Maintenance, Management and Monitoring of Investigational Supply Kim McConnell, PharmD, CCRP CCOP Annual Investigators Meeting Houston, Texas March 3, 2011

Objectives To present and review regulations that apply to the maintenance, management and monitoring of Investigational doses To review milestones for an Investigational Protocol as they relate to Investigational doses To provide pointers for practical application of this information for the management and maintenance of Investigational inventory

Regulations Pertaining to Investigational Doses and Supply

Roles and Responsibilities of the Investigator Properly administer doses to enrolled Patients 21 CFR 312.61, ICH GCP 4.6.5 Maintain complete documented accountability of inventory 21 CFR 312.62, ICH GCP 4.6.3 Maintain proper storage conditions ICH GCP 4.6.4 Return/Destroy all unused inventory as instructed 21 CFR 312.62 Delegation of duties where applicable ICH GCP 4.6.2 Document retention* 21 CFR 312.62, ICH GCP 4.9.5

Roles and Responsibilities of the Sponsor Document retention* 21 CFR 312.57, ICH GCP 5.5.11 Provide information on Investigational Product 21 CFR 312.23, 21 CFR312.50, ICH GCP 5.12 Proper delivery, packaging and labeling of Investigational Product 21 CFR 312.53, 21 CFR 312.56-57, 21 CFR 312.6, ICH GCP 5.13, 5.14 Proper instruction for use and maintenance of Investigational Product 21 CFR 312.50, 21 CFR 312.59, ICH GCP 5.14 Verification of proper usage of Product 21 CFR 312.50, ICH GCP 5.18 Provide safety information regarding product 21 CFR 312.23, 21 CFR 312.32, 21 CFR 312.50, 21 CFR312.56

Additional Regulations and Guidelines Additional Federal Guidelines State Law Institutional Policy and Procedures Departmental Policy and Procedures

Protocol Milestones

Protocol Milestones Site Activation Inventory Request and Receipt Maintenance of Supply Storage Dispensing Maintaining the Blind Expiration/Recall Study Monitoring Study Closeout

Site Activation Supporting Documentation Requested IRB Approval Letter Policies and Procedures Destruction Policy Accountability Records Contact Information Unblinded Team Members

Requesting Inventory Determining Initial Supply Needs Number of Patients Dosing Schedule Blinding and Supply Presentation Study Specific Order Form Site Contact Information Protocol Number Protocol Title Quantity Needed Date Needed Turnaround Time

Inventory Receipt Documentation of Receipt Shipment Acknowledgement Packing Slip Accountability Record Shipment Acknowledgement Recordkeeping

Maintenance of Supply Storage Conditions and Monitoring Security Room Temperature Refrigerated Security Secure area with limited access Documentation

Dispensing Medication Methods for Preparation Proper Labeling Required components of labeling Blinded Presentation Verification of Doses and Dispensing Accuracy Confirmation of Kit Number/Treatment Recording of Information Record Retention

Dispensing Medication: Mailing Supply Requirements for Mail Out IND Status Permission to Mail Out Record Retention Requirements and Guidelines Federal Regulations 21 CFR 312.110, 21 CFR 312.120 State Regulation Institutional Policies

Maintaining the Blind Randomization Record Familiarity with Study Design and Schedule Identification of Blinded and Unblinded Personnel Access to Treatment Assignment Steps for Randomization Steps for Verifying Randomization

Expiration or Recall of Stock Notification Final Accountability Final Disposition Destruction vs Return to Supplier Documentation

Study Monitoring Record Requests Count Review Discrepancies

Study Closeout Complete Accountability Final Disposition Documentation

Practical Application

Ideas for Practical Application REMEMBER THE PATIENT Organization of Records Knowing the Inventory Knowing the Protocol Randomization and Maintaining the Blind Maintaining Contact Asking Questions Documentation

REMEMBER THE PATIENT

Organization of Records

Organization of Records Maintain a consistent filing system Include a copy of the treatment plan Include instructions for coverage Find a system that works

Knowing the Inventory

Knowing the Inventory How is it supplied? How must it be taken? Appearance and Blinding Tear off Labels and Kit Numbers

Knowing the Protocol

Knowing the Protocol Understand and be aware of the milestones and treatment plan throughout the Protocol Review for information as it pertains to inventory Storage Conditions Emergency Reassignment Unblinding Unused Medication

Randomization and Maintaining the Blind

Randomization and Maintaining the Blind How does randomization work? Access and Procedures for Computerized Randomization How will this inventory be presented to the Patient? What is everyone’s blinding status on the Study Team?

Keep In Contact

Communication and Asking Questions

Summary REMEMBER THE PATIENT Know and understand the responsibilities of the Sponsor and Site Investigator Stay within the definition of local, state and Federal requirements Be aware of your resources Maintain perpetual, timely and accurate documentation Be familiar with the Protocol and the Product Maintain blinding If in doubt, ask

kmcconnell@mdanderson.org invdrugs@mdanderson.org