cobas® HIV-1/HIV-2 Qualitative nucleic acid test for use on the cobas® 5800/6800/8800 systems

BK251233 · Roche Molecular Systems, Inc Pleasanton, CA 94588 · QST · Jun 27, 2025 · Microbiology

Device Facts

• Record ID: BK251233
• Device Name: cobas® HIV-1/HIV-2 Qualitative nucleic acid test for use on the cobas® 5800/6800/8800 systems
• Applicant: Roche Molecular Systems, Inc Pleasanton, CA 94588
• Product Code: QST · Microbiology
• Decision Date: Jun 27, 2025
• Decision: SESE
• Regulation: 21 CFR 866.3957
• Device Class: Class 2
• Attributes: Pediatric

Indications for Use

cobas® HIV-1/HIV-2 Qualitative for use on the cobas® 5800/6800/8800 systems is an in vitro nucleic acid amplification test for the qualitative detection and differentiation of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) RNA in human serum and plasma. The test is intended to be used as an aid in diagnosis of HIV-1/HIV-2 infection. Detection of HIV-1 or HIV-2 nucleic acid is indicative of HIV-1 or HIV-2 infection, respectively. The presence of HIV-1 or HIV-2 nucleic acid in the plasma or serum of individuals without antibodies to HIV-1 or HIV-2 is indicative of acute or primary infection. The cobas® HIV-1/HIV-2 Qualitative may also be used as an additional test to confirm the presence of HIV-1 or HIV-2 infection in an individual with specimens reactive for HIV-1 or HIV-2 antibodies or antigens. The assay may also be used as an aid in the diagnosis of infection with HIV-1 and/or HIV-2 in pediatric subjects and pregnant women. This assay is not intended to be used for monitoring patient status, or for screening donors of blood, plasma, or human cells, tissues, and cellular and tissue-based products (HCT/Ps) for HIV.

Device Story

Fully automated in vitro diagnostic test for HIV-1/HIV-2 RNA detection; utilizes nucleic acid extraction, purification, and real-time PCR amplification. Input: human serum or plasma samples. Process: automated sample preparation via magnetic glass particles; selective amplification of HIV-1 gag, HIV-1 LTR, and HIV-2 LTR regions using thermostable DNA polymerase; real-time detection via fluorescently labeled probes (TaqMan). Output: qualitative results (non-reactive, reactive, or invalid) displayed on system screen, exported, or printed. Used in clinical laboratory settings; operated by trained laboratory personnel. System software manages data and interprets results. Benefits: provides rapid, automated diagnostic confirmation of HIV infection, aiding clinical decision-making for patient management.

Clinical Evidence

No new clinical studies performed; reliance on non-clinical performance evaluation. Bench testing included reproducibility, diagnostic specificity, and correlation studies using cobas® MPX as a representative assay. Reproducibility study (n=90 replicates per concentration) showed >95% detection rate at 1.5x and 3x LoD. Specificity study (n=601 specimens) demonstrated 99.55% NPA. Correlation study (n=155 spiked specimens per target) showed 100% PPA and 100% NPA. All studies met acceptance criteria.

Technological Characteristics

Automated nucleic acid amplification test (NAAT) using real-time PCR. Materials: magnetic glass particles for extraction, proteinase/lysis reagents. Detection: fluorescent reporter/quencher probes (TaqMan). Hardware: cobas® 5800/6800/8800 systems with updated LED light source and digital camera. Connectivity: networked system software (v2.0). Software: automated data management and result interpretation. Sterilization: N/A (reagents).

Indications for Use

Indicated for qualitative detection and differentiation of HIV-1 and HIV-2 RNA in human serum and plasma. Patient population includes individuals suspected of active HIV-1/HIV-2 infection, including pediatric subjects and pregnant women. Used as an aid in diagnosis or as a supplemental test for individuals reactive for HIV antibodies/antigens. Not for monitoring patient status or donor screening.

