1. Investigational Drug Management
Nancy Knudsen, RN
NRG Oncology February 2017

2. Why do we do this? Regulations Good Clinical Practice (GCP) 21 CFR 312

3. Terminology CTEP: Cancer Therapy Evaluation Program
PMB: Pharmaceutical Management Branch
DCTD: Division of Cancer Treatment and Diagnosis
IND: Investigational New Drug
NSC: National Service Center number
OAOP: Online Agent Order Processing
DARF: Drug Accountability Record Form

4. Investigational Drug Accountability Training Videos
PMB has video tutorials that provide detailed step-by-step guidance on various aspects of drug accountability. The following videos are available on the PMB website:
DARF Basics, DARF Header
Oral DARF
Agent Receipt
Agent Dispensing
Patient-Specific DARFs
Agent Transfers
Agent Returns
Local Destruction

5. What you need to know . . .
Who is the responsible drug physician; are they eligible to participate?
Is the investigator’s institution eligible to participate in the study?
Who orders the investigational drug?
How are the drugs ordered; where are they stored?
Where are the logs, shipping receipts, return and transfer forms kept?

6. Where do I find Policy and Guidelines for the PMB?
PMB Main page
- Links to agent management, registration,
forms, video training
Investigator Resources
- Investigator’s Handbook

7. Investigator Requirements
Physician must be registered with CTEP
Registration must be current (renewed annually)
- Statement of Investigator Form (FDA Form 1572)
- Supplemental Investigator Data Form
- Financial Disclosure Form
Ordering investigator is study-eligible

8. Online Agent Order Process (OAOP)
Agent ordering should be done online through OAOP
You must have a valid IAM account in order to access OAOP
Investigators and Designees can order drug
Remember to take into account Federal holidays and week-ends

9. OAOP
OAOP enables you to perform the following operations based on your account access:
Log into the application
Create (Blinded, Regular) orders online
Modify orders
View/Receive order status
Ship orders
Track orders

10. OAOP
You can also access the following in OAOP based on your account access role:
Stock notification letters (expiration, protocol status, recalls, IND withdrawal, and extension of expiration)
Investigator Brochures - obtain current versions of investigator brochures and other IB documents of CTEP-IND agents.

11. Drug Shipping
Normally shipped within 2 working days, shipped Monday through Thursday only - domestic sites
Orders will only be shipped to the investigator’s designated shipping address
Next Day Delivery Requests - Orders must received by PMB by 2:00 pm EST with a site-provided courier account number to assure next day delivery

12. Drug Shipping – Patient Specific Agent
Allow extra time for shipping
 Protocol to see who orders the study drug; it may be ordered automatically by NRG Oncology (or other NCTN group) or it could be ordered by the site. Initial vs. subsequent ordering can be different.

13. Drug Storage Control Access – secure, locked location
Store agents separately by protocol, by agent, and agent strength
Maintain proper conditions

14. Transporting Investigational Agents
Agents can be transported from Control Pharmacy to a Satellite Dispensing Area/Pharmacy via staff or institutional courier using appropriate temperature controls and transportation procedures
Secondary distribution: A NO-NO! PMB supplied investigational agents must NOT be re-shipped by mail or overnight delivery services to another institution, site, or study subject

15. Transporting Investigational Agents
Note: If NCTN group holds the IND, it is possible they will allow you to mail the oral study drug to a patient; check the protocol or check with the group
Must be able to track if sending by mail

16. Investigational Agent Accountability Record (DARF)

17. Investigational Agent Accountability Record – Oral Agents
Allows you to track agents received and dispensed and also agents returned by the patient

18. DARF Transactions Other Than Patient Dispensing:
Agent receipt from NCI
Agent moved to satellite dispensing
Agent returns to NCI or to the control location
Agent transfers
Breakage or waste
Agent destruction at local site – per protocol

19. Good Record Keeping Use black ink
Write the entire date, i.e. write 2/22/17, not 2/22
Complete the header on the form and fill out each line completely
Do not use ditto marks
When a mistake is made (on that rare occasion)
NEVER use white out
Draw one line through the mistake, date and initial – no write-overs

20. Proper Accounting of Agents
Most drugs are accounted for by the vial/bottle/kits.
Multi-use vials may be accounted for by dose e.g. Herceptin
Some are accounted for by the capsule/tablet
Most are not participant specific; however, double- blind studies are participant specific
Check each protocol for any special requirements

21. Proper Accounting of Agents
Maintain DARFs at each location where drug is stored
DARFs are maintained by drug, strength, and protocol
Electronic accountability allowed in CTEP policy

22. Patient-Specific Agents
Usually placebo-controlled blinded studies
Unique patient identifier and initials
Initial orders and re-ordering – check protocol
Subsequent shipments may be automatic or may require confirmation at select intervals for future shipments or may require ordering by site

