(273 days)
Not Found
No
The device description outlines a standard ELISA assay with spectrophotometric reading and qualitative/semi-quantitative results based on a cutoff. There is no mention of AI/ML in the device description, intended use, or performance studies.
No.
This device is an in vitro diagnostic (IVD) test designed to detect antibodies to aid in the diagnosis of primary biliary cirrhosis, not to treat or directly manage a condition in a patient.
Yes
This device is a diagnostic device as its intended use is to "aid in the diagnosis of primary biliary cirrhosis (PBC)".
No
The device description clearly outlines a laboratory-based immunoassay (ELISA) that involves physical components like microwells, reagents, and a spectrophotometer for reading results. This is a hardware-based diagnostic test, not a software-only device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states the device is for the "qualitative detection of anti-mitochondria antibodies (AMA) in human serum to aid in the diagnosis of primary biliary cirrhosis (PBC)". This indicates the device is used to examine specimens derived from the human body (serum) to provide information for diagnostic purposes.
- Device Description: The description details a laboratory test (ELISA) performed on human serum samples. This aligns with the definition of an in vitro diagnostic device, which is used to examine specimens from the human body.
- Performance Studies: The document describes clinical studies and performance metrics (sensitivity, specificity, agreement) based on testing human serum samples from individuals with and without primary biliary cirrhosis. This is typical for the validation of an IVD.
- Predicate Devices: The mention of predicate devices (INOVA QUANTA Lite™ M2 EP (MIT3); Trinity Captia™ Mitochondria IgA/IgG/IgM Screen) which are also IVDs, further supports that this device falls into the same category.
The core function of the device is to analyze a human biological sample (serum) outside of the body to provide information that aids in a medical diagnosis. This is the defining characteristic of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
An enzyme linked immunosorbent assay (ELISA) for the qualitative detection of anti-mitochondria antibodies (AMA) in human serum to aid in the diagnosis of primary biliary cirrhosis (PBC) in conjunction with other laboratory tests and clinical findings.
An enzyme linked immunoassay (ELISA) for the qualitative or semi-quantitative detection of anti-mitochondria IgG antibodies in human serum to aid in the diagnosis of primary biliary cirrhosis (PBC) in conjunction with other laboratory tests and clinical findings.
Product codes (comma separated list FDA assigned to the subject device)
DBM
Device Description
Primary billiary cirrhosis (PBC) is a disease of the liver characterized by inflammatory obliteration of the intrahepatic bile ducts. PBC is characterized by the presence of antibodies (AMA). AMA detected by indirect immunofluorescence (IF) occur in approximately 90% of patients with autoimmune hepatitis as well as in certain other disorders such as syphils and drug induced hepatitis. As many as nine different staining reactions have been described by indirect IF, but only one, the M2 reaction is specific for PBC. Inability to easily different AMA reactions compromises the utility of indirect IF test methods for diachemical and immunochemical studies have identified the E2 component of pyruvate dehydrogenase complex (PDC-E2) to be the immunodomina antigen. Other significant autoantibody markers for PBC are the E2 subunit of the 2-oxoglutarate dehydrogenase complex (OGDC-E2) and the E2 subunit of the branched-chain 2-oxoacid dehydrogenase complex (BCOADC-E2). Antibodies are typically detected by IgG; however, literature reports a number of cases with elevated levels of lgA and/or lgM isotype antibodies rather than lgG. A combination of individual anti-mitochondrial antigens are coated in one well to facilitate immunoassay senstivity for the detection of AMA associated with PBC.
This test is performed as a solid phase immunoassy. Microwells are coated with recombinant Mitochondrial antigen. Controls, calibrators and patient sera are incubated in the antibodies present in the serum to bind to the Mitochondria antigen. Bound antibodies are detected by adding an enzyme labeled anti-human IgG or IgA/JgG/JgM conjugate. Specific enzyme substrate (TMB) is then added and the presence of antibodies is detected by a color change that is read by a spectrophotometer at 450 nm. Results are expressed in ELISA units per milliliter (EU/ml) and reported as positive or negative.