Regulatory Classification

Identification

Human immunodeficiency virus (HIV) nucleic acid (NAT) diagnostic and supplemental tests are prescription devices for the qualitative detection of HIV nucleic acid in human body fluids or tissues. The tests are intended for use as an aid in the diagnosis of infection with HIV and are for professional use only. The test results are intended to be interpreted in conjunction with other relevant clinical and laboratory findings. These tests are not intended to be used for monitoring patient status, or for screening donors of blood or blood products, or human cells, tissues, or cellular or tissue-based products (HCT/Ps).

Special Controls

*Classification.* Class II (special controls). The special controls for this device are:(1) For all HIV NAT diagnostic and/or supplemental tests (i) The labeling must include: (A) An intended use that states that the device is not intended for use for screening donors of blood or blood products, or HCT/Ps. (B) A detailed explanation of the principles of operation and procedures used for performing the assay. (C) A detailed explanation of the interpretation of results and recommended actions to take based on results. (D) Limitations, which must be updated to reflect current clinical practice and disease presentation and management. The limitations must include, but are not limited to, statements that indicate: ( *1* ) The matrices with which the device has been cleared, and that use of this test kit with specimen types other than those specifically cleared for this device may result in inaccurate test results.( *2* ) The test is not intended to be used to monitor individuals who are undergoing treatment for HIV infection.( *3* ) A specimen with a reactive result should be investigated further following current guidelines.( *4* ) All test results should be interpreted in conjunction with the individual's clinical presentation, history, and other laboratory results.( *5* ) A test result that is nonreactive does not exclude the possibility of exposure to or infection with HIV. Nonreactive results in this assay may be due to analyte levels that are below the limit of detection of this assay.(ii) Device verification and validation must include: (A) Detailed device description, including the device components, ancillary reagents required but not provided, and an explanation of the methodology. Additional information appropriate to the technology must be included, such as design of primers and probes. (B) For devices with assay calibrators, the design and nature of all primary, secondary, and subsequent quantitation standards used for calibration as well as their traceability to a reference material. In addition, analytical testing must be performed following the release of a new lot of the standard material that was used for device clearance, or when there is a transition to a new calibration standard. (C) Detailed documentation of analytical performance studies conducted as appropriate to the technology, specimen types tested, and intended use of the device, including, but not limited to, limit of blank, limit of detection, cutoff determination, precision, endogenous and exogenous interferences, cross reactivity, carryover, quality control, matrix equivalency, and sample and reagent stability. Samples selected for use in analytical studies or used to prepare samples for use in analytical studies must be from subjects with clinically relevant circulating genotypes in the United States. The effect of each claimed nucleic-acid isolation and purification procedure on detection must be evaluated. (D) Multisite reproducibility study that includes the testing of three independent production lots. (E) Analytical sensitivity of the test must be the same as or better than that of other cleared or approved tests. Samples tested must include appropriate numbers and types of samples, including real clinical samples near the lower limit of detection. Analytical specificity of the test must be as the same as or better than that of other cleared or approved tests. Samples must include appropriate numbers and types of samples from patients with different underlying illnesses or infections and from patients with potential endogenous interfering substances. (F) Detailed documentation of performance from a multisite clinical study. Performance must be analyzed relative to an FDA cleared or approved comparator. This study must be conducted using appropriate patient samples, with appropriate numbers of HIV positive and negative samples in applicable risk categories. Additional subtype, strain, or types must be validated using appropriate numbers and types of samples. The samples may be a combination of fresh and repository samples, sourced from within and outside the United States, as appropriate. The study designs, including number of samples tested, must be sufficient to meet the following criteria: ( *1* ) Clinical sensitivity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 99 percent.( *2* ) Clinical specificity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 99 percent.