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The MiSeqDx Universal Kit 1.0 is a set of reagents and consumables used in the processing of human genomic DNA samples derived from peripheral whole blood, and in the subsequent targeted re-sequencing of the resulting sample libraries. User-supplied analyte specific reagents are required for the preparation of libraries targeting specific genomic regions of interest. The MiSeqDx Universal Kit 1.0 is intended for use with the MiSeqDx instrument.
The MiSeqDx Universal Kit 1.0 is intended for use with the MiSeqDx Platform. The MiSeqDx Universal Kit 1.0 consists of 5 boxes.
This document describes the acceptance criteria and the study proving the MiSeqDx Universal Kit 1.0 meets those criteria, based on the provided text.
1. Table of Acceptance Criteria and Reported Device Performance
The provided text focuses on the classification and intended use of the MiSeqDx Universal Kit 1.0 as a component for high-throughput genomic sequencing. While specific numerical acceptance criteria for all performance characteristics are not explicitly detailed in the provided excerpt (many refer to an associated 510(k) K123989), the text does outline some critical operational specifications and general requirements.
| Acceptance Criteria (from text) | Reported Device Performance (from text) |
|---|---|
| Operational Specifications: | |
| Sequencing output > 1 Gb | The system is designed to deliver this. |
| Reads > 3 million | The system is designed to deliver this. |
| Read length (in paired end run) 2 x 150 bp | The system is designed to deliver this. |
| Bases higher than Q30 > 75% (Greater than 75% of bases have Phred scale quality score greater than 30, indicating base call accuracy > 99.9%) | The system is designed to deliver this. |
| Detection of SNVs and up to 3 base deletions | The system has been validated for this. |
| Qualitative (genotype) results | The system is designed to deliver this. |
| Recommended minimal coverage per amplicon for accurate variant calling (Q(max_gt | poly_site) >= 100) is 75x | This is a recommended use condition. |
| Limitations/Known Performance: | |
| Problems detecting 1 base insertions or deletions in homopolymer tracts (e.g., polyA) | This is a known limitation. |
| Evaluation of 1 base insertions limited to 3 different insertions on 3 separate chromosomes | This states the extent of validation. |
| Underlying polymorphisms or mutations in oligonucleotide-binding regions can affect calls | This is an inherent characteristic of hybridization-based workflows. |
| Stability: | |
| Shelf life of 12 months when stored at appropriate conditions | Real-time stability testing for 6 months supports this; ongoing for 12 months. |
2. Sample Size Used for the Test Set and Data Provenance
The provided text repeatedly refers to an associated 510(k) submission, K123989, for detailed performance studies. Therefore, the specific sample sizes used for the test set and the data provenance (e.g., country of origin, retrospective/prospective) are not detailed in this document. The studies mentioned in this document are for:
- Precision/Reproducibility
- Stability (related to blood samples)
- Detection Limit
- Analytical Specificity
- Accuracy
All these reference K123989, meaning the details about the specific test sets, sample sizes, and provenance would be found in that separate submission.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not provide this information. The MiSeqDx Universal Kit 1.0 is a reagent kit that facilitates the creation of a library for genomic sequencing. The 'ground truth' for variant calling (SNVs, deletions, insertions) would typically be established based on orthogonal sequencing methods or well-characterized reference materials, rather than expert human interpretation of images or other subjective data. Details relating to the validation of variant calling would reside in K123989.
4. Adjudication Method for the Test Set
This information is not available in the provided text. Given the nature of a reagent kit for genomic sequencing, human adjudication methods like 2+1 or 3+1 are typically not applied to the primary sequencing data itself. The 'ground truth' for genomic variants is usually based on molecular methods.
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
No MRMC comparative effectiveness study was mentioned or implied. The MiSeqDx Universal Kit 1.0 is a reagent kit used in a genomic sequencing workflow. It does not involve human "readers" in the context of interpreting diagnostic images or output in a way that would necessitate an MRMC study with AI assistance. The device's role is to prepare genetic material for sequencing, not to interpret the sequencing results themselves.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
The device itself is a reagent kit. It is not an algorithm, and therefore the concept of "standalone" algorithm performance as typically applied to AI/software clinical decision support systems does not directly apply here. The performance of the sequencing system (which the kit is a part of) would be evaluated in terms of its ability to accurately detect genetic variants, which is an "algorithm only" type of assessment in terms of sequence analysis (without human interpretation of the raw data). However, the specific details of this would be in K123989.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
The document refers to studies establishing the "accuracy of high throughput DNA targeted sequencing of human genomic DNA" in K123989. For genomic sequencing, ground truth is typically established using:
- Orthogonal Sequencing Methods: Such as Sanger sequencing, whole genome sequencing (WGS), or other highly reliable sequencing technologies on the same samples.
- Reference Materials: Certified reference materials with known genetic variants.
- Synthetic DNA Constructs: With precisely known mutations.
The specific type of ground truth used would be detailed in K123989.
8. The Sample Size for the Training Set
The provided text does not contain any information regarding a "training set." The MiSeqDx Universal Kit 1.0 is a reagent kit, not a machine learning algorithm that requires a training set. The performance studies referenced in K123989 would evaluate the analytical performance of the kit and the sequencing platform, not the training of an algorithm.
9. How the Ground Truth for the Training Set Was Established
As no training set is mentioned or applicable to a reagent kit in the context of machine learning, this information is not provided and is irrelevant for this specific device.
§ 862.3800 Reagents for molecular diagnostic instrument test systems.
(a)
Identification. Reagents for molecular diagnostic test systems are reagents other than analyte specific reagents used as part of molecular diagnostic test systems, such as polymerases, nucleotides and nucleotide mixes, master mixes in which individual reagents are optimized to be used together, and labeled nucleic acid molecules.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedure in subpart E of part 807 of this chapter, subject to the limitations in § 862.9.