← Product Code [QUM](/productcode/QUM) · BK231025 # Aptima® HIV-1 Quant Dx Assay (BK231025) _Hologic, Inc. San Diego, CA · QUM · Aug 6, 2024 · Microbiology · SESE_ **Canonical URL:** https://fda.innolitics.com/device/BK231025 ## Device Facts - **Applicant:** Hologic, Inc. San Diego, CA - **Product Code:** [QUM](/productcode/QUM.md) - **Decision Date:** Aug 6, 2024 - **Decision:** SESE - **Regulation:** 21 CFR 866.3958 - **Device Class:** Class 2 - **Review Panel:** Microbiology ## Indications for Use The Aptima® HIV-1 Quant Dx assay is an in vitro nucleic acid amplification test (NAAT) for the detection and quantitation of human immunodeficiency virus type 1 (HIV-1) on the fully automated Panther® system and Panther Fusion® system. It is intended to be used as an aid in diagnosis for HIV-1 infection using appropriate HIV testing algorithms. The presence of HIV-1 nucleic acid in the plasma or serum of individuals without antibodies to HIV-1 is indicative of acute or primary infection. The Aptima HIV-1 Quant Dx assay may also be used as a supplemental test, when it is reactive, to confirm HIV-1 infection in an individual whose plasma or serum specimen is reactive with an approved assay with an indication as an aid in the diagnosis of HIV-1 infection. The Aptima HIV-1 Quant Dx assay is intended for use in conjunction with clinical presentation and other laboratory markers for disease prognosis and for use as an aid in monitoring the effects of antiretroviral treatment, as measured by changes in plasma HIV-1 RNA levels. The Aptima HIV-1 Quant Dx assay quantitates HIV-1 RNA groups M, N, and O over the range of 30 to 10,000,000 copies/ mL. One international unit is equivalent to 0.35 copies of HIV-1 RNA for the 3rd HIV-1 WHO International Standard (subtype B, NIBSC code: 10/152). This assay is not intended to be used as a donor screening test for HIV-1. Performance of this test has not been evaluated for use in pregnant women or in a pediatric population. ## Device Story Aptima HIV-1 Quant Dx assay is an in vitro NAAT for HIV-1 RNA detection/quantitation; operates on Panther/Panther Fusion systems. Uses Target Capture (TC) and Transcription-Mediated Amplification (TMA). Input: plasma or serum samples. Output: qualitative/quantitative HIV-1 RNA levels (30–10,000,000 copies/mL). Used in clinical laboratory settings by trained personnel. Software updates include logic for pol/LTR channel validity checks and improved fault detection for instrument LED flickering. Healthcare providers use results alongside clinical presentation for prognosis and treatment monitoring. Benefits include improved diagnostic sensitivity and robust performance under varied reagent loading conditions. ## Clinical Evidence No new clinical testing performed. Original clinical validation data from BP150318 reanalyzed with updated software parameters. Method comparison study (n=210) showed no difference in quantitative results across assay range. Updated logic improved detection of low-positive specimens compared to previous sequence file. All true/known negative specimens remained non-reactive. ## Technological Characteristics In vitro NAAT using Target Capture and Transcription-Mediated Amplification (TMA). Automated platform (Panther/Panther Fusion). Quantitates HIV-1 RNA groups M, N, O. Software-based logic for signal validity (pol/LTR channels) and hardware fault detection. Reagent stability supports 8 on-board cycles. ## Regulatory Identification A human immunodeficiency virus (HIV) viral load monitoring test is an in vitro diagnostic prescription device for the quantitation of the amount of HIV ribonucleic acid (RNA) in human body fluids. The test is intended for use in the clinical management of individuals living with HIV and is for professional use only. The test results are intended to be interpreted in conjunction with other relevant clinical and laboratory findings. The test is not intended to be used as an aid in diagnosis or for screening donors of blood or blood products or human cells, tissues, or cellular and tissue-based products (HCT/Ps). ## Special Controls *Classification.* Class II (special controls). The special controls for this device are:(1) The labeling must include: (i) An intended use that states that the device is not intended for use as an aid in diagnosis or for use in screening donors of blood or blood products, or HCT/Ps. (ii) A detailed explanation of the principles of operation and procedures used for assay performance. (iii) A detailed explanation of the interpretation of results and that recommended actions should be based on current clinical guidelines. (iv) Limitations, which must be updated to reflect current clinical practice and patient management. The limitations must include, but are not limited to, statements that indicate: (A) The matrices and sample types with which the device has been cleared and that use of this test with specimen types other than those specifically cleared for this device may cause inaccurate test results. (B) Mutations in highly conserved regions may affect binding of primers and/or probes resulting in the under-quantitation of virus or failure to detect the presence