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 GuidelinesState Law Institutional Policy and ProceduresDepartmental 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 Packing Slip Accountability Record

Shipment AcknowledgementRecordkeeping

Maintenance of Supply

Storage Conditions and Monitoring Room Temperature Refrigerated

Security Secure area with limited access

Documentation

Dispensing Medication

Methods for PreparationProper Labeling

Required components of labelingBlinded PresentationVerification of Doses and Dispensing

Accuracy Confirmation of Kit Number/Treatment

Recording of InformationRecord Retention

Dispensing Medication: Mailing Supply

Requirements for Mail Out IND Status Permission to Mail Out

Record RetentionRequirements 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

PersonnelAccess to Treatment Assignment

Steps for Randomization Steps for Verifying Randomization

Expiration or Recall of Stock

NotificationFinal AccountabilityFinal DispositionDestruction vs Return to SupplierDocumentation

Study Monitoring

Record RequestsCount ReviewDiscrepancies

Study Closeout

Complete AccountabilityFinal DispositionDocumentation

Practical Application

Ideas for Practical Application

REMEMBER THE PATIENTOrganization of RecordsKnowing the InventoryKnowing the ProtocolRandomization and Maintaining the

BlindMaintaining ContactAsking QuestionsDocumentation

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 RandomizationHow 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 If in doubt, ask If in doubt, ask

kmcconnell@mdanderson.orginvdrugs@mdanderson.org