Office of Human Research
Page Title

SOP No.: 502    INVESTIGATIONAL PRODUCT INVENTORY MANAGEMENT

Author:    Office of Human Research

Effective Date:  October 1, 2007

Supercedes document dated:              N/A

Last Reviewed on:     N/A                                 

Results of Review:               N/A

This SOP pertains to:  Any investigation product (drug, biologic, medical device)

Responsibility for executing this SOP:  Investigator and Designated Research Personnel

Approved By:

 

J. Bruce Smith, MD

 

Associate Vice President for Research

 

(signature on file at OHR)

Approved By:

 

Steven E. McKenzie, MD, Ph.D.

 

Vice President for Research

 

(signature on file at OHR)

 

1. INTRODUCTION AND PURPOSE

This procedure describes the methods to be used for the labeling, distribution, receipt, dispensation, accounting, and return of investigational products used for FDA-regulated human subject research. While some Good Manufacturing Practice (GMP) issues are addressed, this procedure does not address GMP regulations for the manufacture of investigational products.

2. GENERAL INSTRUCTIONS AND RESPONSIBILITIES

  1. The Investigator is responsible for ensuring that investigational product manufacture, labeling and packaging is conducted in compliance with GMP.
  2. The Investigator is responsible for accurate and complete accountability and proper storage of the investigational products used in a clinical study.
  3. The Department of Pharmacy Services’ Investigational Drug Service (IDS) may assist the Sponsor Investigator with drug inventory and accountability requirements.
  4. The Investigator and all other participating Investigators or their designees are responsible for maintaining drug, biologic, or medical device accountability records from the time of receipt to the time of final disposition (e.g., return to the Investigator) on a per subject basis.
  5. Neither the Investigator nor any other participating Investigator will represent the investigational product as safe or effective for the purposes for which it is under clinical study or otherwise promote the product.
  6. The Investigator or designee is responsible for providing Monitors to assess investigational product accountability during monitoring visits.

3. SPECIFIC PROCEDURES

3.1 Labeling and Release of Investigational Product

  1. The Investigator will consult with the Office of Human Research (OHR) on any questions pertaining to investigational product manufacture, labeling and release. The Sponsor Investigator may consult with the OHR regarding retaining a qualified contractor to manufacture, label, or release the investigational product.
  2. The Investigator should provide a copy of the protocol to the manufacturer (e.g., contract manufacturer) of the investigational product for ascertaining the final configuration (content, packaging) of the investigational product. The description includes but is not limited to:
    • The number of subjects on each type of drug/device
    • The dosing schedule
    • Randomization code, if necessary
    • A description of the size, type and components of subject kits
    • Package sterility requirements
  3. The investigational product will be packaged in a manner consistent with the protocol requirements and, if blinded, the blind should be established and maintained as instructed in the protocol.
  4. The Investigator should confirm that, prior to shipping, the investigational product is checked to confirm it is packaged properly and the labels and/or labeling provide the information that is required by the applicable regulations. The Investigator should refer to the specific regulations and OHR for the information that is required.
  5. The information required on the product label or in accompanying labeling may include but is not limited to the following:
    • Study name and number
    • Drug/biologic/medical device name
    • Dosage and formulation
    • Lot number
    • Sponsor name and place of business
    • FDA required statement: "CAUTION: New Drug (or Investigational Device) - Limited by US law to investigational use."
    • Subject numbers and/or visit numbers
    • Special instructions regarding dosage or storage
    • For investigational devices, a draft package insert, user manual or other labeling that includes contraindications, hazards, warnings, precautions, adverse effects, interfering substances and devices
    • Expiration date
    • Quantity in container
    • Any other information required in the applicable investigational product labeling regulations
  6. The Investigator must give the manufacturer final authorization to ship investigational products to the investigative site(s) when all initiation visit training and applicable regulatory requirements have been fulfilled by the site(s).
  7. The carrier that is used must be one that provides signed receipts for delivery to the site(s). A copy of the signed receipt should be obtained and filed in the appropriate section of the Regulatory Master File.
  8. The investigational product shipment to the investigative site(s) should include an Investigational Product Release/Transfer Form (See SOP 502 Attachment A), which serves as a shipping record for the manufacturer/shipper, and after it is completed, signed and returned from the site(s) to the shipper (see below), it also serves as confirmation of investigational product receipt at the site(s), and will be maintained in the Regulatory Master File.
  9. The shipper will retain a copy of the Investigational Product Release Form until the signed copy is received back from the investigative site(s). The shipper retains the two forms and also provides copies to the Investigator for the appropriate section of the Regulatory Master File.
  10. If the Investigator is manufacturing the investigational product at his/her site, he/she or a designee will perform the steps outlined above.
  11. All investigational products must be released in a manner that allows for adequate stock control throughout the duration of the clinical study.
  12. If required by FDA, the Investigator will retain reserve samples of investigational products for further examination if necessary. OHR may be consulted about these requirements.
  13. The Investigator is required to submit to OHR any available documentation showing product manufacturing compliance when the Sponsor Investigator or his agents are manufacturing investigational product.

