PREP WORKSHOP #11 Investigational Drug Disposal

Transcription

1 PREP WORKSHOP #11 Investigational Drug Disposal Presented by: Ji-Eun Kim, Research Pharmacist Investigational Pharmacy Core, Clinical Research Service Miyuki Yoshida-Hay, RSO, MLSO, CHSP Safety Office, The Feinstein Institute

2 CME Disclosure Statement The North Shore LIJ Health System adheres to the ACCME s new Standards for Commercial Support. Any individuals in a position to control the content of a CME activity, including faculty, planners, and managers, are required to disclose all financial relationships with commercial interests. All identified potential conflicts of interest are thoroughly vetted by the North Shore-LIJ for fair balance and scientific objectivity and to ensure appropriateness of patient care recommendations. Course Director and Course Planner, Kevin Tracey, MD and Tina Chuck, MPH have nothing to disclose. Ji-Eun Kim and Miyuki Yoshida-Hay have nothing to disclose.

3 OBJECTIVES To review regulatory requirements and discuss procedures and documentation for investigational drug disposal in clinical research o o o o o Hazardous drugs Non-hazardous drugs Radioactive pharmaceuticals Controlled substances Biological agents

4 MANAGEMENT OF INVESTIGATIONAL DRUGS FDA/IRB/Institutional Approval Subject Enrollment Prescription/Order Subject Return Expiration Study Completion STUDY FEASIBILITY PROCUREMENT DISPENSATION DISPOSAL Drug Info Plans Order Receipt Storage Preparation Administration Return On-site Disposal

5 DISPOSAL INQUIRIES I am contacting you in regards to on-site destruction of unused study drug. What do I write for destruction method in a disposal record? The sponsor requested SOPs on on-site drug disposal. Where can I find it? I found a controlled substance left from a previous investigator. What should I do?

6 BARRIERS Lack of specific instructions and documentation from the sponsor or sponsor-investigator Lack of site-specific procedures o Standard Operating Procedures for the investigational drug management o Exit procedures for investigators and research staff STUDY FEASIBILITY Establish plans Assess any cost

7 INVESTIGATIONAL DRUG DISPOSAL Regulations & Standards Facility/Site Procedures Sponsor Procedures Documentation

8 REGULATIONS & STANDARDS

9 FEDERAL REGULATIONS Sponsor Disposition of unused supply of investigational drug The sponsor shall assure the return of all unused supplies of the investigational drug from each individual investigator. The sponsor may authorize alternative disposition of unused supplies of the investigational drug provided this alternative disposition does not expose humans to risks from the drug. The sponsor shall maintain written records of any disposition of the drug. <CFR Title 21 Section 312>

10 FEDERAL REGULATIONS Investigator Investigator recordkeeping and record retention (a) Disposition of drug. An investigator is required to maintain adequate records of the disposition of the drug, including dates, quantity, and use by subjects. If the investigation is terminated, suspended, discontinued, or completed, the investigator shall return the unused supplies of the drug to the sponsor, or otherwise provide for disposition of the unused supplies of the drug under <CFR Title 21 Section 312>

11 <E6 GCP: 4. Investigator and 5. Sponsor > GCP STANDARDS Maintaining documentation of IP management The sponsor s responsibilities to provide the procedures on adequate and safe return of unused investigational product(s) to the sponsor or alternative disposition if authorized by the sponsor and in compliance with the applicable regulatory requirement(s).

