(48 days)
Multichem Alc control is intended for use as an assayed quality control to monitor the precision of laboratory testing procedures for the analyte, HbA1c, as listed in the package insert.
The use of quality control materials is indicated as an objective assessment of the precision of methods and techniques in use and is an integral part of good laboratory practices. A minimum of two levels of control are available to allow performance monitoring within the clinical range of HbA1c assay method. Multichem A1c control is prepared from human red blood cells with added chemicals and stabilizers. The control is provided in liquid form for convenience.
The provided document describes the Multichem A1c device, which is an assayed quality control material for monitoring the precision of laboratory testing procedures for HbA1c. The study described focuses on the stability and value assignment of this quality control material, rather than the performance of a diagnostic algorithm or device in detecting disease. Therefore, many of the requested categories for a diagnostic device (like sample size for test set, data provenance, number of experts for ground truth, adjudication method, MRMC study, and standalone performance) are not applicable in the traditional sense.
Here's the information that can be extracted and presented based on the context of a quality control device:
1. Acceptance Criteria and Reported Device Performance
Device: Multichem A1c (Assayed) Control
Purpose: Quality Control Material for HbA1c testing.
| Acceptance Criteria Category | Specific Criteria | Reported Device Performance (Summary) |
|---|---|---|
| Value Assignment Ranges | Level 1: - % HbA1c (DCCT/NGSP): Target 4.00-7.00% - A1c (IFCC mmol/mol): Target 20.2-53.0 mmol/mol Level 2: - % HbA1c (DCCT/NGSP): Target 8.00-13.00% - A1c (IFCC mmol/mol): Target 63.9-119.0 mmol/mol | Value assignments performed successfully on Tosoh, Beckman, and Trinity analysers, with targets and ranges established for each. Specific targets and ranges for each level and analyzer combination are provided in Section 8.0. The control ranges are set based on 3 standard deviations of imprecision with a minimum applied range of ±10%. |
| Open Vial Stability | Maximum Allowable Degradation / Drift Limit < 10% | Supports 30 days at 2°C to 8°C |
| Closed Vial Stability (Accelerated Stress Test) | Drift Limit of ≤ 10% | Supports a shelf-life of ≥ 12 months. |
| Closed Vial Stability (Real-time) | Drift Limit of ≤ 10% | Real-time stability program implemented, expected to confirm shelf life using 3 lots at -20°C and -80°C. |
2. Sample Size Used for the Test Set and Data Provenance
Given this is a quality control material, the "test set" refers to the samples used in the value assignment and stability studies.
- Value Assignment Test Set:
- Tosoh: n = 45 replicates (over 5 days) for each level.
- Beckman: n = 23 replicates (over 5 days) for each level.
- Trinity Biotech: n = 15 replicates (over 5 days) for each level.
- Data Provenance: Not explicitly stated, but the submission is from Technopath Manufacturing Ltd. in Ireland. The study was conducted in-house. It is a prospective study in the sense that the testing was performed specifically to establish these values.
- Open Vial Stability Test Set: Vials were tested in replicates of 3 at each time-point against a freshly thawed, unopened vial. The number of time points or total number of replicates is not specified but infers a series of measurements over the 30-day period.
- Closed Vial Stability (Accelerated Stress Test) Test Set: 3 separate HbA1c Control lots were tested. Each lot involved testing stressed vials (in duplicate) and fresh (unstressed) samples (in duplicate).
- Closed Vial Stability (Real-time) Test Set: A minimum of 3 lots will be tested at specific time points over the proposed shelf life.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts
For a quality control material, "ground truth" is typically established by reference methods or validated laboratory procedures, not by human experts adjudicating clinical cases.
- The "ground truth" (target values) for the control material is assigned through a rigorous value assignment process using calibrated analytical instruments (Tosoh, Beckman, Trinity), performing multiple replicates over several days to establish a mean value. There is no mention of human experts defining the "ground truth" in this context.