3.2 Investigational Product Receipt and Inventory

  1. For investigational drug studies, the Investigator or designee will contact the Department of Pharmacy Services' Investigational Drug Service (IDS) to ensure coordination and compliance with (or exemption from) existing University policies and procedures for the control and accountability of investigational drugs.
  2. The IDS web site should be consulted to access any required IDS forms or instructions, such  the "Prescription Labeling Requirements."
  3. Upon receiving investigational products from the Investigator (or other manufacturing source or IDS), the Investigator or designee at each investigative site will perform an inventory, including verifying lot numbers, study participant numbers, and the contents of each kit, against the information provided on the Investigational Product Release Form, labels and labeling.
  4. The Investigator or designee will sign the form and return it to the Investigator (or other shipper) with comments on any missing investigational product or other discrepancies.
  5. If there is an urgent need to replace any missing or otherwise discrepant contents, the Investigator (or other shipper) should be contacted immediately.
  6. A copy of the form is kept in each site's study file and is subject to review during routine monitoring visits by the Monitor.

3.3 Storage and Dispensing

  1. The Investigator Brochure and/or FDA-approved package insert (if applicable) and/or the IRB-approved protocol should be reviewed for information about the investigational product, its proper use (including distribution by protocol-specified randomization schema) and storage during the study.
  2. The investigational product must be stored in a secure place with access limited to those directly involved in the study.
  3. If the investigational drug is a controlled substance, it must be kept in a controlled, locked area with access provided only to key study personnel who have the appropriate authorization.
  4. Storage conditions (room temperature, refrigeration, etc.) specific to the investigational product will be observed and monitored, i.e., if refrigeration is required, the investigational product must be kept in a secure refrigerator; with appropriate equipment monitoring performed and documented.
  5. If the investigational product is blinded, the blind will not be broken except in the case of an emergency or a protocol-defined situation.
  6. The protocol should be consulted for explicit directions about breaking the blind for the investigational product.
  7. If the blind is broken, the Investigator will be notified, and the exact manner in which the code was broken and the rationale are noted in writing in the site's file.
  8. Any instance of unblinding of investigational product will be reported to the IRB
  9. During the study a Study Subject Investigational Product Dispensing Form will be kept on each subject including visit number, date, lot number, and the amount dispensed, returned, and lost by each study subject (See SOP 502 Attachment B).
  10. Using a baseline count or inventory as the starting point, and as each medication is dispensed, a record will be made in the dispensing log. At the end of the study this list will be totaled and compared with the final drug/device inventory and discrepancies are noted.
  11. Empty containers of investigational product (if applicable) should be retained until study completion for accountability purposes
  12. An Investigational Product Accountability Form should always be kept with the investigational product supplies, and using a baseline count or inventory as the starting point, a notation must be made every time an investigational product is dispensed or returned (See SOP 502, Attachment C).
  13. During routine monitoring visits and the study closeout visit, the Monitor will verify that investigational product documentation has been accurate and complete throughout the study.

