Point of Care TestingNed D. [email protected] do these have in common?And this? (thermometer)And this?And this?And this?And even this?& this, THE Most Popular!THESE ARE ALLPOINT-OF-CARE (POC)ASSAY KITSNow Just What is “Point-of-Care”?Answer: Home, bed-side, officeWHY PERFORM “POINT-OF-CARE”?• $7.50 vs. $55.20 [careful here!]•1 minute response vs. 24 hour response• Therapy (response) can be instantly coupled to the measurement• Patient sees consequences of action• Patient can receive results confidentiallyWHAT’S THE ROLE OF FDA IN POC DIAGNOSTICS?How Does FDA View Pt-of-Care?• Will test results be used to alter patient therapy? If so…FDA approval neededBlood glucose?Blood pressure?Pregnancy? Ovulation? • Will assay be sold overseas? If in totalFDA approval needed, if in part, not.Ya Gotta Have a Specific “Bio-Marker” or POC Won’t WorkBeta-HCG, 244 amino acids, 36,700 D, made by embryoOther Bio-markersElevated glucose in urine or bloodHigh Blood Pressure or Body TemperatureCardiac (or liver) enzymes ex-organLuteinizing HormoneAnd many, many others! (some observational)“Ferning” & Fertility“High Content Screening”[This is an insult to Chemists!!!]Guiacol, Fertility, Blood, and Steve Klasko, LU B.A. ‘74OHOCH3What Clinical Conditions do we Test for by POC?• Glucose (ca 65%)• Pregnancy/ovulation/sperm count (ca 12%)FertilMARQ “yes” v “no” at 20M swimmers/mL• Cardiological assays (ca 10%)• Coagulation• Infectious Diseases• a) HIV• b) hepatitis• c) bladder infections• Electrolytes, Blood Gases• Alcohol Intoxication• Heart Attack• Rupture of Liver Cells• Impaired Metabolism of Multi-Drug Prescriptions (Saladax)How do We Get Specificity?• A Specific Chromatographic Migration• Enzymatic Recognition• Immuno-Recognition• Electrochemical ReductionElectrochem SpecificityPharmaceutical ExamplesDRUG + e-à [DRUG]-(at precise potential)Misonidazole -0.64 vClotrimazole -0.19 vStreptozotocin -1.34 vRitonavir -1.91 vPrecise potential for reduction identifies the drug, total current flow measures the amountWhat are the Justifications?Most are obvious…a few not so.Monitoring anticancer drug metabolism at home or at labChallenges in Configuring the Assay• What should we sample?• “Yes” vs. “No” (cut-off assay) or precise measurement assay• Simplicity of Use (the ‘blue line’ rushes past)• Checks-and-balances (air, water, sun, decomp of reagents, stabilizing reagents)• Handling confirmation of serious findingHandling ReagentsCONSTRUCTING AN ASSAY with MAbheavy chains = yellow & light blue, light chains green & dark blue. carbohydrate = redCONSTRUCTING AN ASSAYMAb[tag] + analyte = MAb[tag]--analyte thenAnti-MAb to MAb[tag]--analytegrabs & holds this combo ina narrow target zoneVisual “tag” not bound covalently can be released by the binding eventAssembling the AssayWhat Can Go Wrong?• Untrained assayer • Test is inherently less accurate• Community medicine misses a community trend• Insurance seldom covers “point-of-care”A FEW FAMOUS FAILURES• Toilet paper fecal blood test• Fecal sampling spoon and rubbing paper• Ejaculate on bulls eye and microwave• Heated patch for sweat sampling• Home-use “ferning” assay with scopeWHAT’s THE FUTURE?• A bright future for R&D and investment where chemistry, biology, & medicine meet• Possible cost savings to the patient (For now, a few tests do appear to cost more per test)• Major increase in medical effectiveness• Confidentiality and increased patient responsibility for personal healthLet’s Look at it as a Business• Time to market for a diagnostic = 3.5 yr• Time to market for a drug = 9.2 yr• ROI per year for diagnostic ca 8.5%• ROI per year for a drug ca 18%• Legal protection for a diagnostic ca $65K / year/ product• Legal protection for a drug > $150K/yr/product“Better things for better livingthrough