1. Drug Supply Chain Security Act, Implications for the Hospital Pharmacy Pamela Kindall, BBA Pharmacy Business Specialist Joshua Bright, PharmD Director of Pharmacy Services North Arkansas Regional Medical Center September 29, 2016

2. Conflicts of Interest Josh Bright and Pam Kindall declare no conflicts of interest Josh and Pam are not lawyers

3. Objectives Describe the need for the Drug Supply Chain Security Act (DSCSA) in today’s pharmacy supply chain Explain the steps that should be taken during the phases of DSCSA rollout Outline future impacts to the industry as DSCSA becomes fully implemented over the next 10 years

4. Quality and Security, the Why: Counterfeits: –Tamiflu (oseltamivir) A AB B

5. B A AB B

6. Quality and Security, the Why: Counterfeits: –Botox (onabotulinumtoxin A) http://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/CounterfeitMedicine/default.htm AB

7. B http://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/CounterfeitMedicine/default.htm AB

8. Quality and Security, the Why: 2007- Crude Heparin linked to 246 deaths –“economically motivated adulteration 1 ” Heparin Supply Chain Small pig farms in China  village casing facilities  Consolidators buy individual lots from village facilities  Consolidators combine individual lots into single, large heparin lots  mfgs buy consolidated lots and refine crude heparin into API  mfgs produce product for human consumption –GAO: 100 million pigs short 2 1.Http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm291390.pdfHttp://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm291390.pdf 2.http://www.gao.gov/assets/320/311879.pdfhttp://www.gao.gov/assets/320/311879.pdf

9. Quality and Security, the Why: New England Compounding Center 2012 –17,000 vials of methylprednisolone for injection contaminated with fungi –73 facilities in 23 states –Linked to 64 deaths, 751 non-fatal injuries –https://en.wikipedia.org/wiki/New_England_Compounding_Center_meningitis_outbreak#Caseshttps://en.wikipedia.org/wiki/New_England_Compounding_Center_meningitis_outbreak#Cases

11. Title I Section 503(b) FDA Registered Outsourcing Facilities –http://www.fda.gov/Drugs/GuidanceComplianceRegulato ryInformation/PharmacyCompounding/ucm378645.htmhttp://www.fda.gov/Drugs/GuidanceComplianceRegulato ryInformation/PharmacyCompounding/ucm378645.htm ASHP Guidelines on Outsourcing Sterile Compounding Services –http://www.ashp.org/DocLibrary/BestPractices/MgmtGdl OutsourcingSterileComp.aspxhttp://www.ashp.org/DocLibrary/BestPractices/MgmtGdl OutsourcingSterileComp.aspx Read 483’s and personally inspect the facility

12. What DSCSA- electronic, interoperable system to track each unit of medication by 2023 throughout the supply chain: –Identify legitimate products to the unit level –Detect and remove illegitimate products –More efficient and effective recall process

13. How Trading Partners (mfg, repackagers, wholesalers, dispensers, 3PLs) –Provide transaction documentation downstream –Store 6 years (paper or electronic)

14. Timeline Nov 2013 DQSA Enacted FDA Guidance Issued Jan 1, 2015 Mfgs send and distributors receive/pass transaction information Mfgs, wholesalers, and dispensers verify suspect and illegitimate product Transactions made only between authorized trading partners July 1, 2015; November 2015… March 2016 Dispensers receive transaction information and maintain for 6 years

15. Timeline 2017-2019 Interim Period Time for mfgs and repackagers to serialize: Trace Lot, Exp, Serial number on each package Nov 2017 Mfg serialize product Transaction information electronic Nov 2018 Repackagers serialize product Transaction information electronic 2019 Distributors only sell serialized product 2020 Dispensers only utilize serialized product 2023 Unit-level traceability throughout the supply chain

16. One more example Counterfeits: –Nicotine gum? BA

18. DSCSA ~ Authorized Trading Partners ~ 3T Information ~ Exclusion List ~ Suspected or Fraudulent Product

19. Authorized Trading Partners Trading partners- Manufacturers, wholesale distributors, Third-party Logistics Provider or 3PL’s, dispensers, and repackagers. http://www.fda.gov/Drugs/DrugSafety/DrugIntegrityandSupplyChai nSecurity/DrugSupplyChainSecurityAct/ucm376829.htm

