 3-4 outline the technological characteristics (methodologies) of the COBAS INTEGRA Reagents in comparison to those of legally marketed predicate products.
VI. Brief discussion of the clinical and nonclinical tests relied on for a determination of substantial equivalence:
Tables 3-4 demonstrate the results of clinical and nonclinical studies performed using the COBAS INTEGRA Reagent Cassettes. The significant performance characteristics relied upon for a determination of substantial equivalence are summarized in this chart. This information concludes that the performance of this device is essentially equivalent to other legally marketed devices of a similar kind.
{4}------------------------------------------------
| COBAS INTEGRA Acid/Prostatic Phosphatase | Roche Reagent for AcidPhosphatase | |
|---|---|---|
| Intended Use | quantitative determination of bothtotal and prostatic acid phosphatase | quantitative determination of bothtotal and prostatic acid phosphatase |
| Methodology | Hillmann method withnaphthylphosphate.Inhibition of prostatic acidphosphatase by tartrate | Hillmann method withnaphthylphosphate.Inhibition of prostatic acidphosphatase by tartrate |
| Sample type | Serum | Serum |
| Calibrator | Fixed calibration factor-no calibrator required | Fixed calibration factor-no calibrator required |
| Controls | Roche Control Serum N and P(human) | Not specified in labeling |
| Reagent(active ingredients) | R1: Citrate (liquid)1,5 PentanediolR2: Tartrate (liquid)R3: 1-napthylphosphate(granulate) | 1. α-naphthylphosphate (granulate)2. L-Tartrate / Sodium citrate(granulate)3. Acetate Buffer |
| Performance Characteristics: Total Acid Phosphatase | ||
| Assay range | 0 - 100 U/L | Linear to 40 U/L |
| Sensitivity | $8.5 x 10^4$ △A/min per U/L of totalacid phosphatase | Not specified in labeling |
| Precision: | Level 1 Level 2 | Level 1 Level 2 |
| Mean | 4 U/L 11 U/L | 3.1 U/L 22.6 U/L |
| CV (within-run) | 4.5 % 2.5 % | 2.7 % 0.51 % |
| CV (total) | 5.7 % 4.6 % | NA NA |
| Accuracy: | ||
| Sample size (n) | 260 | 118 |
| Corr. Coefficient | 0.978 | 0.990 |
| Linear regression | $1.54x$ - 0.1 U/L | 1.02 + 0.43 U/L |
| Performance Characteristics: Prostatic Acid Phosphatase | ||
| Precision: | Level 1 Level 2 | Not specified in labeling |
| Mean (U/L) | 1 U/L 3 U/L | |
| CV (within-run) | 23 % 9.4 % | |
| CV (total) | 25 % 15 % | |
| Accuracy: | ||
| Sample size (n) | 264 | 118 |
| Corr. Coefficient | 0.996 | 0.997 |
| Linear regression | $1.83x$ + 0.5 U/L | 1.00 - 0.07 U/L |
Table 3 - COBAS INTEGRA Acid/ Prostatic Phosphatase
{5}------------------------------------------------
| COBAS INTEGRABenzodiazepines with β-glucuronidase | COBAS INTEGRABenzodiazepines | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Methodology | Kinetic interaction of microparticlesin a solution | Kinetic interaction of microparticlesin a solution | |||||||
| Sample type | Urine | Urine | |||||||
| Calibrator | Abuscreen OnLine Calibration Pack | Abuscreen OnLine Calibration Pack | |||||||
| Controls | Abuscreen OnLine 1.5x Calibrator /Positive ControlAbuscreen OnLine NegativeControl | Abuscreen OnLine 1.5x Calibrator /Positive ControlAbuscreen OnLine Negative Control | |||||||
| Cutoff | 100 ng/mL | 100, 200 and 300 ng/mL | |||||||
| Reagent(active ingredients) | R1: Sample DiluentR2: Antibody reagent:Benzodiazepines polyclonalantibody (sheep) in bufferR3: Microparticle reagent:conjugated benzodiazepinederivative microparticles inbufferβ-glucuronidase (not provided) | R1: Sample DiluentR2: Antibody reagent:Benzodiazepines polyclonalantibody (sheep) in bufferR3: Microparticle reagent:conjugated benzodiazepinederivative microparticles inbuffer | |||||||
| Performance Characteristics: | |||||||||
| Assay range | 0 - 200 ng/mL | 0 - 300 ng/mL | |||||||
| Precision: | L1 | L2 | L3 | L4 | L5 | Level 1 | Level 2 | Level 3 | Level 4 |
| Mean (ng/mL) | 52 | 86 | 108 | 139 | 171 | 49 | 80 | 101 | 126 |
| % CV (within-run) | 5.1 | 3.0 | 5.2 | 4.4 | 3.4 | 7.1 | 4.3 | 4.4 | 4.4 |
| Sensitivity | 5.0 ng/mL of nordiazepam at > 95% confidence | 5.0 ng/mL of nordiazepam at > 95% confidence | |||||||
| AccuracyPositive Samples | INTEGRAwith β-gluc. | GC/MS | INTEGRA(100 ng/mL cutoff) | GC/MS | |||||
| + | - | + | - | + | - | + | - | ||
| 50 | 0 | 50 | 0 | 50 | 0 | 50 | 0 |
Table 4 - COBAS INTEGRA Benzodiazepines with ß-glucuronidase
: 、
{6}------------------------------------------------
Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three stripes forming its body and wings. The eagle is encircled by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA".
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
MAY 21 1996
Mr. James W. Haynes · Requlatory Affairs Associate Roche Diagnostic Systems, Inc. 1080 U.S. Highway 202 Somerville, New Jersey 08876-3771
Re: K974695/S001 COBAS INTEGRA Acid/Prostatic Phosphatase (ACPP)/COBAS INTEGRA Benzodiazepines with ß-Glucuronidase (BNZGL) Regulatory Class: II Product Code: CKB, JXM March 18, 1998 Dated: Received: March 19, 1998
Dear Mr. Haynes:
We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act). You may, therefore, market the device, subject to the general controls provisions The general controls provisions of the Act of the Act. include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major requlations affecting your device can be found in the Code of Federal Requlations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Read Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory In addition, FDA may publish further announcements action. concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.
{7}------------------------------------------------
Page 2
Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.
This letter will allow you to begin marketing your device as described in your 510 (k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html".
Sincerely yours,
Steven Gutman
Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
{8}------------------------------------------------
Page 1 _of _1
9741,95 510(k) Number (if known)
Device Name:
Roche COBAS INTEGRA Acid / Prostatic Phosphatase Reagent Cassette
Roche COBAS INTEGRA Benzodiazepines with β-glucuronidase
Indications for Use:
ﺐ ﺍﻟ
The cassette COBAS INTEGRA Acid / Prostatic Phosphatase contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the catalytic activity of total and prostatic acid phosphatase in serum.
The cassette Roche COBAS INTEGRA Benzodiazepines contains an in vitro diagnostic reagent system intended for use on the COBAS INTEGRA for the semi-quantitative detection of benzodiazepines in human urine using the enzyme ß-glucuronidase.
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
(Division Sign-Off)
Division: Medical Laboratory Devices
510(k) Number. K97495
Prescription Use (Per 21 CFR 801.109)
OR
Over-The-Counter Use (Optional Format 1-2-96)
§ 862.1020 Acid phosphatase (total or prostatic) test system.
(a)
Identification. An acid phosphatase (total or prostatic) test system is a device intended to measure the activity of the acid phosphatase enzyme in plasma and serum.(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.