Primary biliary cirrhosis (PBC) is a disease of the liver characterized of the intrahepatic bile ducts. PBC is characterized by the presence of antibodies (AMA). AMA detected by indirect immunofluorescence (IF) occur in approximately 90% of patients with autoimmune hepatits as well as in certain other disorders such as syphils and drug induced hepatitis. As many as nine different staining reactions have been described by indirect IF, but only one, the M2 reaction is specific for PBC. Inability to easily different AMA reactions compromises the utility of indirect IF test methods for diagnosing PBC. Biochemical studies have identified the E2 component of pyruvate dehydrogenase complex (PDC-E2) to be immunodominant antigen. Other significant autoantibody markers for PBC are the E2 subunit of the 2-oxoglutarate dehydrogenase complex (OGDC-E2) and the E2 subunit of the branched-chain 2-oxoacid dehydrogenase complex (BCOADC-E2). Anti-M2 mitochondrial antibodies are typically detected by IgG; however, literature reports a number of cases with elevated levels of lgA and/or lgM isotype antibodies rather than lgG. A combination of individual anti-mitochondrial antigens are coated in one well to facilitate immunoassay sensitivity for the detection of AMA associated with PBC.
This test is performed as a solid phase immunoassy. Microwells are coated with recombinant mitochondrial antigen. Controls, calibrators and patient sera are incubated in the antigen coated wells to allow specific antibodies present in the serum to bind to the Mitochondria antigen. Bound antibodies are detected by adding an enzyme labeled anti-human IgG or IgA/gG/lgM conjugate. Specific enzyme substrate (TMB) is then added and the presence of antibodies is detected by a color change that is read by a spectrophotometer at 450 nm. Results are expressed in ELISA units per milliliter (EU/ml) and reported as positive or negative.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Liver
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Prescription Use
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Method Comparison: Both kits were tested with well-characterized primary biliary cirrhosis subjects and disease controls.
ImmuLisa™ AMA IgG ELISAs vs. other AMA IgG ELISA:
Sample size: 434 total. Positive: 123, Indeterminate: 4, Negative: 307.
Borderline considered positive: Positive % Agreement 91.1% (112/123), Negative % Agreement 95.2% (296/311), Overall % Agreement 94.0% (408/434).
Borderline considered negative: Positive % Agreement 91.6% (98/107), Negative % Agreement 92.4% (302/327), Overall % Agreement 92.2% (400/434).
Borderline excluded: Positive % Agreement 94.2% (98/104), Negative % Agreement 95.5% (296/310), Overall % Agreement 95.2% (394/414).
Clinical Study: Sets of clinical samples were tested on the MMCO Mitochondria ELISA. This included 193 primary billary circhosis and 898 autoimmune and infectious disease controls.
Primary biliary cirrhosis Clinical Sensitivity: 85.5% (95%CI 79.5 - 90.0)
Primary biliary cirrhosis Clinical Specificity: 99.0% (95%CI 98.0 - 99.5)
Method Comparison: Both kits were tested with well-characterized primary biliary cirrhosis subjects and disease controls.
Sample size: 453 total. Positive: 131, Indeterminate: 14, Negative: 308.
Borderline considered positive: Positive % Agreement 96.1% (122/127), Negative % Agreement 92.9% (303/326), Overall % Agreement 93.8% (425/453).
Borderline considered negative: Positive % Agreement 92.9% (91/98), Negative % Agreement 88.7% (315/355), Overall % Agreement 89.6% (406/453).
Borderline excluded: Positive % Agreement 96.8% (91/94), Negative % Agreement 94.4% (303/321), Overall % Agreement 94.9% (394/415).
Clinical Study: Sets of clinical samples were tested on the IMMCO Mitochondria EUSA. This included 193 primary billary cirrhosis and 898 autoimmune and infectious disease controls.
Primary biliary cirrhosis Clinical Sensitivity: 87.0% (95%Cl 81.3 - 91.3)
Primary biliary cirrhosis Clinical Specificity: 98.5% (95%CI 97.2 - 99.0)
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Primary biliary cirrhosis Clinical Sensitivity: 85.5% (95%CI 79.5 - 90.0)
Primary biliary cirrhosis Clinical Specificity: 99.0% (95%CI 98.0 - 99.5)
Primary biliary cirrhosis Clinical Sensitivity: 87.0% (95%Cl 81.3 - 91.3)
Primary biliary cirrhosis Clinical Specificity: 98.5% (95%CI 97.2 - 99.0)
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
K991730 - INOVA QUANTA Lite™ M2 EP (MIT3)
K991976 - Trinity Captia™ Mitochondria IgA/IgG/IgM Screen
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 866.5090 Antimitochondrial antibody immunological test system.
