1 January 17, 2008 Test Article Accountability

2 January 17, 2008 Investigator Responsibilities 21 CFR  Maintain control of drug under investigation  Administer drug only to those subjects under investigator’s personal supervision or under supervision of sub investigator responsible to investigator  Supply drug only to those authorized to receive it Investigational Drug Service (IDS) for inpatient studies vs. staff  Security Controlled substance —Secure, locked, substantially constructed enclosure enclosure —Limited access

3 January 17, 2008 Investigator Responsibilities Additional ICH Requirements ICH GCP (E-6): 4.6, 4.7  Investigator Instruct subjects on using, handling, storing, and returning the investigational product(s) Check periodically that subject is in compliance with drug instructions Break blind only per protocol Promptly notify sponsor when blind is broken

4 January 17, 2008 Complete Medication Order   Name and History Number   Name of the medication   Dose with units of measure   Administration route   Time and frequency of administration   Titrated orders must be defined with desired effect   “Range orders” (e.g. 1-2 tabs or mg) eliminated wherever possible

5 January 17, 2008 Unsafe/Unauthorized Abbreviations Do Not UseInstead Use: μmcg or microgram Uunit 2.0 mg2 mg.25 mg0.25 mg MSO4 or MSmorphine MgSO4magnesium sulfate

6 January 17, 2008 Accountability Records General Information  Investigator’s name  Test article identification  Dispensing unit (e.g., vials, tablets, etc.)  Lot or batch number, if available  Protocol number  Number of units received  Investigator’s signature and date (end of study) Note: Product Label should state “Caution: New Drug-Limited by Federal (or United States Law) to investigational us

7 January 17, 2008 Accountability Records Dispensing/Administration Information  Initials/identifier of subject  Label code/identifier of test article  Date test article was dispensed  Quantity dispensed per container  Initials of study personnel dispensing the test article

8 January 17, 2008 Accountability Records Return Information  Date test article or container was returned by subject  Quantity of test article returned by subject  Comments, discrepancies and/or follow-up  Initials of study personnel receiving returned test article returned test article

9 January 17, 2008 Is The Subject Compliant?  Is there documentation of subject education?  Disposition and return discrepancies What is the compliance level? Packaging error? The right dose! At the right time! At the right time! The right way! The right way!

10 January 17, 2008 Is The Subject Compliant?  Other compliance issues Unused test article not returned Inadequate diary documentation Failure to maintain a consistent medication schedule Premature discontinuing of medication Failure to follow other protocol requirements related to medication (e.g. diet, disallowed medications)

11 January 17, 2008 Storage and Maintenance  Per protocol and federal/state laws  Keep storage areas clean, orderly, organized  Maintenance requirements per protocol Temperature logs —Room temperature —Refrigerator/Freezer —What is the back up plan if power fails?  Supplies sufficient?

12 January 17, 2008 Do the Numbers Add Up? Received from the Sponsor Lost, destroyed, returned to sponsor Administered/Dispensed Amount returned by subjects Minus Plus Balance on Hand

13 January 17, 2008 Accountability Check Track the Trail Dispensing/ Accountability Log CRF Source Diaries

14 January 17, 2008 Devices-What’s Different  Documentation of each subject’s use of the device  Calibration Calibration performed at intervals and according to directions specified in protocol Calibration records maintained  Temperature Log, if applicable  Repair and maintenance records maintained  Stored to maintain sterile packaging, if applicable

15 January 17, 2008 Randomization and Blinding  If applicable, randomization and blinding materials are kept intact  Unblinding Is it necessary to unblind? Was appropriate procedure followed and sponsor notified? —Documentation complete and accurate

16 January 17, 2008 Additional Information Site should follow all local regulations for accountability and storage of controlled substances Sponsor permission to destroy test article on site must be in writing

17 January 17, 2008 Investigational Drug Service (IDS)  Must use for inpatient research studies, outpatient optional currently  Handles drugs and biologics (not devices)  Keeps records of receipt, disposition to and return from site and return of drug to sponsor. Site must keep subject accountability records  Contact when considering/planning study  Investigator IND studies –will work with compounding pharmacy, provide packaging and labeling

18 January 17, 2008 Other Pharmacies Involved in Research at Duke   Investigational Cancer Service/“Oncology IDS”   HIV / AIDS Clinical Trials –Infectious Disease Clinic 2J   CHC Clinic Pharmacy –Outpatient Pediatric Studies

19 January 17, 2008 FACILITIES   Secured-Controlled-Monitored Location   Duke South, Room 0101-B, Yellow Zone   Facilities (monitored and alarmed)   800 square feet office/storage space   Class I and II LF Hoods   Biologic isolation chamber   Service Hours   On-site staff from 8 am to 4:30 pm M –F   24/7 On –call

20 January 17, 2008 IDS –IRB Relationship   Membership on IRB’s   Informational support to staff and chairs   Develop protocol preparation checklists: Drug nomenclature standards for consent forms Safe medication practices Eliminate unsafe abbreviations Pharmacy review for inpatient studies

21 January 17, 2008 What IDS Can Do For You   Consolidate activities and skills   Design Implementation Closeout   Integrate research into patient care activities   Comply with laws and standards   Coordinate production & packaging function   Educate staff on specifics of research

22 January 17, 2008 IDS Operations   Protocol Specific Services   Online pharmacy procedures   Online drug data sheets   Randomization, storage/security, accountability, blinding, preparation/compounding, patient counseling, staff education   Audits (FDA, CRO, Sponsor)   Records management

23 January 17, 2008 IDS Features and Benefits   IDS can benefit your study experience by: Reducing overall costs Assuring regulatory compliance Assuring inventory control Reducing unnecessary sponsor demands Eliminating risk due to unsafe medication practices Randomization and non-distribution services Assuring safe forms and label design Help develop education plans for clinical staff providing care, and more…

24 January 17, 2008 How to contact IDS   Room 0101-B, South Hospital, Yellow Zone   Phone: (919)   Fax: (919)   Pagers  