(G) Strategies for detection of new strains, types, subtypes, genotypes, and genetic mutations as they emerge. (H) Risk analysis and management strategies, such as Failure Modes Effects Analysis and/or Hazard Analysis and Critical Control Points summaries and their impact on test performance. (I) Final release criteria to be used for manufactured test lots with appropriate evidence that lots released at the extremes of the specifications will meet the claimed analytical and clinical performance characteristics as well as the stability claims. (J) All stability protocols, including acceptance criteria. (K) Appropriate and acceptable procedure(s) for evaluating customer complaints and other device information that determine when to submit a medical device report. (L) Premarket notification submissions must include the information contained in paragraph (b)(1)(ii)(A) through (K) of this section. (iii) Manufacturers must submit a log of all complaints. The log must include the following information regarding each complaint, if available: The type of event ( *e.g.,* false negative/false nonreactive or false positive/false reactive), lot, date, population, and whether or not the complaint was reported under part 803 of this chapter (Medical Device Reporting). The log must be submitted annually on the anniversary of clearance for 5 years following clearance of a traditional premarket notification.(2) If the test is intended for Point of Care (PoC) use, the following special controls, in addition to those listed in paragraph (b)(1) of this section, apply: (i) The PoC labeling must include a statement that the test is intended for PoC use. (ii) The PoC labeling must include the following information near the statement of the intended use: (A) That the test is for distribution to clinical laboratories that have an adequate quality assurance program, including planned systematic activities that provide adequate confidence that requirements for quality will be met and where there is assurance that operators will receive and use the instructional materials. (B) That the test is for use only by an agent of a clinical laboratory. (C) Instructions for individuals to receive the “Subject Information Notice” prior to specimen collection and appropriate information when test results are provided. (iii) PoC labeling must include instructions to follow current guidelines for informing the individual of the test result and its interpretation. (iv) The instructions in the labeling must state that reactive results are considered preliminary and should be confirmed following current guidelines. (v) Device verification and validation for PoC use must include: (A) Detailed documentation from a well-conducted multisite clinical study conducted at appropriate PoC sites. Performance must be analyzed relative to an FDA cleared or approved comparator. This study must be conducted using patient samples, with appropriate numbers of HIV positive and HIV negative samples in applicable risk categories. Additional subgroup or type claims must be validated using appropriate numbers and types of samples. The samples may be a combination of fresh and repository samples, sourced from within and outside the United States, as appropriate. If the test is intended solely for PoC use, the test must meet only the performance criteria in paragraphs (b)(2)(v)(A)( *1* ) and (*2* ) of this section and not the criteria in paragraph (b)(1)(ii)(F) of this section:( *1* ) Clinical sensitivity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 98 percent.( *2* ) Clinical specificity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 98 percent.(B) Premarket notification submissions must include the information contained in paragraph (b)(2)(v)(A) of this section. (3) If the test is intended for supplemental use in addition to use as an aid in initial diagnosis, the following special controls, in addition to those listed in paragraphs (b)(1) and (2) of this section, as appropriate, apply: (i) The labeling must include a statement that the test is intended for use as an additional test to confirm the presence of HIV viral nucleic acid in specimens found to be repeatedly reactive by a diagnostic screening test. (ii) Device validation and verification for supplemental use must include a clinical study, including samples that were initially reactive and repeatedly reactive on a diagnostic test but were negative or indeterminate on a confirmatory test. Premarket notification submissions must include this information. (4) If the test is intended solely as a supplemental test, the following special controls, in addition to those listed in paragraphs (b)(1) and (2) of this section, except those in paragraphs (b)(1)(ii)(F) and (b)(2)(v)(A) of this section, as appropriate, apply: (i) The labeling must include a statement that the test is intended for use as an additional test to confirm the presence of HIV viral nucleic acid in specimens found to be repeatedly reactive by a diagnostic screening test. (ii) The labeling must clearly state that the test is not for use for initial diagnosis or is not intended as a first-line test. (iii) Device validation and verification must include a clinical study including samples that were initially reactive and repeatedly reactive on a diagnostic test but were negative or indeterminate on a confirmatory test. Premarket notification submissions must include this information. (5) If the test is intended to differentiate different HIV types, the following special controls, in addition to those listed in paragraphs (b)(1) through (4) of this section, as appropriate, apply: (i) The labeling must include the statement that the test is intended for the confirmation of initial results and differentiation of different HIV types. (ii) The results interpretation in the labeling must include instructions for the user on how to interpret the results, including un-typeable and co-infection results. (iii) Device validation and verification must include evaluation of analytical and clinical sensitivity and specificity for each of the types, strains, and subtypes of HIV intended to be differentiated. Premarket notification submissions must include this information.

