Ensuring Compliance with Drug Accountability Requirements - Pharmaceutical Technology

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Ensuring Compliance with Drug Accountability Requirements
An expert discusses regulatory requirements for the drug accountability process.

Pharmaceutical Technology
Volume 37, Issue 10, pp. 126

Kurt Lumsden, Director Client Services at Perceptive Informatics, a subsidiary of PAREXEL , discusses regulatory requirements for the drug accountability process.

Q. How do I ensure my drug accountability process is adequate?

A. Although the need for drug accountability process compliance is essential, there are no clearly defined paths for ensuring the process is adequate. Regulations do not indicate a specific method or modality must be employed (1). However, as with other investigational product (IP) management processes and transactions, such as temperature excursion management and IP release or expiry update, adequate drug accountability is crucial to trial success.  

Accountability should be demonstrated by having full traceability of IMP/IP (investigational medicinal product) from initial release, ordering, allocation, and dispensation through return-to-site, accountability, reconciliation, and eventual destruction. If adequate accountability in these areas cannot be demonstrated, trial results are at risk.

According to 21 CFR 312.57(a), “a sponsor shall maintain adequate records showing the receipt, shipment, or other disposition of the investigational drug. These records are required to include, as appropriate, the name of the investigator to whom the drug is shipped, and the date, quantity, and batch or code mark of each such shipment” (2). Additionally, 21 CFR 312.62(a) states, “An investigator is required to maintain adequate records of the disposition of the drug, including dates, quantity, and use by subjects. If the investigation is terminated, suspended, discontinued, or completed, the investigator shall return the unused supplies of the drug to the sponsor, or otherwise provide for disposition of the unused supplies of the drug under 312.59” (3).

Adequate drug accountability will provide transparency through the IP chain of custody. This involves maintaining records that document past and current IP disposition with relevant dates and other details such as batch, allocated subject, and expiry.


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Use of electronic applications for collection and tracking of accountability data may provide considerable benefits over paper records. One important benefit is enhanced visibility through chain of custody by centralizing accountability trial data in a single system, which also improves reporting. This method allows demonstrated compliance with regulations and mitigates the likelihood of audit findings related to accountability. It also enables rapid completion of end-of-study documentation from one source.

Furthermore, electronic applications help improve the monitoring of ongoing site compliance with accountability activities and error checking, and reduce the overall burden created by the requirement for completion, collation, and tracking of paper records at every site. Process implementation for a specific trial will depend on a number of factors, including but not limited to:

  • IP classification--This will determine whether re-reconciliation is required
  • IP formulation--A liquid or gel vs. capsules or pills will determine if accountability required is quantitative or qualitative
  • IP route of administration (e.g., oral, intravenous, subcutaneous--If the product or packaging could be considered hazardous, then destruction on site may be necessary
  • IP packaging and labeling (uniquely vs. non-uniquely numbered supplies)--Non-uniquely labeled drugs will only be traceable to the batch and quantity level in a blinded trial
  • Accountability process and documentation--Typically, accountability process and documentation involves the following steps:
    • Return of dispensed IP to the site (including used or partially used IP) by the patient (unless product was administered on site by a clinician)
    • IP accountability conducted by the site and confirmation of returned, lost, or damaged product
    • IP reconciliation conducted by the monitor with verification of the accounted product
    • Destruction on-site or return of the IP to the final destruction facility.

Adequate drug accountability is crucial to drug trial success.An adequate process should be clear and understood by stakeholders, with seamless implementation and robust compliance monitoring. Factors such as trial design, jurisdiction, and IP-designation configuration (4), or route of administration, influence the specific steps required for a trial. Electronic applications that track accountability can provide important benefits to effective trial management.

1. ICH, Good Clinical Practice (E6 - 1996 section 4.63), May 1996.
 2. FDA, 21 CFR 312.57, April 1, 2013.
3. FDA, 21 CFR 312.62(a), April 1, 2013.
4. FDA, 21 CFR 3.2(e), April 1, 2013.


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