(79 days)
This product is intended for in vitro diagnostic use as assayed quality control material to monitor the accuracy and reproducibility of analytes listed in the package insert.
Randox Immunoassay Premium Plus Controls are manufactured at three levels, Level 1, Level 2 and Level 3. The materials are supplied as Level 1, Level 2 , Level 3 and a Tri-Level configuration. Each 5 ml vial of lyophilized serum is reconstituted with exactly 5 ml of distilled water at +20 to 25° C.
The base matrix used for the manufacture of Randox Immunoassay Premium Plus Controls is Human Serum with added chemicals.
Human source material from which this product has been derived and has been tested at the donor level for the Human Immunodeficiency Virus (HIV1 & HIV2) antibody, Hepatitis B surface antigen (HbsAg) and the Hepatitis C virus (HCV) antibody and were found to be non-reactive based on FDA approved methods.
However, since no method can offer complete assurance as to the absence of infectious agents, this material and all patient samples should be handled as though capable of transmitting infectious diseases and disposed of accordinaly.
This document describes the stability studies conducted for the Randox Immunoassay Premium Plus Controls Levels 1, 2, and 3, and the Immunoassay Premium Plus Tri-Level Control. These studies establish the acceptance criteria for various stability conditions and demonstrate the device's performance against these criteria.
1. Table of Acceptance Criteria and Reported Device Performance
| Study Type | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Open Vial Stability (General) | Percentage deviation of reconstituted to fresh should be ≤10%. | All analytes (excluding C-Peptide, Thyroglobulin, ACTH, and PTH) in all control levels (1, 2, 3, and Tri-Level) passed the stability test at Day 7 when stored at +2 to +8°C. |
| Open Vial Stability (C-Peptide) | Percentage deviation of reconstituted to fresh should be ≤10%. | C-Peptide in all control levels (1, 2, 3, and Tri-Level) passed the stability test at Day 1 when stored at +2 to +8°C. |
| Open Vial Stability (ACTH, Thyroglobulin, PTH) | Percentage deviation of reconstituted to fresh should be ≤10%. | ACTH, Thyroglobulin, and Parathyroid Hormone (PTH) in all control levels (1, 2, 3, and Tri-Level) passed the stability test at 4 hours when stored at +2 to +8°C. |
| Frozen Stability | Percentage deviation of reconstituted to fresh should be ≤10%. (No claim for ACTH, Aldosterone, C-Peptide) | All analytes (excluding ACTH, Aldosterone, and C-Peptide) in all control levels (1, 2, 3, and Tri-Level) passed the stability test after 4 weeks (28 days) when stored at -18 to -24°C. |
| Accelerated Stability | Percentage deviation to fresh should be ≤10%. | All analytes in all control levels (1, 2, 3, and Tri-Level) passed the accelerated stability test at Week 4 (after storage at elevated temperatures: 28-32 °C, 35-39 °C, and 43-47 °C). This supported a predicted shelf life of 3 years. |
| Real Time Stability | Percentage deviation to controls stored at the routine temperature should be ≤10%. | Current Real Time studies (monitoring controls stored at -75 to -90°C against controls stored at +2 to +8°C at various timepoints) support a 3-year shelf life for all control levels (1, 2, 3, and Tri-Level). The document explicitly states "Current Real Time studies support a 3 year shelf life," implying that the acceptance criteria of ≤10% deviation were met. |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set:
- For open vial stability, frozen stability, and real-time/accelerated stability, the studies were conducted using a "set" of Immunoassay Premium Plus Controls levels 1, 2 & 3.
- Specific lot numbers were used: 972EC, 974EC, 977EC for the individual levels and combination for the Tri-Level control for open vial and frozen stability.
- For accelerated and real-time stability, lot numbers 852EC/941EC, 854EC/943EC, and 857EC/946EC were used.
- The document does not specify the number of individual vials or replicates tested within each lot for these stability studies.