Predicate Devices

• cobas® HIV-1/HIV-2 Qualitative nucleic acid test for use on the cobas® 5800/6800/8800 systems (BP190360)

Submission Summary (Full Text)

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# cobas® HIV-1/HIV-2 Qualitative

## 510(k) Summary

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.

| **Submitter Name** | Roche Molecular Systems, Inc. |
| --- | --- |
| **Address** | 4300 Hacienda Drive Pleasanton, CA 94588-2722 |
| **Contact** | Samantha Logan Phone: (b) (6) Email: [e-mail] |
| **Date Prepared** | April 11, 2025 |
| **Proprietary Name** | cobas® HIV-1/HIV-2 Qualitative nucleic acid test for use on the cobas® 5800/6800/8800 systems |
| **Common Name** | cobas® HIV-1/HIV-2 Qualitative |
| **Classification Name** | Human immunodeficiency virus (HIV) nucleic acid (NAT) diagnostic and/or supplemental test |
| **Product Code** | QST |
| **Predicate Devices** | cobas® HIV-1/HIV-2 Qualitative nucleic acid test for use on the cobas® 5800/6800/8800 systems |
| **Establishment Registration** | Roche Molecular Systems, Inc. (2243471) |

## 1. DEVICE DESCRIPTION

cobas® HIV-1/HIV-2 Qualitative is based on fully automated sample preparation (nucleic acid extraction and purification) followed by PCR amplification and detection. The cobas® 5800 system is designed as one integrated instrument. The cobas® 6800/8800 systems consist of the sample supply module, the transfer module, the processing module, and the analytic module. Automated data management is performed by the cobas® 5800 or cobas® 6800/8800 systems software (SW) which assigns test results for all tests as non-reactive, reactive, or invalid. Results can be reviewed directly on the system screen, exported, or printed as a PDF report.

Nucleic acid from patient samples and added armored RNA internal control (IC) molecules (which serve as the sample preparation and amplification/detection process control) is

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simultaneously extracted. In addition, the test utilizes three external controls: two positive and one negative control. In summary, viral nucleic acid is released by addition of proteinase and lysis reagent to the sample. The released nucleic acid binds to the silica surface of the added magnetic glass particles. Unbound substances and impurities, such as denatured protein, cellular debris and potential PCR inhibitors are removed with subsequent wash steps and purified nucleic acid is eluted from the magnetic glass particles with elution buffer at elevated temperature.

Selective amplification of target nucleic acid from the sample is achieved by the use of target virus-specific forward and reverse primers which are selected from highly conserved regions of the HIV-1 and HIV-2 genomes. The HIV-1 gag gene, the HIV-1 LTR region (dual target for HIV-1) and HIV-2 LTR region are amplified by cobas® HIV-1/HIV-2 Qualitative.

Selective amplification of IC is achieved by the use of sequence-specific forward and reverse primers which are selected to have no homology with the HIV-1 or HIV-2 genomes. A thermostable deoxyribonucleic acid (DNA) polymerase enzyme is used for both reverse-transcription and PCR amplification. The target and IC sequences are amplified simultaneously utilizing a universal PCR amplification profile with predefined temperature steps and number of cycles. The master mix includes deoxyuridine triphosphate (dUTP), instead of deoxythimidine triphosphate (dTTP), which is incorporated into the newly synthesized DNA (amplicon). Any contaminating amplicons from previous PCR runs are eliminated by the AmpErase enzyme, which is included in the PCR master mix, during the first thermal cycling step. However, newly formed amplicons are not eliminated since the AmpErase enzyme is inactivated once exposed to temperatures above 55°C.

cobas® HIV-1/HIV-2 Qualitative master mix contains two detection probes specific for the HIV-1 target sequences, one for HIV-2 target sequences and one for the IC. The probes are labeled with target specific fluorescent reporter dyes allowing simultaneous detection of HIV-1 target, HIV-2 target and IC in three different target channels. When not bound to the target sequence, the fluorescent signal of the intact probes is suppressed by a quencher dye. During the PCR amplification step, hybridization of the probes to the specific single-stranded DNA template results in cleavage of the probe by the 5' to 3' exonuclease activity of the DNA polymerase resulting in separation of the reporter and quencher dyes and the generation of a fluorescent signal. With each PCR cycle, increasing amounts of cleaved probes are generated and the cumulative signal of the reporter dye increases concomitantly. Real-time detection and

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discrimination of PCR products is accomplished by measuring the fluorescence of the released reporter dyes for the viral targets and IC, respectively.

