Biotin Interference: The Impact is Coast to Coast Spencer Waitman, - PowerPoint PPT Presentation

Biotin Interference: The Impact is Coast to Coast Spencer Waitman, MLS (ASCP) cm Laboratory Director Medical Park Family Care Inc. Anchorage, Alaska ADD-00066054

Disclosure Statement This Speaker Program is sponsored by, and on behalf of, Abbott and the content of the presentation is consistent with all applicable FDA requirements. 2 ADD-00066054

Objectives • Describe the use and prevalence of biotin use • Describe the mechanism of biotin interference • Understand biotin pharmacokinetics • Explain my laboratory’s experience with biotin use. • Consider possible strategies to reduce or eliminate the risk of biotin interference. 3 ADD-00066054

What is Biotin? • Biotin is a water-soluble B vitamin, also called vitamin B 7 and formerly known as vitamin H or coenzyme R.It is involved in a wide range of metabolic processes, both in humans and in other organisms, primarily related to the utilization of fats, carbohydrates, and amino acids. 4 ADD-00066054

Health Benefits of Biotin • Biotin is used to enhance the overall health of hair, skin and nails (1,2) • Biotin has also been recommended for conditions such as: - fetal development (3) - multiple sclerosis (4) - Diabetes (5,6) - Hyperlipedemia (5) - Alopecia (6) - Onychorrhexis (brittle nails) (1,6) - Dermatitis (6) - Depression (6) - Basal ganglia disease (Parkinsonism) (30,7) - Metabolic acidosis (8) - Peripheral neuropathy (15) • Current daily doses range from 5 mg to 600 mg (7) • No adverse side affects have been experienced with biotin even at high doses (7) . 1. Hochman L.G. et al. Cutis 1993; 51 (4) : 303-305 2. Zempleni J and Kuroishi T. Adv Nutr. 2012;3:213-214. 3. Combs GF. Biotin. In: Combs, GF. The Vitamins: Fundamental Aspects in Nutrition and Health. San Diego, CA: Elsevier, Inc.; 2008: 331-344. 4. Sedel F et al. Mult Scler Relat Disord 2015; 4: 159-69. 5. Fernandez-Mejia C. Journal of Nutritional Biochemistry 2005; 16: 424 – 4276. 6. Kummer S et al. New England Journal of Medicine 2016; 375 (17): 1699 7. Peyro Saint Paul L, et al. 2016; Expert Opinion on Drug Metabolism & Toxicology, 12:(3), 327-344. 8. Yudkoff M. Biotin Metabolism. In: Siegel GJ, Agranoff BW, Albers RW, et al., editors. Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th edition. Philadelphia: Lippincott-Raven; 1999. Available from: https://www.ncbi.nlm.nih.gov/books/NBK28072/ 15. Meany D. L. et al. Clinical Chemistry 2009; 55(9): 1737 – 1741 25. Kummer S et al. New England Journal of Medicine 2016; 375 (7): 704-706 5 ADD-00066054

̶ Supplement Use Has Increased in Recent Years 300% Growth in Biotin Retail Volume in the Recent Years Biotin Monthly Retail Volume (2013 – 2016) • Nielsen Data – 300 million 300 Biotin Volume (Millions) biotin capsules are sold monthly 250 • Google Analytics – 200 threefold increase in biotin 150 shopping searches 100 • Biotin is Amazon’s #1 50 Supplement Seller Capsules with 5 to 10 mg of biotin represent current supplement formulations 9. Nielsen FDM Data on Biotin Monthly Volume (Ending 03/26/16) 32. Amazon Best Sellers in Vitamin Supplements (Generated July19 2018) 6 ADD-00066054

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Biotin Interference from Massachusetts General Hospital (seen with Roche & Beckman Thyroid assays) 13. Barbesino G. Thyroid. 2016; 26 (6): 860-863 12 ADD-00066054

Biotin Interference Publication from Cleveland Clinic (seen with Roche PTH Assay) 12. Waghray A et al. Endocr Pract. 2013; 19: 451-455 13 ADD-00066054

Biotin Interference Publication from Johns Hopkins (seen with Roche PTH assay) 15. Meany D. L. et al. Clinical Chemistry 2009; 55(9): 1737 – 1741 14 ADD-00066054

Biotin Interference Publication in New England Journal of Medicine 25. Kummer S et al. New England Journal of Medicine 2016; 375 (7): 704-706 15 ADD-00066054

Biotin Interference with Several Other Assays 20. Trambas C. M. et al. New England Journal of Medicine 2016; 375 (17): 1698 16 ADD-00066054