of virus. (C) All test results should be interpreted in conjunction with the individual's clinical presentation, history, and other laboratory results. (2) Device verification and validation must include: (i) Detailed device description, including the device components, ancillary reagents required but not provided, and an explanation of the device methodology. Additional information appropriate to the technology must be included, such as detailed information on the design of primers and probes. (ii) 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. (iii) 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, limit of quantitation, cutoff determination, precision, linearity, endogenous and exogenous interferences, cross-reactivity, carry-over, quality control, matrix equivalency, 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 genotypes circulating in the United States. (iv) Multisite reproducibility study that includes the testing of three independent production lots. (v) Analytical sensitivity of the device must demonstrate acceptable performance at current clinically relevant medical decision points. Samples tested to demonstrate analytical sensitivity must include appropriate numbers and types of samples, including real clinical samples near the lower limit of quantitation and any clinically relevant medical decision points. Analytical specificity of the device must demonstrate acceptable performance. Samples tested to demonstrate analytical specificity must include appropriate numbers and types of samples from patients with different underlying illnesses and infection and from patients with potential interfering substances. (vi) Detailed documentation of performance from a multisite clinical study or a multisite analytical method comparison study. (A) For devices evaluated in a multisite clinical study, the study must use specimens from individuals living with HIV being monitored for changes in viral load, and the test results must be compared to the clinical status of the patients. (B) For tests evaluated in a multisite analytical method comparison study, the performance of the test must be compared to an FDA-cleared or approved comparator. The multisite method comparison study must include appropriate numbers and types of samples with analyte concentrations across the measuring range of the assay, representing clinically relevant genotypes. The multisite method comparison study design, including number of samples tested, must be sufficient to meet the following criteria: ( *1* ) Agreement between the two tests across the measuring range of the assays must have an r2 of greater than or equal to 0.95.( *2* ) The bias between the test and comparator assay, as determined by difference plots, must be less than or equal to 0.5 log copies/mL.(vii) Detailed documentation of a single-site analytical method comparison study between the device and an FDA-cleared or approved comparator if a multisite clinical study is performed under paragraph(b)(2)(vi) of this section. The analytical method comparison study must use appropriate numbers and types of samples with analyte concentrations across the measuring range of the assay, representing clinically relevant genotypes. The results must meet the criteria in paragraphs (b)(2)(vi)(B)( *1* ) and (*2* ) of this section.(viii) Strategies for detection of new strains, types, subtypes, genotypes, and genetic mutations as they emerge. (ix) 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. (x) Final release criteria to be used for manufactured device lots with an appropriate justification that lots released at the extremes of the specifications will meet the claimed analytical and clinical performance characteristics as well as the stability claims. (xi) All stability protocols, including acceptance criteria. (xii) Appropriate and acceptable procedure(s) for addressing complaints and other device information that determines when to submit a medical device report. (xiii) Premarket notification submissions must include the information contained in paragraphs (b)(2)(i) through (xii) of this section. ## Predicate Devices - Aptima HIV-1 Quant Assay (BP150318) ## Submission Summary (Full Text) > This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com. > > Innolitics is a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices, including [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/). {0} # Updated 510(k) Summary: BK231025 (Aptima HIV-1 Quant Dx Assay) ## Contact Details Applicant Name: Howard Liu Applicant Address: 10210 Genetic Center Drive, San Diego, CA 92121, United States Applicant Contact Telephone: 858-410-8853 Applicant Contact: Howard Liu Applicant Contact Email: howard.liu@hologic.com Date summary prepared: July 15, 2024 ## Device Name Device Trade Name: Aptima HIV-1 Quant Dx Assay Common Name: HIV-1 RNA assay Classification Name: Human immunodeficiency virus (HIV) viral load monitoring test Regulation Number: 866.3958 Product Code: QUM ## Legally Marketed Predicate Devices Predicate #: BP150318 Predicate Trade Name (Primary Predicate is listed first): Aptima HIV-1 Quant Assay Product Code: QUM ## Device Description Summary