4. Adjudication Method for the Test Set
Not applicable. The "test set" values are derived from instrument measurements and statistical analysis (mean, standard deviation), not expert adjudication.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done
Not applicable. This is not a diagnostic device involving human readers or interpretation of medical cases. It is a quality control material for instrument performance.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Not applicable. This device is a biochemical control, not an algorithm. Its "performance" refers to its stability and its ability to consistently provide a known reference value for laboratory instrument calibration/quality checks, not interpretive capabilities.
7. The Type of Ground Truth Used
The "ground truth" for the Multichem A1c control material is established through:
- Instrument-specific mean values: Derived from multiple replicates on calibrated HbA1c analyzers (Tosoh, Beckman, Trinity Biotech). These instruments are themselves calibrated against primary or secondary reference methods for HbA1c measurement.
- Statistical calculation: The target value for the control is the mean value of all replicates generated on the specified instrument, and ranges are set based on imprecision (3 x Standard Deviation) with a minimum applied range of ±10%.
8. The Sample Size for the Training Set
Not applicable. This device is not an AI/ML algorithm that requires a "training set." It is a manufactured biochemical product. The "training data" equivalent might be considered the data used to initially establish the manufacturing process and stability characteristics, but those terms don't fit the AI/ML context.
9. How the Ground Truth for the Training Set was Established
Not applicable, as there is no training set in the AI/ML sense. The "ground truth" for its performance as a quality control material is established by the value assignment and stability studies described above.
{0}------------------------------------------------
Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol that resembles a stylized human figure in profile, with three overlapping faces.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
TECHNOPATH MANUFACTURING BERND HASS HEAD OF QUALITY AND REGULATORY AFFAIRS FORT HENRY BUSINESS PARK BALLINA CO. TIPPERARY, IRELAND
October 26, 2016
Re: K162514
Trade/Device Name: Multichem A1c Regulation Number: 21 CFR 862.1660 Regulation Name: Quality control material (assayed and unassayed) Regulatory Class: I, Reserved Product Code: JJX Dated: September 5, 2016 Received: September 26, 2016
Dear Bernd Hass:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21. Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
{1}------------------------------------------------
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours.
Katherine Serrano -S
For : Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
{2}------------------------------------------------
| DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration | |
|---|---|
| Indications for Use | Form Approved: OMB No. 0910-0120Expiration Date: January 31, 2017See PRA Statement below. |
| 510(k) Number (if known) | K162514 |
| Device Name | Multichem Alc |
| Indications for Use (Describe) | Multichem Alc control is intended for use as an assayed quality control to monitor the precision of laboratory testing procedures for the analyte, HbA1c, as listed in the package insert. |
| Type of Use (Select one or both, as applicable) | |
| Prescription Use (Part 21 CFR 801 Subpart D) | |
| Over-The-Counter Use (21 CFR 801 Subpart C) |
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services
Food and Drug Administration
Office of Chief Information Officer
Paperwork Reduction Act (PRA) Staff
PRAStaff@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
| FORM FDA 3881 (8/14) | Page 1 of 1 |
|---|---|
| PSC Publishing Services (301) 443-6740 EF |
{3}------------------------------------------------
510(k) Summary Multichem A1c (Assayed) Control
1.0 Submitter:
Bernd Hass Head of Quality and Regulatory Affairs Technopath Manufacturing Ltd. Fort Henry Business Park Ballina, Co. Tipperary Ireland Telephone: + 353 61 525700 Email: bernd.hass@technopathcd.com
2.0 Date Sumbitted:
26st October 2016
3.0 Device Identification
Proprietary Names: Multichem A1c Common Name: Quality Control material, single (specified) analytes Classification: Class 1, Reserved Product Code: JJX Regulation Number: 21 CFR 862.1660
4.0 Legally Marketed Predicate Device
| Candidate | Predicate | Manufacturer | Document number |
|---|---|---|---|
| Multichem A1c | CONE-TROLHemoglobin A1cControl set | Cone Bioproducts | K121534 |
The Multichem A1c control is substantially equivalent to the Cone Bio product listed above, currently in commercial distribution.
