← Product Code [PAB](/submissions/MI/subpart-d%E2%80%94serological-reagents/PAB) · K243935 # Aptima CMV Quant Assay (K243935) _Hologic, Inc. · PAB · Jan 17, 2025 · Microbiology · SESE_ **Canonical URL:** https://fda.innolitics.com/submissions/MI/subpart-d%E2%80%94serological-reagents/PAB/K243935 ## Device Facts - **Applicant:** Hologic, Inc. - **Product Code:** [PAB](/submissions/MI/subpart-d%E2%80%94serological-reagents/PAB.md) - **Decision Date:** Jan 17, 2025 - **Decision:** SESE - **Submission Type:** Special - **Regulation:** 21 CFR 866.3180 - **Device Class:** Class 2 - **Review Panel:** Microbiology ## Indications for Use The Aptima® CMV Quant Assay is an in vitro nucleic acid amplification test for the quantitation of human cytomegalovirus (CMV) DNA in human EDTA plasma on the fully automated Panther® system. The Aptima CMV Quant Assay is intended for use to aid in the management of solid-organ transplant patients and hematopoietic stem cell transplant patients receiving anti-CMV therapy, serial DNA measurements can be used to assess viral response to treatment. The results from Aptima CMV Quant assay must be interpreted within the context of all relevant clinical and laboratory findings. The Aptima CMV Quant Assay is not intended for use as a screening assay for the presence of CMV in blood or blood products. ## Device Story Aptima CMV Quant Assay; in vitro diagnostic test for CMV nucleic acid quantification in transplant patients. Modification introduces Proteinase K enzyme pretreatment for plasma samples flagged with ML2 (clog) errors. Proteinase K degrades proteins to prevent coagulation during alkaline shock, ensuring valid assay results. Used in clinical laboratories; performed by laboratory technicians. Output provides quantitative CMV viral load data to clinicians for monitoring transplant patient status and therapeutic efficacy. Modification addresses rare (0.54%) sample-specific coagulation issues without altering fundamental assay technology. ## Clinical Evidence Validation study using transplant patient plasma specimens. Comparison of invalid ML2 flag rates: 0.87% (n=1039) without proteinase K treatment vs. 0% (n=4098) with proteinase K treatment. Study confirmed that proteinase K pretreatment does not impact the accuracy of CMV quantification (Youn et al., J Clin Microbiol. 2024). ## Technological Characteristics Real-time transcription-mediated amplification (TMA) targeting the UL56 gene. Standardized to WHO International Standard (NIBSC 09/162). Automated on Panther/Panther Fusion system. Reagents include target capture magnetic microparticles, MMLV reverse transcriptase, and T7 RNA polymerase. Proteinase K (RNA grade, DNase/RNase-free) used for sample pretreatment. Software-based quantification via internal calibrator comparison. ## Regulatory Identification A quantitative cytomegalovirus (CMV) nucleic acid test for transplant patient management is identified as a device intended for prescription use in the detection of CMV and as an aid in the management of transplant patients to measure CMV deoxyribonucleic acid (DNA) levels in human plasma and/or whole blood using specified specimen processing, amplification, and detection instrumentation. The test is intended for use as an aid in the management of transplant patients with active CMV infection or at risk for developing CMV infection. The test results are intended to be interpreted by qualified healthcare professionals in conjunction with other relevant clinical and laboratory findings. ## Special Controls *Classification.* Class II (special controls). The special controls for this device are:(1) The labeling required under § 809.10(b) of this chapter must include: (i) A prominent statement that the device is not intended for use as a donor screening test for the presence of CMV DNA in blood or blood products. (ii) Limitations, which must be updated to reflect current clinical practice. The limitations must include, but are not limited to, statements that indicate: (A) Test results are to be interpreted by qualified licensed healthcare professionals in conjunction with clinical signs and symptoms and other relevant laboratory results; (B) Negative test results do not preclude CMV infection or tissue invasive CMV disease, and that CMV test results must not be the sole basis for patient management decisions. (iii) A detailed explanation of the interpretation of results and acceptance criteria must be provided and include specific warnings regarding the potential for variability in CMV viral load measurement when samples are measured by different devices. Warnings must include the following statement, where applicable: “Due to the potential for variability in CMV viral load measurements across different CMV assays, it is recommended that the same device be used for the quantitation of CMV viral load when managing CMV infection in individual patients.” (iv) A detailed explanation of the principles of operation and procedures for assay performance. (2) Design verification and validation must include the following: (i) Detailed documentation of the device description, including all parts that make up the device, reagents required for use with the CMV assay but not provided, an explanation of the methodology, design of the primer/probe sequences, rationale for the selected gene target, and specifications for amplicon size, guanine-cytosine content, and degree of nucleic acid sequence conservation. The design and nature of all primary, secondary, and tertiary quantitation standards used for calibration must also be described. (ii) A detailed description of the impact of any software, including software applications and hardware-based devices that incorporate software, on the device's function. (iii) Documentation and characterization of all critical reagents ( *e.g.,* determination of the identity, supplier, purity, and stability) and protocols for maintaining product integrity throughout its labeled shelf life.