(83 days)
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No
The device description details a standard immunoassay technology and a "cubic-through-zero curve fitting algorithm" for generating standard curves, which is a traditional statistical method, not AI/ML. There is no mention of AI, ML, or related concepts in the document.
No
This device is an in vitro diagnostic assay used to quantitatively measure complexed prostate specific antigen (cPSA) in human serum, which aids in the management (monitoring) of prostate cancer patients. It does not directly provide therapy or treatment.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device is an "in vitro diagnostic assay." It is used to quantitatively measure cPSA to "aid in the management (monitoring) of prostate cancer patients."
No
The device is an in vitro diagnostic assay that utilizes reagents and a system (Bayer Immuno I™ System) to measure complexed PSA. This involves physical components and chemical reactions, not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the assay is an "in vitro diagnostic assay intended to quantitatively measure complexed prostate specific antigen (cPSA) in human serum". This directly aligns with the definition of an in vitro diagnostic device, which is used to examine specimens taken from the human body to provide information for diagnosis, monitoring, or treatment.
- Device Description: The description details how the assay works by reacting reagents with a "patient sample, calibrator, or control" and performing measurements on the system. This process is characteristic of in vitro diagnostic testing.
- Performance Studies: The performance studies involve analyzing "sequential serum specimens collected from 155 patients" and determining the "distribution of complexed PSA concentrations in healthy females, healthy males, patients with active prostate cancer, etc." This demonstrates the use of the device to analyze human biological samples for clinical purposes.
- Predicate Device: The mention of a "Predicate Device(s)" which is the "Bayer Immuno ITM PSA Assay" further supports its classification as an IVD, as predicate devices are typically other legally marketed IVDs.
The information provided clearly indicates that this device is designed to be used outside of the body to analyze human samples for diagnostic and monitoring purposes, which is the core function of an IVD.
N/A
Intended Use / Indications for Use
The Bayer Immuno 1™ Complexed PSA (cPSA) Assay is an in vitro diagnostic assay intended to quantitatively measure complexed prostate specific antigen (cPSA) in human serum on the Bayer Immuno 1TM System. Complexed prostate specific antigen (cPSA) values obtained should be used as an aid in the management (monitoring) of prostate cancer patients.
Product codes (comma separated list FDA assigned to the subject device)
LTJ
Device Description
The Bayer Immuno ITM cPSA Assay utilizes the same immunoassay technology and the same R1 and R2 reagents as in the Bayer Immuno ITM PSA Assay except for the addition of a third, unlabeled, monoclonal antibody to the R2 reagent. Reagent 1 (or R1) contains monoclonal PSA antibody conjugated to fluorescein while Reagent 2 (or R2) contains polyclonal PSA antibody conjugated to alkaline phosphatase and a third unlabeled antibody specific for free PSA. The R1 and R2 conjugates are reacted with patient sample, calibrator, or control and are incubated at 37℃ on the system. Free PSA in the serum is bound by the unlabeled free PSA antibody while the remaining complexed PSA is bound by the PSA antibody conjugated to alkaline phosphatase. Immuno 1 Magnetic Particles coated with an anti-fluorescein antibody are then added and a second incubation occurs during which the antibody enzyme conjugate complex is bound. Washing of the particles is followed by addition of substrate (PNPP) reagent. The rate of conversion of substrate to a compound with absorbance at 405 and 450 nm is measured and the measured rate is proportional to the concentration of cPSA antigen in the sample. A cubic-through-zero curve fitting algorithm is used to generate standard curves.
The assay has a range of 0.02 to 100 ng/mL. The Bayer Setpoint™ Complexed PSA (cPSA) Calibrators consist of a set of six calibrator levels at 0, 2, 10, 25, 50, and 100 ng/mL. The Bayer Setpoint™ Complexed PSA (cPSA) Controls consist of a set of 3 control levels at approximately 3.5, 15, and 75 ng/mL.
Mentions image processing
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Mentions AI, DNN, or ML
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Input Imaging Modality
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Anatomical Site
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Indicated Patient Age Range
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Intended User / Care Setting
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Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Nonclinical studies were performed at Bayer Corporation, Diagnostics Division, Tarrytown, New York to evaluate the purity of the calibrators, the purity and specificity of the reagents, and the efficacy of the reagent and calibrator preservatives. Data were also collected to evaluate specificity and interfering substances, cross-reactivity, heterophilic antibodies, linearity, hook effect/antigen excess, and parallelism. The clinical evaluation of Immuno I cPSA Assay as a quantitative measure of serum complexed PSA for use as an adjunctive test in the management of prostate cancer patients, was conducted at three US clinical trial sites. In addition, the Immuno 1 cPSA Assay was evaluated at the clinical sites for imprecision/reproducibility and analytical sensitivity.