(a)
Identification. An antimitochondrial antibody immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the antimitochondrial antibodies in human serum. The measurements aid in the diagnosis of diseases that produce a spectrum of autoantibodies (antibodies produced against the body's own tissue), such as primary biliary cirrhosis (degeneration of liver tissue) and chronic active hepatitis (inflammation of the liver).(b)
Classification. Class II (performance standards).
0
Image /page/0/Picture/2 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" arranged around the perimeter. Inside the circle is a stylized symbol resembling an abstract human figure or a caduceus, composed of three interconnected profiles.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
August 8, 2017
IMMCO Diagnostics, Inc. Kevin Lawson VP Regulatory Affairs 9870 Hollingson Road Clarence, New York 14031
Re: K163133
Trade/Device Name: ImmuLisa Enhanced AMA IgG Antibody ELISA ImmuLisa Enhanced AMA IgA/IgG/IgM Antibody ELISA Regulation Number: 21 CFR 866.5090 Regulation Name: Antimitochondrial antibody immunological test system Regulatory Class: Class II Product Code: DBM Dated: July 1, 2017 Received: July 5, 2017
Dear Mr. Lawson:
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. Iisting 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
1
Part 807): labeling (21 CFR Part 801 and Part 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.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and Part 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/ResourcesforYou/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,
Leonthena R. Carrington -S
Lea Carrington Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K163133
Device Name ImmuLisa™ Enhanced Mitochondria Antibody (AMA) IgA/IgG/IgM ELISA
Indications for Use (Describe)
An enzyme linked immunosorbent assay (ELISA) for the qualitative detection of anti-mitochondria antibodies (AMA) in human serum to aid in the diagnosis of primary biliary cirrhosis (PBC) in conjunction with other laboratory tests and clinical findings.
| 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."
3
Indications for Use
510(k) Number (if known) K163133
Device Name ImmuLisa™ Enhanced Mitochondria Antibody (AMA) IgG ELISA
Indications for Use (Describe)
An enzyme linked immunoassay (ELISA) for the qualitative or semi-quantitative detection of anti-mitochondria IgG antibodies in human serum to aid in the diagnosis of primary biliary cirrhosis (PBC) in conjunction with other laboratory tests and clinical findings.
Type of Use (Select one or both, as applicable):
| X 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."
4
Image /page/4/Picture/0 description: The image shows the logo for Immco Diagnostics, a Trinity Biotech Company. The logo features a cluster of blue and green dots on the left, followed by the word "immco" in blue, and the word "DIAGNOSTICS" in green. Below that, the text "A Trinity Biotech Company" is written in a smaller font.
510(k) Summary
| Submitter: | Immco Diagnostics, Inc. |
|---|---|
| Address: | 60 Pineview Dr., Buffalo, NY 14228 |
| Phone Number: | 716-691-0091 ext. 110 |
| Contact: | Kevin Lawson |
| Summary Prepared: | 6-27-2017 |
| Device Name: | ImmuLisa Enhanced™ Anti-Mitochondria IgG Antibody (AMA) ELISA |
| Common Name: | Anti-Mitochondria IgG Antibody (AMA) ELISA |
| Product Code: | Antimitochondrial antibody, indirect immunofluorescent, antigen, control [DBM] |
| Substantially Equivalent to: | INOVA QUANTA Lite™ M2 EP (MIT3) |
General Description: Primary billiary cirrhosis (PBC) is a disease of the liver characterized by inflammatory obliteration of the intrahepatic bile ducts. PBC is characterized by the presence of antibodies (AMA). AMA detected by indirect immunofluorescence (IF) occur in approximately 90% of patients with autoimmune hepatitis as well as in certain other disorders such as syphils and drug induced hepatitis. As many as nine different staining reactions have been described by indirect IF, but only one, the M2 reaction is specific for PBC. Inability to easily different AMA reactions compromises the utility of indirect IF test methods for diachemical and immunochemical studies have identified the E2 component of pyruvate dehydrogenase complex (PDC-E2) to be the immunodomina antigen. Other significant autoantibody markers for PBC are the E2 subunit of the 2-oxoglutarate dehydrogenase complex (OGDC-E2) and the E2 subunit of the branched-chain 2-oxoacid dehydrogenase complex (BCOADC-E2). Antibodies are typically detected by IgG; however, literature reports a number of cases with elevated levels of lgA and/or lgM isotype antibodies rather than lgG. A combination of individual anti-mitochondrial antigens are coated in one well to facilitate immunoassay senstivity for the detection of AMA associated with PBC.
