HBOCLAB.COM - Interference - Existing Data

Clinical Trial Data

ONLY if a laboratory-specific Assay Limitation Sheet or HBOC interference data from the IVD manufacturer is unavailable, should laboratory personnel consider using the informational interference data from previous Hemopure clinical trials as a guideline for determining whether or not to report an assay result from a patient sample containing Hemopure or Oxyglobin.
Data were compiled from direct interference testing of varying concentrations of Hemopure against known analyte concentrations on laboratory instruments used at clinical laboratories from 1994 to 2006.
Summary Assay Limitation Tables are provided below. Results of individual instruments varied. No control was exerted to standardize the method in which these instruments were used; instrument Standard Operating Procedures as well as the type of reagent may have differed among testing sites.

For each instrument, the maximum plasma hemoglobin concentration (mean±Std Dev) is provided. The maximum plasma Hemopure concentration (g/dL) is the plasma Hemoglobin concentration at or below which results were within an acceptable recovery range. Results may be reported to the physician.
The patient's plasma hemoglobin concentration is compared to the value in the chart for each analyte. If the patient plasma Hemopure concentration is greater than the maximal allowable plasma concentration on the chart, then results are considered invalid due to interferences. These results should not be reported to the physician.

Listing of Assay Limitation Tables Available from Clinical Laboratory Testing

Assay Type	IVD Manufacturer	Instrument
Blood Gas	Radiometer	ABL 505, 700, 725, EML 100
Cardiac Markers	Abbott	AxSYM
Cardiac Markers	Bayer	Centaur
Cardiac Markers	Roche	Elecsys
Cardiac Markers	Various	cTnI Abbott Architect, Abbott i-STAT, Bayer Centaur, Beckman Access, Dade Behring Dimension, Ortho-Clinical Diagnostics Vitros ECi cTnT Roche Elecsys 2010
Chemistry	Beckman	Coulter CX3, CX7, CX9, LX20, LXi
Chemistry	Dade Behring	Dimension AR, XL, RXL
Chemistry	Ortho-Clinical Diagnostics	VITROS 250, 500, 700, 750, 950
Chemistry	Roche	Modular & Hitachi 917, 912, 911, 747
Coagulation	Diagnostica	Stago
Coagulation	Fibrometer	Fibrometer
Coagulation	IL	ACL 100, 200, 3000, 7000, Future +
Coagulation	MDA	180
Coagulation	Sysmex	1000, 1500, 6000, 7000
Therapeutic Drugs	Abbott	AxSYM
Therapeutic Drugs	Abbott	TDX

Assay Limitation Tables of Individual Instruments

Assays: Blood Gas
Instruments: Radiometer (ABL 505, 700, 725, EML 100)

Maximum allowable Hemopure concentration (mean±std dev; g/dL) for acceptable results. Concentrations of Hemopure greater than these amounts will affect the assay such that result will be outside of acceptable recovery limits.

Analyte	Maximum Allowable Hemopure (g/dL)	Number Instruments Tested
Calcium (Ionized)	4.7±2.3	7
Chloride	3.0±1.8	6
Glucose	2.5±0.0	2
Lactate	0.9±0.8	4
pCO2	4.5±2.8	2
pH	2.0±0.7	2
pO2	1.3±1.8	2
Potassium	3.6±1.7	5
Sodium	3.9±2.1	6

Results from data obtained from 1996 to 2005.

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Assays: Cardiac Markers
Instrument: Abbott AxSYM

Analyte	Maximum Allowable Hemopure (g/dL)	Number Instruments Tested
CK MB	6.0±1.5	41
Troponin I	5.4±1.9	20

Results obtained from 1996 to 2000

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Assays: Cardiac Markers
Instrument: Bayer Centaur

Analyte	Maximum Allowable Hemopure (g/dL)	Number Instruments Tested
CK-MB	1.5±2.4	4
Troponin I	2.7±3.3	3

Results obtained from 2000 to 2006

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Assays: Cardiac Markers
Instrument: Roche Elecsys

Analyte	Maximum Allowable Hemopure (g/dL)	Number Instruments Tested
CK-MB	4.6±1.8	20
Troponin T	4.3±2.2	22

Results obtained from 1998 to 2007

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Assays: Cardiac Markers
Instruments: Various

Title: Interference and Precision Studies of OPK Biotech's Hemopure (HBOC-201) on Commercial Cardiac Troponin Assays

Investigators: M.M. Murakami, H.E. Quist, F.S. Apple

Laboratory: Hennepin County Medical Center, Minneapolis, MN

Abstract: An interference study was conducted using NCCLS EP-7A guidelines. Three human plasma (heparin) pools based on cTnT concentrations (negative 0.0 ng/mL; medium 0.03 ng/mL; high 0.10 ng/mL) were spiked with varying concentrations of HBOC, ranging from 0.189 g/dL to 12.6 g/dL. The assays studied were: cTnI - Abbott Architect, Abbott i-STAT, Bayer Centaur, Beckman Access, Dade Behring Dimension, Ortho-Clinical Diagnostics Vitros ECi; cTnT - Roche Elecsys 2010. Each aliquot was measured twice with a negative control between each treated specimen. In phase I analytical interference, percent (%) recovery, and % cross-reactivity were evaluated. We observed acceptable recoveries, minimal interference and minimal cross-reactivity from HBOC, for concentration up to 12.6 g/dL, for the Abbott Architect cTnI, Dade cTnI, Beckman cTnI, and Roche cTnT assays. The Ortho, Bayer and i-STAT cTnI assays demonstrated poor recoveries and analytical interferences at HBOC concentrations as low as 0.63 g/dL. Percent cross reactivity was calculated for all pools and was negligible for all assays (<0.00001%).

Phase I	Abbott Arch	Abbott i-STAT	Dade	Bayer	Beckman	Ortho	Roche
% Recovery	85-108	89-165	91-125	94-182	98-114	111-327	83-104

In phase II, a 10-day modified NCCLS precision study was carried out on the assays not prone to HBOC interference, as identified in phase I. The Abbott Architect, Beckman Access, Dade Dimension, and Roche Elecsys cTn assays demonstrated excellent within-run and total precision, range 1.2 to 6.2 %CV, at two HBOC concentrations of 6.3g/dL and 0.63g/dL. These observations were based on using a cTnT-positive plasma pool with a cTnT concentration (0.36 ng/mL) that would be indicative of myocardial injury. In conclusion, 4 cardiac troponin assays were validated to be effective systems to accurately reflect in-vivo myocardial injury, without suspect of interference, cross-reactivity with or variability due to OPK Biotech's Hemopure HBOC-201 product.

(Provided, with consent, from Dr. Fred Apple, personal communication)

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Assays: Chemistry
Instruments: Beckman Coulter (CX3, CX7, CX9, LX20, LXi)