The Aptima® HIV-1 Quant Dx assay is an in vitro nucleic acid amplification test (NAAT) for the detection and quantitation of human immunodeficiency virus type 1 (HIV-1) on the fully automated Panther® system and Panther Fusion® system. It is intended to be used as an aid in diagnosis for HIV-1 infection using appropriate HIV testing algorithms. The presence of HIV-1 nucleic acid in the plasma or serum of individuals without antibodies to HIV-1 is indicative of acute or primary infection. The test is to be performed by laboratory personnel trained to perform the test in a hospital or laboratory setting. Updated 510(k) Summary BK231025/A001 Confidential Page 1 of 7 {1} ## Intended Use/Indications for Use The Aptima® HIV-1 Quant Dx assay is an in vitro nucleic acid amplification test (NAAT) for the detection and quantitation of human immunodeficiency virus type 1 (HIV-1) on the fully automated Panther® system and Panther Fusion® system. It is intended to be used as an aid in diagnosis for HIV-1 infection using appropriate HIV testing algorithms. The presence of HIV-1 nucleic acid in the plasma or serum of individuals without antibodies to HIV-1 is indicative of acute or primary infection. The Aptima HIV-1 Quant Dx assay may also be used as a supplemental test, when it is reactive, to confirm HIV-1 infection in an individual whose plasma or serum specimen is reactive with an approved assay with an indication as an aid in the diagnosis of HIV-1 infection. The Aptima HIV-1 Quant Dx assay is intended for use in conjunction with clinical presentation and other laboratory markers for disease prognosis and for use as an aid in monitoring the effects of antiretroviral treatment, as measured by changes in plasma HIV-1 RNA levels. The Aptima HIV-1 Quant Dx assay quantitates HIV-1 RNA groups M, N, and O over the range of 30 to 10,000,000 copies/ mL. One international unit is equivalent to 0.35 copies of HIV-1 RNA for the 3rd HIV-1 WHO International Standard (subtype B, NIBSC code: 10/152). This assay is not intended to be used as a donor screening test for HIV-1. Performance of this test has not been evaluated for use in pregnant women or in a pediatric population. ## Indications for Use Comparison The indications for use for the device are the same as the predicate device. Updated 510(k) Summary BK231025/A001 Confidential Page 2 of 7 {2} ## Technological Comparison The device has the same technological characteristics as the predicate device(s) identified above. The design, material, chemical composition, principle of operation and energy source are identical. Similarities and differences between the predicate and subject devices are listed below in Tables 1 and 2. **Table 1: Comparison of Similarities Between Predicate Device and Subject Device** | Item | Predicate Device: Aptima HIV-1 Quant Dx assay (BP150318) | Subject Device: Aptima HIV-1 Quant Dx assay | | --- | --- | --- | | Technology Principle of Operation | Target Capture (TC), Transcription-Mediated Amplification (TMA) | Same | | Platform | Automated Panther System and Panther Fusion System | Same | | Assay Targets | HIV-1 RNA | Same | | Assay Results | Qualitative & quantitative | Same | | Function | Detection of RNA from HIV-1 | Same | | Intended Use | The Aptima® HIV-1 Quant Dx assay is an in vitro nucleic acid amplification test (NAAT) for the detection and quantitation of human immunodeficiency virus type 1 (HIV-1) on the fully automated Panther® system and Panther Fusion® system. It is intended to be used as an aid in diagnosis for HIV-1 infection using appropriate HIV testing algorithms. The presence of HIV-1 nucleic acid in the plasma or serum of individuals without antibodies to HIV-1 is indicative of acute or primary infection. The Aptima HIV-1 Quant Dx assay may also be used as a supplemental test, when it is reactive, to confirm HIV-1 infection in an individual whose plasma or serum specimen is reactive with an approved assay with an indication as an aid in the diagnosis of HIV-1 infection. | Same | Updated 510(k) Summary BK231025/A001 Confidential Page 3 of 7 {3} | Item | Predicate Device: Aptima HIV-1 Quant Dx assay (BP150318) | Subject Device: Aptima HIV-1 Quant Dx assay | | --- | --- | --- | | | The Aptima HIV-1 Quant Dx assay is intended for use in conjunction with clinical presentation and other laboratory markers for disease prognosis and for use as an aid in monitoring the effects of antiretroviral treatment, as measured by changes in plasma HIV-1 RNA levels. The Aptima HIV-1 Quant Dx assay quantitates HIV-1 RNA groups M, N, and O over the range of 30 to 10,000,000 copies/ mL. One international unit is equivalent to 0.35 copies of HIV-1 RNA for the 3rd HIV-1 WHO International Standard (subtype B, NIBSC code: 10/152). This assay is not intended to be used as a donor screening test for HIV-1. Performance of this test has not been evaluated for use in pregnant women or in a pediatric population. | | **Table 2: Comparison of Differences Between Predicate Device and Subject Device** | Item | Predicate Device: Aptima HIV-1 Quant Dx assay (BP150318) | Subject Device: Aptima HIV-1 Quant Dx assay | | --- | --- | --- | | LTR software improvement | N/A | 1. Add a logic in the RTF1 (pol) channel that will increase the reported pol positivity: that if the pol RFU range result is above 5000, the ratio cut-off for positivity is not applied. 