This test is performed as a solid phase immunoassy. Microwells are coated with recombinant Mitochondrial antigen. Controls, calibrators and patient sera are incubated in the antibodies present in the serum to bind to the Mitochondria antigen. Bound antibodies are detected by adding an enzyme labeled anti-human IgG or IgA/JgG/JgM conjugate. Specific enzyme substrate (TMB) is then added and the presence of antibodies is detected by a color change that is read by a spectrophotometer at 450 nm. Results are expressed in ELISA units per milliliter (EU/ml) and reported as positive or negative.
Intended Use: An enzyme linked immunoassay (EUSA) for the qualitative detection of anti-mitochondria IgG antibodies in human serum to aid in the diary cirrhosis (PBC) in conjunction with other laboratory tests and clinical findings.
Similarities and Differences: Both kits use mitochondrial antigen coated on 96 well mitochondria lgG antibodies with HRP anti-human conjugate and TMB substrate. Both kits test human serum. The IMMCO kit utilizes a 5 point calibrator curve for semiquantitative results while the predicate kit utilizes a single calibrator. The Immos semi-quantitative results are reported in EU/ml while the Inova kit results are expressed in units. Both kits use a borderline/indeterminate range of 20-25EU/ml.
Non-clinical Tests:
Method Comparison: Both kits were tested with well-characterized primary biliary cirrhosis subjects and disease controls.
ImmuLisa™ AMA IgG ELISAs vs. other AMA IgG ELISA:
| | Immco
AMA IgG
ELISA | | Other AMA IgG ELISA | | |
|---------------|---------------------------|-----|---------------------|-----|-----|
| | | Pos | Indeterminate | Neg | Tot |
| Pos | | 98 | 11 | 14 | 123 |
| Indeterminate | | 3 | 0 | 1 | 4 |
| Neg | | 6 | 5 | 296 | 307 |
| Total | | 107 | 16 | 311 | 434 |
60 Pineview Drive ● Buffalo, NY 14228-2120 ● USA 537-8378
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Image /page/5/Picture/0 description: The image is a logo for Immco Diagnostics, a Trinity Biotech Company. The logo features a cluster of blue and green dots on the left side, followed by the word "immco" in blue, and the word "DIAGNOSTICS" in green. Below that, it says "A Trinity Biotech Company" in a smaller font.
| Borderline considered positive | |||
|---|---|---|---|
| Positive % Agreement | 91.1% | 112/123 | (95%CI 84.2 - 95.2) |
| Neagtive % Agreement | 95.2% | 296/311 | (95%CI 92.0 - 97.2) |
| Overall % Agreement | 94.0% | 408/434 | (95%CI 91.2 - 96.0) |
| Borderline considered negative | |||
| Positive % Agreement | 91.6% | 98/107 | (95%CI 84.2 - 95.8) |
| Neagtive % Agreement | 92.4% | 302/327 | (95%CI 88.8 - 94.9) |
| Overall % Agreement | 92.2% | 400/434 | (95%CI 89.1 - 94.4) |
| Borderline excluded | |||
| Positive % Agreement | 94.2% | 98/104 | (95%CI 87.4 - 97.6) |
| Neagtive % Agreement | 95.5% | 296/310 | (95%CI 92.4 - 97.4) |
| Overall % Agreement | 95.2% | 394/414 | (95%CI 92.5 - 97.0) |
Cross Reactivity: Potentially cross-reactive specimens from individuals with other autoimmune, infectious or related for AMA antibodies using the ImmuLisa™ AMA IgG ELISA.
| Condition | n | n Pos | % Pos |
|---|---|---|---|
| Autoimmune hepatitis (AIH) | 38 | 1 | 2.6% |
| Primary sclerosing cholangitis | 20 | 0 | 0.0% |
| Antiphospholipid syndrome | 48 | 0 | 0.0% |
| Celiac disease | 99 | 0 | 0.0% |
| Crohn's disease | 25 | 0 | 0.0% |
| Mixed connective tissue disorder | 16 | 0 | 0.0% |
| Myositis | 26 | 0 | 0.0% |
| Rheumatoid arthritis | 106 | 1 | 0.9% |
| Sjogren's syndrome | 54 | 0 | 0.0% |
| Systemic lupus erythematosus | 154 | 0 | 0.0% |
| Systemic sclerosis | 26 | 0 | 0.0% |
| Ulcerative colitis | 25 | 0 | 0.0% |
| CMV | 20 | 1 | 5.0% |
| HepC | 74 | 0 | 0.0% |
| HSV 1 | 20 | 0 | 0.0% |
| HSV 2 | 20 | 1 | 5.0% |
| Lyme disease | 16 | 0 | 0.0% |
| Mononucleosis | 20 | 0 | 0.0% |
| Rubella | 26 | 2 | 7.7% |
| Syphilis | 23 | 2 | 8.7% |
| Toxoplasmosis | 20 | 1 | 5.0% |
| Alcoholic liver disease | 12 | 0 | 0.0% |
| Hepatocellular carcinoma | 10 | 0 | 0.0% |
Precision
Precision was tested with positive specimens selected throughout the range of the assay. Seven patients wice per day for 20 days (n=80 replicates per sample). Assays were run by two operators on two different sets of equipment.