12 HAZARDOUS DRUGS USP 800 & NIOSH United States Pharmacopeia (USP) Chapter 800 Disposal of all hazardous drug waste must comply with all applicable federal, state, and local regulations. All personnel who perform routine custodial waste removal and cleaning activities in hazardous drug handling areas must be trained in appropriate procedures to protect themselves and the environment to prevent hazardous drug contamination. The National Institute for Occupational Safety and Health (NIOSH) List of antineoplastic and other hazardous drugs in healthcare settings

13 CONTROLLED SUBSTANCES The Disposal of Controlled Substances final rule (2014) 21 CFR Part 1304, 1307, 1317 DEA Form 41 Inventory of drugs surrendered for disposal NYS CRR Part 80 Rules and Regulations on Controlled Substances Section Surrender and disposal of controlled substances Section Returns to supplier DOH Form 2340 Request for approval of disposal/destruction of controlled substances DOH Form 166 Controlled substance inventory form NOTE: DO NOT dispose of controlled substances for research using the DEA National Prescription Drug Take-back Day. Please follow pertinent procedures and documentation requirements.

14 RADIOACTIVE PHARMACEUTICALS The use of radiopharmaceuticals is highly regulated. Each facility must have a radioactive materials license from one of the following regulatory agencies: Long Island and Upstate NY: NYSDOH Bureau of Environmental Radiation Protection (BERP) 10 NYCRR Part 16 State Sanitary Code New York City (5 boroughs): NYC Department of Health and Mental Hygiene - Office of Radiological Health (ORH) Article 175 of the Health Code It is strongly recommended to consult the Radiation Safety Officer prior to submitting a research protocol to the IRB. Only authorized users named on a license are permitted to prescribe radiopharmaceuticals to human beings.

15 RADIOACTIVE PHARMACEUTICALS Radiopharmaceuticals are utilized in Nuclear Medicine or PET imaging departments in hospitals or imaging facilities. A licensed nuclear medicine technologist (LNMT): is trained to administer radiopharmaceuticals to human beings for diagnostic or therapeutic purposes under the supervision of a physician authorized by a radioactive materials license. has a scope of practice that includes, but is not limited to, preparing the dose, assaying the dose, performing quality control tests and managing radioactive waste.

16 BIOLOGICAL AGENTS NIH Guidelines for research involving recombinant or synthetic nucleic acid molecules Biosafety in Microbiological and Biomedical Laboratories (U.S. Department of Health and Human Services; Public Health Service; Centers for Disease Control and Prevention; NIH) WHO Laboratory Biosafety Manual Institutional Biosafety Committee oversight

17 PROCEDURES Sponsors Local Destruction Department of Pharmacy Occupational and Environmental Safety Environmental Service Radiation Safety Office

18 PROCEDURES Sponsor Protocol Manual of Operating Procedures Other written communications Return to sponsor Local destruction

19 SPONSOR Example: NCI Policy and Guidelines Pharmaceutical Management Branch Cancer Therapy Evaluation Program, DCTD, NCI Return un-dispensed PMB supplied investigational agent to the NCI Clinical Repository when: o o The agent is no longer required for the study and the agent cannot be transferred to another DCTD sponsored protocol. The agent is unsuitable for clinical use. Do not return supplies dispensed to patients to the NCI Clinical Repository. o The purpose of documentation of patient returns on the Oral DARF is to record quantities returned for destruction on site in accordance with institutional policy.

20 SPONSOR Example: NCI Pharmacy Audit Sheet Return of Study Agent (Non-Compliance) NCI-supplied study agent is not returned, not transferred to an appropriate NCI protocol or not destroyed within 90 days. NCI-supplied study agent is destroyed without NCI authorization or not destroyed per local institution s destruction policy. Failure to maintain Return Form or documentation of local destruction. No written NCI authorization for transfer or for local destruction. NCI-supplied study agents not returned, transferred or destroyed when patients are in follow-up and no NCI-supplied study agent is being administered.