5.0 Device Description
The use of quality control materials is indicated as an objective assessment of the precision of methods and techniques in use and is an integral part of good laboratory practices. A minimum of two levels of control are available to allow performance monitoring within the clinical range of HbA1c assay method. Multichem A1c control is prepared from human red blood cells with added chemicals and stabilizers. The control is provided in liquid form for convenience.
{4}------------------------------------------------
The following kit configurations are available: Multichem A1c Model HB000A (bi-level) with Level 1 & 2 control; 12 vials with 1 mL contents Model HB001A with Level 1 control; 12 vials with 1 mL contents Model HB002A with Level 2 control; 12 vials with 1 mL contents Model HB000M (bi-level minipak) with Level 1 & 2 control; 1 vial with 1 mL contents Model HB000T (bi-level) with Level 1 & 2 control; 12 vials with 1 mL contents Model HB001T with Level 1 control; 12 vials with 1 mL contents Model HB002T with Level 2 control; 12 vials with 1 mL contents
Each donor unit used in the preparation of the control material was tested by United States Food and Drug Administration (FDA) approved methods and found to be negative for antibodies to HIV and HCV, and non-reactive for HBsAg.
6.0 Intended Use
Multichem A1c control is intended for use as an assayed quality control material to monitor the precision of laboratory testing procedures for the analyte, HbA1c as listed in the package insert.
7.0 Comparison to the Predicate
Multichem A1c control claims to be substantially equivalent to CONE-TROL Hemoglobin A1c control set. The controls have same/similar design and modes of operation. The key features are summarized in the following table.
| Characteristics | Predicate Device:CONE-TROL Hemoglobin A1cControl Set | Proposed Device:Multichem A1c |
|---|---|---|
| Intended Use: | CONE-TROL Hemoglobin A1cControl Set is intended foruse as a quality controlmaterial to monitor theperformance and precisionof Hemoglobin A1cdetermination methods. | Multichem A1c control isintended for use as anassayed quality controlmaterial to monitor theprecision of laboratorytesting procedures for theanalyte, HbA1c as listed inthe package insert. |
| Analytes | A1c | A1c |
| Form: | Liquid | Liquid |
{5}------------------------------------------------
| Matrix: | Human Blood, Stabilisers, and preservatives | Human Blood and Stabilisers, and preservatives |
|---|---|---|
| Storage | -20°C | -20°C to -80°C |
| Thawed and Open | Open Vial Stability (2°C -8°C)180 days | Open Vial Stability (2°C -8°C)30 days |
| Shelf Life | 2 years | 1 years (12 mth) |
8.0 Value assignment process
The value assignment performance outlined here, was performed using a single analyser with single reagent and calibrator lot. Variability was introduced by performing the testing over multiple days.
Target assigned here were performed on the, Tosoh, Beckman and Trinity analysers, independently, with values claimed on each platform. The control target is the mean value of all the replicates generated on the specified instrument. The number of replicates performed is detailed in the below tables. No data points were excluded. Target values assigned have to be with the following acceptance specifications:
LEVEL 1
| Acceptance Ranges | ||||
|---|---|---|---|---|
| ANALYTES | Analyser Reported Units | TARGET | LOW | HIGH |
| % HbA1c | (DCCT/NGSP) | 5.50 | 4.00 | 7.00 |
| A1c | IFCC mmol/mol | 36.6 | 20.2 | 53.0 |
{6}------------------------------------------------
| Acceptance Ranges | ||||
|---|---|---|---|---|
| ANALYTES | Analyser Reported Units | TARGET | LOW | HIGH |
| % HbA1c | (DCCT/NGSP) | 10.5 | 8.00 | 13.0 |
| A1c | IFCC mmol/mol | 91.3 | 63.9 | 119 |
The control ranges are set based on a review of the imprecision (3 x Standard Deviation) of the (instrument specific) value assignment data with a minimum applied range of ±10%.