| Total | Within Run | Between | Inter-operator | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Imprecision | (Repeatability) | Day | / equipment | ||||||
| Sample | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 1 | 13.8 | 1.4 | 9.8 | 0.8 | 5.8 | 0.6 | 4.2 | 1.1 | 7.9 |
| 2 | 16.0 | 1.6 | 10.0 | 0.7 | 4.1 | 1.2 | 7.7 | 1.0 | 6.0 |
| 3 | 19.7 | 1.5 | 7.6 | 0.7 | 3.7 | 0.4 | 2.0 | 1.3 | 6.7 |
| 4 | 23.6 | 1.3 | 5.5 | 0.7 | 3.1 | 0.6 | 2.3 | 1.1 | 4.5 |
| 5 | 78.1 | 7.2 | 9.2 | 3.2 | 4.1 | 1.9 | 2.5 | 6.4 | 8.2 |
| 6 | 111.2 | 9.0 | 8.1 | 4.5 | 4.0 | 1.1 | 6.9 | 7.8 | 7.0 |
| 7 | 159.9 | 10.0 | 6.3 | 4.9 | 3.0 | 2.7 | 1.7 | 8.8 | 5.5 |
60 Pineview Drive ● • tel. (716) 691-0091 • • fax (716) 691-0466 Toll free (800) 537-8378
6
Image /page/6/Picture/0 description: The image shows the logo for Immco Diagnostics. The logo features a series of blue and green dots arranged in a circular pattern on the left side. To the right of the dots is the company name, "immco," in blue, followed by "DIAGNOSTICS" in green. Below the company name is the text "A Trinity Biotech Company" in a smaller font size.
Reproducibility
80 replicates of samples in the low negative range, near the range, high positive range, high positive range and approximately +/ 20% of the assay cutoffs for each AMA isotype were performed to determine qualitative reproducibility. Assay results for low negative, +20%, moderate positive and high positive speciment. -20% speciment. -20% specimens produced 98% qualitative agreement. Approximate cutoff specimens produced 63% qualitative agreement.
Limit of Detection
Based on 60 replicates of the blank and 10 replicates each of 6 low-level (NHS) samples the limits of detection (LOD) for AMA anibodies were determined to be 3.3 EU/ml.
Linearity and Recovery
Studies were performed using equidistant dilution series of positive samples with values throughout the ar range of the assay. The linear range of the assay was determined to be 3.3 to 160 EU/ml. Results are summarized below.
| Test Range
(EU/ml) | Slope (95% CI) | Y-intercept
(95% CI) | R2 | % Recovery
(Obtnd/Expctd) |
|-----------------------|---------------------|-------------------------|--------|------------------------------|
| 3.4 to 57.4 | 0.99 (.94 to 1.04) | 0.94 (-0.858 to 2.74) | 0.997 | 93% to 102% |
| 6.0 to 81.0 | 1.00 (0.95 to 1.05) | -0.89 (-3.28 to 1.49) | 0.9978 | 100% to 109% |
| 54.9 to 162.4 | 0.96 (0.89 to 1.03) | 3.15 (-5.04 to 11.34) | 0.995 | 95% to 106% |
To assess hook effect, dilutions of high positive specimens with results above the 160 EU/ml measuring range were tested. Hook effect was not demonstrated in dilution samples as high as ~15,356.8 EU/ml within OD range of the microplate reader (~3.50D).
Interference
Interference was studied by mixing sera with known AMA levels for each isotype with potentially interfering serum substances and studying deviation from expected results. No significant interference was demonstrated for the following substances at the levels indicated: Hemoglobin (2 g/L), Bilirubin (342 µmol/L), Rheumatoid Factor (100 EU/ml), Triglycerides (37 mmol/L).
