SOP-304

Investigational Product Management

Number: SOP-304
Category: Study Conduct
Edition: Reference Edition 1.3
Approx. pages: 10

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On this page

1. Purpose
2. Scope
3. Responsibilities
4. Definitions
5. Procedure
6. Related Forms and SOPs
7. References

1. Purpose

This SOP describes how [SITE NAME] receives, stores, secures, dispenses, accounts for, returns and destroys investigational product (IP), so that IP is used only as the protocol directs, its quality is maintained, and every unit can be traced from receipt to final disposition.

2. Scope

This SOP applies to all investigational drugs, biologics and devices (including placebo, comparator and rescue medication supplied by the sponsor) held at any [SITE NAME] location, and to all staff who handle IP or IP records.

In scope: receipt, storage, access control, temperature monitoring, excursions, dispensing, participant returns and compliance counts, accountability, expiry and recalls, controlled substances, investigational devices, transfers between site locations, return and destruction.

Out of scope, covered elsewhere: randomization, blinding and emergency unblinding (SOP-305); IP shipped directly to participants or administered at home (SOP-313); calibration of thermometers and storage equipment (SOP-312); safety reporting for IP-related events (SOP-500, SOP-501).

Where the protocol, pharmacy manual, sponsor or IRB sets a stricter requirement than this SOP, the stricter requirement applies.

3. Responsibilities

Role	Responsibilities
Principal Investigator (PI)	Holds responsibility for IP accountability and control at the site. Delegates IP tasks only to qualified, trained staff on F-302-01 and oversees them. Confirms IP is given only to enrolled participants under investigator supervision and only per protocol. Assesses temperature excursions for participant impact when product was already dispensed.
Sub-Investigator (Sub-I)	Prescribes or orders IP where delegated. Reviews compliance findings and IP-related safety issues.
Research Pharmacist or IP Manager	Receives and acknowledges shipments in IRT, stores and secures IP, reviews temperature records each business day, manages excursions, dispenses or prepares IP, maintains F-304-01 and F-304-02, manages expiry, recalls, returns and destruction. Where the study is blinded and the protocol requires an unblinded IP role, performs the unblinded tasks described in SOP-305.
Clinical Research Coordinator (CRC)	Performs delegated IP tasks (for example dispensing a kit assigned by IRT, collecting returns, performing compliance counts), records them in source and on F-304-01, and reports any IP problem to the IP Manager at once.
Site Director	Provides secure storage, monitored equipment, backup power and alarm response coverage. Holds the DEA registration process with the PI where controlled substances are involved.
Quality Lead	Includes IP accountability in internal QC (SOP-700). Opens CAPA for repeated or significant IP findings (SOP-703).

4. Definitions

Term	Definition
Investigational Product (IP)	A pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial, including a marketed product used or assembled differently from its approved form, used for an unapproved indication, or used to gain further information about an approved use. In this SOP the term also covers investigational devices.
Accountability	The documented trail of every IP unit from receipt through dispensing, return and final disposition, reconciled so that quantities balance.
Interactive Response Technology (IRT)	The sponsor's system (IWRS/IVRS) used to register shipment receipt, assign kits, manage randomization and track IP status.
Temperature Excursion	Any recorded temperature outside the storage range specified by the sponsor, including excursions during shipment.
Quarantine	Physical and system status in which IP is segregated, labeled "Do Not Use" and not dispensed until the sponsor releases it in writing or directs disposition.
Min/Max Thermometer	A device that records the minimum and maximum temperatures reached since it was last reset.
Continuous Monitoring System	An electronic system that records storage temperature at set intervals, keeps the data, and alarms when limits are exceeded.
Controlled Substance	A drug or other substance in Schedules I to V under the Controlled Substances Act and 21 CFR 1308.
Final Disposition	Return of IP to the sponsor or its depot, or destruction, as authorized by the sponsor and documented.

5. Procedure

5.1 Set-up Before First Shipment

5.1.1

The IP Manager reads the protocol, pharmacy manual and IRT manual and records completion of IP and IRT training on F-103-01 before the site initiation visit.

5.1.2

The PI delegates IP tasks on F-302-01. Only staff listed for IP tasks may receive, dispense or reconcile IP. For blinded studies, the PI records which staff hold unblinded roles (SOP-305).