Biotin Interference on Patient Laboratory Test Results 10. Paxton A. CAP Today, September 20, 2016. 17. Wijeratne N.G., Doery, J.C.G and Lu, Z.X. Pathology. 2012; 44(7):674-975 11. Seaborg, E. January 2016: Thyroid Month: Beware of Biotin, Endocrine News, 2016 7. Peyro Saint Paul L et al. Expert Opin on Drug Metab & Toxicol, 2016; 12:(3), 327-344 12. Waghray A et al. Endocr Pract. 2013; 19: 451-455 19. Elston M.S. et al. J Clin Endocrinol Metab 2016; 101: 3251 – 3255. 13. Barbesino G. Thyroid. 2016; 26 (6): 860-863 20. Trambas C. M. et al. New England Journal of Medicine 2016; 375 (17): 1698 14. Minkovsky A et al. AACE) Clinical Case Reports 2016; 2: e370-e373. 21. Piketty ML et al. Clin Chem Lab Med. 2016 Oct 12. 15. Meany D. L. et al. Clinical Chemistry 2009; 55(9): 1737 – 1741 22. Barbesino G. Clinical laboratory News, December, 2016 6. Kummer S et al. New England Journal of Medicine 2016; 375 (7): 704-706 17 ADD-00066054

INCREASE IN ADVERSE (MAUDE) EVENTS RELATED TO BIOTIN INTERFERENCE REPORTED TO FDA Data from US FDA Manufacturer and User Facility Device Experience database. The MAUDE database houses medical device reports submitted to the FDA by mandatory reporters (manufacturers, importers and device user facilities) and voluntary reporters such as health care professionals, patients and consumers https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfmaude/search.cfm 18 ADD-00066054

MAUDE Adverse Event Report due to Biotin Interference ROCHE DIAGNOSTICS TROPONIN T HIGH SENSITIVITY IMMUNOASSAY METHOD, TROPONIN SUBUNIT Device Problem: Low Test Result Event Date: 09/08/2016 Event Type: Death Description: • Patient with M.S. was admitted to the ER with chest pain. The patient’s troponin was tested with the Elecsys hsTroponin T assay and on the Cobas 8000 e602 module and the result was <5ng/L. • Patient was admitted to ICU for an unknown reason. Troponin testing was tested 5 days later and found to be 55ng/L. • Additional information has been requested but not yet provided. 30. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfmaude/detail.cfm?mdrfoi__id=6263188&pc=MMI 19 ADD-00066054

FDA Safety Communication 31. https://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm586505.htm 20 ADD-00066054

FDA Safety Communication 31. https://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm586505.htm ADD-00066054 21

Impact of Interferences • Interfering substances can affect lab test results Incorrect lab results from – Examples: Heterophilic antibodies, HAMA interferences could lead to • Interference could depress or elevate a test result, misdiagnosis of a patient causing false-negative or false positive result Although heterophile antibodies are • Most of these interferences are rare and could affect any found in all people, interference platform occurs rarely, < 0.05% of the time • Test manufacturers usually add blocking agents to the test minimize these interferences HETEROPHILIC Ab INTERFERENCE CHARACTERISTICS BIOTIN INTERFERENCE INTERFERENCES Interference can lead to incorrect test results Yes Yes Prevalence is rare Yes No Interference is innate and unique to an individual Yes No Mostly mitigated by test manufacturers by adding blocking agents Yes No Interfering substance is not a critical component of the impacted test Yes No Interference is not specific to a particular capture method Yes No Source: Levinson SS et al. Clinica Chimica Acta, 2002; 3251 – 15 22 ADD-00066054

Biotin Usage and Awareness Source: Data on File at Abbott 23 ADD-00066054

Biotin Awareness Source: Data on File at Abbott 24 ADD-00066054

Publication from Mayo Clinic on Biotin Usage Results: Conclusion: • Survey • Reported use of of 1944 biotin was common outpatients • Biotin concentrations in ED indicated that 7.7% Objective: patient samples highlights the take biotin magnitude of the biotin To determine the • Quantitation of biotin interference problem and prevalence of biotin in 1442 ED patient identifies a population at risk consumption using samples revealed that for potential harm two distinct methods: 7.4% had biotin • These findings should guide • Surveying the outpatient concentrations at or laboratorians and clinicians population using a above 10 ng/ml which in developing effective questionnaire is the lowest known strategies to mitigate safety threshold for biotin • Quantifying biotin in risks and in assessing biotin interference in the tests samples collected from usage trends within their own utilized at Mayo Clinic patients presenting to the ED patient populations Source: Katzman BM et al, Clinical BioChemistry, 2018; 60: 11-16 25 ADD-00066054

Data on File at Abbott 26 ADD-00066054