21 PROCEDURES Local Destruction Health System Policies Facility Policies and Procedures/Contacts Occupational and Environmental Safety Department Environmental Services Department Radiation Safety Office Site-specific Standard Operating Procedures

22 HEALTH SYSTEM POLICIES Research Policies o o o o GR049 Medications and Investigational New Drugs Used in Clinical Research GR050 Use of Controlled Substances in Research GR087 Use of Radiation in Human Subject Research GR088 Principal Investigator Exit Process Infection Control Policies o INF.1154 Regulated Medical Waste

23 FACILITY POLICIES AND PROCEDURES Hazardous pharmaceutical waste o Safety Manual: Hazardous Materials and Waste Management Plan Non-hazardous pharmaceutical waste Radioactive pharmaceutical waste o Radiation Safety Manual Controlled substances Biological agents

24 FACILITY PROCEDURES Example: LIJ Medical Center Hazardous pharmaceutical waste 1. P-listed and U-listed agents EPA approved container (black or white) Department of Occupational and Environmental Safety 2. non-epa regulated hazardous waste Yellow SharpSafety chemotherapy and sharps containers Environmental Services Non-hazardous pharmaceutical waste Red bags and bins Environmental Services or Stericycle

25 FACILITY PROCEDURES Feinstein & NSUH: Radiopharmaceuticals Radiopharmaceutical waste may be disposed of as regular waste once these two conditions are met: It has been stored for a minimum of 10 half-lives. For example: 18 F has a half life approximately 2 hours. After 24 hours, the waste may be handled as regular trash Surveys with a GM meter are indistinguishable from background.

26 FACILITY PROCEDURES Feinstein & NSUH: Radiopharmaceuticals All sharps waste must be stored in a sharps container. Full containers must be closed, labeled with the date and isotope and stored inside a lead-lined cabinet for 10 half-lives. All non-sharps waste must be collected in a bag, labeled with the date and isotope and stored in a lead-lined cabinet for 10 half-lives. If unit doses are ordered from a radiopharmaceutical vendor (such as Cardinal Health), the syringes and unused doses may be returned to their shielded containers and sent back to the vendor for proper disposal.

27 FACILITY PROCEDURES Biological Agents North Shore-Long Island Jewish Health System, Inc. Infection Control Manual POLICY TITLE: REGULATED MEDICAL WASTE Prepared by: Donna Armellino and site specific Infection Control Committee members Effective Date: 12/13 DEPARTMENT: Epidemiology Last Revised/ Page 1 of 9 Reviewed: 08/07, 12/09, 5/10, 05/11, 12/13 Procedures Red containers with red liners Labeled with the universal biohazard warning symbol and the word biohazard or the words Regulated Medical Waste Environmental Services The facility s plan shall be maintained, reviewed and revised by Environmental Service Director or his/her designee IBC Guidance for each protocol

28 (Site-specific) Standard Operating Procedures Feinstein Institute for Medical Research Home For Professionals» Resources for Investigators» Clinical Research Service» Clinical Trial Standard Operating Procedures (SOPs)» 10. Test Article Management (for clinical research sites) 19. Investigational Drug Service (in the Dept of Pharmacy) Research sites must edit the template to describe site s own practices.

29 DOCUMENTATION

30 DOCUMENTATION Drug Return to Sponsor Return approval and instructions from the sponsor Drug accountability Any drug return records Local Destruction Approval letter from the sponsor Drug accountability Any on-site disposal records < E6 Good Clinical Practice: 8. Essential Documents>

31 Drug Accountability Record Form (DARF) Return to Sponsor North Shore-LIJ Health System Investigational Drug/Biologic Accountability Record Name of Hospital or Center: NSCH Protocol Title: A double-blinded ABC Study Line No. Date Subject Initials Subject ID No. Dose Quantity Dispensed /Received Dispensing Area or Pharmacy: NSCH Pharmacy IRB Number: A Balance Forward Lot/Kit Number Expiration Date Recorder Initials 1 4/30/14 Received A9876 6/30/16 JK 2 5/15/14 JD A13 2 Tabs BID A9876 6/30/16 JK 3 6/1/14 Monthly Inventory 18 A9876 6/30/16 JK 4 6/30/16 Returned to sponsor A9876 6/30/16 JK PAGE No. 1 Investigator Name: Dr. Jones Investigator and/or Site Number: 06 Investigational Drug/Biologic Name: Healept Package Size: 60 tablets/bottle Inventory Unit: Bottle Dosage Form and Strength: Oral Tablet 100 mg Storage Temperature: C (68-77 F) Comments

32 RETURN RECORDS

33 QUIZ & ACTIVITIES

34 QUIZ Where can you discard vials containing residual volume of a non-epa regulated chemotherapeutic agent?

35 QUIZ An investigator disposed of an expired controlled substance in an institutionapproved pharmaceutical waste container with lid and entered this disposal record in the accountability log. Is this appropriate procedure?