5.1.3

The IP Manager confirms the storage location before activation:

storage area is locked and access is limited to delegated staff
equipment holds the sponsor's required range and has been mapped or qualified if the sponsor requires it
each refrigerator, freezer and room used for IP has a continuous monitoring system with alarm, or a calibrated min/max thermometer where continuous monitoring is not available; a min/max location needs the documented closed-day plan in section 5.4.2
each temperature device has a current calibration certificate traceable to a national standard, filed and listed on F-312-01
a backup storage plan exists for equipment failure or power loss (F-705-01)

5.1.4

The Regulatory Coordinator confirms that every location where IP will be stored or dispensed is listed on Form FDA 1572 (drug and biologic studies) or in the investigator agreement and sponsor records (device studies) before IP is shipped there.

5.2 Receipt and Acknowledgment

5.2.1

The IP Manager or delegated CRC receives each shipment on the day it arrives. Staff who are not delegated for IP do not open IP shippers; they place the unopened shipper in the designated receiving area and notify the IP Manager at once.

5.2.1.1

The IP Manager arranges with the sponsor or depot that courier instructions require delivery only to named delegated staff during the site's business hours.

5.2.1.2

If a shipment is left when no delegated person is on site, the first delegated person who finds it records the time found on the packing list, checks the shipper temperature indicator, quarantines the shipment in the labeled storage conditions, and contacts the sponsor or depot the same business day. Any excursion follows section 5.5.

5.2.2

The receiver checks before moving IP to storage:

shipper is intact and addressed to the correct PI and site
temperature monitor in the shipper shows no alarm; the receiver stops the monitor and saves or downloads the reading as the sponsor instructs
contents match the packing list (protocol, kit or lot numbers, quantities, expiry dates)
labels and seals are intact and no units are damaged

5.2.3

If everything matches and no alarm is shown, the receiver places IP in its storage location immediately, then acknowledges receipt in IRT [DEFAULT: the same business day, unless the sponsor sets a shorter time], recording the actual receipt date and time.

5.2.4

If the shipper monitor shows an alarm, the IP is damaged, or the contents do not match, the receiver quarantines the shipment in the correct storage conditions, does not acknowledge it as available in IRT (or marks the affected units as damaged or quarantined, per the IRT manual), and contacts the sponsor or depot the same business day. Excursions follow section 5.5.

5.2.5

The receiver signs and dates the packing list, records receipt on F-304-01 (or the sponsor's accountability log), and files the packing list, shipper temperature record and IRT confirmation in the pharmacy file.

5.3 Storage, Access Control and Separation

5.3.1

The IP Manager stores IP in the locked storage area under the conditions on the label and in the pharmacy manual (temperature, light, humidity, orientation).

5.3.2

Access to IP storage is limited to staff delegated for IP tasks. The Site Director keeps a list of key or badge holders for each IP storage area and reviews it when staff join or leave.

5.3.3

IP is stored separately from commercial stock and from other studies' IP, with each study's supply in its own labeled bin, shelf or compartment. Where the IP is a marketed product supplied by the sponsor for the study, it is kept apart from the site's commercial stock of the same product so neither is used in place of the other.

5.3.4

Quarantined, expired, returned and used IP is stored in a separate labeled area, away from IP available for dispensing.

5.3.5

Food, specimens and non-study items are not stored in IP refrigerators or freezers.

5.4 Temperature Monitoring and Daily Review

5.4.1

This section is the library's single temperature monitoring rule. SOP-311 (specimens and kits) and SOP-312 (storage equipment) point to it. Continuous monitoring means a logger or system that records temperature at set intervals and alarms when limits are exceeded. A min/max thermometer read each business day is not continuous monitoring. Each IP storage unit and room is monitored continuously where a continuous monitoring system is installed. Where a min/max thermometer is used instead, the IP Manager records current, minimum and maximum readings and resets the device on F-304-02.

5.4.2

The IP Manager or delegate reviews the temperature record for every IP storage location each business day and records the review on F-304-02 (or signs the system's daily report). On days the site is closed, continuous monitoring and alarm notification cover the gap at locations that have them. A location monitored only by min/max thermometer has a documented closed-day plan (Site decision in section 5.1): the min/max is read on reopening, and any minimum or maximum outside the range is treated as an excursion under section 5.5 for the whole period since the last in-range reading. The first review after a closure covers the full period since the last review, using the system data or the min/max reading.

5.4.3

The reviewer checks that the record is complete with no gaps. A data gap is treated as a possible excursion until the reviewer can show the product stayed in range.

5.4.4

Thermometers and probes are recalibrated or replaced before their calibration expires (SOP-312). Expired calibration is recorded and assessed as a possible excursion for the period since expiry.