Clinical Study: Sets of clinical samples were tested on the MMCO Mitochondria ELISA. This included 193 primary billary circhosis and 898 autoimmune and infectious disease controls.
Primary biliary cirrhosis Clinical Sensitivity: 85.5% (95%CI 79.5 - 90.0) Primary biliary cirrhosis Clinical Specificity: 99.0% (95%CI 98.0 - 99.5)
Indeterminate samples for these studies were considered positive. NHS were excluded in sensitivity/specificity calculations.
Kur Curz
VP Regulatory Affairs
Image /page/6/Picture/17 description: The image shows the website address "www.immco.com" in blue font. The website address is underlined with a blue line. The background of the image is white.
7
Image /page/7/Picture/0 description: The image shows the logo for Immco Diagnostics, a Trinity Biotech Company. The logo features a cluster of blue and green circles on the left, followed by the word "immco" in blue, with a small circle above the "o". Below "immco" is the word "DIAGNOSTICS" in green, and below that is the text "A Trinity Biotech Company" in a smaller font.
510(k) Summary
| Submitter: | Immco Diagnostics, Inc. |
|---|---|
| Address: | 60 Pineview Dr., Buffalo, NY 14228 |
| Phone Number: | 716-691-0091 ext. 110 |
| Contact: | Kevin Lawson |
| Summary Prepared: | 6-27-2017 |
| Device Name: | ImmuLisa Enhanced™ Anti-Mitochondria IgA/IgG/IgM Antibody (AMA) ELISA |
| Common Name: | Anti-Mitochondria IgA/IgG/IgM Antibody (AMA) ELISA |
| Product Code: | Antimitochondrial antibody, indirect immunofluorescent, antigen, control [DBM] |
| Substantially Equivalent to: | Trinity Captia™ Mitochondria IgA/IgG/IgM Screen |
General Description: Primary biliary cirrhosis (PBC) is a disease of the liver characterized of the intrahepatic bile ducts. PBC is characterized by the presence of antibodies (AMA). AMA detected by indirect immunofluorescence (IF) occur in approximately 90% of patients with autoimmune hepatits as well as in certain other disorders such as syphils and drug induced hepatitis. As many as nine different staining reactions have been described by indirect IF, but only one, the M2 reaction is specific for PBC. Inability to easily different AMA reactions compromises the utility of indirect IF test methods for diagnosing PBC. Biochemical studies have identified the E2 component of pyruvate dehydrogenase complex (PDC-E2) to be immunodominant antigen. Other significant autoantibody markers for PBC are the E2 subunit of the 2-oxoglutarate dehydrogenase complex (OGDC-E2) and the E2 subunit of the branched-chain 2-oxoacid dehydrogenase complex (BCOADC-E2). Anti-M2 mitochondrial antibodies are typically detected by IgG; however, literature reports a number of cases with elevated levels of lgA and/or lgM isotype antibodies rather than lgG. A combination of individual anti-mitochondrial antigens are coated in one well to facilitate immunoassay sensitivity for the detection of AMA associated with PBC.
This test is performed as a solid phase immunoassy. Microwells are coated with recombinant mitochondrial antigen. Controls, calibrators and patient sera are incubated in the antigen coated wells to allow specific antibodies present in the serum to bind to the Mitochondria antigen. Bound antibodies are detected by adding an enzyme labeled anti-human IgG or IgA/gG/lgM conjugate. Specific enzyme substrate (TMB) is then added and the presence of antibodies is detected by a color change that is read by a spectrophotometer at 450 nm. Results are expressed in ELISA units per milliliter (EU/ml) and reported as positive or negative.
Intended Use: An enzyme linked immunosorbent assay (ELISA) for the qualitative detection of anti-mitochondria antibodies (AMA) in human serum to aid in the diagnosis of primary biliary cirrhosis (PBC) in conjunction with other laboratory tests and clinical findings.
Similarities and Differences: Both kits use mitochondrial antigen coated on 96 well plates to detect mitochondria IgA/IgG/IgM antibodies with HRP anti-human conjugate and TMB substrate. Both kits test human serum. The IMMCO kit utilizes a 5 point calibrator curve for semi-quantitative results while the predicate kit utilizes a single calibrator. The lmmco semi-quantitative results are reported in EU/ml while the Trinity Captia kit results are expressed as a ratio. The Immco kit uses a borderline/indeterminate range of 20-25EU/ml while the Trinity Captia kit uses a ratio between sample result and calibrator of 0.9 to 1.1 for the borderline/indeterminate range.