Characterization of the Antigen: The calibrator antigen used in the Bayer Immuno I cPSA assay is purified PSA-ACT which is PSA isolated from human seminal fluid and complexed in vitro with alpha-1-antichymotrypsin (ACT). The antigen is manufactured by Scripps Laboratories (San Diego, CA). Antigen preparations were characterized using SDS-polyacrylamide gels under reducing conditions and results were consistent with the molecular weight of the antigen reported in the literature. Isoelectric focusing of the PSA-ACT antigen resolved pIs that were consistent with published values.
Immunoreactivity of the Antibodies: The monoclonal and polyclonal anti-PSA antibodies used in the preparation of the R1 and R2 reagent for the Bayer Immuno 1™ Complexed PSA (cPSA) Assay are identical to those used in the Bayer Immuno 1™ PSA Assay. A third unlabeled monoclonal antibody was added to the R2 reagent of the cPSA Assay. The unlabeled monoclonal antibody was characterized in a series of experiments including isotype analysis, relative affinity analysis by ELISA, reducing and nonreducing SDS-PAGE and isoelectric focusing. These results demonstrated that the unlabeled monoclonal antibody bound to the PSA antigen quantitatively and specifically, and displayed biophysical properties expected of mouse monoclonal antibodies.
Reagent Microbial Testing: Preservative challenge testing was performed on the R2 reagent due to the addition of a third unlabeled monoclonal antibody. Results indicated an acceptable preservative system according to US Pharmacopoeia guidelines.
Calibrator Microbial Testing: Immuno 1 cPSA calibrator preservative was challenged with known concentrations of five strains of microorganisms recommended by US Pharmacopoeia standards and performance of the calibrators was tested. Microbial performance challenge testing on cPSA calibrators demonstrated that inoculation of the calibrators with up to 106 of each of the microorganisms per mL of calibrator had no significant effects on calibrator performance.
Specificity (Interference): The recovery of cPSA from patient samples was studied before and after spiking the serum samples with potentially interfering substances (triglycerides, immunoglobulin, hemoglobin, heparin, bilirubin, or albumin, chemotherapeutic drugs, OTC drugs, or vitamins). None of the potential endogenous or exogenous interferents demonstrated any significant interfering effects on cPSA recovery. The test specification was ±10% deviation and none of the substances demonstrated an interference outside of this range.
Cross-Reactivity: Possible cross-reactions were studied by comparing cPSA recoveries in patient samples with and without various spiked amounts of kallikrein, trypsin, and chymotrypsin. The maximum effect seen with each cross-reactant was not significant (≤1%).
Heterophilic Antibodies: A total of 206 patient samples with HAMA, RF titers, or autoimmune diseases were tested for possible interference. The observed cPSA recoveries indicated a lack of significant heterophilic interference and demonstrated the effectiveness of the reagent formulation in minimizing these interferences.
Linearity: Four individual serum samples from prostate cancer patients were diluted (100%, 75%, 50%, 25%, and 0%) with a pool of female human sera. Recoveries of the intermediate dilutions were all between 95 and 103 percent of the expected values. These results demonstrate the linearity of cPSA recoveries over the entire calibration range.
Hook Effect (Antigen Excess): cPSA antigen (PSA-ACT) was diluted in Level 1 Calibrator at concentrations of 50 ng/mL to 100,000 ng/mL. Results clearly demonstrated the lack of a hook effect in the Immuno 1 cPSA Assay at cPSA values ≤12,500 ng/mL.
Parallelism (Dilution Studies): Four patient serum samples containing a high level of cPSA were diluted (100%, 75%, 50%, 25%, and 0%) with Level 1 Calibrator. Linear regression analysis for the determination of deviations from linearity for each of these clinical samples showed no deviation from linearity. The recovery of cPSA assay values ranged from 97.0 to 107.6%. These data demonstrate that Level 1 calibrator is an acceptable diluent for high samples, with accurate recovery of diluted values.
Reproducibility: Intra- and inter-assay reproducibility were evaluated at three clinical trial sites for three levels of Bayer SETpoint Complexed PSA (cPSA) Controls and a human serum pool with complexed PSA concentration
§ 866.6010 Tumor-associated antigen immunological test system.
(a)
Identification. A tumor-associated antigen immunological test system is a device that consists of reagents used to qualitatively or quantitatively measure, by immunochemical techniques, tumor-associated antigens in serum, plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease.(b)
Classification. Class II (special controls). Tumor markers must comply with the following special controls: (1) A guidance document entitled “Guidance Document for the Submission of Tumor Associated Antigen Premarket Notifications (510(k)s) to FDA,” and (2) voluntary assay performance standards issued by the National Committee on Clinical Laboratory Standards.
