6.2 Investigational Product Receipt, Dispensing, and Accountability

Investigational Product Receipt

The chain of custody for an investigational product begins the moment it arrives at the clinical site. A robust receipt process ensures that the site only accepts IP that is safe, intact, and properly documented.

The Receipt Process

When a shipment of IP arrives, the designated site staff must immediately perform the following steps:

1. Verify the Shipment: Check the physical package for signs of damage or tampering. Verify that the shipment is intended for your site and specific protocol.
2. Check the Temperature Monitor: Most IP shipments include a temperature monitor (e.g., a TempTale). The coordinator must stop the monitor, download the data, and verify that the IP remained within the acceptable temperature range during transit. If an excursion occurred, the IP must be quarantined immediately.
3. Inventory the Contents: Unpack the IP and match the physical contents (kit numbers, lot numbers, quantities) against the packing slip. Any discrepancies (e.g., missing kits, extra kits, mismatched numbers) must be noted.
4. Acknowledge Receipt: If the shipment is intact and correct, the coordinator must acknowledge receipt in the Interactive Response Technology (IRT) system or sponsor portal. This updates the site's digital inventory.
5. Update Site Logs: The receipt must be recorded on the Master IP Accountability Log, adding the new stock to the site's active inventory.
6. Store Immediately: Transfer the IP to the appropriate temperature-controlled, secure storage area without delay.

Real-World Example: A site receives a cooler containing a biologic requiring 2-8°C storage. The coordinator immediately stops the TempTale, downloads the PDF report, and confirms the temperature never exceeded 6°C. They verify the 10 vials match the packing slip, log into the IRT system to mark the 10 specific vial numbers as 'Received', sign the packing slip, and place the vials in the locked, monitored refrigerator. The signed packing slip and temperature report are filed in the pharmacy binder.

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Dispensing Investigational Product

Dispensing IP to a subject is a high-risk activity. Errors in dispensing can lead to subjects receiving the wrong dose, the wrong drug, or an expired product, directly impacting their safety and the trial's validity.

The Dispensing Workflow

1. Verify Eligibility and Randomization: Before dispensing, confirm the subject has met all inclusion/exclusion criteria, has signed the current informed consent, and has been randomized or assigned treatment in the IRT system.
2. Obtain the Assignment: The IRT system will assign specific IP kit numbers for the subject. The coordinator must print or document this assignment.
3. Retrieve the IP: Go to the storage area and retrieve only the specific kit numbers assigned by the system.
4. Verify Expiration/Retest Date: Check the label or the IRT system to ensure the IP will not expire before the subject finishes the course of treatment.
5. Double-Check: A best practice (and often a protocol requirement) is to have a second qualified staff member verify that the retrieved kit matches the IRT assignment exactly.
6. Prepare the IP (if applicable): Some protocols require the IP to be reconstituted or drawn into syringes. This must be done using aseptic technique by qualified personnel (often an unblinded pharmacist).
7. Dispense and Educate: Provide the IP to the subject. Crucially, the coordinator must educate the subject on how to take the IP, storage requirements at home, and the importance of returning all empty bottles, unused pills, and packaging at the next visit.
8. Update Logs: Document the dispensing on both the Master IP Accountability Log and the Subject-Specific IP Log.

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IP Accountability Documentation

Accountability is the core of IP management. The FDA and sponsors require sites to account for every single pill, vial, or device from the moment it arrives until it is destroyed or returned.

The Master IP Accountability Log

This log tracks the overall inventory at the site level. It acts like a bank ledger for the IP.

The Subject-Specific IP Log

This log tracks the IP assigned to an individual subject. It details exactly what was given to the subject and what they brought back.

Managing Discrepancies

Discrepancies occur when the physical inventory does not match the written logs. If a subject returns fewer pills than expected, the coordinator must investigate.

• Did the subject lose a pill?
• Did they take an extra dose?
• Did they drop one down the sink?

All discrepancies must be documented with a clear, signed, and dated explanation. Unexplained discrepancies are major red flags during an audit, as they suggest a breakdown in the site's control over the investigational product.