Managing Drug Accountability

The sponsor is responsible for providing the investigator with investigational drug(s). Both the sponsor and the investigator have a role in drug accountability. The sponsor's representative inspects storage of investigational product supplies; checks study site investigational product dispensing records; checks randomization and blinding; and maintains records of investigational product shipments. The monitor reconciles investigational product shipped, dispensed and returned; arranges for shipment of investigational product to core country or investigative sites; checks investiga-tional product supplies at site against enrollment and withdrawals; maintains investigational product accountability records; resolves investigational product inventory problems; implements tracking system for investigational product management on a study and project level; arranges for the return and/or destruction of unused investigational product supplies; and ensures final reconciliation of investigational product supplies.

GCPs require sponsors to be able to account for the drug supplies prepared and shipped to the investigator, the investigator's use of those supplies, and the return and destruction of remaining drug supplies. Planning drug supplies is a detailed and complex activity. Bulk and formulated drug requests must typically be made at least 6 months in advance of the need for those supplies. This is to account for the ordering of intermediates or finished drug, purchasing of comparator agents, and for quality control testing.

Drug packaging should follow as consistent a format as possible within a project and must be identical within multicenter trials. Regulatory documents required for investigational drug use in the core countries must be anticipated and made available when needed, e.g. methods of analysis, stability data, customs declarations. The typical requirements for drug labels is described in Table 3.5.

Once the study is under way, the use of the investigational drug must be accounted for by the investigator's staff. Subjects should return unused medication and empty containers to the investigator. The amount of drug dispensed and the amount used by the patients are compared for discrepancies. This provides a measure of compliance by the study subjects. Monitors must also check that drug

Table 3.5 Typical labeling requirements for investiga-tional drug

Local language

Route of administration

Name of investigator


Study number

Dosage form

Bottle number

Quantity or volume

Lot number

Storage precautions

Drug name or code

Directions for use

Manufacturer name

Note: 'For Clinical Trial'

Manufacturer address

Caution statement

Local affiliate name

Expiry date

supplies are being kept under the required storage conditions.

Study drug must be dispensed according to the randomization schedule. Failure to do so can result in some of the data having to be discarded during statistical analysis. This issue can prove to be problematic when a single site is studying patients at different locations. Finally, the double-blind code must not be broken, except when essential for the management of adverse events. The breaking of treatment codes can make that patient's data unusable for efficacy analyses.

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