Geri Foster, DPh Compounding & Investigational Drug Pharmacist

1. Geri Foster, DPh Compounding & Investigational Drug Pharmacist

2. July 20, 2001, Friday Johns Hopkins Death Brings Halt To U.S.- Financed Human Studies

3. Warning letter to Johns Hopkins • No IND submission • Didn’t mention all risks in consent • Failed to report adverse reactions • Failed to update consents following adverse reactions.

4. Warning letter to Johns Hopkins • Failed to disclose experimental use of drug. • Represented product as a medication and failed to disclose it as chemical grade intended only as lab use. • Failed to submit technical information, such as, source and purity of the drug substance.

5. Warning letter to Johns Hopkins • Poor documentation • Undetermined amount of Sodium Bicarb added to second solution, no records • Changed the dosing conditions in protocol • delivery system • pH, osmolarity • rate of administration • Changed pre-medication

6. DEPARTMENT: INSTITUTIONAL REVIEW BOARD POLICY NUMBER: XI.A SECTION: Investigational Drugs, Biologics & Device REVIEW RESPONSIBILITIES:IRB Policy & Procedure Committee ORIGINAL CREATION DATE: February 04, 2002 REVISION DATES October 17, 2003 Subject: Storage, Handling, and Dispensing of Investigational Drugs, Agents, and/or Biologics in Clinical Trials

7. Definitions:1. Investigational Agents: A pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial. This includes products with a marketing authorization when used or assembled (formulated or packaged) in a way different from the approved form, products used for an unapproved indication, or products used to gain further information about an approved use.

8. 2. Definitions:Investigational Drugs/Investigational Biologics (Test Articles):A new drug/agent or biologic that is used in a clinical investigation. The term investigational biologic also includes a biological product that is used in vitro for diagnostic purposes. Investigational drugs or biologics may include: • Products that are not generally recognized as being safe and effective for any use under the conditions prescribed, recommended, or suggested by the FDA; or • Products already approved by the FDA as safe and effective for specific indications that are being studied for new indications (or doses, strengths, or frequency).

9. 3 Definitions:Investigational Drug Service (IDS): A division of the VUMC Pharmacy Department that provides support for clinical drug studies including Institutional Review Board consultation and dispensing services for investigational drugs, agents, or biologics. This division actively supports all Departments and Investigators involved in research.

10. 4. Definitions:Joint Commission on Accreditation of Healthcare Organizations (JCAHO): A national accrediting body for hospitals and other health care delivery organizations.

11. Policy It is the policy of the Vanderbilt University Institutional Review Board that all investigational drugs, agents and/or biologics used in human subjects research be stored, handled, and dispensed in accordance with governing regulations and Institutional policy.

12. Policy: Storage of Investigational Drugs, Agents, or Biologics. I.A. It is the responsibility of the Investigator to comply with all Institutional, State and Federal regulations in regards to storage of investigational drugs, agents, or biologics.

13. Policy: 1. B. Investigational drugs, agents, or biologics used in the context of research, may be stored in areas other than the IDS under the direct supervision of the Investigator and is in accordance with the sponsor, if applicable.

14. Policy: I. C. Controlled substances may not be stored outside of the pharmacy department.

15. Policy: I. D. Investigational agent storage facilities outside of the IDS must be in compliance with Institutional, State, Federal [Food and Drug Administration (FDA)], and Joint Commission on Accreditation of Hospital Organizations (JCAHO) requirements. Pharmacy monitoring may be incorporated into the IRB auditing process as needed to assure compliance.

16. II. Dispensing of Investigational Drugs, Agents, or Biologics. II. A. All investigational drugs, agents, or biologics administered to inpatients should be dispensed through the IDS pharmacy. This includes all inpatient beds in the Vanderbilt University Medical Center, Clinical Research Center, Stallworth Rehabilitation Hospital, Psychiatric Hospital at Vanderbilt

17. II. B. If IDS is not utilized for the dispensing of investigational drugs, agents, or biologics, it is the responsibility of the Investigator to assure that dispensing is in accordance with all Institutional, State, Federal, and JCAHO requirements.

18. II. C. The Pharmacy must prepare and dispense controlled substances for all inpatients and outpatients.

19. II. D. Compounding of oral and intravenous drugs must be handled by the Pharmacy. The Pharmacy must prepare and dispense such medications for all inpatients and outpatients.

20. III. Investigations of issues related to the potential mishandling of investigational drugs, agents, or biologics will be conducted by the IDS and promptly reported to the IRB.