## 2. INDICATIONS FOR USE

**cobas®** HIV-1/HIV-2 Qualitative for use on the **cobas®** 5800/6800/8800 systems is an in vitro nucleic acid amplification test for the qualitative detection and differentiation of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) RNA in human serum and plasma.

The test is intended to be used as an aid in diagnosis of HIV-1/HIV-2 infection. Detection of HIV-1 or HIV-2 nucleic acid is indicative of HIV-1 or HIV-2 infection, respectively. The presence of HIV-1 or HIV-2 nucleic acid in the plasma or serum of individuals without antibodies to HIV-1 or HIV-2 is indicative of acute or primary infection. The **cobas®** HIV-1/HIV-2 Qualitative may also be used as an additional test to confirm the presence of HIV-1 or HIV-2 infection in an individual with specimens reactive for HIV-1 or HIV-2 antibodies or antigens. The assay may also be used as an aid in the diagnosis of infection with HIV-1 and/or HIV-2 in pediatric subjects and pregnant women.

This assay is not intended to be used for monitoring patient status, or for screening donors of blood, plasma, or human cells, tissues, and cellular and tissue-based products (HCT/Ps) for HIV.

## 3. TECHNOLOGICAL CHARACTERISTICS

The primary technological characteristics and intended use of the **cobas®** HIV-1/HIV-2 Qualitative are substantially equivalent to other legally marketed nucleic acid amplification tests intended for the qualitative detection and differentiation of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) RNA in human serum and plasma. There are no changes to the assay reagents. New labeling for the assay has been included in this submission. This labeling contains revisions related to the use of the assay on the **cobas®** 5800/6800/8800 systems.

The technical characteristics of **cobas®** HIV-1/HIV-2 Qualitative are compared to the identified predicate device, **cobas®** HIV-1/HIV-2 Qualitative nucleic acid test for use on the **cobas®** 5800/6800/8800 systems (**cobas®** HIV-1/HIV-2 Qualitative) (BP190360) in Table 1. The candidate device utilizes an updated analytical cycler with updated light source (Light Emitting Diode, LED) and Light Detection Digital Camera. Additionally, the **cobas®** 6800 system is updated to include two analytical cyclers compared to the predicate device. The system software has also been updated to version 2.0.

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**Table 1: Similarities and Differences between cobas® HIV-1/HIV-2 Qualitative and the Predicate Device.**

| Comparator | Candidate Device: cobas® HIV-1/HIV-2 Qualitative | Predicate Device: cobas® HIV-1/HIV-2 Qualitative (BP190360) |
| --- | --- | --- |
| Proprietary Name | **cobas®** HIV-1/HIV-2 Qualitative Nucleic acid test for use on the **cobas®** 5800/6800/8800 systems | Same |
| Regulation Number | 21 CFR 866.3957 | Same |
| Regulation Name | Human immunodeficiency virus (HIV) nucleic acid (NAT) diagnostic and/or supplemental test | Same |
| Regulatory Class | Class II | Same |
| Product Code | QST | Same |
| Intended Use | **cobas®** HIV-1/HIV-2 Qualitative for use on the **cobas®** 5800/6800/8800 systems is an in vitro nucleic acid amplification test for the qualitative detection and differentiation of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) RNA in human serum and plasma. The test is intended to be used as an aid in diagnosis of HIV-1/HIV-2 infection. Detection of HIV-1 or HIV-2 nucleic acid is indicative of HIV-1 or HIV-2 infection, respectively. The presence of HIV-1 or HIV-2 nucleic acid in the plasma or serum of individuals without antibodies to HIV-1 or HIV-2 is indicative of acute or primary infection. The **cobas®** HIV-1/HIV-2 Qualitative may also be used as an additional test to confirm the presence of HIV-1 or HIV-2 infection in an individual with specimens reactive for HIV-1 or HIV-2 antibodies or antigens. The assay may also be used as an aid in the diagnosis of infection with HIV-1 and/or HIV-2 in pediatric subjects and pregnant women. This assay is not intended to be used for monitoring patient status, or for screening donors of blood, plasma, or human cells, tissues, and cellular and tissue-based products (HCT/Ps) for HIV. | Same |
| Conditions for use | For prescription use | Same |
| Sample Types | Human serum and plasma | Same |
| Subject Status | Individuals suspected of active HIV-1/HIV-2 infection | Same |
| Analyte Targets | HIV-1 HIV-2 | Same |
| Sample Preparation Procedure | Automated by **cobas®** 5800/6800/8800 systems | Same |