Lot A0004150
Tosoh - Value Assignment testing was performed over 5 days with n = 45 replicates
| Hemoglobin A1c | % | Unit | Level 1 | Level 2 | ||
|---|---|---|---|---|---|---|
| Range | Target | Range | Target | Range | ||
| Tosoh(G8) | 10% | NGSP (%)mmol/mol | 5.9741.8 | 5.37 - 6.5735.2 - 48.3 | 10.287.6 | 9.18 - 11.276.8 - 98.9 |
Beckman - Value Assignment testing was performed over 5 days with n = 23 replicates
| Hemoglobin A1c | %Range | Unit | Level 1 | Level 2 | ||
|---|---|---|---|---|---|---|
| Target | Range | Target | Range | |||
| Beckman(AU 5800) | 25% | NGSP (%)mmol/mol | 5.35 | 4.01 - 6.69 | 9.91 | 7.43 - 12.4 |
| 35.0 | 20.3 - 49.6 | 84.9 | 57.7 - 112 |
Trinity Biotech - Value Assignment testing was performed over 5 days with n = 15 replicates
| Hemoglobin A1c | %Range | Unit | Level 1 | Level 2 | ||
|---|---|---|---|---|---|---|
| Target | Range | Target | Range | |||
| Trinity BiotechPremier(Hb9210) | 10% | NGSP (%)mmol/mol | 5.0231.4 | 4.52 - 5.5225.9 - 36.8 | 10.591.5 | 9.47 - 11.680.0 - 103 |
LEVEL 2
{7}------------------------------------------------
9.0 Summary of Performance Data
Stability studies have been performed to determine the open vial stability and shelf life for this control. Product claims are as follows:
Open vial stability: 30 days at 2°C to 8°C Storage (Closed/Shelf-Life): -20°C to -80°C until expiration date.
The submission provides the summary data necessary to demonstrate substantial equivalence to the reference predicate. Additional supporting data is retained on file at Techno-path Manufacturing Ltd. The summary of safety and effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and the implementing regulation 21 CFR 807.92.
Stability (Open Vial)
The Multichem A1c (Assayed) controls were evaluated using an Isochronous (Staggered Start [Backwards / Back-ended]) protocol design as per CLSI EP25-A.
Open Vial testing was performed (at 2°C -8°C) by testing vials which were thawed and opened for pre-defined durations (test vials) against a freshly thawed, unopened vial (reference vials). All analytes from open vial and freshly thawed vial samples were tested in replicates of 3 at each time-point.
Acceptance criteria: Maximum Allowable Degradation / Drift Limit <10%
Stability (Closed Vial)
Accelerated Stress Test:
An in-house study was performed which shows that an accelerated model of 6.5 hours @ 37°C is comparable with ≥ 20 month real-time data and therefore represents a suitable model for the prediction of a shelf-life of (significantly beyond) 12 months.
Testing, using this accelerated model, was performed on 3 separate HbA1c Control lots. The A1c % value of the stressed vials was verified versus the A1c % value of a fresh (unstressed) sample. All samples were tested in duplicate.
Acceptance Criteria: Drift Limit of ≤ 10%
{8}------------------------------------------------
The % shift in HbA1c value is calculated using the following formula.
% shift in A1c = [(mean stressed value % / mean fresh value %) -1] x 100
Testing supports a shelf life of ≥12 months.
A real time stability test program has been implemented at Technopath Manufacturing Ltd.
Stability is assessed by testing the HbA1c analyte at specific time points over the proposed shelf life of the product. Testing will be completed for a minimum of 3 lots of the controls at each time point using product stored at both -20°C and at -80°C.
Acceptance Criteria: Drift Limit of ≤ 10%
10.0 Conclusion.
The Submitted information in this premarket notification is complete and supports a substantial equivalence decision.
§ 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.