23. Patient Specific Agents
Accountability – Patient Specific DARF
Separate log for each patient for each agent
Header must contain patient identifier and patient initials
The Julian Date and order number in the upper right hand corner of the shipping label is used as the lot identifier on the DARF.
Transfers
No agent transfers allowed only treating physician transfers
Returns
Patient identifier and initials (undispensed clinical supplies only)

24. Automatic Drug Shipment
Oral Agents
Dispense according to Stop/Start dates on the bottle
Drugs usually come about one month prior to next dispensing date
To stop drug shipments you must complete study specific Treatment or Off Form

25. Good Communication
Be sure the person/people responsible for drug ordering and drug accountability have the protocol specific information and have been trained
Notify the pharmacist when a patient is off therapy
- to help pharmacist determine how much drug should be ordered
- so patient specific drug can be returned
Notify pharmacist when study is ended and all patients have completed treatment

26. How Did That Happen?#!!? Now What?
When you identify an error involving CTEP-supplied investigational notify the Pharmaceutical Management Branch (PMB) as soon as possible.
Do it in writing or by .
PMB has a FAQ on this topic that tells you what to include in your report.

27. (If) Commercial Agent is Used instead of Investigational Drug
CANNOT REPLACE the drug with stock drug
CANNOT BILL the patient or their insurance company
On the drug accountability log, clearly document that commercial drug was dispensed in error
At audit this will be noncompliance

28. (If) Investigational Drug is Used Instead of Commercial Agent
Oops – you used a CTEP-supplied investigational agent on a patient not enrolled to a CTEP- sponsored trial
Notify PMB of the error
Clearly document on the drug accountability log that an investigational agent was dispensed to a non-study patient
At audit this will be noncompliance

29. Agent Transfers
PMB supplied agents may be transferred from a DCTD sponsored protocol to another DCTD sponsored protocol or between eligible investigators within an institution (intra-institutional transfer) if the protocol utilizes the same agent, strength and formulation supplied by PMB, with PMB approval

30. Agent Transfers
Transfer between NCI registered active investigators only.
The investigator who originally ordered the agent should complete the transfer.
The receiving investigator must be a participant on the receiving trial.
Borrowing is prohibited.

31. Agent Transfers
Transfers must be documented on the Control DARF and written documentation of NCI authorization must be retained as part of the accountability records.

32. Agent Transfers
It is okay to transfer agents without prior NCI approval IF you have an after-hours emergency AND
If it is an Intra-Institutional Transfer
If the investigator on the receiving protocol is NCI- registered with an active status
If it is transferred to a DCTD-sponsored protocol
Transfer forms for urgent medical need should be submitted within 72 hours of the actual transfer.

33. Agent Transfers
Be Aware: There is always a risk that an after hours transfer will not be approved retroactively because it was not a valid transfer.

34. Agent Transfers When is investigational agent transfer prohibited?
Agent being transferred is not the same strength or formulation between protocols
The “Transfer To” investigator does not have an active registration
The “Transfer To” investigator is not an eligible participant on the study
PMB-supplied agent is transferred to a non-DCTD-sponsored protocol
PMB-supplied agent is transferred for commercial use
Commercial agents are transferred to a DCTD-sponsored protocol
Borrowing from one protocol to supply another without an approved transfer
Transfer of partial containers
Transfer of patient-specific agents without prior PMB approval
Transfer requests to retrospectively correct errors in accountability

35. INVESTIGATIONAL AGENT RETURNS
When should an agent be returned to the NCI?
The study is closed to accrual and all patients have completed therapy.
The study using the agent has closed.
The investigational agent was involved in a temperature excursion during shipping or storage.
The investigational agent has been recalled or is expired.

36. INVESTIGATIONAL AGENT RETURNS
Return all NCI-supplied agents to the NCI Clinical Repository unless you obtain prior approval for local destruction from PMB
For non-NCI supplied drugs, consult the protocol; do not send to NCI
Return only unused vials and unopened, oral agents
Return agents within 90 days of study closure and last patient completed treatment

37. Agent Return Checklist

38. Local Destruction
There are special circumstances when local destruction authorization should be requested instead of returning un-dispensed investigational agents to the NCI Clinical Repository.
- Dangerous Good
- International Site
- When otherwise directed by PMB
PMB Authorization is required. Complete and submit the Request for Authorization for Local Destruction form

39. Table - Similarities and differences between patient-specific and protocol-specific supplies

40. Audits – Assess Compliance
What will the auditors examine?
Drug logs – correctly filled out; patient cross-check
Drugs in your inventory – a count will be done
Storage
Shipping receipts, return and transfer forms

41. Audit – Satellite/Affiliate Records
Drug Accountability records will be checked – logs, receipts, return and transfer forms
Patient cross-check
Inventory is generally not checked

42. Questions? CONTACT : Pharmaceutical Management Branch
Cancer Therapy Evaluation Program
Phone: (240)
Fax: (240)
NCI Shady Grove
Room 5W228
9609 Medical Center Drive
Rockville, Maryland 20850