20. Authorized Trading Partners Note: It is possible a trading partner will fall under more than one category. If so the entity must meet all applicable requirements. [section 582(a)(1)]

21. Authorized Trading Partners Validate registration with the FDA ~Wholesale Distributor, Secondary Market, and 3PL’s http://www.accessdata.fda.gov/scripts/cde r/wdd3plreporting/index.cfm

22. Authorized Trading Partners

23. 3 T’s Entities are required to capture the 3T’s Transaction Information Transaction Statement Transaction History

24. Transaction Information Established name of the product Strength and dosage form NDC number Container size Number of units Lot number Date of transaction Date of shipment, if more than 24 hours after the date of the transaction Business name and address from where the product is transferred Business name and address to where the product is transferred

25. Transaction Statement This states the entity transferring the product: Is authorized (licensed) as required Received the product from an authorized source Received transaction information and transaction statement from the prior owner Did not knowingly ship a suspect or illegitimate product Had systems in place to comply with verification requirements Did not knowingly provide false transaction information Did not knowingly alter the transaction history

26. Transaction History This is a statement in paper or electronic form for each prior transaction going back to the manufacturer of the product

27. 3T’s The FDA has issued a guidance

28. 3T’s The transaction information, transaction statement, and transaction history (3T’s) must be captured and maintained for each drug product received for 6 years from the date of transaction.

29. What products are covered Prescription Drugs in finished dosage form for administration to a patient without further manufacturing.

30. Exempt Products Blood or blood components for transfusion Radioactive drugs or radioactive biological products Imaging drugs Medical gases Compounded drugs Dialysis solutions Irrigation solutions Sterile water (irrigation or injectable) IV products intended for replenishment of fluids or electrolytes

31. Exempt Transactions The term ‘transaction’ does not include...

32. Exempt Transactions

33. Suspected or Fraudulent Product The law, in part, requires dispensers to develop protocols to identify suspected and illegitimate products. Identify Quarantine Notify the FDA and trading partners

34. Identify Suspected Product – Reason to believe the product is potentially: Counterfeit, diverted, stolen Subject to fraudulent transaction Intentionally adulterated or appears otherwise unfit for distribution such that would result in serious adverse health consequences or death to humans. Illegitimate Product – Credible evidence that the product actually is any of the above. http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/SmallBusinessAssistance/UCM388945.pdf

35. Scenarios Purchasing from a new source Receiving an unsolicited sales offer from an unknown source Purchasing from an unknown Internet source Purchasing from a source that the entity knows or has reason to believe has transacted business involving suspected products High demand products Products that are on the FDA’s counterfeit or cargo theft alert http://www.fda.gov/drugs/resourcesforyou/consumers/buyingusingmedicinesafely/co 186 unterfeitmedicine/default.htm http://www.fda.gov/iceci/criminalinvestigations/ucm182888.htm

36. Quarantine Quarantine the suspected product and promptly conduct an investigation to determine whether the product is an illegitimate product. HOW WHO POLICIES & PROCEDURES

37. Investigation Closely examine the package and transport package Closely examine the label on the package and the unit Validate the 3T information you were given. Keep records of investigations for not less than 6 years after the conclusion of an investigation

38. Notify Upon determination of an illegitimate product one is to notify the FDA and all immediate trading partners not later than 24 hours after making the determination. Upon request by Federal or State officials, in the event of a recall or for the purpose of investigating a suspect or illegitimate product a dispenser shall, not later than 2 business days or in another reasonable time as determined by the Secretary after receiving the request, provide information.