36 QUIZ Discarding investigational drugs returned from subjects with a label containing subject information. Is this appropriate procedure?

37 QUIZ You received a letter from NCI/CTEP stating that your clinical trial is completed and must destroy investigational drugs returned from subjects. What is your time frame? Return of Study Agent (Non-Compliance) NCI-supplied study agent is not returned, not transferred to an appropriate NCI protocol or not destroyed within 90 days;

38 Drug Accountability Record Form (DARF) Disposal North Shore-LIJ Health System Investigational Drug/Biologic Accountability Record Name of Hospital or Center: NSCH Protocol Title: A double-blinded ABC Study Line No. Date Subject Initials Subject ID No. Dose Quantity Dispensed /Received Balance Forward Lot/Kit Number Expiration Date Recorder Initials 1 4/30/14 Received A /08/15 JK 2 5/15/14 JD A13 2 Tabs BID A /08/15 JK 3 6/1/14 Monthly Inventory 18 A /08/15 JK 4 Dispensing Area or Pharmacy: NSCH Pharmacy IRB Number: A PAGE No. 1 Investigator Name: Dr. Jones Investigator and/or Site Number: 06 Investigational Drug/Biologic Name: Healept Package Size: 60 tablets/bottle Inventory Unit: Bottle Dosage Form and Strength: Oral Tablet 100 mg Storage Temperature: C (68-77 F) 12/08/ A /08/15 JK Local destruction Comments

39 LOCAL DESTRUCTION RECORDS

40 GROUP DISCUSSION 1. I am contacting you in regards to on site destruction of unused study drug. 2. What do I write for destruction method in a disposal record? 3. The sponsor requested SOPs on on-site drug disposal. Where can I find it? 4. I found a controlled substance left from a previous investigator. What should I do?

41 GROUP DISCUSSION I am contacting you in regards to on-site destruction of unused study drug. Procedures o o o Hazardous drugs (EPA-regulated, non-epa-regulated) Non-hazardous drugs Appropriate waste container and collecting department Documentation o o o Written approval from the sponsor Drug accountability Drug disposal records

42 GROUP DISCUSSION What do I write for destruction method in a disposal record? Site-specific procedures o Contractors vs. facility departments o Specific method (e.g., incineration, landfill)

43 GROUP DISCUSSION The sponsor requested SOPs on local drug destruction. Where can I find it? You can find Health System SOP templates under Feinstein/CRS website. o 10. Test Article Management (for clinical research sites) o 19. Investigational Drug Service (in the Dept of Pharmacy) Research sites must edit the template to describe site s own practices.

44 GROUP DISCUSSION I found a controlled substance left from a previous investigator. What should I do? Contact Office of Research Compliance and Clinical Research Service. We will coordinate with a local DEA field office.

45 TOOLS AND GUIDANCE Feinstein Institute for Medical Research Home For Professionals» Resources for Investigators» Clinical Research Service» Investigational Pharmacy Core» Tools and Guidance Tools for Investigational Drug Management Frequently Asked Questions Templates

46 CONTACT INFORMATION Ji-Eun Kim, RPh, PhD Research Pharmacist Investigational Pharmacy Core, Clinical Research Service TEL: Emmelyn Kim, MA, MPH Director Office of Research Compliance TEL: Miyuki Yoshida-Hay, RSO, MLSO, CHSP North Shore University Hospital Radiation Safety Officer, Medical Laser Safety Officer & Safety Officer for the Feinstein Institute TEL: or