5.4.5

If the sponsor requires its own logger or log, the IP Manager uses it in addition to, or instead of, F-304-02 as the sponsor directs, and records which record is the source.

5.5 Temperature Excursions

5.5.1

Any staff member who sees an alarm or an out-of-range reading notifies the IP Manager at once. The IP Manager, or the alarm responder after hours, moves IP to a working unit within range if the storage unit is failing.

5.5.2

The IP Manager quarantines all affected IP: labels it "Quarantine, Do Not Dispense," keeps it under the labeled storage conditions, and marks it quarantined in IRT where the IRT allows.

5.5.3

The IP Manager completes F-304-03, recording:

storage location and affected kit, lot or unit numbers
excursion start and end times, highest or lowest temperature, total duration out of range
how it was found and the immediate action taken
whether any affected IP was dispensed or administered during or after the excursion

5.5.4

The IP Manager reports the excursion to the sponsor using the sponsor's excursion process (often via IRT) within the time the sponsor requires, or [DEFAULT: within 1 business day of discovery] if the sponsor sets no time, and attaches the temperature data.

5.5.5

Affected IP is not dispensed until the sponsor releases it in writing. The IP Manager files the release or disposition instruction with F-304-03 and updates IRT and F-304-01. If the sponsor rejects the IP, it stays in quarantine until returned or destroyed per section 5.10.

5.5.6

If affected IP was dispensed or administered before the excursion was found, the IP Manager notifies the PI the same day. The PI assesses participant safety, contacts affected participants where needed, and records the assessment in source. Any resulting deviation is handled under SOP-308.

5.5.7

The IP Manager records the cause and fix (for example equipment repair, door left open) on F-304-03. Repeat excursions, or any excursion that led to dosing with rejected IP, are referred to the Quality Lead for CAPA (SOP-703).

5.6 Dispensing and Administration

5.6.1

IP is dispensed only to participants who have given consent, been confirmed eligible by an investigator (SOP-303) and been assigned the IP through IRT where IRT is used. IP is administered only under the supervision of the PI or a Sub-I and is never supplied to anyone not authorized to receive it (21 CFR 312.61; 21 CFR 812.110(c)).

5.6.2

The delegated staff member dispenses the exact kit or unit number IRT assigns. Before handing over IP, the staff member checks participant ID, kit number, expiry date and package integrity against the IRT confirmation.

5.6.3

Where the protocol requires IP preparation (for example reconstitution or infusion), only staff delegated and trained for that task prepare it, following the pharmacy manual, and record the preparation in source.

5.6.4

The staff member records the dispensing on F-304-04 Participant IP Dispensing and Return Log (visit, date, kit or unit number, IRT confirmation number, quantity dispensed and their initials) and enters the kit on F-304-01 as issued to the participant. For IP administered at the site, source records the dose, route, time and the person who administered it.

5.6.5

The staff member explains to the participant how to store, take and return the IP, using IRB-approved instructions where provided, and checks the participant's understanding. The explanation is recorded in source.

5.6.6

If the wrong kit is dispensed or a dosing error occurs, the staff member notifies the IP Manager and PI at once. The PI assesses safety, the IP Manager follows the IRT and sponsor process for misallocations, and the event is recorded as a deviation (SOP-308).

5.7 Participant Returns and Compliance

5.7.1

Staff instruct participants to bring back all used and unused IP and packaging at each visit as the protocol requires.

5.7.2

At each return, the delegated staff member counts the returned units in the participant's presence where practical, records the count on F-304-04, and calculates compliance using the method in the protocol or pharmacy manual.

5.7.3

Staff record in source any doses the participant reports missing, lost, damaged or taken outside the instructions, and the reason given. Unreturned IP is recorded as such on F-304-04 and reported to the monitor as the sponsor requires.

5.7.4

The investigator reviews compliance below or above the protocol threshold, records the assessment in source, and decides on retraining or other action. Non-compliance outside protocol limits is assessed under SOP-308.

5.7.5

Returned IP is stored in the returned-IP area, labeled by participant and visit, and is never re-dispensed unless the pharmacy manual explicitly allows it.

5.8 Accountability Records and Reconciliation

5.8.1

The IP Manager maintains F-304-01, or the sponsor's log if the sponsor requires its own, for each study. The record shows for every unit: receipt date and quantity, kit or lot number, expiry date, participant ID and dispensing date, returns, and final disposition. F-304-01 is the site inventory ledger (receipts, transfers, kits issued to participants, returns to sponsor, destruction and running balance); F-304-04 records, for each participant, the visit, date, kit or unit number, IRT confirmation number, quantities dispensed and returned, and compliance.