39. Notify Entities should access the FDA’s Web page at: http://www.accessdata.fda.gov/scripts/cde r/email/drugnotification.cfm

40. FDA Web Page Follow the instructions on the Web page for accessing the Form FDA 3911.

41. Form FDA 3911

42. 3911 12/2015 Drug Notification to FDA (Instructions Supplement) (PDF - 126KB)3911 3911 12/2015 Drug Notification to FDA (PDF) (PDF - 2.1MB)3911

43. FDA 3911

44. Sections of the DSCSA o 581- Definitions o 582- Requirements o 583- Standards for Licensure of WDs o 584- National Standards for 3PL’s o 585- Uniform national policy Additional information can be found in Sections: 203, 204, 205, 206, 207 & the various Guidance's for Industry published by the FDA

45. Resources and References FDA DSCSA Main Website: –http://www.fda.gov/Drugs/DrugSafety/DrugIntegrityandSuppl yChainSecurity/DrugSupplyChainSecurityAct/default.htmhttp://www.fda.gov/Drugs/DrugSafety/DrugIntegrityandSuppl yChainSecurity/DrugSupplyChainSecurityAct/default.htm FDA DSCSA Guidance Documents: –http://www.fda.gov/Drugs/DrugSafety/DrugIntegrityandSuppl yChainSecurity/DrugSupplyChainSecurityAct/ucm424963.ht mhttp://www.fda.gov/Drugs/DrugSafety/DrugIntegrityandSuppl yChainSecurity/DrugSupplyChainSecurityAct/ucm424963.ht m FDA DSCSA Implementation Plan –http://www.fda.gov/drugs/drugsafety/drugintegrityandsupplyc hainsecurity/drugsupplychainsecurityact/ucm382022.htmhttp://www.fda.gov/drugs/drugsafety/drugintegrityandsupplyc hainsecurity/drugsupplychainsecurityact/ucm382022.htm

46. Resources and References Title II of The DQSA: The DSCSA –http://www.fda.gov/Drugs/DrugSafety/DrugIntegrityandSupplyChain Security/DrugSupplyChainSecurityAct/ucm376829.htmhttp://www.fda.gov/Drugs/DrugSafety/DrugIntegrityandSupplyChain Security/DrugSupplyChainSecurityAct/ucm376829.htm To Report an illegitimate product to the FDA: –http://www.accessdata.fda.gov/scripts/cder/email/drugnotific ation.cfmhttp://www.accessdata.fda.gov/scripts/cder/email/drugnotific ation.cfm To Validate FDA registration of a vendor: –http://www.accessdata.fda.gov/scripts/cder/drls/default.cfmhttp://www.accessdata.fda.gov/scripts/cder/drls/default.cfm

47. Resources and References Title II of The DQSA: The DSCSA –http://www.fda.gov/Drugs/DrugSafety/DrugIntegrityandSupplyChain Security/DrugSupplyChainSecurityAct/ucm376829.htmhttp://www.fda.gov/Drugs/DrugSafety/DrugIntegrityandSupplyChain Security/DrugSupplyChainSecurityAct/ucm376829.htm To Report an illegitimate product to the FDA: –http://www.accessdata.fda.gov/scripts/cder/email/drugnotific ation.cfmhttp://www.accessdata.fda.gov/scripts/cder/email/drugnotific ation.cfm To Validate FDA registration of a vendor: –http://www.accessdata.fda.gov/scripts/cder/drls/default.cfmhttp://www.accessdata.fda.gov/scripts/cder/drls/default.cfm

48. References http://www.fda.gov/Drugs/DrugSafety/DrugIntegrityandSupplyChainSec urity/DrugSupplyChainSecurityAct/ucm376829.htmhttp://www.fda.gov/Drugs/DrugSafety/DrugIntegrityandSupplyChainSec urity/DrugSupplyChainSecurityAct/ucm376829.htm http://www.accessdata.fda.gov/scripts/cder/wdd3plreporting/index.cfm http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/S mallBusinessAssistance/UCM388945.pdfhttp://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/S mallBusinessAssistance/UCM388945.pdf http://www.fda.gov/drugs/resourcesforyou/consumers/buyingusingmedi cinesafely/counterfeitmedicine/default.htmhttp://www.fda.gov/drugs/resourcesforyou/consumers/buyingusingmedi cinesafely/counterfeitmedicine/default.htm http://www.fda.gov/iceci/criminalinvestigations/ucm182888.htm http://www.accessdata.fda.gov/scripts/cder/email/drugnotification.cfm http://www.fda.gov/AboutFDA/ReportsManualsForms/Forms/HumanDr ugForms/default.htmhttp://www.fda.gov/AboutFDA/ReportsManualsForms/Forms/HumanDr ugForms/default.htm