Non-clinical Tests:
Method Comparison: Both kits were tested with well-characterized primary biliary cirrhosis subjects and disease controls.
| Other AMA Screen ELISA | |||||
|---|---|---|---|---|---|
| Immco | |||||
| AMA IgA/G/M | |||||
| ELISA | Pos | Indeterminate | Neg | Total | |
| Pos | 91 | 22 | 18 | 131 | |
| Indeterminate | 4 | 5 | 5 | 14 | |
| Neg | 3 | 2 | 303 | 308 | |
| Total | 98 | 29 | 326 | 453 |
60 Pineview Drive Buffalo, NY 14228-2120 USA 537-8378
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Image /page/8/Picture/0 description: The image shows the logo for Immco Diagnostics. The logo features a series of blue and green dots on the left side, followed by the company name in blue, with the word "DIAGNOSTICS" in green below it. Underneath the company name, it says "A Trinity Biotech Company".
60 Pineview Drive ● Buffalo, NY 14228-2120 ● USA Toll free (800) 537-8378 ● tel. (716) 691-0091 ●
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Image /page/9/Picture/0 description: The image shows the logo for Immco Diagnostics. The logo features a cluster of blue and green dots on the left side, followed by the word "immco" in blue, and the word "DIAGNOSTICS" in green below it. The logo is clean and modern, with a focus on the company's name and area of expertise.
A Trinity Biotech Company
| Borderline considered positive | |||
|---|---|---|---|
| Positive % Agreement | 96.1% | 122/127 | (95%CI 90.6-98.5) |
| Neagtive % Agreement | 92.9% | 303/326 | (95%CI 89.5 - 95.4) |
| Overall % Agreement | 93.8% | 425/453 | (95%CI 91.1 - 95.8) |
| Borderline considered negative | |||
| Positive % Agreement | 92.9% | 91/98 | (95%CI 85.3 - 96.8) |
| Neagtive % Agreement | 88.7% | 315/355 | (95%CI 84.9 - 91.7) |
| Overall % Agreement | 89.6% | 406/453 | (95%CI 86.4 -92.2) |
| Borderline excluded | |||
| Positive % Agreement | 96.8% | 91/94 | (95%CI 90.3 -99.2) |
| Neagtive % Agreement | 94.4% | 303/321 | (95%CI 91.1 -96.5) |
| Overall % Agreement | 94.9% | 394/415 | (95%CI 92.3 -96.8) |
Cross Reactivity: Potentially cross-reactive specimens from individuals with other autoimmune, infectious or rested for AMA antibodies using the ImmuLisa™ AMA IgA/IgG/IgM ELISA.
| Condition | n | n Pos | % Pos |
|---|---|---|---|
| Autoimmune hepatitis (AIH) | 38 | 4 | 10.5% |
| Primary sclerosing cholangitis | 20 | 0 | 0.0% |
| Antiphospholipid syndrome | 48 | 0 | 0.0% |
| Celiac disease | 99 | 0 | 0.0% |
| Crohn's disease | 25 | 0 | 0.0% |
| Mixed connective tissue disoder | 16 | 0 | 0.0% |
| Myositis | 26 | 0 | 0.0% |
| Rheumatoid arthritis | 106 | 0 | 0.0% |
| Sjogren's syndrome | 54 | 0 | 0.0% |
| Systemic lupus erythematosus | 154 | 0 | 0.0% |
| Systemic sclerosis | 26 | 1 | 3.8% |
| Ulcerative colitis | 25 | 0 | 0.0% |
| CMV | 20 | 1 | 5.0% |
| HepC | 74 | 0 | 0.0% |
| HSV 1 | 20 | 3 | 15.0% |
| HSV 2 | 20 | 0 | 0.0% |
| Lyme disease | 16 | 0 | 0.0% |
| Mononucleosus | 20 | 3 | 15.0% |
| Rubella | 26 | 0 | 0.0% |
| Syphilis | 23 | 2 | 8.7% |
| Toxoplasmosis | 20 | 0 | 0.0% |
| Alcoholic liver disease | 12 | 1 | 8.3% |
| Hepatocellular carcinoma | 10 | 0 | 0.0% |
Precision
Precision was tested with positive specimens selected throughout the range of the assay. Seven patients wice per day for 20 days (n=80 replicates per sample). Assays were run by two operators on two different sets of equipment.