(iv) Stability data for reagents provided with the device and indicated specimen types, in addition to the basis for the stability acceptance criteria at all time points chosen across the spectrum of the device's indicated life cycle, which must include a time point at the end of shelf life. (v) All stability protocols, including acceptance criteria. (vi) Final lot release criteria, along with documentation of 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. (vii) Risk analysis and documentation demonstrating how risk control measures are implemented to address device system hazards, such as Failure Modes Effects Analysis and/or Hazard Analysis. This documentation must include a detailed description of a protocol (including all procedures and methods) for the continuous monitoring, identification, and handling of genetic mutations and/or novel CMV stains ( *e.g.,* regular review of published literature and annual in silico analysis of target sequences to detect possible primer or probe mismatches). All results of this protocol, including any findings, must be documented.(viii) Analytical performance testing that includes: (A) Detailed documentation of the following analytical performance studies: Limit of detection, upper and lower limits of quantitation, inclusivity, precision, reproducibility, interference, cross reactivity, carryover, quality control, specimen stability studies, and additional studies as applicable to specimen type and intended use for the device. (B) Identification of the CMV strains selected for use in analytical studies, which must be representative of clinically relevant circulating strains. (C) Inclusivity study results obtained with a variety of CMV genotypes as applicable to the specific assay target and supplemented by in silico analysis. (D) Reproducibility studies that include the testing of three independent production lots. (E) Documentation of calibration to a standardized reference material that FDA has determined is appropriate for the quantification of CMV DNA ( *e.g.,* a recognized consensus standard).(F) Documentation of traceability performed each time a new lot of the standardized reference material to which the device is traceable is released, or when the field transitions to a new standardized reference material. (ix) Clinical performance testing that includes: (A) Detailed documentation of device performance data from either a method comparison study with a comparator that FDA has determined is appropriate, or results from a prospective clinical study demonstrating clinical validity of the device. (B) Data from patient samples, with an acceptable number of the CMV positive samples containing an analyte concentration near the lower limit of quantitation and any clinically relevant decision points. (C) The method comparison study must include predefined maximum acceptable differences between the test and comparator method across all primary outcome measures in the clinical study protocol. (D) The final release test results for each lot used in the clinical study. ## Predicate Devices - Aptima CMV Quant Assay ([P210029](/device/P210029.md)) ## 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} FDA U.S. FOOD & DRUG ADMINISTRATION # SPECIAL 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ## I Background Information: A 510(k) Number K243935 B Applicant Hologic, Inc. C Proprietary and Established Names Aptima CMV Quant Assay D Regulatory Information | Product Code(s) | Classification | Regulation Section | Panel | | --- | --- | --- | --- | | PAB | Class II | 21 CFR 866.3180 - Quantitative Cytomegalovirus Nucleic Acid Tests For Transplant Patient Management | MI - Microbiology | ## II Review Summary: This 510(k) submission contains information/data on modifications made to the submitter's own Class II device requiring a 510(k). The following items are present and acceptable: 1. The name and 510(K) number of the SUBMITTER’s previously approved device. 2. Submitter's statement that the INTENDED USE/INDICATIONS FOR USE of the modified device as described in its labeling HAS NOT CHANGED along with the proposed labeling which includes instructions for use, package labeling, and, if available, advertisements or promotional materials (labeling changes are permitted as long as they do not affect the intended use). 3. A description of the device MODIFICATIONS(S), including clearly labeled diagrams, engineering drawings, photographs, user's and/or service manuals in sufficient detail to demonstrate that the FUNDAMENTAL SCIENTIFIC TECHNOLOGY of the modified device has not changed. This change was for the use of proteinase K enzyme to treat plasma samples with an ML2 flag (clog). Manual pretreatment of plasma specimens with proteinase Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov {1} K degrades proteins, preventing coagulation of specimens when exposed to alkaline shock, resulting in valid assay results. Since the prevalence of plasma specimens that cause ML2 flags in the Aptima Assay at customer sites was calculated to be 0.54%, it is expected that the use of the proteinase K protocol will be very limited since it will be used only with samples that already had an ML2 flag invalid result. 4. Comparison Information (i.e., similarities and differences) to the submitter's legally marketed predicate device including, labeling, intended use, and physical characteristics. 5. A Design Control Activities Summary which includes: a) Identification of Risk Analysis method(s) used to assess the impact of the modification on the device and its components, and the results of the analysis. b) Based on the Risk Analysis, an identification of the verification and/or validation activities required, including methods or tests used and acceptance criteria to be applied. The labeling for this modified subject device has been reviewed to verify that the indication/intended use for the device is unaffected by the modification. In addition, the submitter's description of the modification(s) and the comparative information between the modified and unmodified devices demonstrate that the fundamental scientific technology has not changed. The submitter has provided the design control information as specified in the new special 510(k) paradigm and on this basis, I recommend the device be determined substantially equivalent to the previously cleared (or approved) device. K243935 - Page 2 of 2 --- **Source:** [https://fda.innolitics.com/submissions/MI/subpart-d%E2%80%94serological-reagents/PAB/K243935](https://fda.innolitics.com/submissions/MI/subpart-d%E2%80%94serological-reagents/PAB/K243935) **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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