- Data Provenance: The studies were conducted by Randox Laboratories Limited, based in Crumlin, County Antrim, United Kingdom. The data is prospective, as these are stability studies conducted to support the device's shelf life and claims.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts
This device is an in vitro diagnostic quality control material, not an imaging or diagnostic algorithm that relies on expert interpretation of images or clinical data. Therefore, the concept of "experts" establishing a ground truth for a test set in the conventional sense (e.g., radiologists, pathologists) does not directly apply here.
For the Value Assignment (Section 9), which can be considered analogous to establishing "ground truth" for the analyte concentrations within the control material:
- Number of Participants: "Each batch of Immunoassay Premium Plus is submitted to a number of external laboratories" and/or by in-house testing. The exact number of external laboratories is not specified.
- Qualifications of Participants: The document does not specify the qualifications of the personnel or laboratories involved in the value assignment process, beyond stating they are "external laboratories" and "in-house testing." However, for diagnostic control materials, these would typically be certified clinical reference laboratories or laboratories adhering to recognized quality standards for analytical testing.
4. Adjudication Method for the Test Set
For Value Assignment (Section 9):
- Method: Statistical analysis, including the mean, SD, and %CV, were calculated from the results obtained by these laboratories. An assigned value is derived from the mean specific value, and an analyte-specific percentage range is applied. This suggests a form of consensus-based adjudication among the participating laboratories, where the mean value plays a central role.
For Stability Studies:
- Method: The adjudication method for stability studies is direct comparison against predefined acceptance criteria (percentage deviation of ≤10% from fresh or routine controls). This is a direct analytical measurement comparison rather than expert consensus on individual results.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No. This type of study (MRMC) is typically performed for diagnostic devices where human readers (e.g., radiologists) interpret cases, and the study aims to quantify the effect of an AI tool on their performance. The Randox Immunoassay Premium Plus Controls are in vitro diagnostic quality control materials, not an AI-assisted diagnostic tool. Therefore, an MRMC study is not applicable.
6. Standalone Performance Study
Yes, the stability studies (open vial, frozen, accelerated, and real-time stability) described are standalone assessments of the device's performance (specifically its stability) under various conditions. These studies rigorously evaluate the control material itself without human intervention in the performance measurement, beyond handling according to instructions. The value assignment also represents a standalone assessment of the control's intended values.
7. Type of Ground Truth Used
- For Stability Studies: The "ground truth" for stability is established through reference measurements against freshly reconstituted or routinely stored control materials. The acceptance criterion is a predefined percentage deviation (≤10%) from these reference measurements.
- For Value Assignment: The "ground truth" for the assigned analyte values is established by a consensus of results obtained from multiple external laboratories and/or in-house testing, applying statistical analysis (mean, SD, %CV).
8. Sample Size for the Training Set
This document does not describe a "training set" in the context of machine learning. The device is a physical in vitro diagnostic control material, not a software algorithm that is "trained" on data. The manufacturing process and quality control procedures ensure the consistency and performance of the product.
9. How the Ground Truth for the Training Set Was Established
As noted above, there is no "training set" for this device in the conventional sense. The "ground truth" for the assigned values of the control material (which might be analogous to what a "training set" would establish for an AI model) is established through the consensus of results from multiple laboratories and statistical analysis as described in Section 9 of the document.
§ 862.1660 Quality control material (assayed and unassayed).
(a)
Identification. A quality control material (assayed and unassayed) for clinical chemistry is a device intended for medical purposes for use in a test system to estimate test precision and to detect systematic analytical deviations that may arise from reagent or analytical instrument variation. A quality control material (assayed and unassayed) may be used for proficiency testing in interlaboratory surveys. This generic type of device includes controls (assayed and unassayed) for blood gases, electrolytes, enzymes, multianalytes (all kinds), single (specified) analytes, or urinalysis controls.(b)
Classification. Class I (general controls). Except when intended for use in donor screening tests, quality control materials (assayed and unassayed) are exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.