5.8.2

The IP Manager reconciles physical inventory against F-304-01, F-304-04 and IRT [DEFAULT: at least monthly] and before each monitoring visit, and records the reconciliation.

5.8.3

Any discrepancy that cannot be resolved by checking records is reported to the PI and the sponsor and recorded on F-304-01 with the explanation. Unexplained loss of a controlled substance follows section 5.9.6.

5.8.4

The IP Manager makes IP, F-304-01, F-304-02, F-304-03 and IRT reports available to the monitor for verification (SOP-600).

5.8.5

Corrections to accountability records follow SOP-306.

5.9 Controlled Substances

5.9.1

Before receiving any IP that is a controlled substance, the PI confirms the required DEA registration is in place for each storage location:

Schedule I IP requires a separate DEA Schedule I researcher registration, with the research protocol DEA requires (21 CFR 1301.13(e)(1)(vi); 21 CFR 1301.18)
Schedule II to V IP may be handled under the PI's practitioner registration for the schedules it covers, which permits research with those substances (21 CFR 1301.13(e)(1)(iv)); confirm the registration covers the schedule and the address where IP is stored, since registration is by location (21 CFR 1301.12). A mid-level practitioner (for example a nurse practitioner) may conduct research under their registration only to the extent state statute expressly authorizes
state controlled-substance registration or license, where [STATE] requires one (Appendix A)

5.9.2

Controlled-substance IP is stored in a securely locked, substantially constructed cabinet or safe (21 CFR 1301.75; 21 CFR 312.69), separate from other IP, with access limited to the PI and named delegated staff.

5.9.3

The IP Manager keeps the DEA records required by 21 CFR 1304 in addition to F-304-01, including receipt records, dispensing records and initial and biennial inventories. Records for Schedule I and II substances are kept separate from all other records. Schedule II receipts use DEA Form 222 or the electronic equivalent where applicable. DEA records are kept at least 2 years, or longer if the study requires it (SOP-402).

5.9.4

Two staff members count controlled-substance IP at receipt, at each reconciliation and before return or destruction, and both sign the count [DEFAULT: two-person count].

5.9.4.1

In a blinded study with an unblinded IP role, when the count or its records could reveal treatment assignment (for example visibly different products, prepared doses or unblinded dispensing records), the second counter is another staff member named as unblinded for that study on F-302-01, such as the unblinded backup recorded under SOP-305 section 5.1. Where no second unblinded person is available, the count is done only on sealed, identical containers that reveal no assignment, or the unblinded monitor or the sponsor's unblinded designee acts as second counter. A blinded staff member is never the second counter for unblinded records.

5.9.5

Return or destruction of controlled-substance IP follows sponsor instructions and DEA rules (21 CFR 1317), for example transfer to a DEA-registered reverse distributor. The site does not destroy controlled substances on site unless DEA rules and the sponsor allow it and the destruction is recorded as DEA requires.

5.9.6

On discovering theft or significant loss of a controlled substance, the IP Manager informs the PI and Site Director at once. The PI or delegate notifies the DEA Field Division Office in writing within one business day of discovery and files DEA Form 106 within 45 days (21 CFR 1301.76(b)), notifies the sponsor, and notifies state authorities where [STATE] requires.

5.10 Investigational Devices

5.10.1

Investigational devices are used only with participants under the investigator's supervision and are not supplied to anyone not authorized to receive them (21 CFR 812.110(c)).

5.10.2

Device records show the type and quantity of device, dates of receipt, batch, serial or code number, the names of all persons who received, used or disposed of each device, and why and how many units were returned, repaired or disposed of (21 CFR 812.140(a)(2)).

5.10.3

Staff follow the sponsor's instructions for sterilization, reprocessing, maintenance and software versions, and record each in source or the device log.

5.10.4

A device that malfunctions is kept, quarantined and not discarded. Staff report it to the sponsor as a device deficiency and assess for safety reporting (SOP-501). The device is returned only as the sponsor directs.

5.10.5

At the end of the investigation, or when the PI's part ends, devices are returned to the sponsor or disposed of as the sponsor directs (21 CFR 812.110(e)).

5.11 Expiry, Relabeling and Recalls

5.11.1

The IP Manager checks expiry dates during each reconciliation and flags units expiring within [DEFAULT: 60 days]. Expired IP is moved to quarantine and marked expired in IRT where IRT does not do this automatically.

5.11.2

Expired IP is never dispensed. Relabeling with a new expiry date is done only by, or on written instruction of, the sponsor, and is recorded.