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| Comparator | Candidate Device: cobas® HIV-1/HIV-2 Qualitative | Predicate Device: cobas® HIV-1/HIV-2 Qualitative (BP190360) |
| --- | --- | --- |
| Amplification Technology | Real-time PCR | Same |
| Detection Chemistry | Paired reporter and quencher fluorescence labeled probes (TaqMan Technology) | Same |
| Controls used | RNA Internal Control (internal control) **cobas®** HIV-1/HIV-2 Qualitative Control Kit (external positive control) **cobas®** NHP Negative Control Kit (external negative control) | Same |
| Instrument Platform | **cobas®** 5800/6800/8800 systems | Same |
| Amplification/Detection | Updated light source (LED) and Light Detection (Digital Camera) Real-time PCR using fluorescence signal detection. Separate detection and thermal cycler units/modules with specific temperatures and times for denaturation, annealing, and elongation steps, result calculation and interpretation methods, and filter specifications | Same (except updated light source (LED) and Light Detection (Digital Camera)) |
| Number of supported assays per run | 6 assays/run | 3 assays/run |
| Throughput: **cobas®** 6800 (1 analytical cycler) **cobas®** 6800 (2 analytical cycler) **cobas®** 8800 (4 analytical cycler) | 384 tests in 8 hours 480 tests in 8 hours 960 tests in 8 hours | 384 tests in 8 hours N/A 960 tests in 8 hours |
| High Level Instrument Software Architecture | Refactored and modularized instrument control (IC) SW module and instrument management (IM) SW module are combined in one SW module. The x800 Data Manager SW module will replace the IG SW Module. x800 ASAP SW will replace the **cobas®** 6800/8800 ASAP and **cobas®** 5800 ASAP. **cobas®** 5800 system with software version 1.0 (P/N 08707464001), and the **cobas®** 6800/8800 systems with software version 2.0 (P/N 09575154001 and P/N 09575146001) | - Instrument Control (IC) SW - Instrument Management (IM) SW - Instrument Gateway (IG) SW - **cobas®** 6800/8800 Assay-specific analysis packages (ASAP ) SW - **cobas®** 6800/8800 systems with software version 1.4 (P/N 05524245001 or P/N 05412722001) - **cobas®** 5800 Assay-specific analysis packages (ASAP) SW - **cobas®** 5800 system with software version 1.0 (P/N 08707464001) |

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| Comparator | Candidate Device: cobas® HIV-1/HIV-2 Qualitative | Predicate Device: cobas® HIV-1/HIV-2 Qualitative (BP190360) |
| --- | --- | --- |
| Control Scheduling | Default setting will remain the same as cobas® HIV-1/2 Qualitative Additional setting possible for alternate control frequency based on lab requirements and local regulations Note: - Controls will be required at least for each reagent lot change and every 72 hours. - The new control concept is identical to the one with cobas® 5800 system. | Positive control and negative control included on every amplification/detection plate |

#### 4. NON-CLINICAL PERFORMANCE EVALUATION

The update of the analytic cycler with a different LED Source and light detection may potentially affect the Assay performance. To confirm System Performance Equivalency between the new cobas® 6800/8800 Systems 2.0 and the current on-market cobas® 6800/8800 Systems 1.4, three system equivalency studies have been performed testing performance with the cobas® MPX as representative assay. Other analytical studies were completed as part of BP190360. There are no changes to the assay reagents.

