(50 days)
INTROL™ CF Panel I Control is intended for in vitro diagnostic use as a quality control to monitor analytical performance of the extraction, amplification and detection steps of diagnostic assays used in the detection of the Cystic FibrosisTransmembrane Regulator (CFTR) gene mutations and variants. This product is intended to be extracted and analyzed routinely with each CFTR assay run. The INTROL™ CF Panel I Control is designed to monitor the detection of 38 CFTR mutations associated with cystic fibrosis, including the 23 mutations recommended for testing by American College of Medical Genetics (ACMG) and American College of Obstetricians and Gynecologists (ACOG). The INTROL™ CF Panel I Control also monitors 3 polymorphisms (1506V, I507V, F508C) and the 5/7/9T variants.
Modified INTROL™ CF Panel I Control consists of synthetic (recombinant) CFTR DNA suspended in a matrix of carrier DNA of non-human species, preservatives, dye, and stabilizers. CFTR DNA is stabilized in the matrix and released when processed through common extraction methods as if it were a whole blood specimen. INTROL™ CF Panel I Control was modified to contain additional wild type CFTR DNA required for primer annealing of some CFTR detection assays.
The provided document is a 510(k) Summary for a Quality Control Material for Cystic Fibrosis Nucleic Acid Assays, not a medical device in the typical sense of providing diagnostic feedback based on patient data. Therefore, many of the requested criteria related to device performance on patient data, such as sensitivity, specificity, MRMC studies, or ground truth established by experts/pathology/outcomes data, are not applicable in this context.
This document describes a modification to an existing quality control product (INTROL™ CF Panel I Control) and asserts its substantial equivalence to the predicate device (K060070). The acceptance criteria for such a product would primarily revolve around its ability to perform consistently and as intended when used with diagnostic assays.
Here's an analysis based on the provided text, addressing the applicable criteria:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria (Implied for a Quality Control Material) | Reported Device Performance |
|---|---|
| Intended Use: Consistent performance as a quality control for extraction, amplification, and detection steps of CFTR diagnostic assays. | "INTROL™ CF Panel I Control is intended for in vitro diagnostic use as a quality control to monitor analytical performance of the extraction, amplification and detection steps of diagnostic assays used in the detection of the Cystic FibrosisTransmembrane Regulator (CFTR) gene mutations and variants." |
| "Verification and validation testing performed as needed according to risk analysis showed that modified INTROL™ CF Panel I Control performed as well or better than INTROL™ CF Panel I Control (K060070)." | |
| Monitoring Capability: Designed to monitor detection of 38 CFTR mutations, including 23 ACMG/ACOG recommended mutations, 3 polymorphisms, and 5/7/9T variants. | "The INTROL™ CF Panel I Control is designed to monitor the detection of 38 CFTR mutations associated with cystic fibrosis, including the 23 mutations recommended for testing by American College of Medical Genetics (ACMG) and American College of Obstetricians and Gynecologists (ACOG). The INTROL™ CF Panel I Control also monitors 3 polymorphisms (1506V, I507V, F508C) and the 5/7/9T variants." |
| Equivalence to Predicate: Performance is as good as or better than the predicate device. | "Verification and validation testing performed as needed according to risk analysis showed that modified INTROL™ CF Panel I Control performed as well or better than INTROL™ CF Panel I Control (K060070)." |
| "Test methods were the same as those used for 510(k) submission of the predicate." | |
| "Based on analysis and performance testing, we conclude that modified INTROL™ CF Panel I Control is substantially equivalent to INTROL™ CF Panel I Control (K060070), is as safe and effective as the predicate, and performs better than the predicate in certain CFTR detection assays." | |
| Conformance: Meets design inputs in accordance with design control requirements (21 CFR 820.30). | "Design outputs of modified INTROL CF Panel I Control meet design inputs in conformance with design control requirements as specified in 21 CFR 820.30." |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
The document states: "Verification and validation testing performed as needed according to risk analysis showed that modified INTROL™ CF Panel I Control performed as well or better than INTROL™ CF Panel I Control (K060070). Test methods were the same as those used for 510(k) submission of the predicate."
- Sample Size: The specific sample sizes for the "verification and validation testing" are not provided in this 510(k) summary.
- Data Provenance: Not explicitly stated. Given that MMQCI is a US-based company, the testing was likely conducted in the US, but this is not confirmed. The document does not specify if the data was retrospective or prospective, though performance testing of a quality control would typically be prospective for new runs.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This question is not applicable. For a quality control material, there isn't a "ground truth" established by experts in the context of diagnostic interpretation. The "ground truth" for the control material itself is its known genetic composition (synthetic CFTR DNA with specific mutations/polymorphisms), which is validated during manufacturing and characterization.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
Not applicable. Adjudication methods are typically used for interpreting results from diagnostic devices based on patient samples, often involving multiple human readers or expert panels. This is a quality control material, not a diagnostic device.
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 is a quality control material, not an AI-powered diagnostic device, and therefore MRMC studies with human readers are irrelevant.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Not Applicable. This is a physical quality control material for laboratory assays, not an algorithm.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The "ground truth" for the INTROL™ CF Panel I Control is the known, manufactured genetic composition of the synthetic (recombinant) CFTR DNA it contains, including the specific 38 mutations, polymorphisms, and variants it is designed to monitor. This is intrinsic to the product design rather than being derived from external data sources like expert consensus or patient outcomes.
8. The sample size for the training set
Not applicable. This product is a quality control material, not a machine learning algorithm that requires a training set.
9. How the ground truth for the training set was established
Not applicable. This product is a quality control material, not a machine learning algorithm that requires a training set.
§ 866.5910 Quality control material for cystic fibrosis nucleic acid assays.
(a)
Identification. Quality control material for cystic fibrosis nucleic acid assays. A quality control material for cystic fibrosis nucleic acid assays is a device intended to help monitor reliability of a test system by detecting analytical deviations such as those that may arise from reagent or instrument variation in genetic testing. This type of device includes recombinant, synthetic, and cell line-based DNA controls.(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 § 866.9. The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Quality Control Material for Cystic Fibrosis Nucleic Acid Assays.” See § 866.1(e) for the availability of this guidance document.