Sponsors—Can You Answer 6 Questions Regulators ask During Audits?


Applied Clinical Trials

During an audit, the FDA investigates six areas to determine whether a site is in compliance with federal drug accountability regulations-can sponsors answer them?

From 1977-when the FDA began routine clinical trial audits-to 1990 insufficient drug accountability records were found in 25% of audited sites. From 1994 to 2010 FDA investigators found inadequate drug accountability records in about 15% of sites audited in the U.S. and 20% in Europe. 

FDA trial site audits are designed to evaluate the conduct of research and ensure patients’ rights, safety, and welfare have been protected. During an audit, the FDA investigates six areas to determine whether a site is in compliance with federal drug accountability regulations:

  • Who is authorized to administer or dispense the investigational drug?

  • Has the investigational drug been supplied to any unauthorized person?

  • Can the records for investigational drug inventory be reconciled, i.e., the quantities shipped, received, used, and returned or destroyed?

  • Can drug shipments, dispersals, and returns be verified?

  • Is the drug stored in the manner mandated by the protocol?

  • Does the storage of drugs with the potential of abuse meet the federal regulations for controlled substances?

If a sponsor or CRO can’t answer these questions and prove compliance, consequences can be severe and far-reaching. A failed site audit can lead to costly delays, non-approval of the investigational drug, and/or criminal liability. Sites with inadequate drug accountability management may inadvertently increase safety risks for patients. For example, site staff might disperse the wrong dose or the wrong drug to patients. Insufficient drug accountability records may make it difficult for site staff to determine if a patient is treatment compliant or has returned all unused trial drug.

Unfortunately, most sites still use paper records to manage drug accountability. Paper is hard to administer and puts a burden on site staff and monitors. Paper also creates opportunities for illicit activity by staff.

Sponsors and CROs can prevent these problems and ensure trial site comply with federal regulations by adding electronic drug accountability to an existing IRT (Interactive Response Technology) system. Electronic drug accountability is proven to increase patients’ safety, save time and money, and ensure data validity.

IRT systems have been used on thousands of clinical trials for a myriad of tasks from patient randomization to drug supply management and allocation. IRT helps enable drug accountability because it tracks drug dispensing units by warehouse, depot, and site location as well as by batch, bulk lot, packaging step, label group, and patient allocation.

All trials can benefit from using IRT for electronic drug accountability management because IRT is designed with safeguards that reduce the risk of human error. It can automatically timestamp dispensing information; automatically flag entries that do not adhere to protocol; enforce compliance by mandating staff to write summary statements for potential protocol deviations; and, create an audit trail with electronic signatures that helps preserve the integrity of the trial data. IRT also allows for remote, site-level monitoring of drug accountability logs.

These capabilities and the built-in safeguards make electronic drug accountability a more accurate and efficient method than paper. For example, IRT links records, which eliminates time-consuming collating of files at the end of the trial. This timesaving feature is also cost-effective because it reduces the need for costly site visits by the clinical trial monitor, which can account for up to 35% of the overall cost of a Phase III trial.

IRT centralizes information and reports it in a uniform format that is always available for review. This is a vitally important feature for trials investigating drugs with the potential for abuse. For this type of trial, the FDA mandates sponsors provide all information including case report forms and final outcomes on all instances of drug diversion, discrepancies in inventory of the clinical supplies of the study drug, and noncompliance and protocol violations. Complying with this federal mandate requires a substantial increase in the administrative burden on clinical site staff when paper-based methods for drug accountability are used. The availability of centralized trial information provided by an IRT system is invaluable for this and other tasks including reconciling inventories of investigational drug supplies at study termination.

A centralized accountability system allows sponsors to easily track trial drugs from manufacture to shipping, use, return, and/or destruction. IRT also provides site-level, real-time tracking of investigational drug supplies. This reduces the possibility of drug diversion or inappropriate drug assignment by clinical staff as well as patient non-compliance.

Organizations should plan for some resistance to change before undertaking the switch from a paper to electronic drug accountability system. High-level stakeholders should develop an implementation plan for the change and write standard operating procedures for adoption and use of electronic drug accountability. The new procedures should ensure electronic accountability can fully replace paper when implemented. If done correctly, electronic drug accountability combined with an IRT system will help ensure sponsors and CROs can answer those critical six questions regulators ask during audits.


Stefan Düerr, Senior Director of Client Delivery and Head of Drug Supply Center of Excellence at Cenduit LLC. He can be reached at stefan.duerr@cenduit.com


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