##### 4.1. cobas® 6800/8800 Systems 2.0 Equivalency Study – Reproducibility

Reproducibility of the new cobas® 6800/8800 systems 2.0 was assessed by testing co-formulated panels with HIV-1, HBV, and HCV, and single-formulated HIV-2, diluted in pooled negative EDTA-plasma at 1.5×LoD and 3×LoD concentration levels. An HIV/HBV/HCV negative EDTA-Plasma panel member was also tested.

Testing was conducted over five days using three cobas® 6800/8800 Systems 2.0 Instruments and three operators at one internal site, two runs per day and instrument and using three different Kit lots of cobas® MPX. Three replicates per panel member were tested in two runs performed per day. A total of 90 replicates per concentration level and target were distributed.

The detection rate for panel members with target concentration level at 1.5× LoD and 3×LoD on the new cobas® 6800/8800 Systems 2.0 was demonstrated to be greater than 95%. Additionally, all the negative samples tested negative, and the detection rate for the negative/blank panel

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member was demonstrated to be less than the acceptance criteria of 5% on **cobas**$^{®}$ 6800/8800 Systems 2.0. Based on these results, the study met all the acceptance criteria.

#### **4.2. cobas$^{®}$ 6800/8800 Systems 2.0 Equivalency Study – Diagnostic specificity**

601 individual pre-screened, non-reactive individual plasma specimens were selected for this study to demonstrate performance equivalency in regard to specificity. The study was conducted using the 601 negative EDTA plasma specimens (one replicate per specimen per system configuration) with three test specific reagent lots on three new **cobas**$^{®}$ 6800/8800 Systems 2.0 and two **cobas**$^{®}$ 6800/8800 Systems 1.4. Testing was conducted over the course of three days. of which 599 specimens were valid and tested negative.

The Negative Percent Agreement (NPA) between both the new **cobas**$^{®}$ 6800/8800 Systems 2.0 and the current on-market **cobas**$^{®}$ 6800/8800 Systems 1.4 with a lower bound of the one-sided 95% confidence interval is 99.55%. The results met the acceptance criteria.

#### **4.3. cobas$^{®}$ 6800/8800 Systems 2.0 Equivalency Study – Correlation**

155 individually spiked single donor specimen for each target (HIV-1 Group M, HIV-2, HBV, HCV) as well as 155 individual HIV/HBV/HCV negative single donor specimens were used to assess the performance equivalency between the updated and original systems. The individual HIV-1 Group M, and HIV-2, HBV, HCV positive and individual negative specimens were distributed across three **cobas**$^{®}$ MPX kit lots, and tested on three **cobas**$^{®}$ 6800/8800 Systems 2.0. Testing was performed at one site (internal) over the course of four days

Test results showed that for HIV-1, HIV-2, HBV, and HCV specimens the positive percent agreement (PPA) was 100%. The lower bound of the one-sided 95% confidence interval (CI) for PPA was 98.28%. For the negative specimen the negative percent agreement (NPA) was 100%. The lower bound of the one-sided 95% CI for NPA was 98.28%. The overall percent agreement was 100%. These results met the acceptance criteria.

### **5. CLINICAL PERFORMANCE EVALUATION**

Completed as part of BP190360. There are no changes to the assay reagents.

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## 6. CONCLUSIONS

As the **cobas**® HIV-1/HIV-2 Qualitative assay reagents and intended use population have not changed, additional clinical studies were not performed. Non-clinical studies were used to evaluate the performance of the updated **cobas**® HIV-1/HIV-2 Qualitative Assay on the **cobas**® 5800/6800/8800 systems. The conclusions drawn from the nonclinical tests that demonstrate that the device is as safe, as effective, and performs as well as the predicate. These studies support a conclusion of substantial equivalence between the updated **cobas**® HIV-1/HIV-2 Qualitative Assay on the **cobas**® 5800/6800/8800 systems and the current on-market **cobas**® 5800/6800/8800.

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