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510(IK) SUMMARY
FOR THE
BAYER IMMUNO 1™ COMPLEXED PSA (cPSA) ASSAY
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92
The assigned 510(k) number is: _
GENERAL INFORMATION l.
| Trade Name: | Bayer Immuno 1™ Complexed PSA (cPSA) Assay |
|---|---|
| Classification Name: | Tumor-Associated Antigen Immunological Test |
| Systems |
Gabriel J. Murray Jr.
Gabriel J. Muraca, Jr. Manager, Regulatory Affairs Bayer Corporation Business Group Diagnostics
1/29/98
Date
1
This premarket notification is to add the quantitative measurement of complexed prostate specific antigen (cPSA) in human scrum to the intended use of the Baycr Immuno 1TM Immunoassay System. The performance of the Bayer Immuno 1TM Complexed PSA (cPSA) Assay has been established by comparison to a predicate device, the Bayer Immuno ITM PSA Assay, in accordance with the "Guidance Document For Submission of Tumor Associated Antigen Premarket Notifications. 510(k), to the FDA." Clinical evaluations of the Bayer Immuno 1™ Complexed PSA (cPSA) Assay at three US clinical trial sites demonstrated clinical safety and effectiveness and substantial equivalence to the predicate device.
INDICATIONS FOR USE 2.
The Bayer Immuno 17M Complexed PSA (cPSA) Assay is an in vitro diagnostic assay intended to quantitatively measure complexed prostate specific antigen (cPSA) in human serum on the Bayer Immuno 1TM System. Complexed prostate specific antigen (cPSA) values obtained should be used as an aid in the management (monitoring) of prostate cancer patients
DEVICE DESCRIPTION 3.
The Bayer Immuno ITM cPSA Assay utilizes the same immunoassay technology and the same R1 and R2 reagents as in the Bayer Immuno ITM PSA Assay except for the addition of a third, unlabeled, monoclonal antibody to the R2 reagent. Reagent 1 (or R1) contains monoclonal PSA antibody conjugated to fluorescein while Reagent 2 (or R2) contains polyclonal PSA antibody conjugated to alkaline phosphatase and a third unlabeled antibody specific for free PSA. The R1 and R2 conjugates are reacted with patient sample, calibrator, or control and are incubated at 37℃ on the system. Free PSA in the serum is bound by the unlabeled free PSA antibody while the remaining complexed PSA is bound by the PSA antibody conjugated to alkaline phosphatase. Immuno 1 Magnetic Particles coated with an anti-fluorescein antibody are then added and a second incubation occurs during which the antibody enzyme conjugate complex is bound. Washing of the particles is followed by addition of substrate (PNPP) reagent. The rate of conversion of substrate to a compound with absorbance at 405 and 450 nm is measured and the measured rate is proportional to the concentration of cPSA antigen in the sample. A cubic-through-zero curve fitting algorithm is used to generate standard curves.
The assay has a range of 0.02 to 100 ng/mL. The Bayer Setpoint™ Complexed PSA (cPSA) Calibrators consist of a set of six calibrator levels at 0, 2, 10, 25, 50, and 100 ng/mL. The Bayer Setpoint™ Complexed PSA (cPSA) Controls consist of a set of 3 control levels at approximately 3.5, 15, and 75 ng/mL.
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SUMMARY OF STUDIES
Nonclinical studies were performed at Bayer Corporation, Diagnostics Division, Tarrytown, New York to evaluate the purity of the calibrators, the purity and specificity of the reagents, and the efficacy of the reagent and calibrator preservatives. Data were also collected to evaluate specificity and interfering substances, cross-reactivity, heterophilic antibodies, linearity, hook effect/antigen excess, and parallelism. The clinical evaluation of Immuno I cPSA Assay as a quantitative measure of serum complexed PSA for use as an adjunctive test in the management of prostate cancer patients, was conducted at three US clinical trial sites. In addition, the Immuno 1 cPSA Assay was evaluated at the clinical sites for imprecision/reproducibility and analytical sensitivity.
Characterization of the Antigen 4.1
The calibrator antigen used in the Bayer Immuno I cPSA assay is purified PSA-ACT which is PSA isolated from human seminal fluid and complexed in vitro with alpha-1-antichymotrypsin (ACT). The antigen is manufactured by Scripps Laboratories (San Diego, CA) and is supplied to Bayer. Antigen preparations were characterized using SDS-polyacrylamide gels under reducing conditions and results were consistent with the molecular weight of the antigen reported in the literature. Isoelectric focusing of the PSA-ACT antigen resolved pIs that were consistent with published values.