| | | Total
Imprecision | | Within Run
(Repeatability) | | Between Day | | Inter-operator
/ equipment | |
|--------|-------|----------------------|-----|-------------------------------|-----|-------------|-----|-------------------------------|-----|
| Sample | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 1 | 11.2 | 0.7 | 6.6 | 0.3 | 2.2 | 0.3 | 2.2 | 0.7 | 5.8 |
| 2 | 15.5 | 0.6 | 4.0 | 0.2 | 1.2 | 0.3 | 2.0 | 0.5 | 3.2 |
| 3 | 20.3 | 1.1 | 5.6 | 0.3 | 1.4 | 0.9 | 4.4 | 0.7 | 3.2 |
| 4 | 24.5 | 1.5 | 6.1 | 0.5 | 1.8 | 0.7 | 3.0 | 1.2 | 5.0 |
| 5 | 51.6 | 2.0 | 4.0 | 0.5 | 1.1 | 0.2 | 0.3 | 2.0 | 3.8 |
| 6 | 104.7 | 4.4 | 4.2 | 1.4 | 1.4 | 2.3 | 2.2 | 4.2 | 4.0 |
| 7 | 145.3 | 5.0 | 3.4 | 1.4 | 1.0 | 0.1 | 0.1 | 4.8 | 3.3 |
60 Pineview Drive ● USA Toll free (800) 537-8378 • tel. (716) 691-0091 • • fax (716) 691-0466
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Image /page/10/Picture/0 description: The image shows the logo for Immco Diagnostics. The logo features a cluster of blue and green dots on the left, followed by the word "immco" in blue, with a small circle above the "o". Below "immco" is the word "DIAGNOSTICS" in green. Underneath that, it says "A Trinity Biotech Company" in a smaller font.
Reproducibility
80 replicates of samples in the low negative range, near the range, high positive range, high positive range and approximately +/ 20% of the assay cutoffs for each AMA isotype were performed to determine qualitative reproducibility. Assay results for low negative, 20%, moderate positive and high positive speciment 100% qualitative agreement. +20% specimens produced 99% qualitative agreement. Approximate cutoff specimens produced 58% qualitative agreement.
Limit of Detection
Based on 60 replicates of the blank and 10 replicates each of 6 low-level (NHS) samples, the limit of detection (LOD) for AMA anibodies was determined to be 3.3 EU/ml.
Linearity and Recovery
Studies were performed using equidistant dilution series with values throughout the calibrator range to determine linear range of the assay. The linear range of the assay was determined to be 3.3 to 160 EU/ml. Results are summarized below.
| Test Range
(EU/ml) | Slope (95% CI) | Y-intercept
(95% CI) | R2 | % Recovery
(Obtnd/Expctd) |
|-----------------------|---------------------|-------------------------|-------|------------------------------|
| 5.9 to 31.9 | 1.01 (.95 to 1.07) | 0.39 (-0.89 to 1.67) | 0.997 | 95% to 98% |
| 28.9 to 83.4 | 1.08 (0.92 to 1.23) | -5.94 (-15.48 to 3.59) | 0.979 | 96% to 113% |
| 46.6 to 166.5 | 0.93 (0.83 to 1.03) | 5.68 (-5.48 to 16.84) | 0.989 | 95% to 108% |
To assess hook effect, dilutions of high positive speciment with results above the 160 EU/ml measuring range were tested. Hook effect was not demonstrated in dilution samples as high as ~17,915.7 EU/ml within OD range of the microplate reader (~3.50D).
Interference
Interference was studied by mixing sera with potentially interfering serum substances and studying deviation from expected results. No significant interference was demonstrated for the levels indicated: Hemoglobin (2 g/L), Bilirubin (342 µmo//L), Rheumatoid Factor (100 EU/ml), Triglycerides (37 mmo//L), and Cholesterol (13 mmo/l_).
Clinical Study: Sets of clinical samples were tested on the IMMCO Mitochondria EUSA. This included 193 primary billary cirrhosis and 898 autoimmune and infectious disease controls.
Primary biliary cirrhosis Clinical Sensitivity: 87.0% (95%Cl 81.3 - 91.3)
Primary biliary cirrhosis Clinical Specificity: 98.5% (95%CI 97.2 - 99.0)
Indeterminate samples for these studies were considered positive. NHS were excluded in sensitivity/specificity calculations.
Kur Cavez
VP Regulatory Affairs
60 Pineview Drive