2. Add a Validity check in the RTF3 (LTR) channel that: If the specimen GIC Ttime is greater than the Average GIC Ttime of the Kit Calibrator in the run + 2 minutes, the software will invalidate the reported LTR result with a calculated concentration | Updated 510(k) Summary BK231025/A001 Confidential Page 4 of 7 {4} | Item | Predicate Device: Aptima HIV-1 Quant Dx assay (BP150318) | Subject Device: Aptima HIV-1 Quant Dx assay | | --- | --- | --- | | | | between 50 c/mL and 10,000 c/mL. 3. Add another logic in the RTF3 (LTR) channel to invalidate the samples with an abnormal fluorescence curve in the LTR channel or the 'LTR bump.' The software will invalidate the samples that have a reported LTR concentration of greater than 5,000 c/mL with less than LTR RFU Range of 1250. | | Reagents can be loaded onto the Panther system or Panther Fusion system | 5 times | 8 times | | Results impacted by faulty or flickering LED in Panther instrument or Panther Fusion instrument | Read as normal, potentially producing incorrect results | Marked as invalid results | Updated 510(k) Summary BK231025/A001 Confidential Page 5 of 7 {5} # Non-Clinical and/or Clinical Tests Summary & Conclusions # Analytical Study: Results of the reanalysis of line data, from the verification and validation studies in the original Aptima HIV Quant submission (BP150318), with the new logics implemented in the parameters for the RFT1 (pol) and RTF3(LTR) channels, met the original acceptance criteria. There was no change in the acceptance criteria of any of these instrument performance studies when the data was reanalyzed with the new parameters. Field data were analyzed to support the change in new estimated background limits. Process control improvement for flickering LED (high background) demonstrated improved fault detection. # Clinical Study: No new clinical testing was performed. The original clinical validation line data in BP150318 was reanalyzed with the new parameters. There were no clinically relevant changes which would affect study results or assay claims. # Method Comparison: A new method comparison study was performed using HIV-positive samples, and regression analysis was conducted separately across the entire assay range and around the cut-off. The study showed no difference in quantitative results between the current Aptima HIV-1 Quant Dx Panther Assay Sequence File and after reprocessing with the proposed new parameters/logics implemented in the Aptima HIV-1 Quant Dx Assay Sequence File version 6.0.5.2. The proposed new parameters/logics did not have an impact on the low out-of-range specimens (<30 c/mL or <1.48 log10 c/mL) which remained detectable (but not quantitated). Due to the logic in the RTF1 (Pol) channel which removes the Pol ratio cut-off for samples with a Pol RFU of >5000, the new sequence file containing the updated parameters, was able to detect one low positive specimen that was not detected by the current Aptima HIV-1 assay sequence file. This logic also detected pol positivity (with a concentration of <1 c/mL) on one low positive specimen that was positive for LTR target but Updated 510(k) Summary BK231025/A001 Confidential Page 6 of 7 {6} negative for pol by the current Aptima HIV-1 assay sequence file. All true/known negative specimens remain “Not Detected” or “Non-Reactive” in the updated Assay Sequence File version 6.0.5.2. Results are summarized in Table 3 below. **Table 3: Aptima HIV-1 Assay Sequence File version 5.3.5.1 vs 6.0.5.2 Summary Results** | Current (v5.3.5.1) Sequence File | | New (v6.0.5.2) Sequence File | | OLD Seq File (Channel) | New SeqFile Channel | Total Count | | --- | --- | --- | --- | --- | --- | --- | | Reactive | Not Quantified | Reactive | Not Quantified | LTR | pol | 1 | | | Quantified | | Quantified | pol | pol | 31 | | Non-reactive | Not Detected | Non-reactive | Not Detected | pol | pol | 156 | | | | Reactive | Not Quantified | Not Detected | Not Detected | 21 | | Grand Total | | | | | | 1 | | | | | | | | **210** | ### On-Board Stability: Additional reagent cycling on and off board the Panther instrument was conducted using the protocol and panel composition from the original PMA (BP150318), and the HIV Quant Dx Assay was able to successfully complete 10 loads with acceptable assay performance and reagent volume. This supports the proposed change of 5 reagent cycle loads to 8 reagent cycle loads. ### Substantial Equivalence Comparison Conclusion: The results of non-clinical analytical and clinical performance studies demonstrate that the Aptima HIV-1 Quant Dx Assay is as safe, as effective, and performs as well as the predicate device. Updated 510(k) Summary BK231025/A001 Confidential Page 7 of 7 --- **Source:** [https://fda.innolitics.com/device/BK231025](https://fda.innolitics.com/device/BK231025) **Published by [Innolitics](https://innolitics.com)** — a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices. 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