Immunoreactivity of the Antibodies 4.2
The monoclonal and polyclonal anti-PSA antibodies used in the preparation of the R1 and R2 reagent for the Bayer Immuno 1™ Complexed PSA (cPSA) Assay are identical to those used in the Bayer Immuno 1™ PSA Assay. A third unlabeled monoclonal antibody was added to the R2 reagent of the cPSA Assay. The unlabeled monoclonal antibody was characterized in a series of experiments including isotype analysis, relative affinity analysis by ELISA, reducing and nonreducing SDS-PAGE and isoelectric focusing. These results demonstrated that the unlabeled monoclonal antibody bound to the PSA antigen quantitatively and specifically, and displayed biophysical properties expected of mouse monoclonal antibodies.
4.3 Reagent Microbial Testing
The formulation of cPSA Assay R1 reagent is identical to that of the Bayer Immuno 1 PSA Assay R1 reagent, therefore, no additional microbiological testing
3
was required. Preservative challenge testing was performed on the R2 reagent due to the addition of a third unlabeled monoclonal antibody. Results indicated an acceptable preservative system according to US Pharmacopoeia guidelines.
Calibrator Microbial Testing 4.4
Immuno 1 cPSA calibrator preservative was challenged with known concentrations of five strains of microorganisms recommended by US Pharmacopoeia standards and performance of the calibrators was tested. Microbial performance challenge testing on cPSA calibrators demonstrated that inoculation of the calibrators with up to 106 of each of the microorganisms per mL of calibrator had no significant effects on calibrator performance.
Assay Performance 4.5
Specificity: Interference 4.5.1
The recovery of cPSA from patient samples was studied before and after spiking the serum samples with the potentially interfering. Each potential interferent was tested at a maximum concentration.
The Immuno 1 cPSA Assay was performed on serum samples or pools of serum to which was added various concentrations of either triglycerides, immunoglobulin, hemoglobin, heparin, bilirubin, or albumin. cPSA values were also measured in serum samples after spiking with either an individual chemotherapeutic drug, "Over the Counter" (OTC) drug, or vitamin. None of the potential endogenous or exogenous interferents demonstrated any significant interfering effects on cPSA recovery. The test specification was ±10% deviation and none of the substances demonstrated an interforence outside of this range.
4.5.2 Cross-Reactivity
Possible cross-reactions in the Immuno 1 cPSA Assay were studied by comparing cPSA recoveries in patient samples with and without various spiked amounts of kallikrein, trypsin, and chymotrypsin. The maximum effect seen with each cross-reactant was not significant (≤1%).
4.5.3 Heterophilic Antibodies
To investigate the effectiveness of the assay's reagent formulation in minimizing
4
heterophilic antibody interferences, a total of 206 patient samples with HAMA, RF titers, or autoimmune diseascs were tested for possible interference in the cPSA assay. The observed cPSA recoveries indicated a lack of significant heterophilic interference in the assay and demonstrated the effectiveness of the reagent formulation in minimizing these interferences.
Linearity 4.5.4
To determine the linearity of this assay, four individual serum samples from prostate cancer patients were diluted (100%, 75%, 50%, 25%, and 0%) with a pool of female human sera. Recoveries of the intermediate dilutions were all between 95 and 103 percent of the expected values. These results demonstrate the linearity of cPSA recoveries over the entire calibration range.
4.5.5 Hook Effect (Antigen Excess)
Extremely high concentrations of cPSA seen in some malignant conditions may cause a "hook effect" in an assay. An excess of analyte saturates both label and capture antibody and causes the reported concentration to "hook" back into the assay range rather than be flagged as above range. cPSA antigen (PSA-ACT) was diluted in Level 1 Calibrator at concentrations of 50 ng/mL to 100,000 ng/mL. Results clearly demonstrated the lack of a hook effect in the Immuno 1 cPSA Assay at cPSA valucs ≤12,500 ng/mL.
4.5.6 Parallelism (Dilution Studies)
As a further verification of assay linearity, and to qualify the Level 1 Calibrator as a sample diluent, four patient serum samples containing a high level of cPSA were diluted (100%, 75%, 50%, 25%, and 0%) with Level 1 Calibrator. Linear regression analysis for the determination of deviations from linearity for each of these clinical samples showed no deviation from linearity. The recovery of cPSA assay values ranged from 97.0 to 107.6%. These data demonstrate that Level 1 calibrator is an acceptable diluent for high samples, with accurate recovery of diluted values.
4.5.7 Reproducibility
Intra- and inter-assay reproducibility were evaluated at three clinical trial sites for three levels of Bayer SETpoint Complexed PSA (cPSA) Controls and a human serum pool with complexed PSA concentration