21. Pharmacy IRB Ex-Offico Members • Phil Johnston: Asst. Director of Pharmacy • David DiPersio: Clinical Pharmacist Critical Care Pharmacy • Debbie Harrell: Geriatric Pharmacist Specialist

22. Vanderbilt University Institutional Review BoardPharmacy Reviewer’s Comment Form • Name of Drug • Is it FDA Approved? • Is it being used for its approved indication? • IND# for this protocol

23. Are the doses within acceptable dosing limits? • Is the route of administration noted in the protocol? • Are the side effects of all agents listed adequately in the protocol? • Are other clinical considerations (pregnancy, dietary restrictions, or drug interaction potential) clearly addressed in the consent document? • Are the Investigator’s descriptions of handling, storage and dispensing adequate, if not using the IDS?

24. What regulations govern investigational drug policies? • Hospital policy (IRB) • ASHP (residency site) • JCAHO standards (Investigational agents) • Department of Health and Human Services through OHRP and FDA • USP/NF 795 & 797 (FDA enforced)

25. JCAHO Standards MM.7.40 Investigational medications are safely controlled and administered. Specifying that when pharmacy services are provided, the pharmacy controls the storage, dispensing, labeling, and distribution of the investigational medication

26. Why follow the USP/NF Chapter 797standards: • They may be adopted and enforced by State Boards • Surveyed by accreditation organizations (JCAHO). • Enforceable by the FDA

27. USP/NF Chapter 797 • Sterile Products • Training and Competence • Compounding Environment • Labeling and Expiration Dating • Aseptic Technique • Product and Environmental Testing • QC procedures • What to do after the products are made and distributed

28. Who must follow 797 • The standards are applicable to health care institutions, pharmacies, physician practices and other facilities in which compounded sterile products (CSP) are prepared and stored. • Not applicable to sterile products prepared for immediate use.

29. Immediate Use means there is no intermediary step such as laying it down and waiting to give later- Daryl Rich Pharm.D JCAHO Surveyor • Practices that will fall under <797> using this definition: • Drawing up flu vaccine or immunizations into multiple syringes for later use • Anesthesiologists’ practice of drawing up all drugs into syringes at the beginning of the day

30. Is this going to be your office attire? • Booties or shoe covers • Occlusive hair cover • Mask • Gown • Gloves

31. Why use the Investigational Drug Service ?

32. Investigational Drug Service Personnel Phil Johnston, Pharm.D. Assistant Director of Pharmacy Hope Campbell, Pharm.D., BCPS, Coordinator of IDS Geri Foster, D.Ph. Compounding Coordinator Lori Choate, Certified Pharmacy Technician Deborah Allen, Certified Pharmacy Technician

33. Advantages of the IDS • Investigators able to accommodate more protocols • Ensure use is limited to authorized prescribers • Ensures patient consent is obtained • Verification of protocol compliance • Available for monitoring visits and FDA audits • Guaranteed compliance with all applicable state, & federal regulations

34. Advantages of the IDS • Patient specific labeling • Consistency in labeling • Randomization and blinding available • Patient counseling (if needed) • Complete and maintain drug related case report forms • Serve as the un-blinded participant • Order drugs and maintain proper storage • Secured drug storage/space

35. Advantages of the IDS • Placebos identical in appearance to product • Approved sources of products (C of A) • Formulas with sources/documentation/logs • Drug accountability documentation • Quality service • Timely delivery

36. Inpatient Studies & The IDS • Study medication is printed on patient MAR (medication administration record) • Drug interaction check specific to protocol • Drug exclusion check, specific to protocol • Protocol synopsis and nursing sheets on the chart

37. Pharmacy Supported Study

38. Obtain a budget

47. Items needed from Principal Investigator to setup Protocol • Protocol • Amendments • FDA 1572 • IRB approval letter • Consent form copy • Drug Accountability forms (if sponsor provided) • Drug Label Pages (if sponsor provided) • Pharmacy Binder (if sponsor provided) • Investigator’s brochure (if sponsor provided) • Nursing Information Sheet

48. Pharmacy Commitments • Budget • Drug • Horizon Expert Orders (Wiz) • HMM (Horizon Meds Manager) • Outpatient Prescription • Maintain Protocol Specific Binder

49. Pharmacy Binder • Enrollment Log/Randomization Log • Drug Accountability Record • Patient Worksheet • RX How-to • Mixing Instructions • Copy of Current Consent • Copy of Protocol • Correspondence • Current IRB Approval Letter

50. Documentation and Inventory Control Requirements • Date of dispensing • Patients name and or study number • Manufacturer’s lot number • Balance on hand • Retest or expiration date