(427 days)
The GSP Neonatal Creatine Kinase-MM kit, is intended for the quantitative in vitro determination of creatine kinase MM-isoform (CK-MM) concentration in blood specimens dried on filter paper as an aid in screening newborns for Duchenne Muscular Dystrophy (DMD) using the GSP instrument.
The GSP Neonatal Creatine Kinase-MM assay is a solid phase, two-site fluoroimmunometric assay based on the direct sandwich technique and utilizes standard PerkinElmer DELFIA chemistry with the GSP instrument. The kit contains:
- . The CK-MM Calibrators (containing 0, 30, 120, 500, 2000 and 8000 ng/mL of creatine kinase) consisting of 7 cassettes each containing 1 set of dried blood spots.
- The CK-MM Controls (containing 130, 500 and 2000 ng/mL of creatine kinase) consisting of 5 cassettes each containing 2 set of dried blood spots.
- Anti-CK-MM-Eu Tracer ●
- CK-MM Assay Buffer ●
- Anti-CK-MM Microtitration strips ●
- Extra barcodes for the plates ●
Here's an analysis of the GSP Neonatal Creatine Kinase-MM kit's acceptance criteria and the study proving it meets them, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly list "acceptance criteria" for the overall device performance in a summary table. Instead, it describes analytical performance studies (precision, linearity, detection limits, specificity) with implied acceptance based on CLSI guidelines. For clinical performance, the results are presented with different cut-off values, and the benefit-risk assessment provides the overall conclusion regarding the device's benefit.
However, we can infer some key performance metrics from the clinical study results and regulatory context. The primary clinical acceptance is tied to its ability to aid in screening for DMD.
Inferred Acceptance Criteria and Reported Device Performance:
| Performance Metric | Acceptance Criteria (Inferred from regulatory context and benefit/risk) | Reported Device Performance (Clinical Study) |
|---|---|---|
| Clinical Performance | ||
| Ability to screen for DMD | Must effectively identify DMD positive newborns to enable earlier diagnosis and intervention, where benefits outweigh risks of false positives/negatives. (Benefit-risk assessment indicates this was met.) | Cut-off 1250 ng/mL: |
- DMD Positive identified: 34 out of 34 (100%) |
| (False Negative Rate) | As low as possible to prevent delayed diagnosis. (Labeling statement: future lots could range from 0% to 0.48% at 99.5th percentile, and 0% to 0.05% at 97.5th percentile) | Cut-off 1250 ng/mL: 0% (0 false negatives out of 34 confirmed DMD positive samples) |
| (False Positive Rate) | Acceptable trade-off to enable screening benefits, considering the need for confirmatory testing. (Labeling statement: future lots could range from 0.4% to 0.7% at 99.5th percentile, and 2.0% to 3.7% at 97.5th percentile) | Cut-off 1250 ng/mL: 2.26% (Routine samples) (69 presumed negative / 3041 routine samples) |
| | | Cut-off 2040 ng/mL: 0.53% (Routine samples) (16 presumed negative / 3041 routine samples) |
| Analytical Performance | | |
| Reportable Range | Sufficiently broad to cover clinically relevant CK-MM concentrations. (Implied by CLSI EP06 and subsequent claim) | 29.2-8000 ng/mL |
| Limit of Blank (LoB) | Low enough to reliably distinguish between the absence and presence of analyte with a high degree of confidence. (Based on CLSI EP17-A2) | 0.7 ng/mL |
| Limit of Detection (LoD) | Low enough to reliably detect the analyte above background noise. (Based on CLSI EP17-A2) | 2.2 ng/mL |
| Limit of Quantitation (LoQ) | Low enough to quantify the analyte with acceptable precision and accuracy. (Based on CLSI EP17-A2 and (b)% CV acceptance limit) | 6.8 ng/mL |
| Specificity (Absence of Interference) | Substances commonly found in neonatal blood or used in care should not significantly interfere with results within specified limits. (Limit for significant interference defined as (b)(4)%) | Most tested substances (bilirubin, triglycerides, albumin, acetaminophen, etc.) at high concentrations showed no significant interference. Chlorhexidine digluconate (0.04%) and low hematocrit (35-45% at 159 ng/mL CK-MM) showed interference. |
| Cross-reactivity (CK-BB, CK-MB) | Clinically relevant levels of related enzymes (CK-BB, CK-MB) should not significantly cross-react to avoid false positives. (Limit for significant cross-reactivity defined as (b)(4)%) | Cross-reactivity results for CK-BB and CK-MB were provided in tables (values redacted). |
| Stability of DBS Samples | CK-MM in DBS samples must maintain integrity over reasonable storage and shipping conditions for practical use. | - Stable for up to 200 days at +4°C (dry). - Moderate loss (up to 27%) after 6 days at +4℃ (ambient).
- Stable for up to 25 days at -20℃ (ambient).
- Stable for up to 20 days at +21°C (dry).
- Unstable in humid conditions (+21℃ / +35℃,
§ 862.1506 Muscular dystrophy newborn screening test.
(a)
Identification. A muscular dystrophy newborn screening test is an in vitro diagnostic device intended to measure creatine kinase levels obtained from dried blood spot specimens on filter paper from newborns as an aid in screening newborns for muscular dystrophy.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Design verification and validation must include a clinical validation study that includes the following:
(i) Results that demonstrate that the analyte being measured identifies a population of newborns who should be subject to follow up diagnostic testing for the condition being screened.
(ii) Predictive value of the device demonstrated using either well characterized prospectively or retrospectively obtained clinical specimens from the intended use population.
(iii) Testing performed by device users who are representative of the types of operators intended to use the test.
(iv) A design that assesses the effects of sample collection and processing steps on test performance.
(v) Tested confirmed positive specimens must have associated diagnostic outcome information based on confirmatory diagnostic methods, or clinically meaningful information regarding the status of the subject must be obtained.
(vi) Data, provided or referenced, generated in samples from the intended use population, that demonstrates the upper reference interval(s), including sufficient samples to calculate the 97.5th and 99.5th percentile information, for the analyte or analytes measured by the device.
(2) The labeling required under § 809.10(b) of this chapter must include:
(i) A warning which states that test results are not intended to diagnose muscular dystrophies.
(ii) A warning which states that test results are intended to be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, including confirmation by alternative methods, and clinical evaluation as appropriate.
(iii) Detailed information on device performance, including the false positive screen rate and the false negative screen rate observed in the clinical study, and any limitations to the data generated in the clinical study (
e.g., necessity for testing at a specific age).(iv) Information on device performance in relevant subgroups (
e.g., age of newborn at time of sample collection, birth weight, sex, gestational age) observed in the clinical study.