5.11.3

On receiving a recall or quality notice, the IP Manager quarantines affected lots on receipt of the notice, identifies participants holding affected IP using F-304-04, informs the PI, and follows the sponsor's instructions for retrieval and replacement. Actions and participant contacts are recorded.

5.12 Transfer Between Site Locations

5.12.1

IP is moved between [SITE NAME] locations only with written sponsor authorization filed in the pharmacy file, and only to a location listed on Form FDA 1572 or in sponsor records for the study.

5.12.2

The transfer is recorded on F-304-01 at both locations: date, quantity and identity of IP (kit, lot or serial numbers, expiry), means of transport, the person sending and the person receiving.

5.12.3

Temperature-controlled IP is moved in a qualified container with a temperature monitor, as the sponsor directs. The receiving location reviews the monitor reading before storing the IP and handles any excursion under section 5.5.

5.12.4

IRT is updated where the IRT tracks IP by location.

5.13 Return and Destruction

5.13.1

Unused, expired, returned and used IP is returned to the sponsor or destroyed only on the sponsor's written authorization (21 CFR 312.59; 21 CFR 312.62(a)).

5.13.2

Before return or destruction, the monitor verifies accountability where the sponsor requires it. The IP Manager reconciles F-304-01 so that received, dispensed, returned and remaining quantities balance.

5.13.3

For return, the IP Manager completes the sponsor's return form, packs IP as instructed, keeps a copy of the form and the shipping record, and updates IRT and F-304-01.

5.13.4

For on-site or vendor destruction, the IP Manager uses a method and vendor the sponsor has approved, and files the certificate of destruction listing what was destroyed, when, how and by whom. Destruction vendors are qualified under SOP-105.

5.13.5

Hazardous, cytotoxic or biological IP is handled as waste under the site's waste disposal arrangements and any sponsor instructions.

5.14 Direct-to-Participant Supply

5.14.1

Where the protocol allows IP to be shipped to participants or administered at their location, staff follow SOP-313. Accountability for that IP is still recorded on F-304-01.

F-304-04 Participant IP Dispensing and Return Log
F-304-01 Investigational Product Accountability Log
F-304-02 Temperature Monitoring Log
F-304-03 Temperature Excursion Report
F-302-01 Delegation of Authority Log
F-103-01 Staff Training Log
F-312-01 Equipment Inventory and Calibration Log
F-705-01 Business Continuity Plan and Emergency Contacts
SOP-105 Oversight of Service Providers and Vendors
SOP-302 Delegation of Authority
SOP-303 Screening, Eligibility Verification and Enrollment
SOP-305 Randomization, Blinding and Emergency Unblinding
SOP-306 Source Documentation and Data Integrity (ALCOA+)
SOP-308 Protocol Deviations and Noncompliance
SOP-312 Equipment Calibration and Maintenance; Local Laboratory Requirements
SOP-313 Decentralized Trial Elements (Remote Visits, Home Health, Direct-to-Participant IP)
SOP-402 Record Retention, Archiving and Destruction
SOP-501 Serious Adverse Event and Expedited Safety Reporting
SOP-600 Sponsor Monitoring Visits
SOP-703 Corrective and Preventive Action (CAPA)
SOP-904 Shared Staff, Cross-Site Coverage and Central Services (Model N only)
Appendix A State Law Worksheet
Appendix B Central and Site Responsibility Matrix (Model N only)

7. References

Reference	Title
21 CFR 312.59	Disposition of unused supply of investigational drug
21 CFR 312.61	Control of the investigational drug
21 CFR 312.62	Investigator recordkeeping and record retention
21 CFR 312.69	Handling of controlled substances
21 CFR 812.110	Specific responsibilities of investigators
21 CFR 812.140	Records
21 CFR 1301.12, 1301.13, 1301.18	DEA registration by location; registration categories; Schedule I research protocols
21 CFR 1301.75, 1301.76	Physical security controls; theft or loss
21 CFR 1304	Records and reports of registrants
21 CFR 1317	Disposal
ICH E6(R3) Annex 1, 2.10	Investigational Product Management
ICH E6(R3) Annex 1, 2.11	Randomisation Procedures and Unblinding
ISO 14155 (current edition)	Clinical investigation of medical devices for human subjects: Good clinical practice

Independent Site SOP Library. Licensed CC BY-NC 4.0 by the American Institute for Medical Research (AIMR), with added permission for any site's internal use (license terms). Not legal advice: each adopting site confirms state law, IRB and sponsor requirements with its own counsel and owns every step it approves.