3.4 Final Product Accountability Verification

  1. All investigational product records must serve to document the chain of custody for investigational product from the manufacturer to the investigative site and back to the Investigator.
  2. After the study is completed, a complete inventory of the investigational products must be conducted before the unused products are returned to the Investigator, cross-referencing all the forms described in previous sections.
  3. ONLY at the express instruction of the Investigator, and preferably in writing, should any investigational product be destroyed at sites other than his/her own.
  4. Prior to their return (or destruction, if permitted by the Investigator), a full accountability of all investigational product will be performed and any discrepancies in the beginning and ending inventory will be documented in writing and explained on the Investigational Product Accountability Form.
  5. Copies of the Investigational Product Release/Transfer Form, the Investigational Product Accountability Form, including post-study inventory, and all Study Subject Investigational Product Dispensing Forms will be kept in the study files at the site(s).
  6. A copy of the final Investigational Product Accountability Form will be returned to the Investigator with all remaining investigational product.
  7. Investigational product accountability records are kept for two years after a marketing application is approved for the product or if the application is not approved, until two years after shipment and delivery of the product for investigational use is discontinued and the Investigator has notified FDA.

4. APPLICABLE REGULATIONS AND GUIDELINES

21 CFR 312.60

General responsibilities of investigators

21 CFR 312.62

Investigator recordkeeping and record retention

21 CFR 312.68

Inspection of investigator’s records and reports

FDA Information Sheets, October 1995

Recordkeeping in Clinical Investigations

May 9 1997

International Conference on Harmonisation; Good Clinical Practice: Consolidated Guideline

5. REFERENCES TO OTHER APPLICABLE SOPs

GA-102

Responsibilities of the Research Team

SS-204

Protocol Start-Up

PM-304

Sponsor/CRO Monitoring Visits

PM-305

Study Termination Visit

DM-501

Data Management

QA-601

Audits

6. ATTACHMENTS

A.          Investigational Product Release/Transfer Form

B.           Study Subject Investigational Product Dispensing Form

C.          Investigational Product Accountability Form

7. DEFINITIONS AND GLOSSARY

The following definitions from the International Conference on Harmonisation, Good Clinical Practice: Consolidated Guideline apply to this SOP.

Confidentiality: Prevention of disclosure, to other than authorized individuals, of a sponsor’s proprietary information or of a subject’s identity.

Direct Access: Permission to examine, analyze, verify, and reproduce any records and reports that are important to evaluation of a clinical trial. Any party (e.g., domestic and foreign regulatory authorities, sponsors, monitors, and auditors) with direct access should take all reasonable precautions within the constraints of the applicable regulatory requirement(s) to maintain the confidentiality of subjects’ identities and sponsor’s proprietary information.

Documentation: All records, in any form (including, but not limited to, written, electronic, magnetic, and optical records; and scans, x-rays, and electrocardiograms) that describe or record the methods, conduct, and/or results of a trial, the factors affecting a trial, and the actions taken.

Essential Documents: Documents that individually and collectively permit evaluation of the conduct of a study and the quality of the data produced.

Inspection: The act by a regulatory authority(ies) of conducting an official review of documents, facilities, records, and any other resources that are deemed by the authority(ies) to be related to the clinical trial and that may be located at the site of the trial, at the sponsor’s and/or contract research organization’s (CRO’s) facilities, or at other establishments deemed appropriate by the regulatory authority(ies).

Quality Assurance (QA): All those planned and systematic actions that are established to ensure that the trial is performed and the data are generated, documented (recorded), and reported in compliance with GCP and the applicable regulatory requirement(s).

Source Documents: Original documents, data, and records (e.g., hospital records, clinical and office charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions certified after verification as being accurate and complete, microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the laboratories, and at medico-technical departments involved in the clinical trial).

 

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